Transcriptional profiling of Medicago truncatula under salt stress identified a novel CBF transcription factor MtCBF4 that plays an important role in abiotic stress responses

PubMed Central

2011-01-01

Background Salt stress hinders the growth of plants and reduces crop production worldwide. However, different plant species might possess different adaptive mechanisms to mitigate salt stress. We conducted a detailed pathway analysis of transcriptional dynamics in the roots of Medicago truncatula seedlings under salt stress and selected a transcription factor gene, MtCBF4, for experimental validation. Results A microarray experiment was conducted using root samples collected 6, 24, and 48 h after application of 180 mM NaCl. Analysis of 11 statistically significant expression profiles revealed different behaviors between primary and secondary metabolism pathways in response to external stress. Secondary metabolism that helps to maintain osmotic balance was induced. One of the highly induced transcription factor genes was successfully cloned, and was named MtCBF4. Phylogenetic analysis revealed that MtCBF4, which belongs to the AP2-EREBP transcription factor family, is a novel member of the CBF transcription factor in M. truncatula. MtCBF4 is shown to be a nuclear-localized protein. Expression of MtCBF4 in M. truncatula was induced by most of the abiotic stresses, including salt, drought, cold, and abscisic acid, suggesting crosstalk between these abiotic stresses. Transgenic Arabidopsis over-expressing MtCBF4 enhanced tolerance to drought and salt stress, and activated expression of downstream genes that contain DRE elements. Over-expression of MtCBF4 in M. truncatula also enhanced salt tolerance and induced expression level of corresponding downstream genes. Conclusion Comprehensive transcriptomic analysis revealed complex mechanisms exist in plants in response to salt stress. The novel transcription factor gene MtCBF4 identified here played an important role in response to abiotic stresses, indicating that it might be a good candidate gene for genetic improvement to produce stress-tolerant plants. PMID:21718548

Cold-inducible transcription factor, CaCBF, is associated with a homeodomain leucine zipper protein in hot pepper (Capsicum annuum L.).

PubMed

Kim, Sihyun; An, Chung Sun; Hong, Young-Nam; Lee, Kwang-Woong

2004-12-31

C-Repeat/drought responsive element binding factor (CBF1/DREB1b) is a well known transcriptional activator that is induced at low temperature and in turn induces the CBF regulon (CBF-targeted genes). We have cloned and characterized two CBF1-like cDNAs, CaCBF1A and CaCBF1B, from hot pepper. CaCBF1A and CaCBF1B were not produced in response to mechanical wounding or abscisic acid but were induced by low-temperature stress at 4 degrees . When plants were returned to 25 degrees , their transcript levels of the CBF1-like genes decreased markedly within 40 min. Long-term exposure to chilling resulted in continuous expression of these genes. The critical temperature for induction of CaCBF1A was between 10 and 15 degrees . Low temperature led to its transcription in roots, stems, leaves, fruit without seeds, and apical meristems, and a monoclonal antibody against it revealed a significant increase in CaCBF1A protein by 4 h at 4 degrees . Two-hybrid screening led to the isolation of an homeodomain leucine zipper (HD-Zip) protein that interacts with CaCBF1B. Expression of HD-Zip was elevated by low temperature and drought.

Deletion of Core-binding factor β (Cbfβ) in mesenchymal progenitor cells provides new insights into Cbfβ/Runxs complex function in cartilage and bone development

PubMed Central

Wu, Mengrui; Li, Chenguan; Zhu, Guochun; Wang, Yiping; Jules, Joel; Lu, Yun; McConnell, Matthew; Wang, Yong-Jun; Shao, Jian-Zhong; Li, Yi-Ping; Chen, Wei

2015-01-01

Core-binding factor β (Cbfβ) is a subunit of the Cbf family of heterodimeric transcription factors which plays a critical role in skeletal development through its interaction with the Cbfα subunits, also known as Runt-related transcription factors (Runxs). However, the mechanism by which Cbfβ regulates cartilage and bone development remains unclear. Existing Cbfβ-deficient mouse models cannot specify the role of Cbfβ in skeletal cell lineage. Herein, we sought to specifically address the role of Cbfβ in cartilage and bone development by using a conditional knockout (CKO) approach. A mesenchymal-specific Cbfβ CKO mouse model was generated by using the Dermo1-Cre mouse line to specifically delete Cbfβ in mesenchymal stem cells, which give rise to osteoblasts and chondrocytes. Surprisingly, the mutant mice had under-developed larynx and tracheal cartilage causing alveolus defects which led to death shortly after birth from suffocation. Also, the mutant mice exhibited severe skeletal deformities from defective intramembranous and endochondral ossification, owing to delayed chondrocyte maturation and impaired osteoblast differentiation. Almost all bones of the mutant mice, including the calvariae, vertebrae, tibiae, femurs, ribs, limbs and sternums were defective. Importantly, we showed that Cbfβ was expressed throughout the skeleton during both embryonic and postnatal development, which explains the multiple-skeletal defects observed in the mutant mice. Consistently, Cbfβ deficiency impaired both chondrocyte proliferation and hypertrophy zone hypertrophy during growth-plate development in the long bones of mutant mice. Notably, Cbfβ, Runx1 and Runx2 displayed different expression patterns in the growth plates of the wildtype mice indicating that Cbfβ/Runx1 complex and Cbfβ/Runx2 complex may regulate chondrocyte proliferation and hypertrophy, respectively, in a spatial and temporal manner. Cbfβ deletion in the mesenchymal progenitors impacted bone development by dramatically down-regulating Collagen X (Col X) and Osterix (Osx), but had a dispensable effect on osteoclast development. Collectively, the results demonstrate that Cbfβ mediates cartilage and bone development by interacting with Runx1 and Runx2 to regulate the expressions of Col X and Osx for chondrocyte and osteoblast development. These findings not only reveal a critical role for Cbfβ in cartilage and bone development, but also facilitate the design of novel therapeutic approaches for skeletal diseases. PMID:24798493

Deletion of core-binding factor β (Cbfβ) in mesenchymal progenitor cells provides new insights into Cbfβ/Runxs complex function in cartilage and bone development.

PubMed

Wu, Mengrui; Li, Chenguan; Zhu, Guochun; Wang, Yiping; Jules, Joel; Lu, Yun; McConnell, Matthew; Wang, Yong-Jun; Shao, Jian-Zhong; Li, Yi-Ping; Chen, Wei

2014-08-01

Core-binding factor β (Cbfβ) is a subunit of the Cbf family of heterodimeric transcription factors, which plays a critical role in skeletal development through its interaction with the Cbfα subunits, also known as Runt-related transcription factors (Runxs). However, the mechanism by which Cbfβ regulates cartilage and bone development remains unclear. Existing Cbfβ-deficient mouse models cannot specify the role of Cbfβ in skeletal cell lineage. Herein, we sought to specifically address the role of Cbfβ in cartilage and bone development by using a conditional knockout (CKO) approach. A mesenchymal-specific Cbfβ CKO mouse model was generated by using the Dermo1-Cre mouse line to specifically delete Cbfβ in mesenchymal stem cells, which give rise to osteoblasts and chondrocytes. Surprisingly, the mutant mice had under-developed larynx and tracheal cartilage, causing alveolus defects that led to death shortly after birth from suffocation. Also, the mutant mice exhibited severe skeletal deformities from defective intramembranous and endochondral ossification, owing to delayed chondrocyte maturation and impaired osteoblast differentiation. Almost all bones of the mutant mice, including the calvariae, vertebrae, tibiae, femurs, ribs, limbs and sternums were defective. Importantly, we showed that Cbfβ was expressed throughout the skeleton during both embryonic and postnatal development, which explains the multiple-skeletal defects observed in the mutant mice. Consistently, Cbfβ deficiency impaired both chondrocyte proliferation and hypertrophy zone hypertrophy during growth-plate development in the long bones of mutant mice. Notably, Cbfβ, Runx1 and Runx2 displayed different expression patterns in the growth plates of the wild-type mice, indicating that Cbfβ/Runx1 complex and Cbfβ/Runx2 complex may regulate chondrocyte proliferation and hypertrophy, respectively, in a spatial and temporal manner. Cbfβ deletion in the mesenchymal progenitors affected bone development by dramatically down-regulating Collagen X (Col X) and Osterix (Osx) but had a dispensable effect on osteoclast development. Collectively, the results demonstrate that Cbfβ mediates cartilage and bone development by interacting with Runx1 and Runx2 to regulate the expressions of Col X and Osx for chondrocyte and osteoblast development. These findings not only reveal a critical role for Cbfβ in cartilage and bone development but also facilitate the design of novel therapeutic approaches for skeletal diseases. Copyright © 2014. Published by Elsevier Inc.

An investigation of cerebral oxygen utilization, blood flow and cognition in healthy aging.

PubMed

Catchlove, Sarah J; Macpherson, Helen; Hughes, Matthew E; Chen, Yufen; Parrish, Todd B; Pipingas, Andrew

2018-01-01

Understanding how vascular and metabolic factors impact on cognitive function is essential to develop efficient therapies to prevent and treat cognitive losses in older age. Cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF) and venous oxygenation (Yv) comprise key physiologic processes that maintain optimum functioning of neural activity. Changes to these parameters across the lifespan may precede neurodegeneration and contribute to age-related cognitive decline. This study examined differences in blood flow and metabolism between 31 healthy younger (<50 years) and 29 healthy older (>50 years) adults; and investigated whether these parameters contribute to cognitive performance. Participants underwent a cognitive assessment and MRI scan. Grey matter CMRO2 was calculated from measures of CBF (phase contrast MRI), arterial and venous oxygenation (TRUST MRI) to assess group differences in physiological function and the contribution of these parameters to cognition. Performance on memory (p<0.001) and attention tasks (p<0.001) and total CBF were reduced (p<0.05), and Yv trended toward a decrease (p = .06) in the older group, while grey matter CBF and CMRO2 did not differ between the age groups. Attention was negatively associated with CBF when adjusted (p<0.05) in the older adults, but not in the younger group. There was no such relationship with memory. Neither cognitive measure was associated with oxygen metabolism or venous oxygenation in either age group. Findings indicated an age-related imbalance between oxygen delivery, consumption and demand, evidenced by a decreased supply of oxygen with unchanged metabolism resulting in increased oxygen extraction. CBF predicted attention when the age-effect was controlled, suggesting a task- specific CBF- cognition relationship.

Photoperiodic regulation of the C-repeat binding factor (CBF) cold acclimation pathway and freezing tolerance in Arabidopsis thaliana.

PubMed

Lee, Chin-Mei; Thomashow, Michael F

2012-09-11

The CBF (C-repeat binding factor) pathway has a major role in plant cold acclimation, the process whereby certain plants increase in freezing tolerance in response to low nonfreezing temperatures. In Arabidopsis thaliana, the pathway is characterized by rapid cold induction of CBF1, CBF2, and CBF3, which encode transcriptional activators, followed by induction of CBF-targeted genes that impart freezing tolerance. At warm temperatures, CBF transcript levels are low, but oscillate due to circadian regulation with peak expression occurring at 8 h after dawn (zeitgeber time 8; ZT8). Here, we establish that the CBF pathway is also regulated by photoperiod at warm temperatures. At ZT8, CBF transcript levels in short-day (SD; 8-h photoperiod) plants were three- to fivefold higher than in long-day plants (LD; 16-h photoperiod). Moreover, the freezing tolerance of SD plants was greater than that of LD plants. Genetic analysis indicated that phytochrome B (PHYB) and two phytochrome-interacting factors, PIF4 and PIF7, act to down-regulate the CBF pathway and freezing tolerance under LD conditions. Down-regulation of the CBF pathway in LD plants correlated with higher PIF4 and PIF7 transcript levels and greater stability of the PIF4 and PIF7 proteins under LD conditions. Our results indicate that during the warm LD growing season, the CBF pathway is actively repressed by PHYB, PIF4, and PIF7, thus mitigating allocation of energy and nutrient resources toward unneeded frost protection. This repression is relieved by shortening day length resulting in up-regulation of the CBF pathway and increased freezing tolerance in preparation for coming cold temperatures.

Photoperiodic regulation of the C-repeat binding factor (CBF) cold acclimation pathway and freezing tolerance in Arabidopsis thaliana

PubMed Central

Lee, Chin-Mei; Thomashow, Michael F.

2012-01-01

The CBF (C-repeat binding factor) pathway has a major role in plant cold acclimation, the process whereby certain plants increase in freezing tolerance in response to low nonfreezing temperatures. In Arabidopsis thaliana, the pathway is characterized by rapid cold induction of CBF1, CBF2, and CBF3, which encode transcriptional activators, followed by induction of CBF-targeted genes that impart freezing tolerance. At warm temperatures, CBF transcript levels are low, but oscillate due to circadian regulation with peak expression occurring at 8 h after dawn (zeitgeber time 8; ZT8). Here, we establish that the CBF pathway is also regulated by photoperiod at warm temperatures. At ZT8, CBF transcript levels in short-day (SD; 8-h photoperiod) plants were three- to fivefold higher than in long-day plants (LD; 16-h photoperiod). Moreover, the freezing tolerance of SD plants was greater than that of LD plants. Genetic analysis indicated that phytochrome B (PHYB) and two phytochrome-interacting factors, PIF4 and PIF7, act to down-regulate the CBF pathway and freezing tolerance under LD conditions. Down-regulation of the CBF pathway in LD plants correlated with higher PIF4 and PIF7 transcript levels and greater stability of the PIF4 and PIF7 proteins under LD conditions. Our results indicate that during the warm LD growing season, the CBF pathway is actively repressed by PHYB, PIF4, and PIF7, thus mitigating allocation of energy and nutrient resources toward unneeded frost protection. This repression is relieved by shortening day length resulting in up-regulation of the CBF pathway and increased freezing tolerance in preparation for coming cold temperatures. PMID:22927419

Changes in regional cerebral blood flow in the right cortex homologous to left language areas are directly affected by left hemispheric damage in aphasic stroke patients: evaluation by Tc-ECD SPECT and novel analytic software.

PubMed

Uruma, G; Kakuda, W; Abo, M

2010-03-01

The objective of this study was to clarify the influence of regional cerebral blood flow (rCBF) changes in language-relevant areas of the dominant hemisphere on rCBF in each region in the non-dominant hemisphere in post-stroke aphasic patients. The study subjects were 27 aphasic patients who suffered their first symptomatic stroke in the left hemisphere. In each subject, we measured rCBF by means of 99mTc-ethylcysteinate dimmer single photon emission computed tomography (SPECT). The SPECT images were analyzed by the statistical imaging analysis programs easy Z-score Imaging System (eZIS) and voxel-based stereotactic extraction estimation (vbSEE). Segmented into Brodmann Area (BA) levels, Regions of Interest (ROIs) were set in language-relevant areas bilaterally, and changes in the relative rCBF as average negative and positive Z-values were computed fully automatically. To assess the relationship between rCBF changes of each ROIs in the left and right hemispheres, the Spearman ranked correlation analysis and stepwise multiple regression analysis were applied. Globally, a negative and asymmetric influence of rCBF changes in the language-relevant areas of the dominant hemisphere on the right hemisphere was found. The rCBF decrease in left BA22 significantly influenced the rCBF increase in right BA39, BA40, BA44 and BA45. The results suggested that the chronic increase in rCBF in the right language-relevant areas is due at least in part to reduction in the trancallosal inhibitory activity of the language-dominant left hemisphere caused by the stroke lesion itself and that these relationships are not always symmetric.

Relationship of cerebral blood flow to aortic-to-pulmonary collateral/shunt flow in single ventricles

PubMed Central

Fogel, Mark A; Li, Christine; Wilson, Felice; Pawlowski, Tom; Nicolson, Susan C; Montenegro, Lisa M; Berenstein, Laura Diaz; Spray, Thomas L; Gaynor, J William; Fuller, Stephanie; Keller, Marc S; Harris, Matthew A; Whitehead, Kevin K; Clancy, Robert; Elci, Okan; Bethel, Jim; Vossough, Arastoo; Licht, Daniel J

2016-01-01

Objective Patients with single ventricle can develop aortic-to-pulmonary collaterals (APCs). Along with systemic-to-pulmonary artery shunts, these structures represent a direct pathway from systemic to pulmonary circulations, and may limit cerebral blood flow (CBF). This study investigated the relationship between CBF and APC flow on room air and in hypercarbia, which increases CBF in patients with single ventricle. Methods 106 consecutive patients with single ventricle underwent 118 cardiac magnetic resonance (CMR) scans in this cross-sectional study; 34 prior to bidirectional Glenn (BDG) (0.50±0.30 years old), 50 prior to Fontan (3.19±1.03 years old) and 34 3–9 months after Fontan (3.98±1.39 years old). Velocity mapping measured flows in the aorta, cavae and jugular veins. Analysis of variance (ANOVA) and multiple linear regression were used. Significance was p<0.05. Results A strong inverse correlation was noted between CBF and APC/shunt both on room air and with hypercarbia whether CBF was indexed to aortic flow or body surface area, independent of age, cardiopulmonary bypass time, Po2 and Pco2 (R=−0.67–−0.70 for all patients on room air, p<0.01 and R=−0.49–−0.90 in hypercarbia, p<0.01). Correlations were not different between surgical stages. CBF was lower, and APCs/shunt flow was higher prior to BDG than in other stages. Conclusions There is a strong inverse relationship between CBF and APC/shunt flow in patients with single ventricle throughout surgical reconstruction on room air and in hypercarbia independent of other factors. We speculate that APC/shunt flow may have a negative impact on cerebral development and neurodevelopmental outcome. Interventions on APC may modify CBF, holding out the prospect for improving neurodevelopmental trajectory. Trial Registration Number NCT02135081. PMID:26048877

Relationship of cerebral blood flow to aortic-to-pulmonary collateral/shunt flow in single ventricles.

PubMed

Fogel, Mark A; Li, Christine; Wilson, Felice; Pawlowski, Tom; Nicolson, Susan C; Montenegro, Lisa M; Diaz Berenstein, Laura; Spray, Thomas L; Gaynor, J William; Fuller, Stephanie; Keller, Marc S; Harris, Matthew A; Whitehead, Kevin K; Clancy, Robert; Elci, Okan; Bethel, Jim; Vossough, Arastoo; Licht, Daniel J

2015-08-01

Patients with single ventricle can develop aortic-to-pulmonary collaterals (APCs). Along with systemic-to-pulmonary artery shunts, these structures represent a direct pathway from systemic to pulmonary circulations, and may limit cerebral blood flow (CBF). This study investigated the relationship between CBF and APC flow on room air and in hypercarbia, which increases CBF in patients with single ventricle. 106 consecutive patients with single ventricle underwent 118 cardiac magnetic resonance (CMR) scans in this cross-sectional study; 34 prior to bidirectional Glenn (BDG) (0.50±0.30 years old), 50 prior to Fontan (3.19±1.03 years old) and 34 3-9 months after Fontan (3.98±1.39 years old). Velocity mapping measured flows in the aorta, cavae and jugular veins. Analysis of variance (ANOVA) and multiple linear regression were used. Significance was p<0.05. A strong inverse correlation was noted between CBF and APC/shunt both on room air and with hypercarbia whether CBF was indexed to aortic flow or body surface area, independent of age, cardiopulmonary bypass time, Po2 and Pco2 (R=-0.67--0.70 for all patients on room air, p<0.01 and R=-0.49--0.90 in hypercarbia, p<0.01). Correlations were not different between surgical stages. CBF was lower, and APCs/shunt flow was higher prior to BDG than in other stages. There is a strong inverse relationship between CBF and APC/shunt flow in patients with single ventricle throughout surgical reconstruction on room air and in hypercarbia independent of other factors. We speculate that APC/shunt flow may have a negative impact on cerebral development and neurodevelopmental outcome. Interventions on APC may modify CBF, holding out the prospect for improving neurodevelopmental trajectory. NCT02135081. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Transcription Factor CBF4 Is a Regulator of Drought Adaptation in Arabidopsis1

PubMed Central

Haake, Volker; Cook, Daniel; Riechmann, José Luis; Pineda, Omaira; Thomashow, Michael F.; Zhang, James Z.

2002-01-01

In plants, low temperature and dehydration activate a set of genes containing C-repeat/dehydration-responsive elements in their promoter. It has been shown previously that the Arabidopsis CBF/DREB1 transcription activators are critical regulators of gene expression in the signal transduction of cold acclimation. Here, we report the isolation of an apparent homolog of the CBF/DREB1 proteins (CBF4) that plays the equivalent role during drought adaptation. In contrast to the three already identified CBF/DREB1 homologs, which are induced under cold stress, CBF4 gene expression is up-regulated by drought stress, but not by low temperature. Overexpression of CBF4 in transgenic Arabidopsis plants results in the activation of C-repeat/dehydration-responsive element containing downstream genes that are involved in cold acclimation and drought adaptation. As a result, the transgenic plants are more tolerant to freezing and drought stress. Because of the physiological similarity between freezing and drought stress, and the sequence and structural similarity of the CBF/DREB1 and the CBF4 proteins, we propose that the plant's response to cold and drought evolved from a common CBF-like transcription factor, first through gene duplication and then through promoter evolution. PMID:12376631

Voxel-wise meta-analyses of brain blood flow and local synchrony abnormalities in medication-free patients with major depressive disorder

PubMed Central

Chen, Zi-Qi; Du, Ming-Ying; Zhao, You-Jin; Huang, Xiao-Qi; Li, Jing; Lui, Su; Hu, Jun-Mei; Sun, Huai-Qiang; Liu, Jia; Kemp, Graham J.; Gong, Qi-Yong

2015-01-01

Background Published meta-analyses of resting-state regional cerebral blood flow (rCBF) studies of major depressive disorder (MDD) have included patients receiving antidepressants, which might affect brain activity and thus bias the results. To our knowledge, no meta-analysis has investigated regional homogeneity changes in medication-free patients with MDD. Moreover, an association between regional homogeneity and rCBF has been demonstrated in some brain regions in healthy controls. We sought to explore to what extent resting-state rCBF and regional homogeneity changes co-occur in the depressed brain without the potential confound of medication. Methods Using the effect-size signed differential mapping method, we conducted 2 meta-analyses of rCBF and regional homogeneity studies of medication-free patients with MDD. Results Our systematic search identified 14 rCBF studies and 9 regional homogeneity studies. We identified conjoint decreases in resting-state rCBF and regional homogeneity in the insula and superior temporal gyrus in medication-free patients with MDD compared with controls. Other changes included altered resting-state rCBF in the precuneus and in the frontal–limbic–thalamic–striatal neural circuit as well as altered regional homogeneity in the uncus and parahippocampal gyrus. Meta-regression revealed that the percentage of female patients with MDD was negatively associated with resting-state rCBF in the right anterior cingulate cortex and that the age of patients with MDD was negatively associated with rCBF in the left insula and with regional homogeneity in the left uncus. Limitations The analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous. Conclusion The conjoint alterations of rCBF and regional homogeneity in the insula and superior temporal gyrus may be core neuropathological changes in medication-free patients with MDD and serve as a specific region of interest for further studies on MDD. PMID:25853283

Voxel-wise meta-analyses of brain blood flow and local synchrony abnormalities in medication-free patients with major depressive disorder.

PubMed

Chen, Zi-Qi; Du, Ming-Ying; Zhao, You-Jin; Huang, Xiao-Qi; Li, Jing; Lui, Su; Hu, Jun-Mei; Sun, Huai-Qiang; Liu, Jia; Kemp, Graham J; Gong, Qi-Yong

2015-11-01

Published meta-analyses of resting-state regional cerebral blood flow (rCBF) studies of major depressive disorder (MDD) have included patients receiving antidepressants, which might affect brain activity and thus bias the results. To our knowledge, no meta-analysis has investigated regional homogeneity changes in medication-free patients with MDD. Moreover, an association between regional homogeneity and rCBF has been demonstrated in some brain regions in healthy controls. We sought to explore to what extent resting-state rCBF and regional homogeneity changes co-occur in the depressed brain without the potential confound of medication. Using the effect-size signed differential mapping method, we conducted 2 meta-analyses of rCBF and regional homogeneity studies of medication-free patients with MDD. Our systematic search identified 14 rCBF studies and 9 regional homogeneity studies. We identified conjoint decreases in resting-state rCBF and regional homogeneity in the insula and superior temporal gyrus in medication-free patients with MDD compared with controls. Other changes included altered resting-state rCBF in the precuneus and in the frontal-limbic-thalamic-striatal neural circuit as well as altered regional homogeneity in the uncus and parahippocampal gyrus. Meta-regression revealed that the percentage of female patients with MDD was negatively associated with resting-state rCBF in the right anterior cingulate cortex and that the age of patients with MDD was negatively associated with rCBF in the left insula and with regional homogeneity in the left uncus. The analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous. The conjoint alterations of rCBF and regional homogeneity in the insula and superior temporal gyrus may be core neuropathological changes in medication-free patients with MDD and serve as a specific region of interest for further studies on MDD.

Nicotine and non-nicotine smoking factors differentially modulate craving, withdrawal and cerebral blood flow as measured with arterial spin labeling.

PubMed

Addicott, Merideth A; Froeliger, Brett; Kozink, Rachel V; Van Wert, Dana M; Westman, Eric C; Rose, Jed E; McClernon, Francis J

2014-11-01

Smoking cessation results in withdrawal symptoms such as craving and negative mood that may contribute to lapse and relapse. Little is known regarding whether these symptoms are associated with the nicotine or non-nicotine components of cigarette smoke. Using arterial spin labeling, we measured resting-state cerebral blood flow (CBF) in 29 adult smokers across four conditions: (1) nicotine patch+denicotinized cigarette smoking, (2) nicotine patch+abstinence from smoking, (3) placebo patch+denicotinized cigarette smoking, and (4) placebo patch+abstinence from smoking. We found that changes in self-reported craving positively correlated with changes in CBF from the denicotinized cigarette smoking conditions to the abstinent conditions. These correlations were found in several regions throughout the brain. Self-reported craving also increased from the nicotine to the placebo conditions, but had a minimal relationship with changes in CBF. The results of this study suggest that the non-nicotine components of cigarette smoke significantly impact withdrawal symptoms and associated brain areas, independently of the effects of nicotine. As such, the effects of non-nicotine factors are important to consider in the design and development of smoking cessation interventions and tobacco regulation.

Nicotine and Non-Nicotine Smoking Factors Differentially Modulate Craving, Withdrawal and Cerebral Blood Flow as Measured with Arterial Spin Labeling

PubMed Central

Addicott, Merideth A; Froeliger, Brett; Kozink, Rachel V; Van Wert, Dana M; Westman, Eric C; Rose, Jed E; McClernon, Francis J

2014-01-01

Smoking cessation results in withdrawal symptoms such as craving and negative mood that may contribute to lapse and relapse. Little is known regarding whether these symptoms are associated with the nicotine or non-nicotine components of cigarette smoke. Using arterial spin labeling, we measured resting-state cerebral blood flow (CBF) in 29 adult smokers across four conditions: (1) nicotine patch+denicotinized cigarette smoking, (2) nicotine patch+abstinence from smoking, (3) placebo patch+denicotinized cigarette smoking, and (4) placebo patch+abstinence from smoking. We found that changes in self-reported craving positively correlated with changes in CBF from the denicotinized cigarette smoking conditions to the abstinent conditions. These correlations were found in several regions throughout the brain. Self-reported craving also increased from the nicotine to the placebo conditions, but had a minimal relationship with changes in CBF. The results of this study suggest that the non-nicotine components of cigarette smoke significantly impact withdrawal symptoms and associated brain areas, independently of the effects of nicotine. As such, the effects of non-nicotine factors are important to consider in the design and development of smoking cessation interventions and tobacco regulation. PMID:24820539

Ethylene and cold participate in the regulation of LeCBF1 gene expression in postharvest tomato fruits.

PubMed

Zhao, Danying; Shen, Lin; Fan, Bei; Yu, Mengmeng; Zheng, Yang; Lv, Shengnan; Sheng, Jiping

2009-10-20

C-repeat/dehydration-responsive element binding factor (CBF) is a transcription factor regulating cold response in plants, of which little is known in fruits. We showed a double-peak expression pattern of Lycopersicon esculentum putative transcriptional activator CBF1 (LeCBF1) in mature green fruit. The peaks appeared at 2 and 16 h after subjection to cold storage (2 degrees C). The second peak was coincident with, and thus caused by a peak in endogenous ethylene production. We showed that LeCBF1 expression was regulated by exogenous ethylene and 1-methylcyclopropene, and was not expressed without cold induction. LeCBF1 expression was different in the five maturation stages of fruits, but expression peaked at 2 h at all stages.

Recovery from Unrecognized Sleep Loss Accumulated in Daily Life Improved Mood Regulation via Prefrontal Suppression of Amygdala Activity

PubMed Central

Motomura, Yuki; Kitamura, Shingo; Nakazaki, Kyoko; Oba, Kentaro; Katsunuma, Ruri; Terasawa, Yuri; Hida, Akiko; Moriguchi, Yoshiya; Mishima, Kazuo

2017-01-01

Many modern people suffer from sleep debt that has accumulated in everyday life but is not subjectively noticed [potential sleep debt (PSD)]. Our hypothesis for this study was that resolution of PSD through sleep extension optimizes mood regulation by altering the functional connectivity between the amygdala and prefrontal cortex. Fifteen healthy male participants underwent an experiment consisting of a baseline (BL) evaluation followed by two successive interventions, namely, a 9-day sleep extension followed by one night of total sleep deprivation (TSD). Tests performed before and after the interventions included a questionnaire on negative mood and neuroimaging with arterial spin labeling MRI for evaluating regional cerebral blood flow (rCBF) and functional connectivity. Negative mood and amygdala rCBF were significantly reduced after sleep extension compared with BL. The amygdala had a significant negative functional connectivity with the medial prefrontal cortex (FCamg–MPFC), and this negative connectivity was greater after sleep extension than at BL. After TSD, these indices reverted to the same level as at BL. An additional path analysis with structural equation modeling showed that the FCamg–MPFC significantly explained the amygdala rCBF and that the amygdala rCBF significantly explained the negative mood. These findings suggest that the use of our sleep extension protocol normalized amygdala activity via negative amygdala–MPFC functional connectivity. The resolution of unnoticed PSD may improve mood by enhancing frontal suppression of hyperactivity in the amygdala caused by PSD accumulating in everyday life. PMID:28713328

A C-Repeat Binding Factor Transcriptional Activator (CBF/DREB1) from European Bilberry (Vaccinium myrtillus) Induces Freezing Tolerance When Expressed in Arabidopsis thaliana

PubMed Central

Oakenfull, Rachael J.; Baxter, Robert; Knight, Marc R.

2013-01-01

Freezing stress affects all plants from temperate zones to the poles. Global climate change means such freezing events are becoming less predictable. This in turn reduces the ability of plants to predict the approaching low temperatures and cold acclimate. This has consequences for crop yields and distribution of wild plant species. C-repeat binding factors (CBFs) are transcription factors previously shown to play a vital role in the acclimation process of Arabidopsis thaliana, controlling the expression of hundreds of genes whose products are necessary for freezing tolerance. Work in other plant species cements CBFs as key determinants in the trait of freezing tolerance in higher plants. To test the function of CBFs from highly freezing tolerant plants species we cloned and sequenced CBF transcription factors from three Vaccinium species (Vaccinium myrtillus, Vaccinium uliginosum and Vaccinium vitis-idaea) which we collected in the Arctic. We tested the activity of CBF transcription factors from the three Vaccinium species by producing transgenic Arabidopsis lines overexpressing them. Only the Vaccinium myrtillus CBF was able to substantially activate COR (CBF-target) gene expression in the absence of cold. Correspondingly, only the lines expressing the Vaccinium myrtillus CBF were constitutively freezing tolerant. The basis for the differences in potency of the three Vaccinium CBFs was tested by observing cellular localisation and protein levels. All three CBFs were correctly targeted to the nucleus, but Vaccinium uliginosum CBF appeared to be relatively unstable. The reasons for lack of potency for Vaccinium vitis-idaea CBF were not due to stability or targeting, and we speculate that this was due to altered transcription factor function. PMID:23349799

Nitric oxide modulates Lycopersicon esculentum C-repeat binding factor 1 (LeCBF1) transcriptionally as well as post-translationally by nitrosylation.

PubMed

Kashyap, Prakriti; Sehrawat, Ankita; Deswal, Renu

2015-11-01

Nitric oxide (NO) production increases in the cold stress. This cold enhanced NO manifests its effect either by regulating the gene expression or by modulating proteins by NO based post-translational modifications (PTMs) including S-nitrosylation. CBF (C-repeat binding factor) dependent cold stress signaling is most studied cold stress-signaling pathway in plants. SNP (sodium nitroprusside, a NO donor) treatment to tomato seedlings showed four fold induction of LeCBF1 (a cold inducible CBF) transcript in cold stress. S-nitrosylation as PTM of CBF has not been analyzed till date. In silico analysis using GPS-SNO 1.0 software predicted Cys 68 as the probable site for nitrosylation in LeCBF1. The 3D structure and motif prediction showed it to be present in the beta hairpin loop and hence available for S-nitrosylation. LeCBF1 was cloned and expressed in Escherichia coli. LeCBF1 accumulated in the inclusion bodies, which were solubilized under denaturing conditions and purified after on column refolding by Ni-NTA His tag affinity chromatography. Purified LeCBF1 resolved as a 34 kDa spot with a slightly basic pI (8.3) on a 2-D gel. MALDI-TOF mass spectrometry identified it as LeCBF1 and western blotting using anti-LeCBF1 antibodies confirmed its purification. Biotin switch assay and neutravidin affinity chromatography showed LeCBF1 to be S-nitrosylated in presence of GSNO (NO donor) as well as endogenously (without donor) in cold stress treated tomato seedlings. Dual regulation of LeCBF1 by NO at both transcriptional as well as post-translational level (by S-nitrosylation) is shown for the first time. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Perfusion deficits and functional connectivity alterations in patients with post-traumatic stress disorder

NASA Astrophysics Data System (ADS)

Liu, Yang; Li, Baojuan; Zhang, Xi; Zhang, Linchuan; Li, Liang; Lu, Hongbing

2016-03-01

To explore the alteration in cerebral blood flow (CBF) and functional connectivity between survivors with recent onset post-traumatic stress disorder (PTSD) and without PTSD, survived from the same coal mine flood disaster. In this study, a processing pipeline using arterial spin labeling (ASL) sequence was proposed. Considering low spatial resolution of ASL sequence, a linear regression method was firstly used to correct the partial volume (PV) effect for better CBF estimation. Then the alterations of CBF between two groups were analyzed using both uncorrected and PV-corrected CBF maps. Based on altered CBF regions detected from the CBF analysis as seed regions, the functional connectivity abnormities in PTSD patients was investigated. The CBF analysis using PV-corrected maps indicates CBF deficits in the bilateral frontal lobe, right superior frontal gyrus and right corpus callosum of PTSD patients, while only right corpus callosum was identified in uncorrected CBF analysis. Furthermore, the regional CBF of the right superior frontal gyrus exhibits significantly negative correlation with the symptom severity in PTSD patients. The resting-state functional connectivity indicates increased connectivity between left frontal lobe and right parietal lobe. These results indicate that PV-corrected CBF exhibits more subtle perfusion changes and may benefit further perfusion and connectivity analysis. The symptom-specific perfusion deficits and aberrant connectivity in above memory-related regions may be putative biomarkers for recent onset PTSD induced by a single prolonged trauma exposure and help predict the severity of PTSD.

Mutational Evidence for the Critical Role of CBF Transcription Factors in Cold Acclimation in Arabidopsis1

PubMed Central

Zhang, Zhengjing; Li, Yuanya

2016-01-01

The three tandemly arranged CBF genes, CBF1, CBF2, and CBF3, are involved in cold acclimation. Due to the lack of stable loss-of-function Arabidopsis (Arabidopsis thaliana) mutants deficient in all three CBF genes, it is still unclear whether the CBF genes are essential for freezing tolerance and whether they may have other functions besides cold acclimation. In this study, we used the CRISPR/Cas9 system to generate cbf single, double, and triple mutants. Compared to the wild type, the cbf triple mutants are extremely sensitive to freezing after cold acclimation, demonstrating that the three CBF genes are essential for cold acclimation. Our results show that the three CBF genes also contribute to basal freezing tolerance. Unexpectedly, we found that the cbf triple mutants are defective in seedling development and salt stress tolerance. Transcript profiling revealed that the CBF genes regulate 414 cold-responsive (COR) genes, of which 346 are CBF-activated genes and 68 are CBF-repressed genes. The analysis suggested that CBF proteins are extensively involved in the regulation of carbohydrate and lipid metabolism, cell wall modification, and gene transcription. Interestingly, like the triple mutants, cbf2 cbf3 double mutants are more sensitive to freezing after cold acclimation compared to the wild type, but cbf1 cbf3 double mutants are more resistant, suggesting that CBF2 is more important than CBF1 and CBF3 in cold acclimation-dependent freezing tolerance. Our results not only demonstrate that the three CBF genes together are required for cold acclimation and freezing tolerance, but also reveal that they are important for salt tolerance and seedling development. PMID:27252305

Corticotropin-releasing factor: effect on cerebral blood flow in physiologic and ischaemic conditions.

PubMed

De Michele, Manuela; Touzani, Omar; Foster, Alan C; Fieschi, Cesare; Sette, Giuliano; McCulloch, James

2005-09-01

The expression of corticotrophin-releasing factor (CRF) receptors in cerebral arteries and arterioles suggests that CRF may modulate cerebral blood flow (CBF). In the present study, the effects of CRF, CRF-like peptides and the CRF broad spectrum antagonist DPhe-CRF on CBF have been investigated under normal physiologic conditions and in the margins of focal ischaemic insult. The experiments were carried out in anaesthetised and ventilated rats. Changes in CBF after subarachnoid microapplication of CRF and related peptides were assessed with a laser-Doppler flowmetry (LDF) probe. In the ischaemic animals, agents were injected approximately 60 minutes after permanent middle cerebral artery occlusion (MCAo). Microapplication of CRF and related peptides in normal rats into the subarachnoid space produced sustained concentration-dependent increases in CBF. This effect was attenuated by co-application with DPhe-CRF, which did not alter CBF itself. A second microapplication of CRF 30 min after the first failed to produce increases in CBF in normal animals. Microapplication of CRF in the subarachnoid space overlying the ischaemic cortex effected minor increases in CBF whereas D-Phe-CRF had no significant effect on CBF. Activation of the CRF peptidergic system increases CBF in the rat. Repeated activation of CRF receptors results in tachyphylaxis of the vasodilator response. CRF vasodilator response is still present after MCAo in the ischaemic penumbra, suggesting that the CRF peptidergic system may modulate CBF in ischaemic stroke.

Resting-state cerebral blood flow in amygdala is modulated by sex and serotonin transporter genotype.

PubMed

El-Hage, W; Zelaya, F; Radua, J; Gohier, B; Alsop, D C; Phillips, M L; Surguladze, S A

2013-08-01

Serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with modulation of resting-state amygdala level, which was considered to underlie a risk for mood and anxiety disorders. The findings however have been inconsistent which could be related to interactions of the genotype with other factors e.g. sex or personality characteristics. Therefore, the aim of the present study was to explore the modulation of the amygdala perfusion in the resting-state by sex and 5-HTTLPR/rs25531 genotype, controlled for personality dimensions assessed by Temperament and Character Inventory (Cloninger et al., 1994). The resting-state cerebral blood flow (rCBF) was examined using an arterial spin labelling technique. All participants were genotyped for the 5-HTTLPR/rs25531 genotype (L/L-L/S-S/S genotypes and LA-LG variants). The study group comprised 81 right-handed Caucasian healthy volunteers (42 females) aged 19-55 years. We measured rCBF in the amygdala and in the whole-brain grey matter. The data of blood-oxygen-level-dependent (BOLD) response in amygdala to fearful dynamic faces in the same sample were also analysed. There was a significant main effect of sex in both the left and right amygdalae, with higher rCBF in males. Main effect of 5-HTTLPR/rs25531 genotype which was significant in the right amygdala only, was accounted for by higher rCBF in S/S vs. L/L homozygotes. An interaction between sex and 5-HTTLPR/rs25531 genotype was observed in rCBF in the right amygdala. This was accounted for by higher values of rCBF in the right amygdala in males' S allele carriers compared with females. In females, there was a significant negative correlation between the rCBF and BOLD response in the right amygdala, and more so in S carriers. In males, there was no significant correlation between rCBF and BOLD response in the right amygdala. The novelty of our results lies in the demonstration of gene by sex interaction with resting blood flow in the amygdala that elucidates sex-related differences in emotional reactivity. Copyright © 2013 Elsevier Inc. All rights reserved.

Brain-Derived Neurotrophic Factor Val66Met Polymorphism Affects the Relationship Between an Anxiety-Related Personality Trait and Resting Regional Cerebral Blood Flow.

PubMed

Wei, Shau-Ming; Eisenberg, Daniel P; Nabel, Katherine G; Kohn, Philip D; Kippenhan, J Shane; Dickinson, Dwight; Kolachana, Bhaskar; Berman, Karen F

2017-03-01

Brain-derived neurotrophic factor (BDNF) is an important modulator of constitutive stress responses mediated by limbic frontotemporal circuits, and its gene contains a functional polymorphism (Val66Met) that may influence trait stress sensitivity. Reports of an association of this polymorphism with anxiety-related personality traits have been controversial and without clear neurophysiological support. We, therefore, determined the relationship between resting regional cerebral blood flow (rCBF) and a well-validated measure of anxiety-related personality, the TPQ Harm Avoidance (HA) scale, as a function of BDNF Val66Met genotype. Sixty-four healthy participants of European ancestry underwent resting H215O positron emission tomography scans. For each genotype group separately, we first determined the relationship between participants' HA scores and their resting rCBF values in each voxel across the entire brain, and then directly compared these HA-rCBF relationships between Val66Met genotype groups. HA-rCBF relationships differed between Val homozygotes and Met carriers in several regions relevant to stress regulation: subgenual cingulate, orbital frontal cortex, and the hippocampal/parahippocampal region. In each of these areas, the relationship was positive in Val homozygotes and negative in Met carriers. These data demonstrate a coupling between trait anxiety and basal resting blood flow in frontolimbic neurocircuitry that may be determined in part by genetically mediated BDNF signaling. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Constitutive expression of DaCBF7, an Antarctic vascular plant Deschampsia antarctica CBF homolog, resulted in improved cold tolerance in transgenic rice plants.

PubMed

Byun, Mi Young; Lee, Jungeun; Cui, Li Hua; Kang, Yoonjee; Oh, Tae Kyung; Park, Hyun; Lee, Hyoungseok; Kim, Woo Taek

2015-07-01

Deschampsia antarctica is an Antarctic hairgrass that grows on the west coast of the Antarctic peninsula. In this report, we have identified and characterized a transcription factor, D. antarctica C-repeat binding factor 7 (DaCBF7), that is a member of the monocot group V CBF homologs. The protein contains a single AP2 domain, a putative nuclear localization signal, and the typical CBF signature. DaCBF7, like other monocot group V homologs, contains a distinct polypeptide stretch composed of 43 amino acids in front of the AP2 motif. DaCBF7 was predominantly localized to nuclei and interacted with the C-repeat/dehydration responsive element (CRT/DRE) core sequence (ACCGAC) in vitro. DaCBF7 was induced by abiotic stresses, including drought, cold, and salinity. To investigate its possible cellular role in cold tolerance, a transgenic rice system was employed. DaCBF7-overexpressing transgenic rice plants (Ubi:DaCBF7) exhibited markedly increased tolerance to cold stress compared to wild-type plants without growth defects; however, overexpression of DaCBF7 exerted little effect on tolerance to drought or salt stress. Transcriptome analysis of a Ubi:DaCBF7 transgenic line revealed 13 genes that were up-regulated in DaCBF7-overexpressing plants compared to wild-type plants in the absence of cold stress and in short- or long-term cold stress. Five of these genes, dehydrin, remorin, Os03g63870, Os11g34790, and Os10g22630, contained putative CRT/DRE or low-temperature responsive elements in their promoter regions. These results suggest that overexpression of DaCBF7 directly and indirectly induces diverse genes in transgenic rice plants and confers enhanced tolerance to cold stress. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Basal Ganglia Perfusion in Fibromyalgia is Related to Pain Disability and Disease Impact: An Arterial Spin Labeling Study.

PubMed

Shokouhi, Mahsa; Davis, Karen D; Moulin, Dwight E; Morley-Forster, Pat; Nielson, Warren R; Bureau, Yves; St Lawrence, Keith

2016-06-01

Pain disability is a major impediment to fibromyalgia (FM) patients' quality of life. Neuroimaging studies have demonstrated abnormal pain processing in FM. However, it is not known whether there are brain abnormalities linked to pain disability. Understanding neural correlates of pain disability in FM, independent from pain intensity, could provide a framework to guide future more efficient therapy strategies to improve patients' functional ability. We used arterial spin labeling to image cerebral blood flow (CBF) in 23 FM patients and 16 controls. Functional connectivity was also estimated using blood oxygenation level-dependent imaging to further investigate the possible underpinnings of the observed CBF changes. Among patients, CBF in the basal ganglia correlated negatively with pain disability index and positively with the overall impact of FM (Fibromyalgia Impact Questionnaire) but did not correlate with pain intensity. Whole-brain analysis revealed no CBF differences between the 2 groups; however, post hoc analysis in the basal ganglia showed CBF reductions mainly in the right putamen and right lateral globus pallidus in patients, likely reflecting the negative correlation with the pain disability index. However, the connectivity of the corresponding corticobasal ganglia-thalamus loop, that is, motor network (the connection between supplementary motor area, putamen, and thalamus) remained intact. Basal ganglia perfusion reflects long-term symptoms, including somatic and psychological components of FM rather than pain intensity. These CBF findings may reflect differences in behavioral and psychological responses between patients.

A Perfusion MRI Study of Emotional Valence and Arousal in Parkinson's Disease

PubMed Central

Limsoontarakul, Sunsern; Campbell, Meghan C.; Black, Kevin J.

2011-01-01

Background. Brain regions subserving emotion have mostly been studied using functional magnetic resonance imaging (fMRI) during emotion provocation procedures in healthy participants. Objective. To identify neuroanatomical regions associated with spontaneous changes in emotional state over time. Methods. Self-rated emotional valence and arousal scores, and regional cerebral blood flow (rCBF) measured by perfusion MRI, were measured 4 or 8 times spanning at least 2 weeks in each of 21 subjects with Parkinson's disease (PD). A random-effects SPM analysis, corrected for multiple comparisons, identified significant clusters of contiguous voxels in which rCBF varied with valence or arousal. Results. Emotional valence correlated positively with rCBF in several brain regions, including medial globus pallidus, orbital prefrontal cortex (PFC), and white matter near putamen, thalamus, insula, and medial PFC. Valence correlated negatively with rCBF in striatum, subgenual cingulate cortex, ventrolateral PFC, and precuneus—posterior cingulate cortex (PCC). Arousal correlated positively with rCBF in clusters including claustrum-thalamus-ventral striatum and inferior parietal lobule and correlated negatively in clusters including posterior insula—mediodorsal thalamus and midbrain. Conclusion. This study demonstrates that the temporal stability of perfusion MRI allows within-subject investigations of spontaneous fluctuations in mental state, such as mood, over relatively long-time intervals. PMID:21969917

Detrimental effect of systemic vascular risk factors on brain hemodynamic function assessed with MRI.

PubMed

King, Kevin S; Sheng, Min; Liu, Peiying; Maroules, Christopher D; Rubin, Craig D; Peshock, Ron M; McColl, Roderick W; Lu, Hanzhang

2018-06-01

Background and purpose Vascular risk factors have been associated with decreased cerebral blood flow (CBF) but this is etiologically nonspecific and may result from vascular insufficiency or a response to decreased brain metabolic activity. We apply new MRI techniques to measure oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO 2 ), hypothesizing that decreased CBF related to these vascular risk factors will be associated with increased OEF, confirming a primary vascular insufficiency. Methods 3T MRI was obtained on 70 community-based participants in this IRB-approved study with informed consent, with previous assessment of systolic blood pressure, hypertension medication, elevated serum triglycerides, low serum HDL, and diabetes mellitus. CBF was measured using phase contrast adjusted for brain volume (ml/100 g/min), OEF (%) was obtained from T2-Relaxation-Under-Spin-Tagging (TRUST), and CMRO 2 (μmol/100 g/min) was derived using the Fick principle. Stepwise linear regression identified optimal predictors of CBF with age, sex, and hematocrit included for adjustment. This predictive model was then evaluated against OEF and CMRO 2 . Results Hypertriglyceridemia was associated with low CBF and high OEF. High systolic blood pressure was associated with high CBF and low OEF, which was primarily attributable to those with pressures above 160 mmHg. Neither risk factor was associated with significant differences in cerebral metabolic rate. Conclusion Low CBF related to hypertriglyceridemia was accompanied by high OEF with no significant difference in CMRO 2 , confirming subclinical vascular insufficiency. High CBF related to high systolic blood pressure likely reflected limitations of autoregulation at higher blood pressures.

Ectoderm gene activation in sea urchin embryos mediated by the CCAAT-binding factor.

PubMed

Li, Xiaotao; Bhattacharya, Chitralekha; Dayal, Sandeep; Maity, Sankar; Klein, William H

2002-05-01

Transcriptional enhancers are short stretches of DNA that function to achieve highly specific patterns of gene expression. To identify the mechanisms by which enhancers achieve their specificity, we made use of an enhancer from the aboral ectoderm-specific spec2a gene of the sea urchin Strongylocentrotus purpuratus. The spec2a enhancer contains five cis-regulatory elements within 78 base pairs that interact with five distinct DNA-binding proteins to confer aboral ectoderm expression. Here, we present an analysis of the sea urchin CCAAT binding factor (CBF), which binds to a CCAAT motif within the spec2a enhancer. S. purpuratus CBF and SpOtx, a ubiquitously expressed factor, act together at closely placed cis-regulatory elements to mediate spec2a transcription in the ectoderm. SpCBF was the sole factor that bound to the spec2a CCAAT element, and two of the three subunits that make up the CBF holoprotein were cloned and shown to have high sequence conservation with their vertebrate orthologs. Based on its involvement in the regulation of several other sea urchin genes, SpCBF appears to be a major transcription factor in the sea urchin embryo for positive regulation of ectoderm gene expression. In addition to its role in vertebrate cell growth and proliferation, our results indicate that CBF also functions at the early stages of germ layer formation, namely ectoderm differentiation.

Jasmonate Regulates the INDUCER OF CBF EXPRESSION–C-REPEAT BINDING FACTOR/DRE BINDING FACTOR1 Cascade and Freezing Tolerance in Arabidopsis[W

PubMed Central

Hu, Yanru; Jiang, Liqun; Wang, Fang; Yu, Diqiu

2013-01-01

The INDUCER OF CBF EXPRESSION (ICE)–C-REPEAT BINDING FACTOR/DRE BINDING FACTOR1 (CBF/DREB1) transcriptional pathway plays a critical role in modulating cold stress responses in Arabidopsis thaliana. Dissecting crucial upstream regulatory signals or components of the ICE-CBF/DREB1 cascade will enhance our understanding of plant cold-tolerance mechanisms. Here, we show that jasmonate positively regulates plant responses to freezing stress in Arabidopsis. Exogenous application of jasmonate significantly enhanced plant freezing tolerance with or without cold acclimation. By contrast, blocking endogenous jasmonate biosynthesis and signaling rendered plants hypersensitive to freezing stress. Consistent with the positive role of jasmonate in freezing stress, production of endogenous jasmonate was triggered by cold treatment. In addition, cold induction of genes acting in the CBF/DREB1 signaling pathway was upregulated by jasmonate. Further investigation revealed that several JASMONATE ZIM-DOMAIN (JAZ) proteins, the repressors of jasmonate signaling, physically interact with ICE1 and ICE2 transcription factors. JAZ1 and JAZ4 repress the transcriptional function of ICE1, thereby attenuating the expression of its regulon. Consistent with this, overexpression of JAZ1 or JAZ4 represses freezing stress responses of Arabidopsis. Taken together, our study provides evidence that jasmonate functions as a critical upstream signal of the ICE-CBF/DREB1 pathway to positively regulate Arabidopsis freezing tolerance. PMID:23933884

Jasmonate regulates the inducer of cbf expression-C-repeat binding factor/DRE binding factor1 cascade and freezing tolerance in Arabidopsis.

PubMed

Hu, Yanru; Jiang, Liqun; Wang, Fang; Yu, Diqiu

2013-08-01

The inducer of cbf expression (ICE)-C-repeat binding factor/DRE binding factor1 (CBF/DREB1) transcriptional pathway plays a critical role in modulating cold stress responses in Arabidopsis thaliana. Dissecting crucial upstream regulatory signals or components of the ICE-CBF/DREB1 cascade will enhance our understanding of plant cold-tolerance mechanisms. Here, we show that jasmonate positively regulates plant responses to freezing stress in Arabidopsis. Exogenous application of jasmonate significantly enhanced plant freezing tolerance with or without cold acclimation. By contrast, blocking endogenous jasmonate biosynthesis and signaling rendered plants hypersensitive to freezing stress. Consistent with the positive role of jasmonate in freezing stress, production of endogenous jasmonate was triggered by cold treatment. In addition, cold induction of genes acting in the CBF/DREB1 signaling pathway was upregulated by jasmonate. Further investigation revealed that several jasmonate ZIM-domain (JAZ) proteins, the repressors of jasmonate signaling, physically interact with ICE1 and ICE2 transcription factors. JAZ1 and JAZ4 repress the transcriptional function of ICE1, thereby attenuating the expression of its regulon. Consistent with this, overexpression of JAZ1 or JAZ4 represses freezing stress responses of Arabidopsis. Taken together, our study provides evidence that jasmonate functions as a critical upstream signal of the ICE-CBF/DREB1 pathway to positively regulate Arabidopsis freezing tolerance.

Negative BOLD with Large Increases in Neuronal Activity

PubMed Central

Khubchandani, Manjula; Motelow, Joshua E.; Sanganahalli, Basavaraju G.; Hyder, Fahmeed

2008-01-01

Blood oxygen level–dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used in neuroscience to study brain activity. However, BOLD fMRI does not measure neuronal activity directly but depends on cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO2) consumption. Using fMRI, CBV, CBF, neuronal recordings, and CMRO2 modeling, we investigated how the signals are related during seizures in rats. We found that increases in hemodynamic, neuronal, and metabolic activity were associated with positive BOLD signals in the cortex, but with negative BOLD signals in hippocampus. Our data show that negative BOLD signals do not necessarily imply decreased neuronal activity or CBF, but can result from increased neuronal activity, depending on the interplay between hemodynamics and metabolism. Caution should be used in interpreting fMRI signals because the relationship between neuronal activity and BOLD signals may depend on brain region and state and can be different during normal and pathological conditions. PMID:18063563

KIT mutations correlate with adverse survival in children with core-binding factor acute myeloid leukemia.

PubMed

Chen, Xi; Dou, Hu; Wang, Xingjuan; Huang, Yi; Lu, Ling; Bin, Junqing; Su, Yongchun; Zou, Lin; Yu, Jie; Bao, Liming

2018-04-01

The prevalence and clinical relevance of KIT mutations in childhood core-binding factor (CBF) acute myeloid leukemia (AML) have not been well characterized. In this study, a total of 212 children with de novo AML were enrolled from a Chinese population and 50 (23.5%) of the patients were deemed CBF-AML. KIT mutations were identified in 30% of the CBF-AML cohort. The KIT mutations were clustered in exon 17 and exon 8, and KIT mutations in exons 8 and 17 were correlated with a shorter overall survival (OS) (5-year OS: 30.0 ± 14.5% vs. 73.0 ± 8.5%, p = .007) and event-free survival (EFS) (5-year EFS: 30.0 ± 14.5% vs. 73.0 ± 8.5%, p = .003). Multivariate analysis revealed KIT mutations as an independent risk factor in CBF-AML. Our results suggest that KIT mutations are a molecular marker for an inferior prognosis in pediatric CBF-AML.

Accuracy of Computed Tomographic Perfusion in Diagnosis of Brain Death: A Prospective Cohort Study.

PubMed

Sawicki, Marcin; Sołek-Pastuszka, Joanna; Chamier-Ciemińska, Katarzyna; Walecka, Anna; Bohatyrewicz, Romuald

2018-05-04

BACKGROUND This study was designed to determine diagnostic accuracy of computed tomographic perfusion (CTP) compared to computed tomographic angiography (CTA) for the diagnosis of brain death (BD). MATERIAL AND METHODS Whole-brain CTP was performed in patients diagnosed with BD and in patients with devastating brain injury with preserved brainstem reflexes. CTA was derived from CTP datasets. Cerebral blood flow (CBF) and volume (CBV) were calculated in all brain regions. CTP findings were interpreted as confirming diagnosis of BD (positive) when CBF and CBV in all ROIs were below 10 mL/100 g/min and 1.0 mL/100 g, respectively. CTA findings were interpreted using a 4-point system. RESULTS Fifty brain-dead patients and 5 controls were included. In brain-dead patients, CTP results revealed CBF 0.00-9.98 mL/100 g/min and CBV 0.00-0.99 mL/100 g, and were thus interpreted as positive in all patients. CTA results suggested 7 negative cases, providing 86% sensitivity. In the non-brain-dead group, CTP results revealed CBF 2.37-37.59 mL/100 g/min and CBV 0.73-2.34 mL/100 g. The difference between values of CBF and CBV in the brain-dead and non-brain-dead groups was statistically significant (p=0.002 for CBF and p=0.001 for CBV). CTP findings in all non-brain-dead patients were interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31-1.00) for CTP in the diagnosis of BD. In all non-brain-dead patients, CTA revealed preserved intracranial filling and was interpreted as negative. This resulted in a specificity of 100% (95% CI, 0.31-1.00) for CTA in diagnosis of BD. CONCLUSIONS Whole-brain CTP seems to be a highly sensitive and specific method in diagnosis of BD.

The effects of altered intrathoracic pressure on resting cerebral blood flow and its response to visual stimulation

PubMed Central

Hayen, Anja; Herigstad, Mari; Kelly, Michael; Okell, Thomas W.; Murphy, Kevin; Wise, Richard G.; Pattinson, Kyle T.S.

2013-01-01

Investigating how intrathoracic pressure changes affect cerebral blood flow (CBF) is important for a clear interpretation of neuroimaging data in patients with abnormal respiratory physiology, intensive care patients receiving mechanical ventilation and in research paradigms that manipulate intrathoracic pressure. Here, we investigated the effect of experimentally increased and decreased intrathoracic pressures upon CBF and the stimulus-evoked CBF response to visual stimulation. Twenty healthy volunteers received intermittent inspiratory and expiratory loads (plus or minus 9 cmH2O for 270 s) and viewed an intermittent 2 Hz flashing checkerboard, while maintaining stable end-tidal CO2. CBF was recorded with transcranial Doppler sonography (TCD) and whole-brain pseudo-continuous arterial spin labeling magnetic resonance imaging (PCASL MRI). Application of inspiratory loading (negative intrathoracic pressure) showed an increase in TCD-measured CBF of 4% and a PCASL-measured increase in grey matter CBF of 5%, but did not alter mean arterial pressure (MAP). Expiratory loading (positive intrathoracic pressure) did not alter CBF, while MAP increased by 3%. Neither loading condition altered the perfusion response to visual stimulation in the primary visual cortex. In both loading conditions localized CBF increases were observed in the somatosensory and motor cortices, and in the cerebellum. Altered intrathoracic pressures, whether induced experimentally, therapeutically or through a disease process, have possible significant effects on CBF and should be considered as a potential systematic confound in the interpretation of perfusion-based neuroimaging data. PMID:23108273

Prognostic factors in children with acute myeloid leukaemia and excellent response to remission induction therapy.

PubMed

Karol, Seth E; Coustan-Smith, Elaine; Cao, Xueyuan; Shurtleff, Sheila A; Raimondi, Susana C; Choi, John K; Ribeiro, Raul C; Dahl, Gary V; Bowman, William Paul; Taub, Jeffrey W; Degar, Barbara; Leung, Wing; Downing, James R; Pui, Ching-Hon; Rubnitz, Jeffrey E; Campana, Dario; Inaba, Hiroto

2015-01-01

Minimal residual disease (MRD) is a strong prognostic factor in children and adolescents with acute myeloid leukaemia (AML) but nearly one-quarter of patients who achieve MRD-negative status still relapse. The adverse prognostic factors among MRD-negative patients remain unknown. We analysed the AML02 study cohort to identify demographic and genetic prognostic factors. Among the presenting features, certain 11q23 abnormalities, such as t(6;11) and t(10;11), acute megakaryoblastic leukaemia without the t(1;22), and age ≥10 years were associated with inferior outcome in patients who had MRD-negative status after either remission induction I or II. By contrast, those with rearrangement of CBF genes had superior outcome. Our study identifies patient populations for whom close post-remission MRD monitoring to detect and treat emerging relapse and adjustment in treatment intensity might be indicated. © 2014 John Wiley & Sons Ltd.

Selective Activation of Transcription by a Novel CCAAT Binding Factor

NASA Astrophysics Data System (ADS)

Maity, Sankar N.; Golumbek, Paul T.; Karsenty, Gerard; de Crombrugghe, Benoit

1988-07-01

A novel CCAAT binding factor (CBF) composed of two different subunits has been extensively purified from rat liver. Both subunits are needed for specific binding to DNA. Addition of this purified protein to nuclear extracts of NIH 3T3 fibroblasts stimulates transcription from several promoters including the α 2(I) collagen, the α 1(I) collagen, the Rous sarcoma virus long terminal repeat (RSV-LTR), and the adenovirus major late promoter. Point mutations in the CCAAT motif that show either no binding or a decreased binding of CBF likewise abolish or reduce activation of transcription by CBF. Activation of transcription requires, therefore, the specific binding of CBF to its recognition sites.

The Vitis vinifera C-repeat binding protein 4 (VvCBF4) transcriptional factor enhances freezing tolerance in wine grape

PubMed Central

Tillett, Richard L.; Wheatley, Matthew D.; Tattersall, Elizabeth A.R.; Schlauch, Karen A.; Cramer, Grant R.; Cushman, John C.

2014-01-01

Summary Chilling and freezing can reduce significantly vine survival and fruit set in Vitis vinifera wine grape. To overcome such production losses, a recently identified grapevine C-repeat binding factor (CBF) gene, VvCBF4, was overexpressed in grape vine cv. “Freedom” and found to improve freezing survival and reduced freezing-induced electrolyte leakage by up to 2°C in non-cold-acclimated vines. In addition, overexpression of this transgene caused a reduced growth phenotype similar to that observed for CBF overexpression in Arabidopsis and other species. Both freezing tolerance and reduced growth phenotypes were manifested in a transgene dose-dependent manner. To understand the mechanistic basis of VvCBF4 transgene action, one transgenic line (9–12) was genotyped using microarray-based mRNA expression profiling. Forty-seven and 12 genes were identified in unstressed transgenic shoots with either a greater than 1.5-fold increase or decrease in mRNA abundance, respectively. Comparison of mRNA changes with characterized CBF regulons in woody and herbaceous species revealed partial overlaps suggesting that CBF-mediated cold acclimation responses are widely conserved. Putative VvCBF4-regulon targets included genes with functions in cell wall structure, lipid metabolism, epicuticular wax formation, and stress-responses suggesting that the observed cold tolerance and dwarf phenotypes are the result of a complex network of diverse functional determinants. PMID:21914113

Cerebral blood flow changes in hemodialysis and peritoneal dialysis patients: an arterial-spin labeling MR imaging.

PubMed

Jiang, Xiao Lu; Wen, Ji Qiu; Zhang, Long Jiang; Zheng, Gang; Li, Xue; Zhang, Zhe; Liu, Ya; Zheng, Li Juan; Wu, Long; Chen, Hui Juan; Kong, Xiang; Luo, Song; Lu, Guang Ming; Ji, Xue Man; Zhang, Zong Jun

2016-08-01

We used arterial-spin labeling (ASL) MR imaging, a non-invasive technique to evaluate cerebral blood flow (CBF) changes in patients with end-stage renal disease (ESRD) undergoing peritoneal dialysis (PD) and hemodialysis (HD), and nondialysis ESRD patients compared with healthy cohort. Ninety seven ESRD patients including 32 PD patients (20 male, 12 female; mean age 33 ± 8 years), 33 HD patients (22 male, 11 female; mean age 33 ± 8 years) and 32 nondialysis patients (20 male, 12 female; mean age 35 ± 7 years) and 31 age- and gender-matched healthy controls (20 male, 11 female; mean age 32 ± 8 years) were included in this study. All subjects underwent ASL MR imaging, neuropsychologic tests, and ESRD patients underwent laboratory testing. CBF values were compared among PD, HD, nondialysis patients and control groups. Correlation analysis and multiple regression analysis were performed to investigate the association between CBF values and hemoglobin, neuropsychologic test results, serum creatinine, urea levels, disease duration, and dialysis duration. Elevated CBFs of whole brain region, gray matter, and white matter were found in all ESRD patient groups compared with healthy controls (all P < 0.001). However, compared with non-dialysis ESRD patients, both PD and HD patients had widespread regional CBF decline mainly in bilateral frontal and anterior cingulate cortices. There were no differences for CBF between PD and HD patient groups. Negative correlations were observed between mean CBFs of whole brain region, gray matter, and white matter and the hemoglobin level in all ESRD patients. Multiple linear regression showed elevated CBF of multiple brain areas correlated with some neuropsychological tests in ESRD patients (all P < 0.001, AlphaSim corrected), but the association was not present or shrank after adjusting hemoglobin level. This study found that mean CBF was predominantly increased in patients with ESRD, which correlated with their hemoglobin level and neurocognitive disorders. There were no differences of CBF change and cognitive function between PD and HD ESRD patients with long-term treatment. The degree of anemia may be a predominant risk factor for cognitive impairment in these ESRD patients.

Complementary regulation of four Eucalyptus CBF genes under various cold conditions

PubMed Central

Navarro, M.; Marque, G.; Ayax, C.; Keller, G.; Borges, J. P.; Marque, C.; Teulières, C.

2009-01-01

CBF transcription factors play central roles in the control of freezing tolerance in plants. The isolation of two additional CBF genes, EguCBF1c and EguCBF1d, from E. gunnii, one of the cold-hardiest Eucalyptus species, is described. While the EguCBF1D protein sequence is very similar to the previously characterized EguCBF1A and EguCBF1B sequences, EguCBF1C is more distinctive, in particular in the AP2-DBD (AP2-DNA binding domain). The expression analysis of the four genes by RT-qPCR reveals that none of them is specific to one stress but they are all preferentially induced by cold, except for the EguCBF1c gene which is more responsive to salt. The calculation of the transcript copy number enables the quantification of constitutive CBF gene expression. This basal level, significant for the four genes, greatly influences the final EguCBF1 transcript level in the cold. A cold shock at 4 °C, as well as a progressive freezing which mimics a natural frost episode, trigger a fast and strong response of the EguCBF1 genes, while growth at acclimating temperatures results in a lower but more durable induction. The differential expression of the four EguCBF1 genes under these cold regimes suggests that there is a complementary regulation. The high accumulation of the CBF transcript, observed in response to the different types of cold conditions, might be a key for the winter survival of this evergreen broad-leaved tree. PMID:19457981

Nuclear localization and transactivation by Vitis CBF transcription factors are regulated by combinations of conserved amino acid domains.

PubMed

Carlow, Chevonne E; Faultless, J Trent; Lee, Christine; Siddiqua, Mahbuba; Edge, Alison; Nassuth, Annette

2017-09-01

The highly conserved CBF pathway is crucial in the regulation of plant responses to low temperatures. Extensive analysis of Arabidopsis CBF proteins revealed that their functions rely on several conserved amino acid domains although the exact function of each domain is disputed. The question was what functions similar domains have in CBFs from other, overwintering woody plants such as Vitis, which likely have a more involved regulation than the model plant Arabidopsis. A total of seven CBF genes were cloned and sequenced from V. riparia and the less frost tolerant V. vinifera. The deduced species-specific amino acid sequences differ in only a few amino acids, mostly in non-conserved regions. Amino acid sequence comparison and phylogenetic analysis showed two distinct groups of Vitis CBFs. One group contains CBF1, CBF2, CBF3 and CBF8 and the other group contains CBF4, CBF5 and CBF6. Transient transactivation assays showed that all Vitis CBFs except CBF5 activate via a CRT or DRE promoter element, whereby Vitis CBF3 and 4 prefer a CRT element. The hydrophobic domains in the C-terminal end of VrCBF6 were shown to be important for how well it activates. The putative nuclear localization domain of Vitis CBF1 was shown to be sufficient for nuclear localization, in contrast to previous reports for AtCBF1, and also important for transactivation. The latter highlights the value of careful analysis of domain functions instead of reliance on computer predictions and published data for other related proteins. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Meta-analysis of the effect of overexpression of CBF/DREB family genes on drought stress response

USDA-ARS?s Scientific Manuscript database

Transcription factors C-repeat/dehydration-responsive element binding proteins (CBF/DREB) play an important role in plant response to abiotic stresses. Over-expression of various CBF/DREB genes in diverse plants have been reported, but inconsistency of gene donor, recipient genus, parameters used i...

Special trends in CBF and DREB2 groups in Eucalyptus gunnii vs Eucalyptus grandis suggest that CBF are master players in the trade-off between growth and stress resistance.

PubMed

Nguyen, Hong C; Cao, Phi B; San Clemente, Hélène; Ployet, Raphaël; Mounet, Fabien; Ladouce, Nathalie; Harvengt, Luc; Marque, Christiane; Teulieres, Chantal

2017-04-01

Annotation of the Eucalyptus grandis genome showed a large amplification of the dehydration-responsive element binding 1/C-repeat binding factor (DREB1/CBF) group without recent DREB2 gene duplication compared with other plant species. The present annotation of the CBF and DREB2 genes from a draft of the Eucalyptus gunnii genome sequence reveals at least one additional CBF copy in the E. gunnii genome compared with E. grandis, suggesting that this group is still evolving, unlike the DREB2 group. This study aims to investigate the redundancy/neo- or sub-functionalization of the duplicates and the relative involvement of the two groups in abiotic stress responses in both E. grandis and E. gunnii (lower growth but higher cold resistance). A comprehensive transcriptional analysis using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR) was performed on leaves, stems and roots from the two Eucalyptus species after cold, heat or drought treatment. A large CBF cluster accounted for most of the cold response in all the organs, whereas heat and drought responses mainly involved a small CBF cluster and the DREB2 genes. In addition, CBF putative target genes, known to be involved in plant tolerance and development, were found to be cold-regulated. The higher transcript amounts of both the CBF and target genes in the cold tolerant E. gunnii contrasted with the higher CBF induction rates in the fast growing E. grandis. Altogether, the present results, in agreement with previous data about Eucalyptus transgenic lines over-expressing CBF, suggest that these factors, which promote both stress protection and growth limitation, participate in the trade-off between growth and resistance in this woody species. © 2016 Scandinavian Plant Physiology Society.

Low cerebral blood flow is associated with lower memory function in metabolic syndrome.

PubMed

Birdsill, Alex C; Carlsson, Cynthia M; Willette, Auriel A; Okonkwo, Ozioma C; Johnson, Sterling C; Xu, Guofan; Oh, Jennifer M; Gallagher, Catherine L; Koscik, Rebecca L; Jonaitis, Erin M; Hermann, Bruce P; LaRue, Asenath; Rowley, Howard A; Asthana, Sanjay; Sager, Mark A; Bendlin, Barbara B

2013-07-01

Metabolic syndrome (MetS)--a cluster of cardiovascular risk factors--is linked with cognitive decline and dementia. However, the brain changes underlying this link are presently unknown. In this study, we tested the relationship between MetS, cerebral blood flow (CBF), white matter hyperintensity burden, and gray matter (GM) volume in cognitively healthy late middle-aged adults. Additionally, the extent to which MetS was associated with cognitive performance was assessed. Late middle-aged adults from the Wisconsin Registry for Alzheimer's Prevention (N = 69, mean age = 60.4 years) underwent a fasting blood draw, arterial spin labeling perfusion MRI, T1-weighted MRI, T2FLAIR MRI, and neuropsychological testing. MetS was defined as abnormalities on three or more factors, including abdominal obesity, triglycerides, HDL-cholesterol, blood pressure, and fasting glucose. Mean GM CBF was 15% lower in MetS compared to controls. Voxel-wise image analysis indicated that the MetS group had lower CBF across a large portion of the cortical surface, with the exception of medial and inferior parts of the occipital and temporal lobes. The MetS group also had lower immediate memory function; a mediation analysis indicated this relationship was partially mediated by CBF. Among the MetS factors, abdominal obesity and elevated triglycerides were most strongly associated with lower CBF. The results underscore the importance of reducing the number of cardiovascular risk factors for maintaining CBF and cognition in an aging population. Copyright © 2012 The Obesity Society.

Measurement of pediatric regional cerebral blood flow from 6 months to 15 years of age in a clinical population.

PubMed

Carsin-Vu, Aline; Corouge, Isabelle; Commowick, Olivier; Bouzillé, Guillaume; Barillot, Christian; Ferré, Jean-Christophe; Proisy, Maia

2018-04-01

To investigate changes in cerebral blood flow (CBF) in gray matter (GM) between 6 months and 15 years of age and to provide CBF values for the brain, GM, white matter (WM), hemispheres and lobes. Between 2013 and 2016, we retrospectively included all clinical MRI examinations with arterial spin labeling (ASL). We excluded subjects with a condition potentially affecting brain perfusion. For each subject, mean values of CBF in the brain, GM, WM, hemispheres and lobes were calculated. GM CBF was fitted using linear, quadratic and cubic polynomial regression against age. Regression models were compared with Akaike's information criterion (AIC), and Likelihood Ratio tests. 84 children were included (44 females/40 males). Mean CBF values were 64.2 ± 13.8 mL/100 g/min in GM, and 29.3 ± 10.0 mL/100 g/min in WM. The best-fit model of brain perfusion was the cubic polynomial function (AIC = 672.7, versus respectively AIC = 673.9 and AIC = 674.1 with the linear negative function and the quadratic polynomial function). A statistically significant difference between the tested models demonstrating the superiority of the quadratic (p = 0.18) or cubic polynomial model (p = 0.06), over the negative linear regression model was not found. No effect of general anesthesia (p = 0.34) or of gender (p = 0.16) was found. we provided values for ASL CBF in the brain, GM, WM, hemispheres, and lobes over a wide pediatric age range, approximately showing inverted U-shaped changes in GM perfusion over the course of childhood. Copyright © 2018 Elsevier B.V. All rights reserved.

The Vitis vinifera C-repeat binding protein 4 (VvCBF4) transcriptional factor enhances freezing tolerance in wine grape.

PubMed

Tillett, Richard L; Wheatley, Matthew D; Tattersall, Elizabeth A R; Schlauch, Karen A; Cramer, Grant R; Cushman, John C

2012-01-01

Chilling and freezing can reduce significantly vine survival and fruit set in Vitis vinifera wine grape. To overcome such production losses, a recently identified grapevine C-repeat binding factor (CBF) gene, VvCBF4, was overexpressed in grape vine cv. 'Freedom' and found to improve freezing survival and reduced freezing-induced electrolyte leakage by up to 2 °C in non-cold-acclimated vines. In addition, overexpression of this transgene caused a reduced growth phenotype similar to that observed for CBF overexpression in Arabidopsis and other species. Both freezing tolerance and reduced growth phenotypes were manifested in a transgene dose-dependent manner. To understand the mechanistic basis of VvCBF4 transgene action, one transgenic line (9-12) was genotyped using microarray-based mRNA expression profiling. Forty-seven and 12 genes were identified in unstressed transgenic shoots with either a >1.5-fold increase or decrease in mRNA abundance, respectively. Comparison of mRNA changes with characterized CBF regulons in woody and herbaceous species revealed partial overlaps, suggesting that CBF-mediated cold acclimation responses are widely conserved. Putative VvCBF4-regulon targets included genes with functions in cell wall structure, lipid metabolism, epicuticular wax formation and stress-responses suggesting that the observed cold tolerance and dwarf phenotypes are the result of a complex network of diverse functional determinants. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

99mTc-d,l-HMPAO and SPECT of the brain in normal aging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waldemar, G.; Hasselbalch, S.G.; Andersen, A.R.

1991-05-01

Single photon emission computed tomography (SPECT) with 99mTc-d,l-hexamethylpropyleneamine oxime (99mTc-d,l-HMPAO) was used to determine global and regional CBF in 53 healthy subjects aged 21-83 years. For the whole group, global CBF normalized to the cerebellum was 86.4% +/- 8.4 (SD). The contribution of age, sex, and atrophy to variations in global CBF was studied using stepwise multiple regression analysis. There was a significant negative correlation of global CBF with subjective ratings of cortical atrophy, but not with ratings of ventricular size, Evans ratio, sex, or age. In a subgroup of 33 subjects, in whom volumetric measurements of atrophy were performed,more » cortical atrophy was the only significant determinant for global CBF, accounting for 27% of its variance. Mean global CBF as measured with the 133Xe inhalation technique and SPECT was 54 +/- 9 ml/100 g/min and did not correlate significantly with age. There was a preferential decline of CBF in the frontal cortex with advancing age. The side-to-side asymmetry of several regions of interest increased with age. A method was described for estimation of subcortical CBF, which decreased with advancing cortical atrophy. The relative area of the subcortical low-flow region increased with age. These results are useful in distinguishing the effects of age and simple atrophy from disease effects, when the 99mTc-d,l-HMPAO method is used.« less

[Immigration and factors associated with breastfeeding. CALINA study].

PubMed

Oves Suárez, B; Escartín Madurga, L; Samper Villagrasa, M P; Cuadrón Andrés, L; Alvarez Sauras, M L; Lasarte Velillas, J J; Moreno Aznar, L A; Rodríguez Martínez, G

2014-07-01

To identify socio-cultural, obstetric and perinatal characteristics associated with complete breastfeeding (CBF) during the first 4 months of age, depending on maternal origin. Socio-cultural, obstetric and perinatal aspects associated with breastfeeding depending on maternal origin were evaluated in a longitudinal study in a representative infant population from Aragon (n = 1452). The prevalence of CBF was higher in immigrant mothers than in those from Spain. CBF was maintained in 37.2% of mothers from Spain at 4 months, compared with 43% of immigrants (P=.039) (RR Spanish/immigrants=0.76; 95% CI: 0.58-0.99); at 6 months this occurred in 13.9% vs. 23.8%, respectively (P<.001) (RR Spanish/immigrants=0.52; 95% CI: 0.37-0.72). The factors associated with CBF at 4 months are different between both groups. Mothers born in Spain are older (P=.002), have higher academic level (P=.001), greater parity (P=.003), and a higher probability of vaginal delivery (P=.005); and their children have the highest anthropometric values at birth. However, in immigrant mothers, the maintenance of CBF was associated with a higher maternal body mass index and with working at home. In both groups, CBF remains more frequently in those mothers who do not smoke (P=.001). The prevalence of CBF during the first months of life is higher in immigrant mothers than in those from Spain, and socio-cultural, obstetric and perinatal factors are different, depending on maternal origin. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

The C-module-binding factor supports amplification of TRE5-A retrotransposons in the Dictyostelium discoideum genome.

PubMed

Bilzer, Annika; Dölz, Heike; Reinhardt, Alexander; Schmith, Anika; Siol, Oliver; Winckler, Thomas

2011-01-01

Retrotransposable elements are molecular parasites that have invaded the genomes of virtually all organisms. Although retrotransposons encode essential proteins to mediate their amplification, they also require assistance by host cell-encoded machineries that perform functions such as DNA transcription and repair. The retrotransposon TRE5-A of the social amoeba Dictyostelium discoideum generates a notable amount of both sense and antisense RNAs, which are generated from element-internal promoters, located in the A module and the C module, respectively. We observed that TRE5-A retrotransposons depend on the C-module-binding factor (CbfA) to maintain high steady-state levels of TRE5-A transcripts and that CbfA supports the retrotransposition activity of TRE5-A elements. The carboxy-terminal domain of CbfA was found to be required and sufficient to mediate the accumulation of TRE5-A transcripts, but it did not support productive retrotransposition of TRE5-A. This result suggests different roles for CbfA protein domains in the regulation of TRE5-A retrotransposition frequency in D. discoideum cells. Although CbfA binds to the C module in vitro, the factor regulates neither C-module nor A-module promoter activity in vivo. We speculate that CbfA supports the amplification of TRE5-A retrotransposons by suppressing the expression of an as yet unidentified component of the cellular posttranscriptional gene silencing machinery.

Multifunctional centromere binding factor 1 is essential for chromosome segregation in the human pathogenic yeast Candida glabrata.

PubMed

Stoyan, T; Gloeckner, G; Diekmann, S; Carbon, J

2001-08-01

The CBF1 (centromere binding factor 1) gene of Candida glabrata was cloned by functional complementation of the methionine biosynthesis defect of a Saccharomyces cerevisiae cbf1 deletion mutant. The C. glabrata-coded protein, CgCbf1, contains a basic-helix-loop-helix leucine zipper domain and has features similar to those of other budding yeast Cbf1 proteins. CgCbf1p binds in vitro to the centromere DNA element I (CDEI) sequence GTCACATG with high affinity (0.9 x 10(9) M(-1)). Bandshift experiments revealed a pattern of protein-DNA complexes on CgCEN DNA different from that known for S. cerevisiae. We examined the effect of altering the CDEI binding site on CEN plasmid segregation, using a newly developed colony-sectoring assay. Internal deletion of the CDEI binding site led only to a fivefold increase in rates of plasmid loss, indicating that direct binding of Cbf1p to the centromere DNA is not required for full function. Additional deletion of sequences to the left of CDEI, however, led to a 70-fold increase in plasmid loss rates. Deletion of the CBF1 gene proved to be lethal in C. glabrata. C. glabrata cells containing the CBF1 gene under the influence of a shutdown promoter (tetO-ScHOP) arrested their growth after 5 h of cultivation in the presence of the reactive drug doxycycline. DAPI (4',6'-diamidino-2-phenylindole) staining of the arrested cells revealed a significant increase in the number of large-budded cells with single nuclei, 2C DNA content, and short spindles, indicating a defect in the G(2)/M transition of the cell cycle. Thus, we conclude that Cbf1p is required for chromosome segregation in C. glabrata.

Autonomic neural control of dynamic cerebral autoregulation in humans

NASA Technical Reports Server (NTRS)

Zhang, Rong; Zuckerman, Julie H.; Iwasaki, Kenichi; Wilson, Thad E.; Crandall, Craig G.; Levine, Benjamin D.

2002-01-01

BACKGROUND: The purpose of the present study was to determine the role of autonomic neural control of dynamic cerebral autoregulation in humans. METHODS AND RESULTS: We measured arterial pressure and cerebral blood flow (CBF) velocity in 12 healthy subjects (aged 29+/-6 years) before and after ganglion blockade with trimethaphan. CBF velocity was measured in the middle cerebral artery using transcranial Doppler. The magnitude of spontaneous changes in mean blood pressure and CBF velocity were quantified by spectral analysis. The transfer function gain, phase, and coherence between these variables were estimated to quantify dynamic cerebral autoregulation. After ganglion blockade, systolic and pulse pressure decreased significantly by 13% and 26%, respectively. CBF velocity decreased by 6% (P<0.05). In the very low frequency range (0.02 to 0.07 Hz), mean blood pressure variability decreased significantly (by 82%), while CBF velocity variability persisted. Thus, transfer function gain increased by 81%. In addition, the phase lead of CBF velocity to arterial pressure diminished. These changes in transfer function gain and phase persisted despite restoration of arterial pressure by infusion of phenylephrine and normalization of mean blood pressure variability by oscillatory lower body negative pressure. CONCLUSIONS: These data suggest that dynamic cerebral autoregulation is altered by ganglion blockade. We speculate that autonomic neural control of the cerebral circulation is tonically active and likely plays a significant role in the regulation of beat-to-beat CBF in humans.

MdHY5 positively regulates cold tolerance via CBF-dependent and CBF-independent pathways in apple.

PubMed

An, Jian-Ping; Yao, Ji-Fang; Wang, Xiao-Na; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

2017-11-01

Cold stress is a major external stimulator that affects crop quality and productivity. The CBF cold regulatory pathway has been regarded as a master regulator in the response to cold stress. In this study, we found that the apple bZIP transcription factor, MdHY5, was responsive to cold treatment both at the transcriptional and at the post-translational levels. Moreover, overexpression of MdHY5 enhanced cold tolerance in apple calli and Arabidopsis. Subsequently, EMSA assay and transient expression assay demonstrated that MdHY5 positively regulated the transcript of MdCBF1 by binding to G-Box motif of its promoter. Furthermore, MdHY5 also regulated the expression of CBF-independent cold-regulated genes. Taken together, our data suggest that MdHY5 positively modulates plant cold tolerance through CBF-dependent and CBF-independent pathways, providing a deeper understanding of MdHY5-regulated cold tolerance in apple. Copyright © 2017 Elsevier GmbH. All rights reserved.

Oil palm EgCBF3 conferred stress tolerance in transgenic tomato plants through modulation of the ethylene signaling pathway.

PubMed

Ebrahimi, Mortaza; Abdullah, Siti Nor Akmar; Abdul Aziz, Maheran; Namasivayam, Parameswari

2016-09-01

CBF/DREB1 is a group of transcription factors that are mainly involved in abiotic stress tolerance in plants. They belong to the AP2/ERF superfamily of plant-specific transcription factors. A gene encoding a new member of this group was isolated from ripening oil palm fruit and designated as EgCBF3. The oil palm fruit demonstrates the characteristics of a climacteric fruit like tomato, in which ethylene has a major impact on the ripening process. A transgenic approach was used for functional characterization of the EgCBF3, using tomato as the model plant. The effects of ectopic expression of EgCBF3 were analyzed based on expression profiling of the ethylene biosynthesis-related genes, anti-freeze proteins (AFPs), abiotic stress tolerance and plant growth and development. The EgCBF3 tomatoes demonstrated altered phenotypes compared to the wild type tomatoes. Delayed leaf senescence and flowering, increased chlorophyll content and abnormal flowering were the consequences of overexpression of EgCBF3 in the transgenic tomatoes. The EgCBF3 tomatoes demonstrated enhanced abiotic stress tolerance under in vitro conditions. Further, transcript levels of ethylene biosynthesis-related genes, including three SlACSs and two SlACOs, were altered in the transgenic plants' leaves and roots compared to that in the wild type tomato plant. Among the eight AFPs studied in the wounded leaves of the EgCBF3 tomato plants, transcript levels of SlOSM-L, SlNP24, SlPR5L and SlTSRF1 decreased, while expression of the other four, SlCHI3, SlPR1, SlPR-P2 and SlLAP2, were up-regulated. These findings indicate the possible functions of EgCBF3 in plant growth and development as a regulator of ethylene biosynthesis-related and AFP genes, and as a stimulator of abiotic stress tolerance. Copyright © 2016 Elsevier GmbH. All rights reserved.

Structure and Biophysics of CBFβ/RUNX and Its Translocation Products.

PubMed

Tahirov, Tahir H; Bushweller, John

2017-01-01

The core binding factor (CBF) transcription factor is somewhat unique in that it is composed of a DNA binding RUNX subunit (RUNX1, 2, or 3) and a non-DNA binding CBFβ subunit, which modulates RUNX protein activity by modulating the auto-inhibition of the RUNX subunits. Since the discovery of this fascinating transcription factor more than 20 years ago, there has been a robust effort to characterize the structure as well as the biochemical properties of CBF. More recently, these efforts have also extended to the fusion proteins that arise from the subunits of CBF in leukemia. This chapter highlights the work of numerous labs which has provided a detailed understanding of the structure and function of this transcription factor and its fusion proteins.

Regional cerebral blood flow and anxiety: a correlation study in neurologically normal patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez, G.; Cogorno, P.; Gris, A.

1989-06-01

Regional CBF (rCBF) was evaluated by the /sup 133/Xe inhalation method in 60 neurologically normal patients (30 men and 30 women) and hemispheric and regional values were correlated with anxiety measurements collected by a self-rating questionnaire before and after the examination. Statistically significant negative correlations between rCBF and anxiety measures were found. rCBF reduction for high anxiety levels is in line with results previously reported by others and could be related to lower performance levels for moderately high anxiety scores as those reported in the present population. This could perhaps be explained by rearrangement of flow from cortical zones tomore » deeper areas of the brain, classically known to be implicated in the control of emotions. However, these results should be interpreted cautiously, since they were obtained in patients and not in normal subjects.« less

Wheat CBF gene family: identification of polymorphisms in the CBF coding sequence.

PubMed

Mohseni, Sara; Che, Hua; Djillali, Zakia; Dumont, Estelle; Nankeu, Joseph; Danyluk, Jean

2012-12-01

Expression of cold-regulated genes needed for protection against freezing stress is mediated, in part, by the CBF transcription factor family. Previous studies with temperate cereals suggested that the CBF gene family in wheat was large, and that CBF genes were at the base of an important low temperature tolerance trait. Therefore, the goal of our study was to identify the CBF repertoire in the freezing-tolerant hexaploid wheat cultivar Norstar, and then to examine if the coding region of CBF genes in two spring cultivars contain polymorphisms that could affect the protein sequence and structure. Our analyses reveal that hexaploid wheat contains a complex CBF family consisting of at least 65 CBF genes of which 60 are known to be expressed in the cultivar Norstar. They represent 27 paralogous genes with 1-3 homeologous copies for the A, B, and D genomes. The cultivar Norstar contains two pseudogenes and at least 24 additional proteins having sequences and (or) structures that deviate from the consensus in the conserved AP2 DNA-binding and (or) C-terminal activation-domains. This suggests that in cultivars such as Norstar, low temperature tolerance may be increased through breeding of additional optimal alleles. The examination of the CBF repertoire present in the two spring cultivars, Chinese Spring and Manitou, reveals that they have additional polymorphisms affecting conserved positions in these domains. Understanding the effects of these polymorphisms will provide additional information for the selection of optimum CBF alleles in Triticeae breeding programs.

Cbf11 and Cbf12, the fission yeast CSL proteins, play opposing roles in cell adhesion and coordination of cell and nuclear division

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prevorovsky, Martin; Grousl, Tomas; Stanurova, Jana

The CSL (CBF1/RBP-J{kappa}/Suppressor of Hairless/LAG-1) family is comprised of transcription factors essential for metazoan development, mostly due to their involvement in the Notch receptor signaling pathway. Recently, we identified two novel classes of CSL genes in the genomes of several fungal species, organisms lacking the Notch pathway. In this study, we characterized experimentally cbf11{sup +} and cbf12{sup +}, the two CSL genes of Schizosaccharomyces pombe, in order to elucidate the CSL function in fungi. We provide evidence supporting their identity as genuine CSL genes. Both cbf11{sup +} and cbf12{sup +} are non-essential; they have distinct expression profiles and code formore » nuclear proteins with transcription activation potential. Significantly, we demonstrated that Cbf11 recognizes specifically the canonical CSL response element GTG{sup A}/{sub G}GAA in vitro. The deletion of cbf11{sup +} is associated with growth phenotypes and altered colony morphology. Furthermore, we found that Cbf11 and Cbf12 play opposite roles in cell adhesion, nuclear and cell division and their coordination. Disturbed balance of the two CSL proteins leads to cell separation defects (sep phenotype), cut phenotype, and high-frequency diploidization in heterothallic strains. Our data show that CSL proteins operate in an organism predating the Notch pathway, which should be of relevance to the understanding of (Notch-independent) CSL functions in metazoans.« less

Expression of the leukemia-associated CBF{beta}/SMMHC chimeric gene causes transformation of 3T3 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hajra, A.; Liu, P.; Collins, E.S.

1994-09-01

A pericentric inversion of chromosome 16 (inv(16)(p13;q22)) is consistently seen in acute myeloid leukemia of the M4Eo subtype. This inversion fuses almost the entire coding region of the gene encoding of the {beta} subunit of the heterodimeric transcription factor CBF/PEBP2 to the region of the MYH11 gene encoding the rod domain for the smooth muscle myosin heavy chain (SMMHC). To investigate the biological properties of the CBF{beta}/SMMHC fusion protein, we have generated 3T3 cell lines that stably express the CBF{beta}/SMMHC chimeric cDNA or the normal, nonchimeric CBF{beta} and SMMHC cDNAs. 3T3 cells expressing CBF{beta}/SMMHC acquire a transformed phenotype, as indicatedmore » by altered cell morphology, formation of foci, and growth in soft agar. Cells constitutively overexpressing the normal CBF{beta} cDNA or the rod region of SMMHC remain nontransformed. Western blot analysis using antibodies to CBF{beta} and the SMMHC rod demonstrates that stably transfected cells express the appropriate chimeric or normal protein. Electrophoretic mobility shift assays reveal that cells transformed by the chimeric cDNA do not have a CBF-DNA complex of the expected mobility, but instead contain a large complex with CBF DNA-binding activity that fails to migrate out of the gel wells. In order to define the regions of CBF{beta}/SMMHC necessary for 3T3 transformation, we have stably transfected cells with mutant CBF{beta}/SMMHC cDNAs containing various deletions of the coding region. Analysis of these cell lines indicates that the transformation property of CBF{beta}/SMMHC requires regions of CBF{beta} known to be necessary for association with the DNA-binding CBF{alpha} subunit, and also requires an intact SMMHC carboxyl terminus, which is necessary for formation of the coiled coil domain of the myosin rod.« less

A prominent role for the CBF cold response pathway in configuring the low-temperature metabolome of Arabidopsis

PubMed Central

Cook, Daniel; Fowler, Sarah; Fiehn, Oliver; Thomashow, Michael F.

2004-01-01

The Arabidopsis CBF cold response pathway has a central role in cold acclimation, the process whereby plants increase in freezing tolerance in response to low nonfreezing temperatures. Here we examined the changes that occur in the Arabidopsis metabolome in response to low temperature and assessed the role of the CBF cold response pathway in bringing about these modifications. Of 434 metabolites monitored by GC-time-of-flight MS, 325 (75%) were found to increase in Arabidopsis Wassilewskija-2 (Ws-2) plants in response to low temperature. Of these 325 metabolites, 256 (79%) also increased in nonacclimated Ws-2 plants in response to overexpression of C-repeat/dehydration responsive element-binding factor (CBF)3. Extensive cold-induced changes also occurred in the metabolome of Arabidopsis Cape Verde Islands-1 (Cvi-1) plants, which were found to be less freezing tolerant than Ws-2 plants. However, low-temperature-induced expression of CBF1, CBF2, CBF3, and CBF-targeted genes was much lower in Cvi-1 than in Ws-2 plants, and the low-temperature metabolome of Cvi-1 plants was depleted in metabolites affected by CBF3 overexpression. Taken together, the results indicate that the metabolome of Arabidopsis is extensively reconfigured in response to low temperature, and that the CBF cold response pathway has a prominent role in this process. PMID:15383661

RNA helicase-like protein as an early regulator of transcription factors for plant chilling and freezing tolerance

PubMed Central

Gong, Zhizhong; Lee, Hojoung; Xiong, Liming; Jagendorf, André; Stevenson, Becky; Zhu, Jian-Kang

2002-01-01

Susceptibility to chilling injury prevents the cultivation of many important crops and limits the extended storage of horticultural commodities. Although freezing tolerance is acquired through cold-induced gene expression changes mediated in part by the CBF family of transcriptional activators, whether plant chilling resistance or sensitivity involves the CBF genes is not known. We report here that an Arabidopsis thaliana mutant impaired in the cold-regulated expression of CBF genes and their downstream target genes is sensitive to chilling stress. Expression of CBF3 under a strong constitutive promoter restores chilling resistance to the mutant plants. The mutated gene was cloned and found to encode a nuclear localized RNA helicase. Our results identify a regulator of CBF genes, and demonstrate the importance of gene regulation and the CBF transcriptional activators in plant chilling resistance. PMID:12165572

The C-Module-Binding Factor Supports Amplification of TRE5-A Retrotransposons in the Dictyostelium discoideum Genome ▿

PubMed Central

Bilzer, Annika; Dölz, Heike; Reinhardt, Alexander; Schmith, Anika; Siol, Oliver; Winckler, Thomas

2011-01-01

Retrotransposable elements are molecular parasites that have invaded the genomes of virtually all organisms. Although retrotransposons encode essential proteins to mediate their amplification, they also require assistance by host cell-encoded machineries that perform functions such as DNA transcription and repair. The retrotransposon TRE5-A of the social amoeba Dictyostelium discoideum generates a notable amount of both sense and antisense RNAs, which are generated from element-internal promoters, located in the A module and the C module, respectively. We observed that TRE5-A retrotransposons depend on the C-module-binding factor (CbfA) to maintain high steady-state levels of TRE5-A transcripts and that CbfA supports the retrotransposition activity of TRE5-A elements. The carboxy-terminal domain of CbfA was found to be required and sufficient to mediate the accumulation of TRE5-A transcripts, but it did not support productive retrotransposition of TRE5-A. This result suggests different roles for CbfA protein domains in the regulation of TRE5-A retrotransposition frequency in D. discoideum cells. Although CbfA binds to the C module in vitro, the factor regulates neither C-module nor A-module promoter activity in vivo. We speculate that CbfA supports the amplification of TRE5-A retrotransposons by suppressing the expression of an as yet unidentified component of the cellular posttranscriptional gene silencing machinery. PMID:21076008

The relationship of resting cerebral blood flow and brain activation during a social cognition task in adolescents with chronic moderate to severe traumatic brain injury: a preliminary investigation.

PubMed

Newsome, Mary R; Scheibel, Randall S; Chu, Zili; Hunter, Jill V; Li, Xiaoqi; Wilde, Elisabeth A; Lu, Hanzhang; Wang, Zhiyue J; Lin, Xiaodi; Steinberg, Joel L; Vasquez, Ana C; Cook, Lori; Levin, Harvey S

2012-05-01

Alterations in cerebrovascular function are evident acutely in moderate to severe traumatic brain injury (TBI), although less is known about their chronic effects. Adolescent and adult patients with moderate to severe TBI have been reported to demonstrate diffuse activation throughout the brain during functional magnetic resonance imaging (fMRI). Because fMRI is a measure related to blood flow, it is possible that any deficits in blood flow may alter activation. An arterial spin labeling (ASL) perfusion sequence was performed on seven adolescents with chronic moderate to severe TBI and seven typically developing (TD) adolescents during the same session in which they had performed a social cognition task during fMRI. In the TD group, prefrontal CBF was positively related to prefrontal activation and negatively related to non-prefrontal, posterior, brain activation. This relationship was not seen in the TBI group, who demonstrated a greater positive relationship between prefrontal CBF and non-prefrontal activation than the TD group. An analysis of CBF data independent of fMRI showed reduced CBF in the right non-prefrontal region (p<.055) in the TBI group. To understand any role reduced CBF may play in diffuse extra-activation, we then related the right non-prefrontal CBF to activation. CBF in the right non-prefrontal region in the TD group was positively associated with prefrontal activation, suggesting an interactive role of non-prefrontal and prefrontal blood flow throughout the right hemisphere in healthy brains. However, the TBI group demonstrated a positive association with activation constrained to the right non-prefrontal region. These data suggest a relationship between impaired non-prefrontal CBF and the presence of non-prefrontal extra-activation, where the region with more limited blood flow is associated with activation limited to that region. In a secondary analysis, pathology associated with hyperintensities on T2-weighted FLAIR imaging over the whole brain was related to whole brain activation, revealing a negative relationship between lesion volume and frontal activation, and a positive relationship between lesion volume and posterior activation. These preliminary data, albeit collected with small sample sizes, suggest that reduced non-prefrontal CBF, and possibly pathological tissue associated with T2-hyperintensities, may provide contributions to the diffuse, primarily posterior extra-activation observed in adolescents following moderate to severe TBI. Published by Elsevier Ltd.

Nonlinear coupling between cerebral blood flow, oxygen consumption, and ATP production in human visual cortex.

PubMed

Lin, Ai-Ling; Fox, Peter T; Hardies, Jean; Duong, Timothy Q; Gao, Jia-Hong

2010-05-04

The purpose of this study was to investigate activation-induced hypermetabolism and hyperemia by using a multifrequency (4, 8, and 16 Hz) reversing-checkerboard visual stimulation paradigm. Specifically, we sought to (i) quantify the relative contributions of the oxidative and nonoxidative metabolic pathways in meeting the increased energy demands [i.e., ATP production (J(ATP))] of task-induced neuronal activation and (ii) determine whether task-induced cerebral blood flow (CBF) augmentation was driven by oxidative or nonoxidative metabolic pathways. Focal increases in CBF, cerebral metabolic rate of oxygen (CMRO(2); i.e., index of aerobic metabolism), and lactate production (J(Lac); i.e., index of anaerobic metabolism) were measured by using physiologically quantitative MRI and spectroscopy methods. Task-induced increases in J(ATP) were small (12.2-16.7%) at all stimulation frequencies and were generated by aerobic metabolism (approximately 98%), with %DeltaJ(ATP) being linearly correlated with the percentage change in CMRO(2) (r = 1.00, P < 0.001). In contrast, task-induced increases in CBF were large (51.7-65.1%) and negatively correlated with the percentage change in CMRO(2) (r = -0.64, P = 0.024), but positively correlated with %DeltaJ(Lac) (r = 0.91, P < 0.001). These results indicate that (i) the energy demand of task-induced brain activation is small (approximately 15%) relative to the hyperemic response (approximately 60%), (ii) this energy demand is met through oxidative metabolism, and (iii) the CBF response is mediated by factors other than oxygen demand.

Cerebral perfusion characteristics show differences in younger versus older children with sickle cell anaemia: Results from a multiple-inflow-time arterial spin labelling study.

PubMed

Kawadler, Jamie M; Hales, Patrick W; Barker, Simon; Cox, Timothy C S; Kirkham, Fenella J; Clark, Chris A

2018-03-30

Sickle cell anaemia (SCA) is associated with chronic anaemia and oxygen desaturation, which elevate cerebral blood flow (CBF) and increase the risk of neurocognitive complications. Arterial spin labelling (ASL) provides a methodology for measuring CBF non-invasively; however, ASL techniques using only a single inflow time are not sufficient to fully characterize abnormal haemodynamic behaviour in SCA. This study investigated haemodynamic parameters from a multi-inflow-time ASL acquisition in younger (8-12 years) and older (13-18 years) children with SCA with and without silent cerebral infarction (SCI+/-) (n = 20 and 19 respectively, 6 and 4 SCI+ respectively) and healthy controls (n = 9 and 7 respectively). Compared with controls, CBF was elevated globally in both groups of patients. In the younger SCA patients, blood oxygen content was negatively correlated with CBF in the middle and posterior cerebral artery territories and significantly positively correlated with bolus arrival time (BAT) in the anterior and middle cerebral artery territories. In older children, SCA patients had significantly shorter BAT than healthy controls and there was a significant negative correlation between CBF and oxygen content only in the territory of the posterior cerebral artery, with a trend for a correlation in the anterior cerebral artery but no relationship for the middle cerebral artery territory. In the younger group, SCI+ patients had significantly higher CBF in the posterior cerebral artery territory (SCI+ mean = 92.78 ml/100 g/min; SCI- mean = 72.71 ml/100 g/min; F = 4.28, p = 0.04), but this no longer reached significance when two children with abnormal transcranial Doppler and one with haemoglobin SC disease were excluded, and there were no significant differences between patients with and without SCI in the older children. With age, there appears to be increasing disparity between patients and controls in terms of the relationship between CBF and oxygen content in the anterior circulation, potentially predicting the risk of acute and chronic compromise of brain tissue. Copyright © 2018 John Wiley & Sons, Ltd.

Accounting for the role of hematocrit in between-subject variations of MRI-derived baseline cerebral hemodynamic parameters and functional BOLD responses.

PubMed

Xu, Feng; Li, Wenbo; Liu, Peiying; Hua, Jun; Strouse, John J; Pekar, James J; Lu, Hanzhang; van Zijl, Peter C M; Qin, Qin

2018-01-01

Baseline hematocrit fraction (Hct) is a determinant for baseline cerebral blood flow (CBF) and between-subject variation of Hct thus causes variation in task-based BOLD fMRI signal changes. We first verified in healthy volunteers (n = 12) that Hct values can be derived reliably from venous blood T 1 values by comparison with the conventional lab test. Together with CBF measured using phase-contrast MRI, this noninvasive estimation of Hct, instead of using a population-averaged Hct value, enabled more individual determination of oxygen delivery (DO 2 ), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ). The inverse correlation of CBF and Hct explained about 80% of between-subject variation of CBF in this relatively uniform cohort of subjects, as expected based on the regulation of DO 2 to maintain constant CMRO 2 . Furthermore, we compared the relationships of visual task-evoked BOLD response with Hct and CBF. We showed that Hct and CBF contributed 22%-33% of variance in BOLD signal and removing the positive correlation with Hct and negative correlation with CBF allowed normalization of BOLD signal with 16%-22% lower variability. The results of this study suggest that adjustment for Hct effects is useful for studies of MRI perfusion and BOLD fMRI. Hum Brain Mapp 39:344-353, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Elevated global cerebral blood flow, oxygen extraction fraction and unchanged metabolic rate of oxygen in young adults with end-stage renal disease: an MRI study.

PubMed

Zheng, Gang; Wen, Jiqiu; Lu, Hanzhang; Lou, Yaxian; Pan, Zhiying; Liu, Wei; Liu, Hui; Li, Xue; Zhang, Zhe; Chen, Huijuan; Kong, Xiang; Luo, Song; Jiang, Xiaolu; Liu, Ya; Zhang, Zongjun; Zhang, Long Jiang; Lu, Guang Ming

2016-06-01

To noninvasively assess global cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) in young adults with end-stage renal disease (ESRD). Thirty-six patients and 38 healthy volunteers were included and took part in MR examinations, blood and neuropsychological tests. CBF and OEF were measured by phase-contrast and T2-relaxation-under-spin-tagging MRI techniques, respectively. CMRO2 was computed from CBF, OEF and hematocrit according to Fick's principle. Correlations were performed between MR measurements, blood biochemistry measurements and neuropsychological test scores. Compared with controls, ESRD patients had elevated CBF (72.9 ± 12.5 vs. 63.8 ± 8.5 ml min(-1) 100 g(-1), P < 0.001), elevated OEF (47.2 ± 10.2 vs. 35.8 ± 5.4 %, P < 0.001), but unaffected CMRO2 (199.5 ± 36.4 vs. 193.8 ± 28.6 μmol O2 min(-1) 100 g(-1), P = 0.879). Hematocrit negatively correlated with CBF (r = -0.640, P < 0.001) and OEF (r = -0.701, P < 0.001), but not with CMRO2. Altered neuropsychological test scores of ESRD patients were associated with OEF and CBF, but not with CMRO2. There were weak relationships between eGFR and hematocrit (r = 0.308, P = 0.068) or CBF (r = 0.318, P = 0.059). Our findings suggested that anaemic young adults with ESRD may afford higher CBF and OEF to maintain a normal CMRO2. Despite this compensatory process, however, cognitive function was still impaired and its severity was correlated with their CBF and OEF abnormality. • Anaemic young adults with ESRD may afford higher CBF and OEF. • Anaemic young adults with ESRD maintain a normal CMRO 2 . • Cognitive function was still impaired in young ESRD adults. • The severity of cognitive dysfunction correlated with CBF and OEF changes.

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica

PubMed Central

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 (DaCBF4), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4-overexpressing transgenic rice plant (Ubi:DaCBF4) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice. PMID:29774046

Identification of Rice Genes Associated With Enhanced Cold Tolerance by Comparative Transcriptome Analysis With Two Transgenic Rice Plants Overexpressing DaCBF4 or DaCBF7, Isolated From Antarctic Flowering Plant Deschampsia antarctica.

PubMed

Byun, Mi Young; Cui, Li Hua; Lee, Jungeun; Park, Hyun; Lee, Andosung; Kim, Woo Taek; Lee, Hyoungseok

2018-01-01

Few plant species can survive in Antarctica, the harshest environment for living organisms. Deschampsia antarctica is the only natural grass species to have adapted to and colonized the maritime Antarctic. To investigate the molecular mechanism of the Antarctic adaptation of this plant, we identified and characterized D. antarctica C-repeat binding factor 4 ( DaCBF4 ), which belongs to monocot CBF group IV. The transcript level of DaCBF4 in D. antarctica was markedly increased by cold and dehydration stress. To assess the roles of DaCBF4 in plants, we generated a DaCBF4 -overexpressing transgenic rice plant ( Ubi:DaCBF4 ) and analyzed its abiotic stress response phenotype. Ubi:DaCBF4 displayed enhanced tolerance to cold stress without growth retardation under any condition compared to wild-type plants. Because the cold-specific phenotype of Ubi:DaCBF4 was similar to that of Ubi:DaCBF7 (Byun et al., 2015), we screened for the genes responsible for the improved cold tolerance in rice by selecting differentially regulated genes in both transgenic rice lines. By comparative transcriptome analysis using RNA-seq, we identified 9 and 15 genes under normal and cold-stress conditions, respectively, as putative downstream targets of the two D. antarctica CBFs. Overall, our results suggest that Antarctic hairgrass DaCBF4 mediates the cold-stress response of transgenic rice plants by adjusting the expression levels of a set of stress-responsive genes in transgenic rice plants. Moreover, selected downstream target genes will be useful for genetic engineering to enhance the cold tolerance of cereal plants, including rice.

Cochlear blood flow and speech perception ability in cochlear implant users.

PubMed

Nakashima, Tsutomu; Hattori, Taku; Sone, Michihiko; Asahi, Kiyomitsu; Matsuda, Naoko; Teranishi, Masaaki; Yoshida, Tadao; Kato, Ken; Sato, Eisuke

2012-02-01

The effect of cochlear blood flow (CBF) on speech perception ability in cochlear implant (CI) users has not been reported. We investigated various factors influencing speech perception including CBF in CI users. Eighty-two patients who received CI surgery at an academic hospital. CBF was measured during CI surgery using laser Doppler flowmetry. The speech perception level was measured after a sufficient interval after CI surgery. Multivariate analysis was used to evaluate the influences of age, duration of deafness, sex, cause of deafness, and CBF on the speech perception level. CBF decreased significantly with age but was not related to the speech perception level. In patients with congenital hearing loss, the speech perception level was significantly worse in children who received a CI at 3 years of age than in those who received a CI at 2 years of age or younger. Duration of deafness before CI surgery had deteriorative effects on the speech perception level. CBF may be associated with progression of hearing loss. However, measuring CBF during CI surgery is not useful for predicting postoperative speech perception.

Dynamic association between perfusion and white matter integrity across time since injury in Veterans with history of TBI.

PubMed

Clark, Alexandra L; Bangen, Katherine J; Sorg, Scott F; Schiehser, Dawn M; Evangelista, Nicole D; McKenna, Benjamin; Liu, Thomas T; Delano-Wood, Lisa

2017-01-01

Cerebral blood flow (CBF) plays a critical role in the maintenance of neuronal integrity, and CBF alterations have been linked to deleterious white matter changes. Although both CBF and white matter microstructural alterations have been observed within the context of traumatic brain injury (TBI), the degree to which these pathological changes relate to one another and whether this association is altered by time since injury have not been examined. The current study therefore sought to clarify associations between resting CBF and white matter microstructure post-TBI. 37 veterans with history of mild or moderate TBI (mmTBI) underwent neuroimaging and completed health and psychiatric symptom questionnaires. Resting CBF was measured with multiphase pseudocontinuous arterial spin labeling (MPPCASL), and white matter microstructural integrity was measured with diffusion tensor imaging (DTI). The cingulate cortex and cingulum bundle were selected as a priori regions of interest for the ASL and DTI data, respectively, given the known vulnerability of these regions to TBI. Regression analyses controlling for age, sex, and posttraumatic stress disorder (PTSD) symptoms revealed a significant time since injury × resting CBF interaction for the left cingulum ( p  < 0.005). Decreased CBF was significantly associated with reduced cingulum fractional anisotropy (FA) in the chronic phase; however, no such association was observed for participants with less remote TBI. Our results showed that reduced CBF was associated with poorer white matter integrity in those who were further removed from their brain injury. Findings provide preliminary evidence of a possible dynamic association between CBF and white matter microstructure that warrants additional consideration within the context of the negative long-term clinical outcomes frequently observed in those with history of TBI. Additional cross-disciplinary studies integrating multiple imaging modalities (e.g., DTI, ASL) and refined neuropsychiatric assessment are needed to better understand the nature, temporal course, and dynamic association between brain changes and clinical outcomes post-injury.

Does preoperative measurement of cerebral blood flow with acetazolamide challenge in addition to preoperative measurement of cerebral blood flow at the resting state increase the predictive accuracy of development of cerebral hyperperfusion after carotid endarterectomy? Results from 500 cases with brain perfusion single-photon emission computed tomography study.

PubMed

Oshida, Sotaro; Ogasawara, Kuniaki; Saura, Hiroaki; Yoshida, Koji; Fujiwara, Shunro; Kojima, Daigo; Kobayashi, Masakazu; Yoshida, Kenji; Kubo, Yoshitaka; Ogawa, Akira

2015-01-01

The purpose of the present study was to determine whether preoperative measurement of cerebral blood flow (CBF) with acetazolamide in addition to preoperative measurement of CBF at the resting state increases the predictive accuracy of development of cerebral hyperperfusion after carotid endarterectomy (CEA). CBF at the resting state and cerebrovascular reactivity (CVR) to acetazolamide were quantitatively assessed using N-isopropyl-p-[(123)I]-iodoamphetamine (IMP)-autoradiography method with single-photon emission computed tomography (SPECT) before CEA in 500 patients with ipsilateral internal carotid artery stenosis (≥ 70%). CBF measurement using (123)I-IMP SPECT was also performed immediately and 3 days after CEA. A region of interest (ROI) was automatically placed in the middle cerebral artery territory in the affected cerebral hemisphere using a three-dimensional stereotactic ROI template. Preoperative decreases in CBF at the resting state [95% confidence intervals (CIs), 0.855 to 0.967; P = 0.0023] and preoperative decreases in CVR to acetazolamide (95% CIs, 0.844 to 0.912; P < 0.0001) were significant independent predictors of post-CEA hyperperfusion. The area under the receiver operating characteristic curve for prediction of the development of post-CEA hyperperfusion was significantly greater for CVR to acetazolamide than for CBF at the resting state (difference between areas, 0.173; P < 0.0001). Sensitivity, specificity, and positive- and negative-predictive values for the prediction of the development of post-CEA hyperperfusion were significantly greater for CVR to acetazolamide than for CBF at the resting state (P < 0.05, respectively). The present study demonstrated that preoperative measurement of CBF with acetazolamide in addition to preoperative measurement of CBF at the resting state increases the predictive accuracy of the development of post-CEA hyperperfusion.

Divergent Regulation of CBF Regulon on Cold Tolerance and Plant Phenotype in Cassava Overexpressing Arabidopsis CBF3 Gene.

PubMed

An, Dong; Ma, Qiuxiang; Yan, Wei; Zhou, Wenzhi; Liu, Guanghua; Zhang, Peng

2016-01-01

Cassava is a tropical origin plant that is sensitive to chilling stress. In order to understand the CBF cold response pathway, a well-recognized regulatory mechanism in temperate plants, in cassava, overexpression of an Arabidopsis CBF3 gene is studied. This gene renders cassava increasingly tolerant to cold and drought stresses but is associated with retarded plant growth, leaf curling, reduced storage root yield, and reduced anthocyanin accumulation in a transcript abundance-dependent manner. Physiological analysis revealed that the transgenic cassava increased proline accumulation, reduced malondialdehyde production, and electrolyte leakage under cold stress. These transgenic lines also showed high relative water content when faced with drought. The expression of partial CBF-targeted genes in response to cold displayed temporal and spatial variations in the wild-type and transgenic plants: highly inducible in leaves and less altered in apical buds. In addition, anthocyanin accumulation was inhibited by downregulating the expression of genes involved in its biosynthesis and by interplaying between the CBF3 and the endogenous transcription factors. Thus, the heterologous CBF3 modulates the expression of stress-related genes and carries out a series of physiological adjustments under stressful conditions, showing a varied regulation pattern of CBF regulon from that of cassava CBFs.

Specific cerebral perfusion patterns in three schizophrenia symptom dimensions.

PubMed

Stegmayer, Katharina; Strik, Werner; Federspiel, Andrea; Wiest, Roland; Bohlhalter, Stephan; Walther, Sebastian

2017-12-01

Dimensional concepts such as the Research Domain Criteria initiative have been proposed to disentangle the heterogeneity of schizophrenia. One model introduced three neurobiologically informed behavioral dimensions: language, affectivity and motor behavior. To study the brain-behavior associations of these three dimensions, we investigated whether current behavioral alterations were linked to resting state perfusion in distinct brain circuits in schizophrenia. In total, 47 patients with schizophrenia spectrum disorders and 44 healthy controls were included. Psychopathology was assessed with the Positive And Negative Syndrome Scale and the Bern Psychopathology scale (BPS). The BPS provides severity ratings of three behavioral dimensions (language, affectivity and motor). Patients were classified according to the severity of alterations (severe, mild, no) in each dimension. Whole brain resting state cerebral blood flow (CBF) was compared between patient subgroups and controls. Two symptom dimensions were associated with distinct CBF changes. Behavioral alterations in the language dimension were linked to increased CBF in Heschl's gyrus. Altered affectivity was related to increased CBF in amygdala. The ratings of motor behavior instead were not specifically associated with CBF. Investigating behavioral alterations in three schizophrenia symptom dimensions identified distinct regional CBF changes in the language and limbic brain circuits. The results demonstrate a hitherto unknown segregation of pathophysiological pathways underlying a limited number of specific symptom dimensions in schizophrenia. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

PpCBF3 from Cold-Tolerant Kentucky Bluegrass Involved in Freezing Tolerance Associated with Up-Regulation of Cold-Related Genes in Transgenic Arabidopsis thaliana

PubMed Central

Chen, Yu; Xu, Bin; Yang, Zhimin; Huang, Bingru

2015-01-01

Dehydration-Responsive Element Binding proteins (DREB)/C-repeat (CRT) Binding Factors (CBF) have been identified as transcriptional activators during plant responses to cold stress. The objective of this study was to determine the physiological roles of a CBF gene isolated from a cold-tolerant perennial grass species, Kentucky bluegrass (Poa pratensis L.), which designated as PpCBF3, in regulating plant tolerance to freezing stress. Transient transformation of Arabidopsis thaliana mesophyll protoplast with PpCBF3-eGFP fused protein showed that PpCBF3 was localized to the nucleus. RT-PCR analysis showed that PpCBF3 was specifically induced by cold stress (4°C) but not by drought stress [induced by 20% polyethylene glycol 6000 solution (PEG-6000)] or salt stress (150 mM NaCl). Transgenic Arabidopsis overexpressing PpCBF3 showed significant improvement in freezing (-20°C) tolerance demonstrated by a lower percentage of chlorotic leaves, lower cellular electrolyte leakage (EL) and H2O2 and O2 .- content, and higher chlorophyll content and photochemical efficiency compared to the wild type. Relative mRNA expression level analysis by qRT-PCR indicated that the improved freezing tolerance of transgenic Arabidopsis plants overexpressing PpCBF3 was conferred by sustained activation of downstream cold responsive (COR) genes. Other interesting phenotypic changes in the PpCBF3-transgenic Arabidopsis plants included late flowering and slow growth or ‘dwarfism’, both of which are desirable phenotypic traits for perennial turfgrasses. Therefore, PpCBF3 has potential to be used in genetic engineering for improvement of turfgrass freezing tolerance and other desirable traits. PMID:26177510

Dynamic change in cerebral microcirculation and focal cerebral metabolism in experimental subarachnoid hemorrhage in rabbits.

PubMed

Song, Jin-Ning; Chen, Hu; Zhang, Ming; Zhao, Yong-Lin; Ma, Xu-Dong

2013-03-01

Regional cerebral blood flow (rCBF) in the cerebral metabolism and energy metabolism measurements can be used to assess blood flow of brain cells and to detect cell activity. Changes of rCBF in the cerebral microcirculation and energy metabolism were determined in an experimental model of subarachnoid hemorrhage (SAH) model in 56 large-eared Japanese rabbits about 12 to 16-month old. Laser Doppler flowmetry was used to detect the blood supply to brain cells. Internal carotid artery and vein blood samples were used for duplicate blood gas analysis to assess the energy metabolism of brain cells. Cerebral blood flow (CBF) was detected by single photon emission computed tomography (SPECT) perfusion imaging using Tc-99m ethyl cysteinate dimer (Tc-99m ECD) as an imaging reagent. The percentage of injected dose per gram of brain tissue was calculated and analyzed. There were positive correlations between the percentage of radionuclide injected per gram of brain tissue and rCBF supply and cerebral metabolic rate for oxygen (P < 0.05). However, there was a negative correlation between radioactivity counts per unit volume detected on the SPECT rheoencephalogram and lactic acid concentration in the homolateral internal carotid artery and vein. In summary, this study found abnormal CBF in metabolism and utilization of brain cells after SAH, and also found that deterioration of energy metabolism of brain cells played a significant role in the development of SAH. There are matched reductions in CBF and metabolism. Thus, SPECT imaging could be used as a noninvasive method to detect CBF.

Roles of CAMTA transcription factors and salicylic acid in configuring the low-temperature transcriptome and freezing tolerance of Arabidopsis.

PubMed

Kim, YongSig; Park, Sunchung; Gilmour, Sarah J; Thomashow, Michael F

2013-08-01

Previous studies in Arabidopsis thaliana established roles for CALMODULIN BINDING TRANSCRIPTION ACTIVATOR 3 (CAMTA3) in the rapid cold induction of CRT/DRE BINDING FACTOR (CBF) genes CBF1 and CBF2, and the repression of salicylic acid (SA) biosynthesis at warm temperature. Here we show that CAMTA1 and CAMTA2 work in concert with CAMTA3 at low temperature (4°C) to induce peak transcript levels of CBF1, CBF2 and CBF3 at 2 h, contribute to up-regulation of approximately 15% of the genes induced at 24 h, most of which fall outside the CBF pathway, and increase plant freezing tolerance. In addition, CAMTA1, CAMTA2 and CAMTA3 function together to inhibit SA biosynthesis at warm temperature (22°C). However, SA levels increase in Arabidopsis plants that are exposed to low temperature for more than 1 week. We show that this chilling-induced SA biosynthesis proceeds through the isochorismate synthase (ICS) pathway, with cold induction of ICS1 (which encodes ICS), and two genes encoding transcription factors that positively regulate ICS1 - CBP60g and SARD1 -, paralleling SA accumulation. The three CAMTA proteins effectively repress the accumulation of ICS1, CBP60g and SARD1 transcripts at warm temperature but not at low temperature. This impairment of CAMTA function may involve post-transcriptional regulation, as CAMTA transcript levels did not decrease at low temperature. Salicylic acid biosynthesis at low temperature did not contribute to freezing tolerance, but had a major role in configuring the transcriptome, including the induction of 'defense response' genes, suggesting the possible existence of a pre-emptive defense strategy programmed by prolonged chilling temperatures. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Cerebral blood flow and freezing of gait in Parkinson's disease.

PubMed

Imamura, K; Okayasu, N; Nagatsu, T

2012-09-01

We investigated the relationship between freezing of gait (FOG) severity in Parkinson's disease (PD) and regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) and evaluated the effect of selegiline therapy. We evaluated 54 patients with PD (FOG positive: 21 patients, and FOG negative: 33 patients) with N-isopropyl-p-[I-123] iodoamphetamine ((123) I-IMP) SPECT and the Unified Parkinson's Disease Rating Scale (UPDRS) part III, Mini-Mental State Examination (MMSE), and Beck Depression Inventory. [Correction added on 18 April 2012, after online publication: In the preceding statement, 55 instead of 54 patients with PD were evaluated, and FOG negative consisted of 34 instead of 33 patients] Furthermore, we examined rCBF in FOG-negative patients treated with levodopa with or without selegiline. Z-values of bilateral Brodmann areas (BA) 10 and 11 and left BA32 showed significant increases in the FOG-positive group compared with the FOG-negative group. [Correction added on 18 April 2012, after online publication: In the preceding statement, Z-values was changed to Z-scores] There were significantly positive correlations between Z-values of these areas and FOG score, especially on both sides of BA11. [Correction added on 18 April 2012, after online publication: In the preceding statement, Z-values was changed to Z-scores] An increase in Z-values in bilateral BA10 and 11 and left BA32 in the levodopa-selegiline treatment group after 1 year was significantly inhibited compared with the levodopa treatment group. [Correction added on 18 April 2012, after online publication: In the preceding statement, left BA32 was changed to right BA32, and Z-values was changed to Z-scores] There was a close relationship between FOG severity in PD and an increase in rCBF in BA 10, 11 and 32. Furthermore, selegiline's FOG prevention effect may be related to maintaining rCBF in these same areas. © 2012 John Wiley & Sons A/S.

Analysis of the interaction between human RITA and Drosophila Suppressor of Hairless.

PubMed

Brockmann, Birgit; Mastel, Helena; Oswald, Franz; Maier, Dieter

2014-12-01

Notch signalling mediates intercellular communication, which is effected by the transcription factor CSL, an acronym for vertebrate CBF1/RBP-J, Drosophila Suppressor of Hairless [Su(H)] and C. elegans Lag1. Nuclear import of CBF1/RBP-J depends on co-activators and co-repressors, whereas the export relies on RITA. RITA is a tubulin and CBF1/RBP-J binding protein acting as a negative regulator of Notch signalling in vertebrates. RITA protein is highly conserved in eumatazoa, but no Drosophila homologue was yet identified. In this work, the activity of human RITA in the fly was addressed. To this end, we generated transgenic flies that allow a tissue specific induction of human RITA, which was demonstrated by Western blotting and in fly tissues. Unexpectedly, overexpression of RITA during fly development had little phenotypic consequences, even when overexpressed simultaneously with either Su(H) or the Notch antagonist Hairless. We demonstrate the in vivo binding of human RITA to Su(H) and to tubulin by co-immune precipitation. Moreover, RITA and tubulin co-localized to some degree in several Drosophila tissues. Overall our data show that human RITA, albeit binding to Drosophila Su(H) and tubulin, cannot influence the Notch signalling pathway in the fly, suggesting that a nuclear export mechanism of Su(H), if existent in Drosophila, does not depend on RITA. © 2015 The Authors.

The H/ACA RNP assembly factor SHQ1 functions as an RNA mimic.

PubMed

Walbott, Hélène; Machado-Pinilla, Rosario; Liger, Dominique; Blaud, Magali; Réty, Stéphane; Grozdanov, Petar N; Godin, Kate; van Tilbeurgh, Herman; Varani, Gabriele; Meier, U Thomas; Leulliot, Nicolas

2011-11-15

SHQ1 is an essential assembly factor for H/ACA ribonucleoproteins (RNPs) required for ribosome biogenesis, pre-mRNA splicing, and telomere maintenance. SHQ1 binds dyskerin/NAP57, the catalytic subunit of human H/ACA RNPs, and this interaction is modulated by mutations causing X-linked dyskeratosis congenita. We report the crystal structure of the C-terminal domain of yeast SHQ1, Shq1p, and its complex with yeast dyskerin/NAP57, Cbf5p, lacking its catalytic domain. The C-terminal domain of Shq1p interacts with the RNA-binding domain of Cbf5p and, through structural mimicry, uses the RNA-protein-binding sites to achieve a specific protein-protein interface. We propose that Shq1p operates as a Cbf5p chaperone during RNP assembly by acting as an RNA placeholder, thereby preventing Cbf5p from nonspecific RNA binding before association with an H/ACA RNA and the other core RNP proteins.

The H/ACA RNP assembly factor SHQ1 functions as an RNA mimic

PubMed Central

Walbott, Hélène; Machado-Pinilla, Rosario; Liger, Dominique; Blaud, Magali; Réty, Stéphane; Grozdanov, Petar N.; Godin, Kate; van Tilbeurgh, Herman; Varani, Gabriele; Meier, U. Thomas; Leulliot, Nicolas

2011-01-01

SHQ1 is an essential assembly factor for H/ACA ribonucleoproteins (RNPs) required for ribosome biogenesis, pre-mRNA splicing, and telomere maintenance. SHQ1 binds dyskerin/NAP57, the catalytic subunit of human H/ACA RNPs, and this interaction is modulated by mutations causing X-linked dyskeratosis congenita. We report the crystal structure of the C-terminal domain of yeast SHQ1, Shq1p, and its complex with yeast dyskerin/NAP57, Cbf5p, lacking its catalytic domain. The C-terminal domain of Shq1p interacts with the RNA-binding domain of Cbf5p and, through structural mimicry, uses the RNA–protein-binding sites to achieve a specific protein–protein interface. We propose that Shq1p operates as a Cbf5p chaperone during RNP assembly by acting as an RNA placeholder, thereby preventing Cbf5p from nonspecific RNA binding before association with an H/ACA RNA and the other core RNP proteins. PMID:22085966

Evaluation of the cerebral vasodilatory capacity by the acetazolamide test before EC-IC bypass surgery in patients with occlusion of the internal carotid artery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vorstrup, S.; Brun, B.; Lassen, N.A.

1986-11-01

Cerebral blood flow (CBF) was measured by xenon-133 inhalation tomography in 18 patients with cerebrovascular disease before and 4 months after extracranial-intracranial bypass surgery. Only patients who showed a reduced CBF in areas that were intact on the CT scan and relevant to the clinical and angiographical findings were operated. The majority of the patients had suffered a minor stroke with or without subsequent transient ischemic attacks. They were studied at least 6 weeks following the stroke. All patients had an occlusion of the relevant internal carotid artery. To identify preoperatively the patients with a compromised collateral circulation and hencemore » reduced CBF due to reduced perfusion pressure, a cerebral vasodilatory stress test was performed using acetazolamide (Diamox). In normal subjects, Diamox has been shown to increase tomographic CBF without change of the flow distribution. In the present series 9 patients showed a significant redistribution of flow in favor of the non-occluded side (positive Diamox test). Two of these 9 patients showed even a paradoxical decrease in focal CBF preoperatively, i.e., a steal effect. These 2 patients were the only patients who improved in focal CBF after shunting. The remaining 9 patients all showed uniform flow responses (negative Diamox test), and none of these increased in focal CBF postoperatively. The finding of an unchanged flow map postoperatively confirmed that the low flow areas were not due to restricted flow via collateral pathways. However, an increase in the regional vasodilatory capacity was observed postoperatively in the majority of patients.« less

Using arterial spin labeling to examine mood states in youth.

PubMed

Mikita, Nina; Mehta, Mitul A; Zelaya, Fernando O; Stringaris, Argyris

2015-06-01

Little is known about the neural correlates of mood states and the specific physiological changes associated with their valence and duration, especially in young people. Arterial spin labeling (ASL) imaging is particularly well-suited to study sustained cerebral states in young people, due to its robustness to low-frequency drift, excellent interscan reliability, and noninvasiveness. Yet, it has so far been underutilized for understanding the neural mechanisms underlying mood states in youth. In this exploratory study, 21 healthy adolescents aged 16 to 18 took part in a mood induction experiment. Neutral, sad, and happy mood states were induced using film clips and explicit instructions. An ASL scan was obtained following presentation of each film clip. Mood induction led to robust changes in self-reported mood ratings. Compared to neutral, sad mood was associated with increased regional cerebral blood flow (rCBF) in the left middle frontal gyrus and anterior prefrontal cortex, and decreased rCBF in the right middle frontal gyrus and the inferior parietal lobule. A decrease in self-reported mood from neutral to sad condition was associated with increased rCBF in the precuneus. Happy mood was associated with increased rCBF in medial frontal and cingulate gyri, the subgenual anterior cingulate cortex, and ventral striatum, and decreased rCBF in the inferior parietal lobule. The level of current self-reported depressive symptoms was negatively associated with rCBF change in the cerebellum and lingual gyrus following both sad and happy mood inductions. Arterial spin labeling is sensitive to experimentally induced mood changes in healthy young people. The effects of happy mood on rCBF patterns were generally stronger than the effects of sad mood.

Brain-derived neurotrophic factor mediates cognitive improvements following acute exercise.

PubMed

Borror, Andrew

2017-09-01

The mechanisms causing improved cognition following acute exercise are poorly understood. This article proposes that brain-derived neurotrophic factor (BDNF) is the main factor contributing to improved cognition following exercise. Additionally, it argues that cerebral blood flow (CBF) and oxidative stress explain the release of BDNF from cerebral endothelial cells. One way to test these hypotheses is to block endothelial function and measure the effect on BDNF levels and cognitive performance. The CBF and oxidative stress can also be examined in relationship to BDNF using a multiple linear regression. If these hypotheses are true, there would be a linear relationship between CBF+oxidative stress and BDNF levels as well as between BDNF levels and cognitive performance. The novelty of these hypotheses comes from the emphasis on the cerebral endothelium and the interplay between BDNF, CBF, and oxidative stress. If found to be valid, these hypotheses would draw attention to the cerebral endothelium and provide direction for future research regarding methods to optimize BDNF release and enhance cognition. Elucidating these mechanisms would provide direction for expediting recovery in clinical populations, such as stroke, and maintaining quality of life in the elderly. Copyright © 2017 Elsevier Ltd. All rights reserved.

Age differences in arterial and venous extra-cerebral blood flow in healthy adults: contributions of vascular risk factors and genetic variants.

PubMed

Raz, Naftali; Daugherty, Ana M; Sethi, Sean K; Arshad, Muzamil; Haacke, E Mark

2017-08-01

Sufficient cerebral blood flow (CBF) and venous drainage are critical for normal brain function, and their alterations can affect brain aging. However, to date, most studies focused on arterial CBF (inflow) with little attention paid to the age differences in venous outflow. We measured extra-cerebral arterial and venous blood flow rates with phase-contrast MRI and assessed the influence of vascular risk factors and genetic polymorphisms (ACE insertion/deletion, COMT val158met, and APOEε4) in 73 adults (age 18-74 years). Advanced age, elevated vascular risk, ACE Deletion, and COMT met alleles were linked to lower in- and outflow, with no effects of APOE ε4 noted. Lower age-related CBF rate was unrelated to brain volume and was observed only in val homozygotes of COMTval158met. Thus, in a disease-free population, age differences in CBF may be notable only in persons with high vascular risk and carriers of genetic variants associated with vasoconstriction and lower dopamine availability. It remains to be established if treatments targeting alleviation of the mutable factors can improve the course of cerebrovascular aging in spite of the immutable genetic influence.

Spatial heterogeneity of the relation between resting-state connectivity and blood flow: an important consideration for pharmacological studies.

PubMed

Khalili-Mahani, Najmeh; van Osch, Matthias J; de Rooij, Mark; Beckmann, Christian F; van Buchem, Mark A; Dahan, Albert; van Gerven, Johannes M; Rombouts, Serge A R B

2014-03-01

Resting state fMRI (RSfMRI) and arterial spin labeling (ASL) provide the field of pharmacological Neuroimaging tool for investigating states of brain activity in terms of functional connectivity or cerebral blood flow (CBF). Functional connectivity reflects the degree of synchrony or correlation of spontaneous fluctuations--mostly in the blood oxygen level dependent (BOLD) signal--across brain networks; but CBF reflects mean delivery of arterial blood to the brain tissue over time. The BOLD and CBF signals are linked to common neurovascular and hemodynamic mechanisms that necessitate increased oxygen transportation to the site of neuronal activation; however, the scale and the sources of variation in static CBF and spatiotemporal BOLD correlations are likely different. We tested this hypothesis by examining the relation between CBF and resting-state-network consistency (RSNC)--representing average intranetwork connectivity, determined from dual regression analysis with eight standard networks of interest (NOIs)--in a crossover placebo-controlled study of morphine and alcohol. Overall, we observed spatially heterogeneous relations between RSNC and CBF, and between the experimental factors (drug-by-time, time, drug and physiological rates) and each of these metrics. The drug-by-time effects on CBF were significant in all networks, but significant RSNC changes were limited to the sensorimotor, the executive/salience and the working memory networks. The post-hoc voxel-wise statistics revealed similar dissociations, perhaps suggesting differential sensitivity of RSNC and CBF to neuronal and vascular endpoints of drug actions. The spatial heterogeneity of RSNC/CBF relations encourages further investigation into the role of neuroreceptor distribution and cerebrovascular anatomy in predicting spontaneous fluctuations under drugs. Copyright © 2012 Wiley Periodicals, Inc.

A comparison of the low temperature transcriptomes and CBF regulons of three plant species that differ in freezing tolerance: Solanum commersonii, Solanum tuberosum, and Arabidopsis thaliana

PubMed Central

Pino, María-Teresa; Jeknić, Zoran; Zou, Cheng; Shiu, Shin-Han; Chen, Tony H. H.; Thomashow, Michael F.

2011-01-01

Solanum commersonii and Solanum tuberosum are closely related plant species that differ in their abilities to cold acclimate; whereas S. commersonii increases in freezing tolerance in response to low temperature, S. tuberosum does not. In Arabidopsis thaliana, cold-regulated genes have been shown to contribute to freezing tolerance, including those that comprise the CBF regulon, genes that are controlled by the CBF transcription factors. The low temperature transcriptomes and CBF regulons of S. commersonii and S. tuberosum were therefore compared to determine whether there might be differences that contribute to their differences in ability to cold acclimate. The results indicated that both plants alter gene expression in response to low temperature to similar degrees with similar kinetics and that both plants have CBF regulons composed of hundreds of genes. However, there were considerable differences in the sets of genes that comprised the low temperature transcriptomes and CBF regulons of the two species. Thus differences in cold regulatory programmes may contribute to the differences in freezing tolerance of these two species. However, 53 groups of putative orthologous genes that are cold-regulated in S. commersonii, S. tuberosum, and A. thaliana were identified. Given that the evolutionary distance between the two Solanum species and A. thaliana is 112–156 million years, it seems likely that these conserved cold-regulated genes—many of which encode transcription factors and proteins of unknown function—have fundamental roles in plant growth and development at low temperature. PMID:21511909

A comparison of the low temperature transcriptomes and CBF regulons of three plant species that differ in freezing tolerance: Solanum commersonii, Solanum tuberosum, and Arabidopsis thaliana.

PubMed

Carvallo, Marcela A; Pino, María-Teresa; Jeknic, Zoran; Zou, Cheng; Doherty, Colleen J; Shiu, Shin-Han; Chen, Tony H H; Thomashow, Michael F

2011-07-01

Solanum commersonii and Solanum tuberosum are closely related plant species that differ in their abilities to cold acclimate; whereas S. commersonii increases in freezing tolerance in response to low temperature, S. tuberosum does not. In Arabidopsis thaliana, cold-regulated genes have been shown to contribute to freezing tolerance, including those that comprise the CBF regulon, genes that are controlled by the CBF transcription factors. The low temperature transcriptomes and CBF regulons of S. commersonii and S. tuberosum were therefore compared to determine whether there might be differences that contribute to their differences in ability to cold acclimate. The results indicated that both plants alter gene expression in response to low temperature to similar degrees with similar kinetics and that both plants have CBF regulons composed of hundreds of genes. However, there were considerable differences in the sets of genes that comprised the low temperature transcriptomes and CBF regulons of the two species. Thus differences in cold regulatory programmes may contribute to the differences in freezing tolerance of these two species. However, 53 groups of putative orthologous genes that are cold-regulated in S. commersonii, S. tuberosum, and A. thaliana were identified. Given that the evolutionary distance between the two Solanum species and A. thaliana is 112-156 million years, it seems likely that these conserved cold-regulated genes-many of which encode transcription factors and proteins of unknown function-have fundamental roles in plant growth and development at low temperature.

Numerical study of the influence of applied voltage on the current balance factor of single layer organic light-emitting diodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Fei-ping, E-mail: lufp-sysu@163.com; Liu, Xiao-bin; Xing, Yong-zhong

2014-04-28

Current balance factor (CBF) value, the ratio of the recombination current density and the total current density of a device, has an important function in fluorescence-based organic light-emitting diodes (OLEDs), as well as in the performance of the organic electrophosphorescent devices. This paper investigates the influence of the applied voltage of a device on the CBF value of single layer OLED based on the numerical model of a bipolar single layer OLED with organic layer trap free and without doping. Results show that the largest CBF value can be achieved when the electron injection barrier (ϕ{sub n}) is equal tomore » the hole injection barrier (ϕ{sub p}) in the lower voltage region at any instance. The largest CBF in the higher voltage region can be achieved in the case of ϕ{sub n} > ϕ{sub p} under the condition of electron mobility (μ{sub 0n}) > hole mobility (μ{sub 0p}), whereas the result for the case of μ{sub 0n} < μ{sub 0p}, is opposite. The largest CBF when μ{sub 0n} = μ{sub 0p} can be achieved in the case of ϕ{sub n} = ϕ{sub p} in the entire region of the applied voltage. In addition, the CBF value of the device increases with increasing applied voltage. The results obtained in this paper can present an in-depth understanding of the OLED working mechanism and help in the future fabrication of high efficiency OLEDs.« less

Common and Dissociable Regional Cerebral Blood Flow Differences Associate with Dimensions of Psychopathology Across Categorical Diagnoses

PubMed Central

Kaczkurkin, Antonia N.; Moore, Tyler M.; Calkins, Monica E.; Ciric, Rastko; Detre, John A.; Elliott, Mark A.; Foa, Edna B.; de La Garza, Angel Garcia; Roalf, David R.; Rosen, Adon; Ruparel, Kosha; Shinohara, Russell T.; Xia, Cedric H.; Wolf, Daniel H.; Gur, Raquel E.; Gur, Ruben C.; Satterthwaite, Theodore D.

2017-01-01

The high comorbidity among neuropsychiatric disorders suggests a possible common neurobiological phenotype. Resting-state regional cerebral blood flow (CBF) can be measured noninvasively with MRI and abnormalities in regional CBF are present in many neuropsychiatric disorders. Regional CBF may also provide a useful biological marker across different types of psychopathology. To investigate CBF changes common across psychiatric disorders, we capitalized upon a sample of 1,042 youths (ages 11 to 23 years) who completed cross-sectional imaging as part of the Philadelphia Neurodevelopmental Cohort. CBF during a resting state was quantified on a voxelwise basis using arterial spin labeled perfusion MRI at 3T. A dimensional measure of psychopathology was constructed using a bifactor model of item-level data from a psychiatric screening interview, which delineated four factors (fear, anxious-misery, psychosis, and behavioral symptoms) plus a general factor: overall psychopathology. Overall psychopathology was associated with elevated perfusion in several regions including the right dorsal anterior cingulate cortex (ACC) and left rostral ACC. Furthermore, several clusters were associated with specific dimensions of psychopathology. Psychosis symptoms were related to reduced perfusion in the left frontal operculum and insula, whereas fear symptoms were associated with less perfusion in the right occipital/fusiform gyrus and left subgenual ACC. Follow-up functional connectivity analyses using resting-state fMRI collected in the same participants revealed that overall psychopathology was associated with decreased connectivity between the dorsal ACC and bilateral caudate. Together, the results of this study demonstrate common and dissociable CBF abnormalities across neuropsychiatric disorders in youth. PMID:28924181

Regional cerebral blood flow and abnormal eating behavior in Prader-Willi syndrome.

PubMed

Ogura, Kaeko; Fujii, Toshikatsu; Abe, Nobuhito; Hosokai, Yoshiyuki; Shinohara, Mayumi; Fukuda, Hiroshi; Mori, Etsuro

2013-05-01

Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder and is generally regarded as a genetic model of obesity. Individuals with PWS exhibit behavioral symptoms including temper tantrums, rigid thinking, and compulsive behavior. The most striking feature of PWS is abnormal eating behavior, including hyperphagia, intense preoccupation with food, and incessant food seeking. To explore brain regions associated with the behavioral symptoms of PWS, we investigated differences in resting-state regional cerebral blood flow (rCBF) between individuals with PWS and healthy controls. Correlation analyses were also performed to examine the relationship between rCBF and altered eating behavior in PWS individuals. Twelve adults with PWS and 13 age- and gender-matched controls underwent resting-state single photon emission computerized tomography (SPECT) with N-isopropyl-p-[(123)I] iodoamphetamine (IMP). The rCBF data were analyzed on a voxel-by-voxel basis using SPM5 software. The results demonstrated that compared with controls, individuals with PWS had significantly lower rCBF in the right thalamus, left insular cortex, bilateral lingual gyrus, and bilateral cerebellum. They had significantly higher rCBF in the right inferior frontal gyrus, left middle/inferior frontal gyrus (anterior and posterior clusters), and bilateral angular gyrus. Additionally, rCBF in the left insula, which was significantly lower in PWS individuals, was negatively correlated with the eating behavior severity score. These results suggest that specific brain regions, particularly the left insula, may be partly responsible for the behavioral symptoms in PWS. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Cerebral blood flow relationships associated with a difficult tone recognition task in trained normal volunteers.

PubMed

Holcomb, H H; Medoff, D R; Caudill, P J; Zhao, Z; Lahti, A C; Dannals, R F; Tamminga, C A

1998-09-01

Tone recognition is partially subserved by neural activity in the right frontal and primary auditory cortices. First we determined the brain areas associated with tone perception and recognition. This study then examined how regional cerebral blood flow (rCBF) in these and other brain regions correlates with the behavioral characteristics of a difficult tone recognition task. rCBF changes were assessed using H2(15)O positron emission tomography. Subtraction procedures were used to localize significant change regions and correlational analyses were applied to determine how response times (RT) predicted rCBF patterns. Twelve trained normal volunteers were studied in three conditions: REST, sensory motor control (SMC) and decision (DEC). The SMC-REST contrast revealed bilateral activation of primary auditory cortices, cerebellum and bilateral inferior frontal gyri. DEC-SMC produced significant clusters in the right middle and inferior frontal gyri, insula and claustrum; the anterior cingulate gyrus and supplementary motor area; the left insula/claustrum; and the left cerebellum. Correlational analyses, RT versus rCBF from DEC scans, showed a positive correlation in right inferior and middle frontal cortex; rCBF in bilateral auditory cortices and cerebellum exhibited significant negative correlations with RT These changes suggest that neural activity in the right frontal, superior temporal and cerebellar regions shifts back and forth in magnitude depending on whether tone recognition RT is relatively fast or slow, during a difficult, accurate assessment.

Evaluating the methods used for measuring cerebral blood flow at rest and during exercise in humans.

PubMed

Tymko, Michael M; Ainslie, Philip N; Smith, Kurt J

2018-05-16

The first accounts of measuring cerebral blood flow (CBF) in humans were made by Angelo Mosso in ~1880, who recorded brain pulsations in patients with skull defects. In 1890, Charles Roy and Charles Sherrington determined in animals that brain pulsations-assessed via a similar method used by Mosso-were altered during a variety of stimuli including sensory nerve stimulation, asphyxia, and pharmacological interventions. Between 1880 and 1944, measurements for CBF were typically relied on skull abnormalities in humans. Thereafter, Kety and Schmidt introduced a new methodological approach in 1945 that involved nitrous oxide dilution combined with serial arterial and jugular venous blood sampling. Less than a decade later (1950's), several research groups employed the Kety-Schmidt technique to assess the effects of exercise on global CBF and metabolism; these studies demonstrated an uncoupling of CBF and metabolism during exercise, which was contrary to early hypotheses. However, there were several limitations to this technique related to low temporal resolution and the inability to measure regional CBF. These limitations were overcome in the 1960's when transcranial Doppler ultrasound (TCD) was developed as a method to measure beat-by-beat cerebral blood velocity. Between 1990 and 2010, TCD further progressed our understanding of CBF regulation and allowed for insight into other mechanistic factors, independent of local metabolism, involved in regulating CBF during exercise. Recently, it was discovered that TCD may not be accurate under several physiological conditions. Other measures of indexing CBF such as Duplex ultrasound and magnetic resonance imaging, although not without some limitations, may be more applicable for future investigations.

SNP-array lesions in core binding factor acute myeloid leukemia

PubMed Central

Duployez, Nicolas; Boudry-Labis, Elise; Roumier, Christophe; Boissel, Nicolas; Petit, Arnaud; Geffroy, Sandrine; Helevaut, Nathalie; Celli-Lebras, Karine; Terré, Christine; Fenneteau, Odile; Cuccuini, Wendy; Luquet, Isabelle; Lapillonne, Hélène; Lacombe, Catherine; Cornillet, Pascale; Ifrah, Norbert; Dombret, Hervé; Leverger, Guy; Jourdan, Eric; Preudhomme, Claude

2018-01-01

Acute myeloid leukemia (AML) with t(8;21) and inv(16), together referred as core binding factor (CBF)-AML, are recognized as unique entities. Both rearrangements share a common pathophysiology, the disruption of the CBF, and a relatively good prognosis. Experiments have demonstrated that CBF rearrangements were insufficient to induce leukemia, implying the existence of cooperating events. To explore these aberrations, we performed single nucleotide polymorphism (SNP)-array in a well-annotated cohort of 198 patients with CBF-AML. Excluding breakpoint-associated lesions, the most frequent events included loss of a sex chromosome (53%), deletions at 9q21 (12%) and 7q36 (9%) in patients with t(8;21) compared with trisomy 22 (13%), trisomy 8 (10%) and 7q36 deletions (12%) in patients with inv(16). SNP-array revealed novel recurrent genetic alterations likely to be involved in CBF-AML leukemogenesis. ZBTB7A mutations (20% of t(8;21)-AML) were shown to be a target of copy-neutral losses of heterozygosity (CN-LOH) at chromosome 19p. FOXP1 focal deletions were identified in 5% of inv(16)-AML while sequence analysis revealed that 2% carried FOXP1 truncating mutations. Finally, CCDC26 disruption was found in both subtypes (4.5% of the whole cohort) and possibly highlighted a new lesion associated with aberrant tyrosine kinase signaling in this particular subtype of leukemia. PMID:29464086

SNP-array lesions in core binding factor acute myeloid leukemia.

PubMed

Duployez, Nicolas; Boudry-Labis, Elise; Roumier, Christophe; Boissel, Nicolas; Petit, Arnaud; Geffroy, Sandrine; Helevaut, Nathalie; Celli-Lebras, Karine; Terré, Christine; Fenneteau, Odile; Cuccuini, Wendy; Luquet, Isabelle; Lapillonne, Hélène; Lacombe, Catherine; Cornillet, Pascale; Ifrah, Norbert; Dombret, Hervé; Leverger, Guy; Jourdan, Eric; Preudhomme, Claude

2018-01-19

Acute myeloid leukemia (AML) with t(8;21) and inv(16), together referred as core binding factor (CBF)-AML, are recognized as unique entities. Both rearrangements share a common pathophysiology, the disruption of the CBF, and a relatively good prognosis. Experiments have demonstrated that CBF rearrangements were insufficient to induce leukemia, implying the existence of cooperating events. To explore these aberrations, we performed single nucleotide polymorphism (SNP)-array in a well-annotated cohort of 198 patients with CBF-AML. Excluding breakpoint-associated lesions, the most frequent events included loss of a sex chromosome (53%), deletions at 9q21 (12%) and 7q36 (9%) in patients with t(8;21) compared with trisomy 22 (13%), trisomy 8 (10%) and 7q36 deletions (12%) in patients with inv(16). SNP-array revealed novel recurrent genetic alterations likely to be involved in CBF-AML leukemogenesis. ZBTB7A mutations (20% of t(8;21)-AML) were shown to be a target of copy-neutral losses of heterozygosity (CN-LOH) at chromosome 19p. FOXP1 focal deletions were identified in 5% of inv(16)-AML while sequence analysis revealed that 2% carried FOXP1 truncating mutations. Finally, CCDC26 disruption was found in both subtypes (4.5% of the whole cohort) and possibly highlighted a new lesion associated with aberrant tyrosine kinase signaling in this particular subtype of leukemia.

Vascular and parenchymal amyloid pathology in an Alzheimer disease knock-in mouse model: interplay with cerebral blood flow.

PubMed

Li, Hongmei; Guo, Qinxi; Inoue, Taeko; Polito, Vinicia A; Tabuchi, Katsuhiko; Hammer, Robert E; Pautler, Robia G; Taffet, George E; Zheng, Hui

2014-08-09

Accumulation and deposition of β-amyloid peptides (Aβ) in the brain is a central event in the pathogenesis of Alzheimer's disease (AD). Besides the parenchymal pathology, Aβ is known to undergo active transport across the blood-brain barrier and cerebral amyloid angiopathy (CAA) is a prominent feature in the majority of AD. Although impaired cerebral blood flow (CBF) has been implicated in faulty Aβ transport and clearance, and cerebral hypoperfusion can exist in the pre-clinical phase of Alzheimer's disease (AD), it is still unclear whether it is one of the causal factors for AD pathogenesis, or an early consequence of a multi-factor condition that would lead to AD at late stage. To study the potential interaction between faulty CBF and amyloid accumulation in clinical-relevant situation, we generated a new amyloid precursor protein (APP) knock-in allele that expresses humanized Aβ and a Dutch mutation in addition to Swedish/London mutations and compared this line with an equivalent knock-in line but in the absence of the Dutch mutation, both crossed onto the PS1M146V knock-in background. Introduction of the Dutch mutation results in robust CAA and parenchymal Aβ pathology, age-dependent reduction of spatial learning and memory deficits, and CBF reduction as detected by fMRI. Direct manipulation of CBF by transverse aortic constriction surgery on the left common carotid artery caused differential changes in CBF in the anterior and middle region of the cortex, where it is reduced on the left side and increased on the right side. However these perturbations in CBF resulted in the same effect: both significantly exacerbate CAA and amyloid pathology. Our study reveals a direct and positive link between vascular and parenchymal Aβ; both can be modulated by CBF. The new APP knock-in mouse model recapitulates many symptoms of AD including progressive vascular and parenchymal Aβ pathology and behavioral deficits in the absence of APP overexpression.

Crosstalk of PmCBFs and PmDAMs Based on the Changes of Phytohormones under Seasonal Cold Stress in the Stem of Prunus mume

PubMed Central

Zhou, Yuzhen; Li, Yushu; Zhuo, Xiaokang; Ahmad, Sagheer; Han, Yu; Yong, Xue; Zhang, Qixiang

2018-01-01

Plants facing the seasonal variations always need a growth restraining mechanism when temperatures turn down. C-repeat binding factor (CBF) genes work essentially in the cold perception. Despite lots of researches on CBFs, the multiple crosstalk is still interesting on their interaction with hormones and dormancy-associated MADS (DAM) genes in the growth and dormancy control. Therefore, this study highlights roles of PmCBFs in cold-induced dormancy from different orgens. And a sense-response relationship between PmCBFs and PmDAMs is exhibited in this process, jointly regulated by six PmCBFs and PmDAM4–6. Meantime, GA3 and ABA showed negative and positive correlation with PmCBFs expression levels, respectively. We also find a high correlation between IAA and PmDAM1–3. Finally, we display the interaction mode of PmCBFs and PmDAMs, especially PmCBF1-PmDAM1. These results can disclose another view of molecular mechanism in plant growth between cold-response pathway and dormancy regulation together with genes and hormones. PMID:29360732

CCAAT-binding factor regulates expression of the beta1 subunit of soluble guanylyl cyclase gene in the BE2 human neuroblastoma cell line

NASA Technical Reports Server (NTRS)

Sharina, Iraida G.; Martin, Emil; Thomas, Anthony; Uray, Karen L.; Murad, Ferid

2003-01-01

Soluble guanylyl cyclase (sGC) is a cytosolic enzyme producing the intracellular messenger cyclic guanosine monophosphate (cGMP) on activation with nitric oxide (NO). sGC is an obligatory heterodimer composed of alpha and beta subunits. We investigated human beta1 sGC transcriptional regulation in BE2 human neuroblastoma cells. The 5' upstream region of the beta1 sGC gene was isolated and analyzed for promoter activity by using luciferase reporter constructs. The transcriptional start site of the beta1 sGC gene in BE2 cells was identified. The functional significance of consensus transcriptional factor binding sites proximal to the transcriptional start site was investigated by site deletions in the 800-bp promoter fragment. The elimination of CCAAT-binding factor (CBF) and growth factor independence 1 (GFI1) binding cores significantly diminished whereas deletion of the NF1 core elevated the transcription. Electrophoretic mobility-shift assay (EMSA) and Western analysis of proteins bound to biotinated EMSA probes confirmed the interaction of GFI1, CBF, and NF1 factors with the beta1 sGC promoter. Treatment of BE2 cells with genistein, known to inhibit the CBF binding to DNA, significantly reduced protein levels of beta1 sGC by inhibiting transcription. In summary, our study represents an analysis of the human beta1 sGC promoter regulation in human neuroblastoma BE2 cells and identifies CBF as a critically important factor in beta1 sGC expression.

[Factor structure of regional CBF and CMRglu values as a tool for the study of default mode of the brain].

PubMed

Kataev, G V; Korotkov, A D; Kireev, M V; Medvedev, S V

2013-01-01

In the present article it was shown that the functional connectivity of brain structures, revealed by factor analysis of resting PET CBF and rCMRglu data, is an adequate tool to study the default mode of the human brain. The identification of neuroanatomic systems of default mode (default mode network) during routine clinical PET investigations is important for further studying the functional organization of the normal brain and its reorganizations in pathological conditions.

The effect of topically administered latanoprost on the cochlear blood flow and hearing.

PubMed

Jang, Chul Ho; Cho, Yong Beom; Choi, Cheol Hee; Um, Jae-Young; Wang, Pa-Chun; Pak, Sok Cheon

2013-06-01

The application of intratympanic latanoprost (PGF2α analog) has been recently used to alleviate vertigo, disequilibrium and to improve hearing in Meniere's disease patients. However, there is no known report on the effect of topically applied latanoprost on hearing and cochlear hemodynamic parameters including cochlear blood flow (CBF) and vascular conductance. Our goal was to assess the influence of topically applied latanoprost on cochlear blood flow (CBF) and hearing. Twenty male Sprague-Dawley rats were randomly divided into the group A, 50 μl of latanoprost (1 ml containing 50 μg, n=10) and group B, 100 μl (1 ml containing 50 μg, n=10). Topical application of latanoprost was performed at the right side, and the left side was applied with phosphate buffered saline (PBS) as a negative control. Five rats at each group were used to measure cochlear blood flow (CBF). And the others at each group were used for hearing test by auditory brainstem response (ABR). After physiological examination, bullas were extracted. The changes of cochlear hair cells were observed by performing the field emission-scanning electron microscopy (FE-SEM). The CBF of both groups was found to be decreased compared to the PBS applied left side. Significant decrement of CBF was observed in group B compared to the group A. Significant elevation of hearing threshold at high frequencies was observed in both groups compared to the PBS applied group. However, inner and outer hair cells were intact. Topically administered latanoprost decreased the CBF and impaired hearing. Based on our findings, additional studies are required to evaluate the side effects of intratympanic latanoprost before its use in clinical practice. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Importance of Nitric Oxide for Local Increases of Blood Flow in Rat Cerebellar Cortex During Electrical Stimulation

NASA Astrophysics Data System (ADS)

Akgoren, Nuran; Fabricius, Martin; Lauritzen, Martin

1994-06-01

The endothelium-derived relaxing factor, probably nitric oxide (NO), is a potent vasodilator that regulates the vascular tone in several vascular beds, including the brain. We explored the possibility that NO might be of importance for the increase of cerebral blood flow (CBF) associated with activity of the well-defined neuronal circuits of the rat cerebellar cortex. Laser-Doppler flowmetry was used to measure increases of cerebellar blood flow evoked by trains of electrical stimulations of the dorsal surface. The evoked increases of CBF were frequency-dependent, being larger on than off the parallel fiber tracts, suggesting that conduction along parallel fibers and synaptic activation of target cells were important for the increase of CBF. This was verified experimentally since the evoked CBF increases were abolished by tetrodotoxin and reduced by 10 mM Mg2+ and selective antagonists for non-N-methyl-D-aspartate receptors. The cerebellar cortex contains high levels of NO synthase. This raised the possibility that NO was involved in the increase of CBF associated with neuronal activation. NO synthase inhibition by topical application of N^G-nitro-L-arginine attenuated the evoked CBF increase by about 50%. This effect was partially reversed by pretreatment with L-arginine, the natural substrate for the enzyme, while N^G-nitro-D-arginine, the inactive enantiomer, had no effect on the evoked CBF increases. Simultaneous blockade of non-N-methyl-D-aspartate receptors and NO synthase had no further suppressing effect on the blood flow increase than either substance alone, suggesting that the NO-dependent flow rise was dependent on postsynaptic mechanisms. These findings are consistent with the idea that local synthesis of NO is involved in the transduction mechanism between neuronal activity and increased CBF.

Cerebral Hyperperfusion Syndrome After Revascularization Surgery in Moyamoya Disease: Region-Symptom Mapping and Estimating a Critical Threshold.

PubMed

Kazumata, Ken; Uchino, Haruto; Tokairin, Kikutaro; Ito, Masaki; Shiga, Tohru; Osanai, Toshiya; Kawabori, Masahito

2018-06-01

Cerebral hyperperfusion complicates the postoperative course of patients with moyamoya disease after direct revascularization surgery. There is no clear distinction between cerebral hyperperfusion syndrome and benign postoperative increase in regional cerebral blood flow (rCBF). The present study aimed to determine clinically relevant changes in rCBF, anatomical correlations, and factors associated with transient neurologic symptoms after revascularization surgery in moyamoya disease. Whole-brain voxel-based perfusion mapping was used to identify regions involved in cerebral hyperperfusion and quantify the changes in 105 hemispheric surgeries with the use of single-photon computed tomography acquired on postoperative day 7. The changes in rCBF were quantitatively analyzed, and associations with cerebral hyperperfusion syndrome were determined. Transient neurologic symptoms appeared with rCBF increase in 37.9% of adults. Speech impairments were associated with an increase in rCBF in the operculo-insula region. Cheiro-oral syndrome was associated with the posterior insula as well as the prefrontal region. A receiver operating curve analysis yielded transient neurologic symptoms with maximum accuracy at >15.5% increase from baseline. Age and preoperative rCBF were independently associated with transient neurologic symptoms (P < 0.001). Areas showing rCBF increase during the experience of transient neurologic symptoms were spatially compatible with the known functional anatomy of the brain. An increase of approximately 15% from baseline was found to be critical, which is a far lower threshold than what has been reported previously. Increasing age was significantly associated with the occurrence of symptomatic hyperperfusion. Furthermore, patients with preserved rCBF also showed symptomatic hyperperfusion. Copyright © 2018 Elsevier Inc. All rights reserved.

Comprehensive mutational profiling of core binding factor acute myeloid leukemia

PubMed Central

Duployez, Nicolas; Marceau-Renaut, Alice; Boissel, Nicolas; Petit, Arnaud; Bucci, Maxime; Geffroy, Sandrine; Lapillonne, Hélène; Renneville, Aline; Ragu, Christine; Figeac, Martin; Celli-Lebras, Karine; Lacombe, Catherine; Micol, Jean-Baptiste; Abdel-Wahab, Omar; Cornillet, Pascale; Ifrah, Norbert; Dombret, Hervé; Leverger, Guy; Jourdan, Eric

2016-01-01

Acute myeloid leukemia (AML) with t(8;21) or inv(16) have been recognized as unique entities within AML and are usually reported together as core binding factor AML (CBF-AML). However, there is considerable clinical and biological heterogeneity within this group of diseases, and relapse incidence reaches up to 40%. Moreover, translocations involving CBFs are not sufficient to induce AML on its own and the full spectrum of mutations coexisting with CBF translocations has not been elucidated. To address these issues, we performed extensive mutational analysis by high-throughput sequencing in 215 patients with CBF-AML enrolled in the Phase 3 Trial of Systematic Versus Response-adapted Timed-Sequential Induction in Patients With Core Binding Factor Acute Myeloid Leukemia and Treating Patients with Childhood Acute Myeloid Leukemia with Interleukin-2 trials (age, 1-60 years). Mutations in genes activating tyrosine kinase signaling (including KIT, N/KRAS, and FLT3) were frequent in both subtypes of CBF-AML. In contrast, mutations in genes that regulate chromatin conformation or encode members of the cohesin complex were observed with high frequencies in t(8;21) AML (42% and 18%, respectively), whereas they were nearly absent in inv(16) AML. High KIT mutant allele ratios defined a group of t(8;21) AML patients with poor prognosis, whereas high N/KRAS mutant allele ratios were associated with the lack of KIT or FLT3 mutations and a favorable outcome. In addition, mutations in epigenetic modifying or cohesin genes were associated with a poor prognosis in patients with tyrosine kinase pathway mutations, suggesting synergic cooperation between these events. These data suggest that diverse cooperating mutations may influence CBF-AML pathophysiology as well as clinical behavior and point to potential unique pathogenesis of t(8;21) vs inv(16) AML. PMID:26980726

NIRS-based noninvasive cerebrovascular regulation assessment

NASA Astrophysics Data System (ADS)

Miller, S.; Richmond, I.; Borgos, J.; Mitra, K.

2016-03-01

Alterations to cerebral blood flow (CBF) have been implicated in diverse neurological conditions, including mild traumatic brain injury, microgravity induced intracranial pressure (ICP) increases, mild cognitive impairment, and Alzheimer's disease. Near infrared spectroscopy (NIRS)-measured regional cerebral tissue oxygen saturation (rSO2) provides an estimate of oxygenation of the interrogated cerebral volume that is useful in identifying trends and changes in oxygen supply to cerebral tissue and has been used to monitor cerebrovascular function during surgery and ventilation. In this study, CO2-inhalation-based hypercapnic breathing challenges were used as a tool to simulate CBF dysregulation, and NIRS was used to monitor the CBF autoregulatory response. A breathing circuit for the selective administration of CO2-compressed air mixtures was designed and used to assess CBF regulatory responses to hypercapnia in 26 healthy young adults using non-invasive methods and real-time sensors. After a 5 or 10 minute baseline period, 1 to 3 hypercapnic challenges of 5 or 10 minutes duration were delivered to each subject while rSO2, partial pressure of end tidal CO2 (PETCO2), and vital signs were continuously monitored. Change in rSO2 measurements from pre- to intrachallenge (ΔrSO2) detected periods of hypercapnic challenges. Subjects were grouped into three exercise factor levels (hr/wk), 1: 0, 2:>0 and <10, and 3:>10. Exercise factor level 3 subjects showed significantly greater ΔrSO2 responses to CO2 challenges than level 2 and 1 subjects. No significant difference in ΔPETCO2 existed between these factor levels. Establishing baseline values of rSO2 in clinical practice may be useful in early detection of CBF changes.

Cerebral Perfusion Is Perturbed by Preterm Birth and Brain Injury.

PubMed

Mahdi, E S; Bouyssi-Kobar, M; Jacobs, M B; Murnick, J; Chang, T; Limperopoulos, C

2018-05-10

Early disturbances in systemic and cerebral hemodynamics are thought to mediate prematurity-related brain injury. However, the extent to which CBF is perturbed by preterm birth is unknown. Our aim was to compare global and regional CBF in preterm infants with and without brain injury on conventional MR imaging using arterial spin-labeling during the third trimester of ex utero life and to examine the relationship between clinical risk factors and CBF. We prospectively enrolled preterm infants younger than 32 weeks' gestational age and <1500 g and performed arterial spin-labeling MR imaging studies. Global and regional CBF in the cerebral cortex, thalami, pons, and cerebellum was quantified. Preterm infants were stratified into those with and without structural brain injury. We further categorized preterm infants by brain injury severity: moderate-severe and mild. We studied 78 preterm infants: 31 without brain injury and 47 with brain injury (29 with mild and 18 with moderate-severe injury). Global CBF showed a borderline significant increase with increasing gestational age at birth ( P = .05) and trended lower in preterm infants with brain injury ( P = .07). Similarly, regional CBF was significantly lower in the right thalamus and midpons ( P < .05) and trended lower in the midtemporal, left thalamus, and anterior vermis regions ( P < .1) in preterm infants with brain injury. Regional CBF in preterm infants with moderate-severe brain injury trended lower in the midpons, right cerebellar hemisphere, and dentate nuclei compared with mild brain injury ( P < .1). In addition, a significant, lower regional CBF was associated with ventilation, sepsis, and cesarean delivery ( P < .05). We report early disturbances in global and regional CBF in preterm infants following brain injury. Regional cerebral perfusion alterations were evident in the thalamus and pons, suggesting regional vulnerability of the developing cerebro-cerebellar circuitry. © 2018 by American Journal of Neuroradiology.

Cerebral blood flow measured by arterial spin labeling MRI at resting state in normal aging and Alzheimer's disease.

PubMed

Zhang, Nan; Gordon, Marc L; Goldberg, Terry E

2017-01-01

Arterial spin labeling (ASL) magnetic resonance imaging uses arterial blood water as an endogenous tracer to measure cerebral blood flow (CBF). In this review, based on ASL studies in the resting state, we discuss state-of-the-art technical and data processing improvements in ASL, and ASL CBF changes in normal aging, mild cognitive impairment (MCI), Alzheimer's disease (AD), and other types of dementia. We propose that vascular and AD risk factors should be considered when evaluating CBF changes in aging, and that other validated biomarkers should be used as inclusion criteria or covariates when evaluating CBF changes in MCI and AD. With improvements in hardware and experimental design, ASL is proving to be an increasingly promising tool for exploring pathogenetic mechanisms, early detection, monitoring disease progression and pharmacological response, and differential diagnosis of AD. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Gene Regulation and Signal Transduction in the ICE-CBF-COR Signaling Pathway during Cold Stress in Plants.

PubMed

Wang, Da-Zhi; Jin, Ya-Nan; Ding, Xi-Han; Wang, Wen-Jia; Zhai, Shan-Shan; Bai, Li-Ping; Guo, Zhi-Fu

2017-10-01

Low temperature is an abiotic stress that adversely affects the growth and production of plants. Resistance and adaptation of plants to cold stress is dependent upon the activation of molecular networks and pathways involved in signal transduction and the regulation of cold-stress related genes. Because it has numerous and complex genes, regulation factors, and pathways, research on the ICE-CBF-COR signaling pathway is the most studied and detailed, which is thought to be rather important for cold resistance of plants. In this review, we focus on the function of each member, interrelation among members, and the influence of manipulators and repressors in the ICE-CBF-COR pathway. In addition, regulation and signal transduction concerning plant hormones, circadian clock, and light are discussed. The studies presented provide a detailed picture of the ICE-CBF-COR pathway.

Runx1 and Cbfβ regulate the development of Flt3+ dendritic cell progenitors and restrict myeloproliferative disorder

PubMed Central

Satpathy, Ansuman T.; Briseño, Carlos G.; Cai, Xiongwei; Michael, Drew G.; Chou, Chun; Hsiung, Sunnie; Bhattacharya, Deepta; Speck, Nancy A.

2014-01-01

Runx1 and Cbfβ are critical for the establishment of definitive hematopoiesis and are implicated in leukemic transformation. Despite the absolute requirements for these factors in the development of hematopoietic stem cells and lymphocytes, their roles in the development of bone marrow progenitor subsets have not been defined. Here, we demonstrate that Cbfβ is essential for the development of Flt3+ macrophage-dendritic cell (DC) progenitors in the bone marrow and all DC subsets in the periphery. Besides the loss of DC progenitors, pan-hematopoietic Cbfb-deficient mice also lack CD105+ erythroid progenitors, leading to severe anemia at 3 to 4 months of age. Instead, Cbfb deficiency results in aberrant progenitor differentiation toward granulocyte-macrophage progenitors (GMPs), resulting in a myeloproliferative phenotype with accumulation of GMPs in the periphery and cellular infiltration of the liver. Expression of the transcription factor Irf8 is severely reduced in Cbfb-deficient progenitors, and overexpression of Irf8 restors DC differentiation. These results demonstrate that Runx proteins and Cbfβ restrict granulocyte lineage commitment to facilitate multilineage hematopoietic differentiation and thus identify their novel tumor suppressor function in myeloid leukemia. PMID:24677539

Cerebrovascular Responses During Lower Body Negative Pressure-Induced Presyncope

NASA Technical Reports Server (NTRS)

Kuriyama, Kana; Watenpaugh, D. E.; Hargens, Alan R.; Ueno, T.; Ballard, R. E.; Fortney, S. M.

1996-01-01

Reduced orthostatic tolerance is commonly observed after space flight, occasionally causing presyncopal conditions. Although the cerebrovascular system may play an important role in presyncope, there have been few reports concerning cerebral hemodynamics during presyncope. The purpose of this study was to investigate cerebrovascular responses during presyncope induced by lower body negative pressure (LBNP). Seven healthy male volunteers were exposed to LBNP in steps of -10 mmHg every 3 min until presyncopal symptoms were detected. Blood pressure (BP) and heart rate (HR) were measured with a finger cuff. Cerebral tissue oxy- and deoxy- hemoglobin (Hb) concentrations were estimated using near infrared spectroscopy (NIRS). Cerebral blood flow (CBF) velocity at the middle cerebral artery was measured with Transcranial Doppler Sonography (TCD). We focused on the data during the 2 min before endpoint. BP marked a gradual decrease (91 to 86 mmHg from 2 min to 30 sec before endpoint), which was accelerated along with HR decrease during the final 30 sec (86 to 71 mmHg). Cerebral oxy-Hb concentration decreases as presyncope is approached while total-Hb concentration remains fairly constant. TCD reveals a decrease in the CBF velocity. The TCD and NIRS results suggest that CBF decreases along with the BP decrease. Cerebrovascular responses during presyncope are closely related to cardiovascular responses.

Granulocyte-Colony Stimulating Factor Increases Cerebral Blood Flow via a NO Surge Mediated by Akt/eNOS Pathway to Reduce Ischemic Injury

PubMed Central

Kuo, Jon-Son; Wang, Jia-Yi

2015-01-01

Granulocyte-colony stimulating factor (G-CSF) protects brain from ischemic/reperfusion (I/R) injury, and inhibition of nitric oxide (NO) synthases partially reduces G-CSF protection. We thus further investigated the effects of G-CSF on ischemia-induced NO production and its consequence on regional cerebral blood flow (rCBF) and neurological deficit. Endothelin-1 (ET-1) microinfused above middle cerebral artery caused a rapid reduction of rCBF (ischemia) which lasted for 30 minutes and was followed by a gradual recovery of blood flow (reperfusion) within the striatal region. Regional NO concentration increased rapidly (NO surge) during ischemia and recovered soon to the baseline. G-CSF increased rCBF resulting in shorter ischemic duration and an earlier onset of reperfusion. The enhancement of the ischemia-induced NO by G-CSF accompanied by elevation of phospho-Akt and phospho-eNOS was noted, suggesting an activation of Akt/eNOS. I/R-induced infarct volume and neurological deficits were also reduced by G-CSF treatment. Inhibition of NO synthesis by L-NG-Nitroarginine Methyl Ester (L-NAME) significantly reduced the effects of G-CSF on rCBF, NO surge, infarct volume, and neurological deficits. We conclude that G-CSF increases rCBF through a NO surge mediated by Akt/eNOS, which partially contributes to the beneficial effect of G-CSF on brain I/R injury. PMID:26146654

Overexpression of a wheat (Triticum aestivum L.) bZIP transcription factor gene, TabZIP6, decreased the freezing tolerance of transgenic Arabidopsis seedlings by down-regulating the expression of CBFs.

PubMed

Cai, Wangting; Yang, Yaling; Wang, Weiwei; Guo, Guangyan; Liu, Wei; Bi, Caili

2018-03-01

The basic leucine zipper (bZIP) proteins play important roles against abiotic stress in plants, including cold stress. However, most bZIPs involved in plant freezing tolerance are positive regulators. Only a few bZIPs function negatively in cold stress response. In this study, TabZIP6, a Group C bZIP transcription factor gene from common wheat (Triticum aestivum L.), was cloned and characterized. The transcript of TabZIP6 was strongly induced by cold treatment (4 °C). TabZIP6 is a nuclear-localized protein with transcriptional activation activity. Arabidopsis plants overexpressing TabZIP6 showed decreased tolerance to freezing stress. Microarray as well as quantitative real-time PCR (qRT-PCR) analysis showed that CBFs and some key COR genes, including COR47 and COR15B, were down-regulated by cold treatment in TabZIP6-overexpressing Arabidopsis lines. TabZIP6 was capable of binding to the G-box motif and the CBF1 and CBF3 promoters in yeast cells. A yeast two-hybrid assay revealed that TabZIP6, as well as the other two Group S bZIP proteins involved in cold stress tolerance in wheat, Wlip19 and TaOBF1, can form homodimers by themselves and heterodimers with each other. These results suggest that TabZIP6 may function negatively in the cold stress response by binding to the promoters of CBFs, and thereby decreasing the expression of downstream COR genes in TabZIP6-overexpressing Arabidopsis seedlings. Copyright © 2018. Published by Elsevier Masson SAS.

Hypoxemia, oxygen content, and the regulation of cerebral blood flow

PubMed Central

Bain, Anthony R.; Rieger, Mathew G.; Bailey, Damian M; Ainslie, Philip N.

2015-01-01

This review highlights the influence of oxygen (O2) availability on cerebral blood flow (CBF). Evidence for reductions in O2 content (CaO2) rather than arterial O2 tension (PaO2) as the chief regulator of cerebral vasodilation, with deoxyhemoglobin as the primary O2 sensor and upstream response effector, is discussed. We review in vitro and in vivo data to summarize the molecular mechanisms underpinning CBF responses during changes in CaO2. We surmise that 1) during hypoxemic hypoxia in healthy humans (e.g., conditions of acute and chronic exposure to normobaric and hypobaric hypoxia), elevations in CBF compensate for reductions in CaO2 and thus maintain cerebral O2 delivery; 2) evidence from studies implementing iso- and hypervolumic hemodilution, anemia, and polycythemia indicate that CaO2 has an independent influence on CBF; however, the increase in CBF does not fully compensate for the lower CaO2 during hemodilution, and delivery is reduced; and 3) the mechanisms underpinning CBF regulation during changes in O2 content are multifactorial, involving deoxyhemoglobin-mediated release of nitric oxide metabolites and ATP, deoxyhemoglobin nitrite reductase activity, and the downstream interplay of several vasoactive factors including adenosine and epoxyeicosatrienoic acids. The emerging picture supports the role of deoxyhemoglobin (associated with changes in CaO2) as the primary biological regulator of CBF. The mechanisms for vasodilation therefore appear more robust during hypoxemic hypoxia than during changes in CaO2 via hemodilution. Clinical implications (e.g., disorders associated with anemia and polycythemia) and future study directions are considered. PMID:26676248

Distraction decreases prefrontal oxygenation: A NIRS study.

PubMed

Ozawa, Sachiyo; Hiraki, Kazuo

2017-04-01

When near-infrared spectroscopy (NIRS) is used to measure emotion-related cerebral blood flow (CBF) changes in the prefrontal cortex regions, the functional distinction of CBF changes is often difficult because NIRS is unable to measure neural activity in deeper brain regions that play major roles in emotional processing. The CBF changes could represent cognitive control of emotion and emotional responses to emotional materials. Supposing that emotion-related CBF changes in the prefrontal cortex regions during distraction are emotional responses, we examined whether oxygenated hemoglobin (oxyHb) decreases. Attention-demanding tasks cause blood flow decreases, and we thus compared the effects of visually paced tapping with different tempos, on distraction. The results showed that the oxyHb level induced by emotional stimulation decreased with fast-tempo tapping significantly more than slow-tempo tapping in ventral medial prefrontal cortex regions. Moreover, a Global-Local task following tapping showed significantly greater local-minus-global response time (RT) difference scores in the fast- and mid-tempo condition compared with those in the slow-tempo, suggesting an increased attentional focus, and decreased negative emotion. The overall findings indicate that oxyHb changes in a relatively long distraction task, as measured by NIRS, are associated with emotional responses, and oxyHb can be decreased by successfully performing attention-demanding distraction tasks. Copyright © 2017 Elsevier Inc. All rights reserved.

The cold-induced basic helix-loop-helix transcription factor gene MdCIbHLH1 encodes an ICE-like protein in apple

PubMed Central

2012-01-01

Background Plant growth is greatly affected by low temperatures, and the expression of a number of genes is induced by cold stress. Although many genes in the cold signaling pathway have been identified in Arabidopsis, little is known about the transcription factors involved in the cold stress response in apple. Results Here, we show that the apple bHLH (basic helix-loop-helix) gene MdCIbHLH1 (Cold-Induced bHLH1), which encodes an ICE-like protein, was noticeably induced in response to cold stress. The MdCIbHLH1 protein specifically bound to the MYC recognition sequences in the AtCBF3 promoter, and MdCIbHLH1 overexpression enhanced cold tolerance in transgenic Arabidopsis. In addition, the MdCIbHLH1 protein bound to the promoters of MdCBF2 and favorably contributed to cold tolerance in transgenic apple plants by upregulating the expression of MdCBF2 through the CBF (C-repeat-binding factor) pathway. Our findings indicate that MdCIbHLH1 functions in stress tolerance in different species. For example, ectopic MdCIbHLH1 expression conferred enhanced chilling tolerance in transgenic tobacco. Finally, we observed that cold induces the degradation of the MdCIbHLH1 protein in apple and that this degradation was potentially mediated by ubiquitination and sumoylation. Conclusions Based on these findings, MdCIbHLH1 encodes a transcription factor that is important for the cold tolerance response in apple. PMID:22336381

D816 mutation of the KIT gene in core binding factor acute myeloid leukemia is associated with poorer prognosis than other KIT gene mutations.

PubMed

Yui, Shunsuke; Kurosawa, Saiko; Yamaguchi, Hiroki; Kanamori, Heiwa; Ueki, Toshimitsu; Uoshima, Nobuhiko; Mizuno, Ishikazu; Shono, Katsuhiro; Usuki, Kensuke; Chiba, Shigeru; Nakamura, Yukinori; Yanada, Masamitsu; Kanda, Junya; Tajika, Kenji; Gomi, Seiji; Fukunaga, Keiko; Wakita, Satoshi; Ryotokuji, Takeshi; Fukuda, Takahiro; Inokuchi, Koiti

2017-10-01

The clinical impact of KIT mutations in core binding factor acute myeloid leukemia (CBF-AML) is still unclear. In the present study, we analyzed the prognostic significance of each KIT mutation (D816, N822K, and other mutations) in Japanese patients with CBF-AML. We retrospectively analyzed 136 cases of CBF-AML that had gone into complete remission (CR). KIT mutations were found in 61 (45%) of the patients with CBF-AML. D816, N822K, D816 and N822K, and other mutations of the KIT gene were detected in 29 cases (21%), 20 cases (15%), 7 cases (5%), and 5 cases (4%), respectively. The rate of relapse-free survival (RFS) and overall survival (OS) in patients with D816 and with both D816 and N822K mutations was significantly lower than in patients with other or with no KIT mutations (RFS: p < 0.001, OS: p < 0.001). Moreover, stratified analysis of the chromosomal abnormalities t(8;21)(q22;q22) and inv(16)(p13.1q22), t(16;16)(p13.1;q22) showed that D816 mutation was associated with a significantly worse prognosis. In a further multivariate analysis of RFS and OS, D816 mutation was found to be an independent risk factor for significantly poorer prognosis. In the present study, we were able to establish that, of all KIT mutations, D816 mutation alone is an unfavorable prognostic factor.

Genome-Wide Analysis of the AP2/ERF Family in Eucalyptus grandis: An Intriguing Over-Representation of Stress-Responsive DREB1/CBF Genes

PubMed Central

SanClemente, H.; Mounet, F.; Dunand, C.; Marque, G.; Marque, C.; Teulières, C.

2015-01-01

Background The AP2/ERF family includes a large number of developmentally and physiologically important transcription factors sharing an AP2 DNA-binding domain. Among them DREB1/CBF and DREB2 factors are known as master regulators respectively of cold and heat/osmotic stress responses. Experimental Approaches The manual annotation of AP2/ERF family from Eucalyptus grandis, Malus, Populus and Vitis genomes allowed a complete phylogenetic study for comparing the structure of this family in woody species and the model Arabidopsis thaliana. Expression profiles of the whole groups of EgrDREB1 and EgrDREB2 were investigated through RNAseq database survey and RT-qPCR analyses. Results The structure and the size of the AP2/ERF family show a global conservation for the plant species under comparison. In addition to an expansion of the ERF subfamily, the tree genomes mainly differ with respect to the group representation within the subfamilies. With regard to the E. grandis DREB subfamily, an obvious feature is the presence of 17 DREB1/CBF genes, the maximum reported to date for dicotyledons. In contrast, only six DREB2 have been identified, which is similar to the other plants species under study, except for Malus. All the DREB1/CBF and DREB2 genes from E. grandis are expressed in at least one condition and all are heat-responsive. Regulation by cold and drought depends on the genes but is not specific of one group; DREB1/CBF group is more cold-inducible than DREB2 which is mainly drought responsive. Conclusion These features suggest that the dramatic expansion of the DREB1/CBF group might be related to the adaptation of this evergreen tree to climate changes when it expanded in Australia. PMID:25849589

Effect of hematocrit and systolic blood pressure on cerebral blood flow in newborn infants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Younkin, D.P.; Reivich, M.; Jaggi, J.L.

1987-06-01

The effects of hematocrit and systolic blood pressure on cerebral blood flow were measured in 15 stable, low birth weight babies. CBF was measured with a modification of the xenon-133 (/sup 133/Xe) clearance technique, which uses an intravenous bolus of /sup 133/Xe, an external chest detector to estimate arterial /sup 133/Xe concentration, eight external cranial detectors to measure cephalic /sup 133/Xe clearance curves, and a two-compartmental analysis of the cephalic /sup 133/Xe clearance curves to estimate CBF. There was a significant inverse correlation between hematocrit and CBF, presumably due to alterations in arterial oxygen content and blood viscosity. Newborn CBFmore » varied independently of systolic blood pressure between 60 and 84 mm Hg, suggesting an intact cerebrovascular autoregulatory mechanism. These results indicate that at least two of the factors that affect newborn animal CBF are operational in human newborns and may have important clinical implications.« less

Evaluation of the default-mode network by quantitative 15O-PET: comparative study between cerebral blood flow and oxygen consumption.

PubMed

Aoe, Jo; Watabe, Tadashi; Shimosegawa, Eku; Kato, Hiroki; Kanai, Yasukazu; Naka, Sadahiro; Matsunaga, Keiko; Isohashi, Kayako; Tatsumi, Mitsuaki; Hatazawa, Jun

2018-06-22

Resting-state functional MRI (rs-fMRI) has revealed the existence of a default-mode network (DMN) based on spontaneous oscillations of the blood oxygenation level-dependent (BOLD) signal. The BOLD signal reflects the deoxyhemoglobin concentration, which depends on the relationship between the regional cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO 2 ). However, these two factors cannot be separated in BOLD rs-fMRI. In this study, we attempted to estimate the functional correlations in the DMN by means of quantitative 15 O-labeled gases and water PET, and to compare the contribution of the CBF and CMRO 2 to the DMN. Nine healthy volunteers (5 men and 4 women; mean age, 47.0 ± 1.2 years) were studied by means of 15 O-O 2 , 15 O-CO gases and 15 O-water PET. Quantitative CBF and CMRO 2 images were generated by an autoradiographic method and transformed into MNI standardized brain template. Regions of interest were placed on normalized PET images according to the previous rs-fMRI study. For the functional correlation analysis, the intersubject Pearson's correlation coefficients (r) were calculated for all pairs in the brain regions and correlation matrices were obtained for CBF and CMRO 2 , respectively. We defined r > 0.7 as a significant positive correlation and compared the correlation matrices of CBF and CMRO 2 . Significant positive correlations (r > 0.7) were observed in 24 pairs of brain regions for the CBF and 22 pairs of brain regions for the CMRO 2 . Among them, 12 overlapping networks were observed between CBF and CMRO 2 . Correlation analysis of CBF led to the detection of more brain networks as compared to that of CMRO 2 , indicating that the CBF can capture the state of the spontaneous activity with a higher sensitivity. We estimated the functional correlations in the DMN by means of quantitative PET using 15 O-labeled gases and water. The correlation matrix derived from the CBF revealed a larger number of brain networks as compared to that derived from the CMRO 2 , indicating that contribution to the functional correlation in the DMN is higher in the blood flow more than the oxygen consumption.

CSL protein regulates transcription of genes required to prevent catastrophic mitosis in fission yeast.

PubMed

Převorovský, Martin; Oravcová, Martina; Zach, Róbert; Jordáková, Anna; Bähler, Jürg; Půta, František; Folk, Petr

2016-11-16

For every eukaryotic cell to grow and divide, intricately coordinated action of numerous proteins is required to ensure proper cell-cycle progression. The fission yeast Schizosaccharomyces pombe has been instrumental in elucidating the fundamental principles of cell-cycle control. Mutations in S. pombe 'cut' (cell untimely torn) genes cause failed coordination between cell and nuclear division, resulting in catastrophic mitosis. Deletion of cbf11, a fission yeast CSL transcription factor gene, triggers a 'cut' phenotype, but the precise role of Cbf11 in promoting mitotic fidelity is not known. We report that Cbf11 directly activates the transcription of the acetyl-coenzyme A carboxylase gene cut6, and the biotin uptake/biosynthesis genes vht1 and bio2, with the former 2 implicated in mitotic fidelity. Cbf11 binds to a canonical, metazoan-like CSL response element (GTGGGAA) in the cut6 promoter. Expression of Cbf11 target genes shows apparent oscillations during the cell cycle using temperature-sensitive cdc25-22 and cdc10-M17 block-release experiments, but not with other synchronization methods. The penetrance of catastrophic mitosis in cbf11 and cut6 mutants is nutrient-dependent. We also show that drastic decrease in biotin availability arrests cell proliferation but does not cause mitotic defects. Taken together, our results raise the possibility that CSL proteins play conserved roles in regulating cell-cycle progression, and they could guide experiments into mitotic CSL functions in mammals.

Comprehensive mutational profiling of core binding factor acute myeloid leukemia.

PubMed

Duployez, Nicolas; Marceau-Renaut, Alice; Boissel, Nicolas; Petit, Arnaud; Bucci, Maxime; Geffroy, Sandrine; Lapillonne, Hélène; Renneville, Aline; Ragu, Christine; Figeac, Martin; Celli-Lebras, Karine; Lacombe, Catherine; Micol, Jean-Baptiste; Abdel-Wahab, Omar; Cornillet, Pascale; Ifrah, Norbert; Dombret, Hervé; Leverger, Guy; Jourdan, Eric; Preudhomme, Claude

2016-05-19

Acute myeloid leukemia (AML) with t(8;21) or inv(16) have been recognized as unique entities within AML and are usually reported together as core binding factor AML (CBF-AML). However, there is considerable clinical and biological heterogeneity within this group of diseases, and relapse incidence reaches up to 40%. Moreover, translocations involving CBFs are not sufficient to induce AML on its own and the full spectrum of mutations coexisting with CBF translocations has not been elucidated. To address these issues, we performed extensive mutational analysis by high-throughput sequencing in 215 patients with CBF-AML enrolled in the Phase 3 Trial of Systematic Versus Response-adapted Timed-Sequential Induction in Patients With Core Binding Factor Acute Myeloid Leukemia and Treating Patients with Childhood Acute Myeloid Leukemia with Interleukin-2 trials (age, 1-60 years). Mutations in genes activating tyrosine kinase signaling (including KIT, N/KRAS, and FLT3) were frequent in both subtypes of CBF-AML. In contrast, mutations in genes that regulate chromatin conformation or encode members of the cohesin complex were observed with high frequencies in t(8;21) AML (42% and 18%, respectively), whereas they were nearly absent in inv(16) AML. High KIT mutant allele ratios defined a group of t(8;21) AML patients with poor prognosis, whereas high N/KRAS mutant allele ratios were associated with the lack of KIT or FLT3 mutations and a favorable outcome. In addition, mutations in epigenetic modifying or cohesin genes were associated with a poor prognosis in patients with tyrosine kinase pathway mutations, suggesting synergic cooperation between these events. These data suggest that diverse cooperating mutations may influence CBF-AML pathophysiology as well as clinical behavior and point to potential unique pathogenesis of t(8;21) vs inv(16) AML. © 2016 by The American Society of Hematology.

Expression of CD33 is a predictive factor for effect of gemtuzumab ozogamicin at different doses in adult acute myeloid leukaemia.

PubMed

Khan, N; Hills, R K; Virgo, P; Couzens, S; Clark, N; Gilkes, A; Richardson, P; Knapper, S; Grimwade, D; Russell, N H; Burnett, A K; Freeman, S D

2017-05-01

It remains unclear in adult acute myeloid leukaemia (AML) whether leukaemic expression of CD33, the target antigen for gemtuzumab ozogamicin (GO), adds prognostic information on GO effectiveness at different doses. CD33 expression quantified in 1583 patients recruited to UK-NCRI-AML17 (younger adults) and UK-NCRI-AML16 (older adults) trials was correlated with clinical outcomes and benefit from GO including a dose randomisation. CD33 expression associated with genetic subgroups, including lower levels in both adverse karyotype and core-binding factor (CBF)-AML, but was not independently prognostic. When comparing GO versus no GO (n=393, CBF-AMLs excluded) by stratified subgroup-adjusted analysis, patients with lowest quartile (Q1) %CD33-positivity had no benefit from GO (relapse risk, HR 2.41 (1.27-4.56), P=0.009 for trend; overall survival, HR 1.52 (0.92-2.52)). However, from the dose randomisation (NCRI-AML17, n=464, CBF-AMLs included), 6 mg/m 2 GO only had a relapse benefit without increased early mortality in CD33-low (Q1) patients (relapse risk HR 0.64 (0.36-1.12) versus 1.70 (0.99-2.92) for CD33-high, P=0.007 for trend). Thus CD33 expression is a predictive factor for GO effect in adult AML; although GO does not appear to benefit the non-CBF AML patients with lowest CD33 expression a higher GO dose may be more effective for CD33-low but not CD33-high younger adults.

Perfusion functional MRI reveals cerebral blood flow pattern under psychological stress

NASA Astrophysics Data System (ADS)

Wang, Jiongjiong; Rao, Hengyi; Wetmore, Gabriel S.; Furlan, Patricia M.; Korczykowski, Marc; Dinges, David F.; Detre, John A.

2005-12-01

Despite the prevalence of stress in everyday life and its impact on happiness, health, and cognition, little is known about the neural substrate of the experience of everyday stress in humans. We use a quantitative and noninvasive neuroimaging technique, arterial spin-labeling perfusion MRI, to measure cerebral blood flow (CBF) changes associated with mild to moderate stress induced by a mental arithmetic task with performance monitoring. Elicitation of stress was verified by self-report of stress and emotional state and measures of heart rate and salivary-cortisol level. The change in CBF induced by the stress task was positively correlated with subjective stress rating in the ventral right prefrontal cortex (RPFC) and left insula/putamen area. The ventral RPFC along with right insula/putamen and anterior cingulate showed sustained activation after task completion in subjects reporting a high stress level during arithmetic tasks. Additionally, variations of baseline CBF in the ventral RPFC and right orbitofrontal cortex were found to correlate with changes in salivary-cortisol level and heart rate caused by undergoing stress tasks. We further demonstrated that the observed right prefrontal activation could not be attributed to increased cognitive demand accompanying stress tasks and extended beyond neural pathways associated with negative emotions. Our results provide neuroimaging evidence that psychological stress induces negative emotion and vigilance and that the ventral RPFC plays a key role in the central stress response. anterior cingulate cortex | arterial spin labeling | right prefrontal cortex

Effects of finite spatial resolution on quantitative CBF images from dynamic PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phelps, M.E.; Huang, S.C.; Mahoney, D.K.

1985-05-01

The finite spatial resolution of PET causes the time-activity responses on pixels around the boundaries between gray and white matter regions to contain kinetic components from tissues of different CBF's. CBF values estimated from kinetics of such mixtures are underestimated because of the nonlinear relationship between the time-activity response and the estimated CBF. Computer simulation is used to investigate these effects on phantoms of circular structures and realistic brain slice in terms of object size and quantitative CBF values. The CBF image calculated is compared to the case of having resolution loss alone. Results show that the size of amore » high flow region in the CBF image is decreased while that of a low flow region is increased. For brain phantoms, the qualitative appearance of CBF images is not seriously affected, but the estimated CBF's are underestimated by 11 to 16 percent in local gray matter regions (of size 1 cm/sup 2/) with about 14 percent reduction in global CBF over the whole slice. It is concluded that the combined effect of finite spatial resolution and the nonlinearity in estimating CBF from dynamic PET is quite significant and must be considered in processing and interpreting quantitative CBF images.« less

Comparative Study on the Antivirus Activity of Shuang–Huang–Lian Injectable Powder and Its Bioactive Compound Mixture against Human Adenovirus III In Vitro

PubMed Central

Ma, Qinhai; Liang, Dedong; Song, Shuai; Yu, Qintian; Shi, Chunyu; Xing, Xuefeng; Luo, Jia-Bo

2017-01-01

Shuang–Huang–Lian injectable powder (SHL)—a classical purified herbal preparation extracted from Scutellaria baicalensis, Lonicera japonica, and Forsythia suspense—has been used against human adenovirus III (HAdV3) for many years. The combination herb and its major bioactive compounds, including chlorogenic acid, baicalin, and forsythia glycosides A, are effective inhibitors of the virus. However, no comprehensive studies are available on the antiviral effects of SHL against HAdV3. Moreover, it remains unclear whether the mixture of chlorogenic acid, baicalin, and forsythia glycosides A (CBF) has enhanced antiviral activity compared with SHL. Therefore, a comparative study was performed to investigate the combination which is promising for further antiviral drug development. To evaluate their antivirus activity in parallel, the combination ratio and dose of CBF were controlled and consistent with SHL. First, the fingerprint and the ratio of CBF in SHL were determined by high performance liquid chromatography. Then, a plaque reduction assay, reverse transcription polymerase chain reaction (PCR), real-time polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA) were used to explore its therapeutic effects on viral infection and replication, respectively. The results showed that SHL and CBF inhibited dose- and time-dependently HAdV3-induced plaque formation in A549 and HEp-2 cells. SHL was more effective than CBF when supplemented prior to and after viral inoculation. SHL prevented viral attachment, internalization, and replication at high concentration and decreased viral levels within and out of cells at non-toxic concentrations in both cell types. Moreover, the expression of tumor necrosis factor alpha (TNF)-α, interleukin (IL)-1ß, and IL-6 was lower and the expression of interferon (IFN)-γ was higher in both cell types treated with SHL than with CBF. In conclusion, SHL is much more effective and slightly less toxic than CBF. PMID:28417913

Deciphering the Role of CBF/DREB Transcription Factors and Dehydrins in Maintaining the Quality of Table Grapes cv. Autumn Royal Treated with High CO2 Levels and Stored at 0°C

PubMed Central

Vazquez-Hernandez, Maria; Romero, Irene; Escribano, M. I.; Merodio, Carmen; Sanchez-Ballesta, M. T.

2017-01-01

C-repeat/dehydration-responsive element binding factors (CBF/DREB) are transcription factors which play a role in improving plant cold stress resistance and recognize the DRE/CRT element in the promoter of a set of cold regulated genes. Dehydrins (DHNs) are proteins that accumulate in plants in response to cold stress, which present, in some cases, CBF/DREB recognition sequences in their promoters and are activated by members of this transcription factor family. The application of a 3-day gaseous treatment with 20 kPa CO2 at 0°C to table grapes cv. Autumn Royal maintained the quality of the bunches during postharvest storage at 0°C, reducing weight loss and rachis browning. In order to determine the role of CBF/DREB genes in the beneficial effect of the gaseous treatment by regulating DHNs, we have analyzed the gene expression pattern of three VviDREBA1s (VviDREBA1-1, VviDREBA1-6, and VviDREBA1-7) as well as three VviDHNs (VviDHN1a, VviDHN2, and VviDHN4), in both alternative splicing forms. Results showed that the differences in VviDREBA1s expression were tissue and atmosphere composition dependent, although the application of high levels of CO2 caused a greater increase of VviDREBA1-1 in the skin, VviDREBA1-6 in the pulp and VviDREBA1-7 in the skin and pulp. Likewise, the application of high levels of CO2 regulated the retention of introns in the transcripts of the dehydrins studied in the different tissues analyzed. The DHNs promoter analysis showed that VviDHN2 presented the cis-acting DRE and CRT elements, whereas VviDHN1a presented only the DRE motif. Our electrophoretic mobility shift assays (EMSA) showed that VviDREBA1-1 was the only transcription factor that had in vitro binding capacity to the CRT element of the VviDHN2 promoter region, indicating that the transcriptional regulation of VviDHN1a and VviDHN4 would be carried out by activating other independent routes of these transcription factors. Our results suggest that the application of high CO2 levels to maintain table grape quality during storage at 0°C, leads to an activation of CBF/DREBs transcription factors. Among these factors, VviDREBA1-1 seems to participate in the transcriptional activation of VviDHN2 via CRT binding, with the unspliced form of this DHN being activated by high CO2 levels in all the tissues analyzed. PMID:28970842

Spatial nonuniformity of the resting CBF and BOLD responses to sevoflurane: in vivo study of normal human subjects with magnetic resonance imaging.

PubMed

Qiu, Maolin; Ramani, Ramachandran; Swetye, Michael; Constable, Robert Todd

2008-12-01

Pulsed arterial spin labeling magnetic resonance imaging (MRI) was performed to investigate the local coupling between resting regional cerebral blood flow (rCBF) and BOLD (blood oxygen level dependent) signal changes in 22 normal human subjects during the administration of 0.25 MAC (minimum alveolar concentration) sevoflurane. Two states were compared with subjects at rest: anesthesia and no-anesthesia. Regions of both significantly increased and decreased resting-state rCBF were observed. Increases were limited primarily to subcortical structures and insula, whereas, decreases were observed primarily in neocortical regions. No significant change was found in global CBF (gCBF). By simultaneously measuring rCBF and BOLD, region-specific anesthetic effects on the coupling between rCBF and BOLD were identified. Multiple comparisons of the agent-induced rCBF and BOLD changes demonstrated significant (P < 0.05) spatial variability in rCBF-BOLD coupling. The slope of the linear regression line for AC, where rCBF was increased by sevoflurane, was markedly smaller than the slope for those ROIs where rCBF was decreased by sevoflurane, indicating a bigger change in BOLD per unit change in rCBF in regions where rCBF was increased by sevoflurane. These results suggest that it would be inaccurate to use a global quantitative model to describe coupling across all brain regions and in all anesthesia conditions. The observed spatial nonuniformity of rCBF and BOLD signal changes suggests that any interpretation of BOLD fMRI data in the presence of an anesthetic requires consideration of these insights. Copyright 2007 Wiley-Liss, Inc.

Paradoxical reduction of cerebral blood flow after acetazolamide loading: a hemodynamic and metabolic study with (15)O PET.

PubMed

Watabe, Tadashi; Shimosegawa, Eku; Kato, Hiroki; Isohashi, Kayako; Ishibashi, Mana; Tatsumi, Mitsuaki; Kitagawa, Kazuo; Fujinaka, Toshiyuki; Yoshimine, Toshiki; Hatazawa, Jun

2014-10-01

Paradoxical reduction of cerebral blood flow (CBF) after administration of the vasodilator acetazolamide is the most severe stage of cerebrovascular reactivity failure and is often associated with an increased oxygen extraction fraction (OEF). In this study, we aimed to reveal the mechanism underlying this phenomenon by focusing on the ratio of CBF to cerebral blood volume (CBV) as a marker of regional cerebral perfusion pressure (CPP). In 37 patients with unilateral internal carotid or middle cerebral arterial (MCA) steno-occlusive disease and 8 normal controls, the baseline CBF (CBF(b)), CBV, OEF, cerebral oxygen metabolic rate (CMRO2), and CBF after acetazolamide loading in the anterior and posterior MCA territories were measured by (15)O positron emission tomography. Paradoxical CBF reduction was found in 28 of 74 regions (18 of 37 patients) in the ipsilateral hemisphere. High CBF(b) (> 47.6 mL/100 mL/min, n = 7) was associated with normal CBF(b)/CBV, increased CBV, decreased OEF, and normal CMRO2. Low CBF(b) (< 31.8 mL/100 mL/min, n = 9) was associated with decreased CBF(b)/CBV, increased CBV, increased OEF, and decreased CMRO2. These findings demonstrated that paradoxical CBF reduction is not always associated with reduction of CPP, but partly includes high-CBF(b) regions with normal CPP, which has not been described in previous studies.

Brain Regional Blood Flow and Working Memory Performance Predict Change in Blood Pressure Over 2 Years.

PubMed

Jennings, J Richard; Heim, Alicia F; Sheu, Lei K; Muldoon, Matthew F; Ryan, Christopher; Gach, H Michael; Schirda, Claudiu; Gianaros, Peter J

2017-12-01

Hypertension is a presumptive risk factor for premature cognitive decline. However, lowering blood pressure (BP) does not uniformly reverse cognitive decline, suggesting that high BP per se may not cause cognitive decline. We hypothesized that essential hypertension has initial effects on the brain that, over time, manifest as cognitive dysfunction in conjunction with both brain vascular abnormalities and systemic BP elevation. Accordingly, we tested whether neuropsychological function and brain blood flow responses to cognitive challenges among prehypertensive individuals would predict subsequent progression of BP. Midlife adults (n=154; mean age, 49; 45% men) with prehypertensive BP underwent neuropsychological testing and assessment of regional cerebral blood flow (rCBF) response to cognitive challenges. Neuropsychological performance measures were derived for verbal and logical memory (memory), executive function, working memory, mental efficiency, and attention. A pseudo-continuous arterial spin labeling magnetic resonance imaging sequence compared rCBF responses with control and active phases of cognitive challenges. Brain areas previously associated with BP were grouped into composites for frontoparietal, frontostriatal, and insular-subcortical rCBF areas. Multiple regression models tested whether BP after 2 years was predicted by initial BP, initial neuropsychological scores, and initial rCBF responses to cognitive challenge. The neuropsychological composite of working memory (standardized beta, -0.276; se=0.116; P =0.02) and the frontostriatal rCBF response to cognitive challenge (standardized beta, 0.234; se=0.108; P =0.03) significantly predicted follow-up BP. Initial BP failed to significantly predict subsequent cognitive performance or rCBF. Changes in brain function may precede or co-occur with progression of BP toward hypertensive levels in midlife. © 2017 American Heart Association, Inc.

Mutation in the peb1A Locus of Campylobacter jejuni Reduces Interactions with Epithelial Cells and Intestinal Colonization of Mice

PubMed Central

Pei, Zhiheng; Burucoa, Christophe; Grignon, Bernadette; Baqar, Shahida; Huang, Xiao-Zhe; Kopecko, Dennis J.; Bourgeois, A. L.; Fauchere, Jean-Louis; Blaser, Martin J.

1998-01-01

Campylobacter jejuni is one of the leading causes of bacterial diarrhea throughout the world. We previously found that PEB1 is a homolog of cluster 3 binding proteins of bacterial ABC transporters and that a C. jejuni adhesin, cell-binding factor 1 (CBF1), if not identical to, contains PEB1. A single protein migrating at approximately 27 to 28 kDa was recognized by anti-CBF1 and anti-PEB1. To determine the role that the operon encoding PEB1 plays in C. jejuni adherence, peb1A, the gene encoding PEB1, was disrupted in strain 81-176 by insertion of a kanamycin resistance gene through homologous recombination. Inactivation of this operon completely abolished expression of CBF1, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. In comparison to the wild-type strain, the mutant strain showed 50- to 100-fold less adherence to and 15-fold less invasion of epithelial cells in culture. Mouse challenge studies showed that the rate and duration of intestinal colonization by the mutant were significantly lower and shorter than with the wild-type strain. In summary, PEB1 is identical to a previously identified cell-binding factor, CBF1, in C. jejuni, and the peb1A locus plays an important role in epithelial cell interactions and in intestinal colonization in a mouse model. PMID:9488379

Arterial spin labeling fMRI measurements of decreased blood flow in primary visual cortex correlates with decreased visual function in human glaucoma.

PubMed

Duncan, Robert O; Sample, Pamela A; Bowd, Christopher; Weinreb, Robert N; Zangwill, Linda M

2012-05-01

Altered metabolic activity has been identified as a potential contributing factor to the neurodegeneration associated with primary open angle glaucoma (POAG). Consequently, we sought to determine whether there is a relationship between the loss of visual function in human glaucoma and resting blood perfusion within primary visual cortex (V1). Arterial spin labeling (ASL) functional magnetic resonance imaging (fMRI) was conducted in 10 participants with POAG. Resting cerebral blood flow (CBF) was measured from dorsal and ventral V1. Behavioral measurements of visual function were obtained using standard automated perimetry (SAP), short-wavelength automated perimetry (SWAP), and frequency-doubling technology perimetry (FDT). Measurements of CBF were compared to differences in visual function for the superior and inferior hemifield. Differences in CBF between ventral and dorsal V1 were correlated with differences in visual function for the superior versus inferior visual field. A statistical bootstrapping analysis indicated that the observed correlations between fMRI responses and measurements of visual function for SAP (r=0.49), SWAP (r=0.63), and FDT (r=0.43) were statistically significant (all p<0.05). Resting blood perfusion in human V1 is correlated with the loss of visual function in POAG. Altered CBF may be a contributing factor to glaucomatous optic neuropathy, or it may be an indication of post-retinal glaucomatous neurodegeneration caused by damage to the retinal ganglion cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Static and Dynamic Characteristics of Cerebral Blood Flow During the Resting State in Schizophrenia

PubMed Central

Kindler, Jochen; Jann, Kay; Homan, Philipp; Hauf, Martinus; Walther, Sebastian; Strik, Werner; Dierks, Thomas; Hubl, Daniela

2015-01-01

Background: The cerebral network that is active during rest and is deactivated during goal-oriented activity is called the default mode network (DMN). It appears to be involved in self-referential mental activity. Atypical functional connectivity in the DMN has been observed in schizophrenia. One hypothesis suggests that pathologically increased DMN connectivity in schizophrenia is linked with a main symptom of psychosis, namely, misattribution of thoughts. Methods: A resting-state pseudocontinuous arterial spin labeling (ASL) study was conducted to measure absolute cerebral blood flow (CBF) in 34 schizophrenia patients and 27 healthy controls. Using independent component analysis (ICA), the DMN was extracted from ASL data. Mean CBF and DMN connectivity were compared between groups using a 2-sample t test. Results: Schizophrenia patients showed decreased mean CBF in the frontal and temporal regions (P < .001). ICA demonstrated significantly increased DMN connectivity in the precuneus (x/y/z = −16/−64/38) in patients than in controls (P < .001). CBF was not elevated in the respective regions. DMN connectivity in the precuneus was significantly correlated with the Positive and Negative Syndrome Scale scores (P < .01). Conclusions: In schizophrenia patients, the posterior hub—which is considered the strongest part of the DMN—showed increased DMN connectivity. We hypothesize that this increase hinders the deactivation of the DMN and, thus, the translation of cognitive processes from an internal to an external focus. This might explain symptoms related to defective self-monitoring, such as auditory verbal hallucinations or ego disturbances. PMID:24327756

Spatial Nonuniformity of the Resting CBF and BOLD Responses to Sevoflurane: In Vivo Study of Normal Human Subjects With Magnetic Resonance Imaging

PubMed Central

Qiu, Maolin; Ramani, Ramachandran; Swetye, Michael; Constable, Robert Todd

2009-01-01

Pulsed arterial spin labeling magnetic resonance imaging (MRI) was performed to investigate the local coupling between resting regional cerebral blood flow (rCBF) and BOLD (blood oxygen level dependent) signal changes in 22 normal human subjects during the administration of 0.25 MAC (minimum alveolar concentration) sevoflurane. Two states were compared with subjects at rest: anesthesia and no-anesthesia. Regions of both significantly increased and decreased resting-state rCBF were observed. Increases were limited primarily to subcortical structures and insula, whereas, decreases were observed primarily in neocortical regions. No significant change was found in global CBF (gCBF). By simultaneously measuring rCBF and BOLD, region-specific anesthetic effects on the coupling between rCBF and BOLD were identified. Multiple comparisons of the agent-induced rCBF and BOLD changes demonstrated significant (P < 0.05) spatial variability in rCBF–BOLD coupling. The slope of the linear regression line for AC, where rCBF was increased by sevoflurane, was markedly smaller than the slope for those ROIs where rCBF was decreased by sevoflurane, indicating a bigger change in BOLD per unit change in rCBF in regions where rCBF was increased by sevoflurane. These results suggest that it would be inaccurate to use a global quantitative model to describe coupling across all brain regions and in all anesthesia conditions. The observed spatial nonuniformity of rCBF and BOLD signal changes suggests that any interpretation of BOLD fMRI data in the presence of an anesthetic requires consideration of these insights. PMID:17948882

An Arabidopsis mutation in translation elongation factor 2 causes superinduction of CBF/DREB1 transcription factor genes but blocks the induction of their downstream targets under low temperatures.

PubMed

Guo, Yan; Xiong, Liming; Ishitani, Manabu; Zhu, Jian-Kang

2002-05-28

Low temperature regulates gene expression in bacteria, yeast, and animals as well as in plants. However, the signal transduction cascades mediating the low temperature responses are not well understood in any organism. To identify components in low temperature signaling genetically, we isolated Arabidopsis thaliana mutants in which cold-responsive genes are no longer induced by low temperatures. One of these mutations, los1-1, specifically blocks low temperature-induced transcription of cold-responsive genes. Surprisingly, cold-induced expression of the early response transcriptional activators, C-repeat/dehydration responsive element binding factors (CBF/DREB1s), is enhanced by the los1-1 mutation. The los1-1 mutation also reduces the capacity of plants to develop freezing tolerance but does not impair the vernalization response. Genetic analysis indicated that los1-1 is a recessive mutation in a single nuclear gene. The LOS1 gene encodes a translation elongation factor 2-like protein. Protein labeling studies show that new protein synthesis is blocked in los1-1 mutant plants specifically in the cold. These results reveal a critical role of new protein synthesis in the proper transduction of low temperature signals. Our results also suggest that cold-induced transcription of CBF/DREB1s is feedback inhibited by their gene products or by products of their downstream target genes.

Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia.

PubMed

Jourdan, Eric; Boissel, Nicolas; Chevret, Sylvie; Delabesse, Eric; Renneville, Aline; Cornillet, Pascale; Blanchet, Odile; Cayuela, Jean-Michel; Recher, Christian; Raffoux, Emmanuel; Delaunay, Jacques; Pigneux, Arnaud; Bulabois, Claude-Eric; Berthon, Céline; Pautas, Cécile; Vey, Norbert; Lioure, Bruno; Thomas, Xavier; Luquet, Isabelle; Terré, Christine; Guardiola, Philippe; Béné, Marie C; Preudhomme, Claude; Ifrah, Norbert; Dombret, Hervé

2013-03-21

Not all patients with core binding factor acute myeloid leukemia (CBF-AML) display a good outcome. Modern risk factors include KIT and/or FLT3 gene mutations and minimal residual disease (MRD) levels, but their respective values have never been prospectively assessed. A total of 198 CBF-AML patients were randomized between a reinforced and a standard induction course, followed by 3 high-dose cytarabine consolidation courses. MRD levels were monitored prospectively. Gene mutations were screened at diagnosis. Despite a more rapid MRD decrease after reinforced induction, induction arm did not influence relapse-free survival (RFS) (64% in both arms; P = .91). Higher WBC, KIT, and/or FLT3-ITD/TKD gene mutations, and a less than 3-log MRD reduction after first consolidation, were associated with a higher specific hazard of relapse, but MRD remained the sole prognostic factor in multivariate analysis. At 36 months, cumulative incidence of relapse and RFS were 22% vs 54% (P < .001) and 73% vs 44% (P < .001) in patients who achieved 3-log MRD reduction vs the others. These results suggest that MRD, rather than gene mutations, should be used for future treatment stratifications in CBF-AML patients. This trial was registered at EudraCT as #2006-005163-26 and at www.clinicaltrials.gov as #NCT 00428558.

Transcriptome Profiling of Pediatric Core Binding Factor AML

PubMed Central

Hsu, Chih-Hao; Nguyen, Cu; Yan, Chunhua; Ries, Rhonda E.; Chen, Qing-Rong; Hu, Ying; Ostronoff, Fabiana; Stirewalt, Derek L.; Komatsoulis, George; Levy, Shawn

2015-01-01

The t(8;21) and Inv(16) translocations disrupt the normal function of core binding factors alpha (CBFA) and beta (CBFB), respectively. These translocations represent two of the most common genomic abnormalities in acute myeloid leukemia (AML) patients, occurring in approximately 25% pediatric and 15% of adult with this malignancy. Both translocations are associated with favorable clinical outcomes after intensive chemotherapy, and given the perceived mechanistic similarities, patients with these translocations are frequently referred to as having CBF-AML. It remains uncertain as to whether, collectively, these translocations are mechanistically the same or impact different pathways in subtle ways that have both biological and clinical significance. Therefore, we used transcriptome sequencing (RNA-seq) to investigate the similarities and differences in genes and pathways between these subtypes of pediatric AMLs. Diagnostic RNA from patients with t(8;21) (N = 17), Inv(16) (N = 14), and normal karyotype (NK, N = 33) were subjected to RNA-seq. Analyses compared the transcriptomes across these three cytogenetic subtypes, using the NK cohort as the control. A total of 1291 genes in t(8;21) and 474 genes in Inv(16) were differentially expressed relative to the NK controls, with 198 genes differentially expressed in both subtypes. The majority of these genes (175/198; binomial test p-value < 10−30) are consistent in expression changes among the two subtypes suggesting the expression profiles are more similar between the CBF cohorts than in the NK cohort. Our analysis also revealed alternative splicing events (ASEs) differentially expressed across subtypes, with 337 t(8;21)-specific and 407 Inv(16)-specific ASEs detected, the majority of which were acetylated proteins (p = 1.5x10-51 and p = 1.8x10-54 for the two subsets). In addition to known fusions, we identified and verified 16 de novo fusions in 43 patients, including three fusions involving NUP98 in six patients. Clustering of differentially expressed genes indicated that the homeobox (HOX) gene family, including two transcription factors (MEIS1 and NKX2-3) were down-regulated in CBF compared to NK samples. This finding supports existing data that the dysregulation of HOX genes play a central role in biology CBF-AML hematopoiesis. These data provide comprehensive transcriptome profiling of CBF-AML and delineate genes and pathways that are differentially expressed, providing insights into the shared biology as well as differences in the two CBF subsets. PMID:26397705

Correction for Delay and Dispersion Results in More Accurate Cerebral Blood Flow Ischemic Core Measurement in Acute Stroke.

PubMed

Lin, Longting; Bivard, Andrew; Kleinig, Timothy; Spratt, Neil J; Levi, Christopher R; Yang, Qing; Parsons, Mark W

2018-04-01

This study aimed to assess how the ischemic core measured by perfusion computed tomography (CTP) was affected by the delay and dispersion effect. Ischemic stroke patients having CTP performed within 6 hours of onset were included. The CTP data were processed twice, generating standard cerebral blood flow (sCBF) and delay- and dispersion-corrected CBF (ddCBF), respectively. Ischemic core measured by the sCBF and ddCBF was then compared at the relative threshold <30% of normal tissue. Two references for ischemic core were used: acute diffusion-weighted imaging or 24-hour diffusion-weighted imaging in patients with complete recanalization. Difference of core volume between CTP and diffusion-weighted imaging was estimated by Mann-Whitney U test and limits of agreement. Patients were also classified into favorable and unfavorable CTP patterns. The imaging pattern classification by sCBF and ddCBF was compared by the χ 2 test; their respective ability to predict good clinical outcome (3-month modified Rankin Scale score) was tested in logistic regression. Fifty-five patients were included in this study. Median sCBF ischemic core volume was 38.5 mL (12.4-61.9 mL), much larger than the median core volume of 17.2 mL measured by ddCBF (interquartile range, 5.5-38.8; P <0.001). Moreover, compared with sCBF <30%, ddCBF <30% measured the ischemic core much closer to diffusion-weighted imaging core references, with the mean volume difference of -0.1 mL (95% limits of agreement, -25.4 to 25.2; P =0.97) and 16.7 mL (95% limits of agreement, -21.7 to 55.2; P <0.001), respectively. Imaging patterns defined by sCBF showed a difference to that defined by ddCBF ( P <0.001), with 12 patients classified as favorable imaging patterns by ddCBF but as unfavorable by sCBF. The favorable imaging pattern classified by ddCBF, compared with sCBF classification, had higher predictive power for good clinical outcome (odds ratio, 7.8 [2-30.5] and 3.1 [0.9-11], respectively). Delay and dispersion correction increases the accuracy of ischemic core measurement on CTP. © 2018 American Heart Association, Inc.

Factors influencing breastfeeding in children less than 2 years of age in Lao PDR.

PubMed

Putthakeo, Pornpai; Ali, Moazzam; Ito, Chiaki; Vilayhong, Panome; Kuroiwa, Chushi

2009-09-01

This study aimed to investigate the prevalence of, and factors influencing, exclusive breastfeeding (EBF) at 6 months and continued breastfeeding (CBF) at 2 years. Between January and February 2007, a cross-sectional study was conducted using a semi-structured questionnaire in 40 villages in the Vientiane capital and the Vientiane province of Lao PDR. A total of 400 mothers with children less than 2 years old were recruited by multistage random sampling. Based on the 1991 World Health Organization Breastfeeding Indicators, children were classified into three groups, 6-23-month-old children for assessing EBF at 6 months, 12-15-month-old children for CBF at 1 year and 20-23-month-old children for CBF at 2 years. The prevalence of EBF at 6 months and CBF at 2 years were 19.4% (n= 283) and 18.6% (n= 43), respectively. Some of the factors influencing EBF at 6 months in a univariate logistic regression model included: location of residence, (OR: 19.19, 95% CI 6.96-57.01), ethnicity (OR: 3.15, 95% CI 1.63-6.08), encouragement of the child's father (OR: 9.03, 95%CI 1.21-67.57) and inter-spousal communication (OR: 5.20, 95% CI 2.34-11.56). A majority of the mothers (75.0%) had watched television advertisements for infant formula from Thailand, and 48.4% reported that they wanted to buy formula milk after having watched them. This study showed a low prevalence of EBF at 6 months in the studied area in Lao PDR. Some of the factors that had a strong impact on EBF at 6 months included: location of residence, ethnicity, father's involvement, early breastfeeding plan, Mother's Card in antenatal care and television advertisement. There may be opportunities for government to review a range of policies relating to paternal involvement, antenatal care and formula advertising that could help to improve EBF rate.

Copy number and haplotype variation at the VRN-A1 and central FR-A2 loci are associated with frost tolerance in hexaploid wheat.

PubMed

Zhu, Jie; Pearce, Stephen; Burke, Adrienne; See, Deven Robert; Skinner, Daniel Z; Dubcovsky, Jorge; Garland-Campbell, Kimberly

2014-05-01

The interaction between VRN - A1 and FR - A2 largely affect the frost tolerance of hexaploid wheat. Frost tolerance is critical for wheat survival during cold winters. Natural variation for this trait is mainly associated with allelic differences at the VERNALIZATION 1 (VRN1) and FROST RESISTANCE 2 (FR2) loci. VRN1 regulates the transition between vegetative and reproductive stages and FR2, a locus including several tandemly duplicated C-REPEAT BINDING FACTOR (CBF) transcription factors, regulates the expression of Cold-regulated genes. We identified sequence and copy number variation at these two loci among winter and spring wheat varieties and characterized their association with frost tolerance. We identified two FR-A2 haplotypes-'FR-A2-S' and 'FR-A2-T'-distinguished by two insertion/deletions and ten single nucleotide polymorphisms within the CBF-A12 and CBF-A15 genes. Increased copy number of CBF-A14 was frequently associated with the FR-A2-T haplotype and with higher CBF14 transcript levels in response to cold. Factorial ANOVAs revealed significant interactions between VRN1 and FR-A2 for frost tolerance in both winter and spring panels suggesting a crosstalk between vernalization and cold acclimation pathways. The model including these two loci and their interaction explained 32.0 and 20.7 % of the variation in frost tolerance in the winter and spring panels, respectively. The interaction was validated in a winter wheat F 4:5 population segregating for both genes. Increased VRN-A1 copy number was associated with improved frost tolerance among varieties carrying the FR-A2-T allele but not among those carrying the FR-A2-S allele. These results suggest that selection of varieties carrying the FR-A2-T allele and three copies of the recessive vrn-A1 allele would be a good strategy to improve frost tolerance in wheat.

Cerebral blood flow and carbon dioxide reactivity in children with bacterial meningitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashwal, S.; Stringer, W.; Tomasi, L.

1990-10-01

We examined total and regional cerebral blood flow (CBF) by stable xenon computed tomography in 20 seriously ill children with acute bacterial meningitis to determine whether CBF was reduced and to examine the changes in CBF during hyperventilation. In 13 children, total CBF was normal (62 +/- 20 ml/min/100 gm) but marked local variability of flow was seen. In five other children, total CBF was significantly reduced (26 +/- 10 ml/min/100 gm; p less than 0.05), with flow reduced more in white matter (8 +/- 5 ml/min/100 gm) than in gray matter (30 +/- 15 ml/min/100 gm). Autoregulation of CBFmore » appeared to be present in these 18 children within a range of mean arterial blood pressure from 56 to 102 mm Hg. In the remaining two infants, brain dead within the first 24 hours, total flow was uniformly absent, averaging 3 +/- 3 ml/min/100 gm. In seven children, CBF was determined at two carbon dioxide tension (PCO2) levels: 40 (+/- 3) mm Hg and 29 (+/- 3) mm Hg. In six children, total CBF decreased 33%, from 52 (+/- 25) to 35 (+/- 15) ml/min/100 gm; the mean percentage of change in CBF per millimeter of mercury of PCO2 was 3.0%. Regional variability of perfusion to changes in PCO2 was marked in all six children. The percentage of change in CBF per millimeter of mercury of PCO2 was similar in frontal gray matter (3.1%) but higher in white matter (4.5%). In the seventh patient a paradoxical response was observed; total and regional CBF increased 25% after hyperventilation. Our findings demonstrate that (1) CBF in children with bacterial meningitis may be substantially decreased globally, with even more variability noted regionally, (2) autoregulation of CBF is preserved, (3) CBF/CO2 responsitivity varies among patients and in different regions of the brain in the same patient, and (4) hyperventilation can reduce CBF below ischemic thresholds.« less

Cerebral blood flow in acute mountain sickness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jensen, J.B.; Wright, A.D.; Lassen, N.A.

1990-08-01

Changes in cerebral blood flow (CBF) were measured using the radioactive xenon technique and were related to the development of acute mountain sickness (AMS). In 12 subjects, ascending from 150 to 3,475 m, CBF was 24% increased at 24 h (45.1 to 55.9 initial slope index (ISI) units) and 4% increased at 6 days (47.1 ISI units). Four subjects had similar increases of CBF when ascending to 3,200 m 3 mo later, indicating the reproducibility of the measurements. In nine subjects, ascending from 3,200 to 4,785-5,430 m, CBF increased to 76.4 ISI units, 53% above estimated sea-level values. CBF andmore » increases in CBF were similar in subjects with or without AMS. In six subjects, CBF was measured before and after therapeutic intervention. At 2 h CBF increased 22% (71.3 to 87.3 ISI units) above pretreatment values in three subjects given 1.5 g acetazolamide, while three subjects given placebo showed no change. Symptoms remained unaltered in all subjects during the 2 h of the study. Overall, the results indicated that increases in CBF were similar in subjects with or without AMS while acetazolamide-provoked increases of CBF in AMS subjects caused no acute change in symptoms. Alterations in CBF cannot be directly implicated in the pathogenesis of AMS.« less

The role of magnetic resonance diffusion-weighted imaging and three-dimensional arterial spin labelling perfusion imaging in the differentiation of parasellar meningioma and cavernous haemangioma.

PubMed

Xiao, Hua-Feng; Lou, Xin; Liu, Meng-Yu; Wang, Yu-Lin; Wang, Yan; Chen, Zhi-Ye; Shi, Kai-Ning; Ma, Lin

2014-08-01

To evaluate the diagnostic value of magnetic resonance diffusion-weighted imaging (DWI) and three-dimensional arterial spin labelling perfusion imaging (3D-ASL) in distinguishing cavernous haemangioma from parasellar meningioma, using histological data as a reference standard. Patients with parasellar meningioma or parasellar cavernous haemangioma underwent conventional T1- and T2-weighted magnetic resonance imaging (MRI) followed by DWI and 3D-ASL using a 3.0 Tesla MRI. The minimum apparent diffusion coefficient (minADC) from DWI and the maximal normalized cerebral blood flow (nCBF) from 3D-ASL were measured in each tumour. Diagnosis was confirmed by histology. MinADC was significantly lower and nCBF significantly higher in meningioma (n = 19) than cavernous haemangioma (n = 15). There was a significant negative correlation between minADC and nCBF (r = -0.605). DWI and 3D-ASL are useful in differentiating cavernous haemangiomas from parasellar meningiomas, particularly in situations when the appearance on conventional MRI sequences is otherwise ambiguous. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Bridging macroscopic and microscopic methods for the measurements of cerebral blood flow: Toward finding the determinants in maintaining the CBF homeostasis.

PubMed

Kanno, I; Masamoto, K

Methods exist to evaluate the cerebral blood flow (CBF) at both the macroscopic and microscopic spatial scales. These methods provide complementary information for understanding the mechanism in maintaining an adequate blood supply in response to neural demand. The macroscopic CBF assesses perfusion flow, which is usually measured using radioactive tracers, such as diffusible, nondiffusible, or microsphere. Each of them determines CBF based on indicator dilution principle or particle fraction principle under the assumption that CBF is steady state during the measurement. Macroscopic CBF therefore represents averaged CBF over a certain space and time domains. On the other hand, the microscopic CBF assesses bulk flow, usually measures using real-time microscopy. The method assesses hemodynamics of microvessels, ie, vascular dimensions and flow velocities of fluorescently labeled or nonlabeled RBC and plasma markers. The microscopic CBF continuously fluctuates in time and space. Smoothing out this heterogeneity may lead to underestimation in the macroscopic CBF. To link the two measurements, it is needed to introduce a common parameter which is measurable for the both methods, such as mean transit time. Additionally, applying the defined physiological and/or pharmacological perturbation may provide a good exercise to determine how the specific perturbations interfere the quantitative relationships between the macroscopic and microscopic CBF. Finally, bridging these two-scale methods potentially gives a further indication how the absolute CBF is regulated with respect to a specific type of the cerebrovascular tones or capillary flow velocities in the brain. © 2016 Elsevier B.V. All rights reserved.

Cerebral blood flow variations in CNS lupus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kushner, M.J.; Tobin, M.; Fazekas, F.

1990-01-01

We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebralmore » ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery.« less

Cerebral correlates of delta waves during non-REM sleep revisited.

PubMed

Dang-Vu, Thien Thanh; Desseilles, Martin; Laureys, Steven; Degueldre, Christian; Perrin, Fabien; Phillips, Christophe; Maquet, Pierre; Peigneux, Philippe

2005-10-15

We aimed at characterizing the neural correlates of delta activity during Non Rapid Eye Movement (NREM) sleep in non-sleep-deprived normal young adults, based on the statistical analysis of a positron emission tomography (PET) sleep data set. One hundred fifteen PET scans were obtained using H(2)(15)O under continuous polygraphic monitoring during stages 2-4 of NREM sleep. Correlations between regional cerebral blood flow (rCBF) and delta power (1.5-4 Hz) spectral density were analyzed using statistical parametric mapping (SPM2). Delta power values obtained at central scalp locations negatively correlated during NREM sleep with rCBF in the ventromedial prefrontal cortex, the basal forebrain, the striatum, the anterior insula, and the precuneus. These regions embrace the set of brain areas in which rCBF decreases during slow wave sleep (SWS) as compared to Rapid Eye Movement (REM) sleep and wakefulness (Maquet, P., Degueldre, C., Delfiore, G., Aerts, J., Peters, J.M., Luxen, A., Franck, G., 1997. Functional neuroanatomy of human slow wave sleep. J. Neurosci. 17, 2807-S2812), supporting the notion that delta activity is a valuable prominent feature of NREM sleep. A strong association was observed between rCBF in the ventromedial prefrontal regions and delta power, in agreement with electrophysiological studies. In contrast to the results of a previous PET study investigating the brain correlates of delta activity (Hofle, N., Paus, T., Reutens, D., Fiset, P., Gotman, J., Evans, A.C., Jones, B.E., 1997. Regional cerebral blood flow changes as a function of delta and spindle activity during slow wave sleep in humans. J. Neurosci. 17, 4800-4808), in which waking scans were mixed with NREM sleep scans, no correlation was found with thalamus activity. This latter result stresses the importance of an extra-thalamic delta rhythm among the synchronous NREM sleep oscillations. Consequently, this rCBF distribution might preferentially reflect a particular modulation of the cellular processes involved in the generation of cortical delta waves during NREM sleep.

Quantitative assessment of cerebral hemodynamic parameters by QUASAR arterial spin labeling in Alzheimer's disease and cognitively normal Elderly adults at 3-tesla.

PubMed

Mak, Henry K F; Chan, Queenie; Zhang, Zhipeng; Petersen, Esben T; Qiu, Deqiang; Zhang, Linda; Yau, Kelvin K W; Chu, Leung-Wing; Golay, Xavier

2012-01-01

QUASAR arterial spin labeling (ASL) was used to investigate the role of vascular impairment in Alzheimer's disease (AD). We hypothesized that the hemodynamic parameters monitoring cerebrovascular integrity, i.e., cerebral blood flow (CBF), arterial blood volume (aBV), and arterial transit time (aTT), would be affected. 13 AD patients and 15 healthy control (HC) subjects underwent 3T MRI scanning. Two separate blood flow acquisitions were obtained with 1 slice overlap for whole brain coverage. CBF, aBV, and aTT maps were calculated using in-house software. Preprocessing and statistical analyses were performed on SPM5. Region-of-interest (ROI) studies of ten selected cerebral regions were also conducted. There were significant differences in mini mental status exam (MMSE) (AD: 16.3 ± 4.55, HC: 28.5 ± 2.00) and Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) scores (AD: 25.25 ± 9.64, HC: 5.51 ± 2.62) between the 2 groups (p < 0.001) but none in age (p = 0.068). CBF decreased significantly (p < 0.01) in AD compared to controls in the right middle cingulate, left cuneus, left inferior and middle frontal, right superior frontal, left inferior parietal, and right supramarginal gyri. ROI studies confirmed significant hemodynamic impairments in AD compared to HC (p < 0.05): CBF in middle and posterior cingulate, aBV in left superior temporal, right inferior parietal, and posterior cingulate, and aTT in left inferior frontal and middle cingulate gyri. CBF correlated positively while aTT correlated negatively to MMSE, and vice versa for ADAS-cog. Using QUASAR ASL, we found patterns of regional hemodynamic impairment typical of moderate AD, suggesting underlying vascular abnormality. As potential biomarkers, these hemodynamic parameters could differentiate patients from volunteers, and possibly indicate the conversion from healthy aging to mild cognitive impairment to AD.

Salicylic-Acid-Induced Chilling- and Oxidative-Stress Tolerance in Relation to Gibberellin Homeostasis, C-Repeat/Dehydration-Responsive Element Binding Factor Pathway, and Antioxidant Enzyme Systems in Cold-Stored Tomato Fruit.

PubMed

Ding, Yang; Zhao, Jinhong; Nie, Ying; Fan, Bei; Wu, Shujuan; Zhang, Yu; Sheng, Jiping; Shen, Lin; Zhao, Ruirui; Tang, Xuanming

2016-11-02

Effects of salicylic acid (SA) on gibberellin (GA) homeostasis, C-repeat/dehydration-responsive element binding factor (CBF) pathway, and antioxidant enzyme systems linked to chilling- and oxidative-stress tolerance in tomato fruit were investigated. Mature green tomatoes (Solanum lycopersicum L. cv. Moneymaker) were treated with 0, 0.5, and 1 mM SA solution for 15 min before storage at 4 °C for 28 days. In comparison to 0 or 0.5 mM SA, 1 mM SA significantly decreased the chilling injury (CI) index in tomato fruit. In the SA-treated fruit, the upregulation of GA biosynthetic gene (GA3ox1) expression was followed by gibberellic acid (GA 3 ) surge and DELLA protein degradation. CBF1 participated in the SA-modulated tolerance and stimulated the expression of GA catabolic gene (GA2ox1). Furthermore, 1 mM SA enhanced activities of antioxidant enzymes and, thus, reduced reactive oxygen species accumulation. Our findings suggest that SA might protect tomato fruit from CI and oxidative damage through regulating GA metabolism, CBF1 gene expression, and antioxidant enzyme activities.

Model-free arterial spin labelling for cerebral blood flow quantification: introduction of regional arterial input functions identified by factor analysis.

PubMed

Knutsson, Linda; Bloch, Karin Markenroth; Holtås, Stig; Wirestam, Ronnie; Ståhlberg, Freddy

2008-05-01

To identify regional arterial input functions (AIFs) using factor analysis of dynamic studies (FADS) when quantification of perfusion is performed using model-free arterial spin labelling. Five healthy volunteers and one patient were examined on a 3-T Philips unit using quantitative STAR labelling of arterial regions (QUASAR). Two sets of images were retrieved, one where the arterial signal had been crushed and another where it was retained. FADS was applied to the arterial signal curves to acquire the AIFs. Perfusion maps were obtained using block-circulant SVD deconvolution and regional AIFs obtained by FADS. In the volunteers, the ASL experiment was repeated within 24 h. The patient was also examined using dynamic susceptibility contrast MRI. In the healthy volunteers, CBF was 64+/-10 ml/[min 100 g] (mean+/-S.D.) in GM and 24+/-4 ml/[min 100 g] in WM, while the mean aBV was 0.94% in GM and 0.25% in WM. Good CBF image quality and reasonable quantitative CBF values were obtained using the combined QUASAR/FADS technique. We conclude that FADS may be a useful supplement in the evaluation of ASL data using QUASAR.

Neuroprotection by dimethyloxalylglycine following permanent and transient focal cerebral ischemia in rats

PubMed Central

Nagel, Simon; Papadakis, Michalis; Chen, Ruoli; Hoyte, Lisa C; Brooks, Keith J; Gallichan, Daniel; Sibson, Nicola R; Pugh, Chris; Buchan, Alastair M

2011-01-01

Dimethyloxalylglycine (DMOG) is an inhibitor of prolyl-4-hydroxylase domain (PHD) enzymes that regulate the stability of hypoxia-inducible factor (HIF). We investigated the effect of DMOG on the outcome after permanent and transient middle cerebral artery occlusion (p/tMCAO) in the rat. Before and after pMCAO, rats were treated with 40 mg/kg, 200 mg/kg DMOG, or vehicle, and with 40 mg/kg or vehicle after tMCAO. Serial magnetic resonance imaging (MRI) was performed to assess infarct evolution and regional cerebral blood flow (rCBF). Both doses significantly reduced infarct volumes, but only 40 mg/kg improved the behavior after 24 hours of pMCAO. Animals receiving 40 mg/kg were more likely to maintain rCBF values above 30% from the contralateral hemisphere within 24 hours of pMCAO. DMOG after tMCAO significantly reduced the infarct volumes and improved behavior at 24 hours and 8 days and also improved the rCBF after 24 hours. A consistent and significant upregulation of both mRNA and protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) was associated with the observed neuroprotection, although this was not consistently related to HIF-1α levels at 24 hours and 8 days. Thus, DMOG afforded neuroprotection both at 24 hours after pMCAO and at 24 hours and 8 days after tMCAO. This effect was associated with an increase of VEGF and eNOS and was mediated by improved rCBF after DMOG treatment. PMID:20407463

Quantifying regional cerebral blood flow by N-isopropyl-P-[I-123]iodoamphetamine (IMP) using a ring type single-photon emission computed tomography system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahashi, N.; Odano, I.; Ohkubo, M.

1994-05-01

We developed a more accurate quantitative measurement of regional cerebral blood flow (rCBF) with the microsphere model using N-isopropyl-p-[I-123] iodoamphetamine (IMP) and a ring type single photon emission computed tomography (SPECT) system. SPECT studies were performed in 17 patients with brain diseases. A dose of 222 MBq (6 mCi) of [I-123]IMP was injected i.v., at the same time a 5 min period of arterial blood withdrawal was begun. SPECT data were acquired from 25 min to 60 min after tracer injection. For obtaining the brain activity concentration at 5 min after IMP injection, total brain counts collections and one minutemore » period short time SPECT studies were performed at 5, 20, and 60 min. Measurement of the values of rCBF was calculated using short time SPECT images at 5 min (rCBF), static SPECT images corrected with total cerebral counts (rCBF{sub Ct}.) and those corrected with reconstructed counts on short time SPECT images (rCBF{sub Cb}). There was a good relationship (r=0.69) between rCBF and rCBF{sub Ct}, however, rCBF{sub Ct} tends to be underestimated in high flow areas and overestimated in low flow areas. There was better relationship between rCBF and rCBF{sub Cb}(r=0.92). The overestimation and underestimation shown in rCBF{sub Ct} was considered to be due to the correction of reconstructed counts using a total cerebral time activity curve, because of the kinetic behavior of [I-123]IMP was different in each region. We concluded that more accurate rCBF values could be obtained using the regional time activity curves.« less

Low Temperature Induction of Arabidopsis CBF1, 2, and 3 Is Gated by the Circadian Clock1

PubMed Central

Fowler, Sarah G.; Cook, Daniel; Thomashow, Michael F.

2005-01-01

Exposing Arabidopsis (Arabidopsis thaliana) plants to low temperature results in rapid induction of CBF1, 2, and 3 (CBF1-3; also known as DREB1B, C, and A, respectively), which encode transcriptional activators that induce expression of a battery of genes that increase plant freezing and chilling tolerance. Recently, it has been shown that basal levels of CBF3 transcripts and those of certain CBF-regulated genes exhibit circadian cycling. Here, we further explored the regulation of CBF1-3 by the circadian clock. The results indicated that the extent to which CBF1-3 transcripts accumulated in response to low temperature was dependent on the time of day that the plants were exposed to low temperature and that this was regulated by the circadian clock. The highest and lowest levels of cold-induced CBF1-3 transcript accumulation occurred at 4 and 16 h after subjective dawn, respectively. An analysis of CBF2 promoter-reporter gene fusions indicated that this control included transcriptional regulation. In addition, the cold responsiveness of RAV1 and ZAT12, genes that are cold induced in parallel with CBF1-3, was also subject to circadian regulation. However, whereas the maximum level of cold-induced RAV1 transcript accumulation occurred at the same time of day as did CBF1-3 transcripts, that of ZAT12 was in reverse phase, i.e. the highest level of cold-induced ZAT12 transcript accumulation occurred 16 h after subjective dawn. These results indicate that cold-induced expression of CBF1-3, RAV1, and ZAT12 is gated by the circadian clock and suggest that this regulation likely occurs through at least two nonidentical (though potentially overlapping) signaling pathways. PMID:15728337

The Effect of Isovolemic Hemodilution with Oxycyte®, a Perfluorocarbon Emulsion, on Cerebral Blood Flow in Rats

PubMed Central

Yang, Zhong-jin; Price, Chrystal D.; Bosco, Gerardo; Tucci, Micheal; El-Badri, Nagwa S.; Mangar, Devanand; Camporesi, Enrico M.

2008-01-01

Background Cerebral blood flow (CBF) is auto-regulated to meet the brain's metabolic requirements. Oxycyte® is a perfluorocarbon emulsion that acts as a highly effective oxygen carrier compared to blood. The aim of this study is to determine the effects of Oxycyte® on regional CBF (rCBF), by evaluating the effects of stepwise isovolemic hemodilution with Oxycyte® on CBF. Methodology Male rats were intubated and ventilated with 100% O2 under isoflurane anesthesia. The regional (striatum) CBF (rCBF) was measured with a laser doppler flowmeter (LDF). Stepwise isovolemic hemodilution was performed by withdrawing 4ml of blood and substituting the same volume of 5% albumin or 2 ml Oxycyte® plus 2 ml albumin at 20-minute intervals until the hematocrit (Hct) values reached 5%. Principal Findings In the albumin-treated group, rCBF progressively increased to approximately twice its baseline level (208±30%) when Hct levels were less than 10%. In the Oxycyte®-treated group on the other hand, rCBF increased by significantly smaller increments, and this group's mean rCBF was only slightly higher than baseline (118±18%) when Hct levels were less than 10%. Similarly, in the albumin-treated group, rCBF started to increase when hemodilution with albumin caused the CaO2 to decrease below 17.5 ml/dl. Thereafter, the increase in rCBF was accompanied by a nearly proportional decrease in the CaO2 level. In the Oxycyte®-treated group, the increase in rCBF was significantly smaller than in the albumin-treated group when the CaO2 level dropped below 10 ml/dl (142±20% vs. 186±26%), and rCBF returned to almost baseline levels (106±15) when the CaO2 level was below 7 ml/dl. Conclusions/Significance Hemodilution with Oxycyte® was accompanied with higher CaO2 and PO2 than control group treated with albumin alone. This effect may be partially responsible for maintaining relatively constant CBF and not allowing the elevated blood flow that was observed with albumin. PMID:18431491

An Arabidopsis mutation in translation elongation factor 2 causes superinduction of CBF/DREB1 transcription factor genes but blocks the induction of their downstream targets under low temperatures

PubMed Central

Guo, Yan; Xiong, Liming; Ishitani, Manabu; Zhu, Jian-Kang

2002-01-01

Low temperature regulates gene expression in bacteria, yeast, and animals as well as in plants. However, the signal transduction cascades mediating the low temperature responses are not well understood in any organism. To identify components in low temperature signaling genetically, we isolated Arabidopsis thaliana mutants in which cold-responsive genes are no longer induced by low temperatures. One of these mutations, los1–1, specifically blocks low temperature-induced transcription of cold-responsive genes. Surprisingly, cold-induced expression of the early response transcriptional activators, C-repeat/dehydration responsive element binding factors (CBF/DREB1s), is enhanced by the los1–1 mutation. The los1–1 mutation also reduces the capacity of plants to develop freezing tolerance but does not impair the vernalization response. Genetic analysis indicated that los1–1 is a recessive mutation in a single nuclear gene. The LOS1 gene encodes a translation elongation factor 2-like protein. Protein labeling studies show that new protein synthesis is blocked in los1–1 mutant plants specifically in the cold. These results reveal a critical role of new protein synthesis in the proper transduction of low temperature signals. Our results also suggest that cold-induced transcription of CBF/DREB1s is feedback inhibited by their gene products or by products of their downstream target genes. PMID:12032361

Network-wise cerebral blood flow redistribution after 20 Hz rTMS on left dorso-lateral prefrontal cortex.

PubMed

Shang, Yuan-Qi; Xie, Jun; Peng, Wei; Zhang, Jian; Chang, Da; Wang, Ze

2018-04-01

The repetitive application of transcranial magnetic stimulation (rTMS) on left dorsolateral prefrontal cortex (DLPFC) has been consistently shown to be beneficial for treating various neuropsychiatric or neuropsychological disorders, but its neural mechanisms still remain unclear. The purpose of this study was to measure the effects of high-frequency left DLPFC rTMS using cerebral blood flow (CBF) collected from 40 young healthy subjects before and after applying 20 Hz left DLPFC rTMS or SHAM stimulations. Relative CBF (rCBF) changes before and after 20 Hz rTMS or SHAM were assessed with paired-t test. The results show that 20 Hz DLPFC rTMS induced CBF redistribution in the default mode network, including increased rCBF in left medial temporal cortex (MTC)/hippocampus, but reduced rCBF in precuneus and cerebellum. Meanwhile, SHAM stimulation didn't produce any rCBF changes. After controlling SHAM effects, only the rCBF increase in MTC/hippocampus remained. Those data suggest that the beneficial effects of high-frequency rTMS may be through a within-network rCBF redistribution. Copyright © 2018 Elsevier B.V. All rights reserved.

Types of traumatic brain injury and regional cerebral blood flow assessed by 99mTc-HMPAO SPECT.

PubMed

Yamakami, I; Yamaura, A; Isobe, K

1993-01-01

To investigate the relationship between focal and diffuse traumatic brain injury (TBI) and regional cerebral blood flow (rCBF), rCBF changes in the first 24 hours post-trauma were studied in 12 severe head trauma patients using single photon emission computed tomography (SPECT) with 99mtechnetium-hexamethyl propyleneamine oxime. Patients were classified as focal or diffuse TBI based on x-ray computed tomographic (X-CT) findings and neurological signs. In six patients with focal damage, SPECT demonstrated 1) perfusion defect (focal severe ischemia) in the brain region larger than the brain contusion by X-CT, 2) hypoperfusion (focal CBF reduction) in the brain region without abnormality by X-CT, and 3) localized hyperperfusion (focal CBF increase) in the surgically decompressed brain after decompressive craniectomy. Focal damage may be associated with a heterogeneous CBF change by causing various focal CBF derangements. In six patients with diffuse damage, SPECT revealed hypoperfusion in only one patient. Diffuse damage may be associated with a homogeneous CBF change by rarely causing focal CBF derangements. The type of TBI, focal or diffuse, determines the type of CBF change, heterogeneous or homogeneous, in the acute severe head trauma patient.

Therapeutic high-frequency stimulation of the subthalamic nucleus in Parkinson's disease produces global increases in cerebral blood flow.

PubMed

Sidtis, John J; Tagliati, Michele; Alterman, Ron; Sidtis, Diana; Dhawan, Vijay; Eidelberg, David

2012-01-01

Chronic, high-frequency electrical stimulation of the subthalamic nuclei (STNs) has become an effective and widely used therapy in Parkinson's disease (PD), but the therapeutic mechanism is not understood. Stimulation of the STN is believed to reorganize neurophysiological activity patterns within the basal ganglia, whereas local field effects extending to tracts adjacent to the STN are viewed as sources of nontherapeutic side effects. This study is part of a larger project investigating the effects of STN stimulation on speech and regional cerebral blood flow (CBF) in human subjects with PD. While generating measures of global CBF (gCBF) to normalize regional CBF values for a subsequent combined analysis of regional CBF and speech data, we observed a third effect of this therapy: a gCBF increase. This effect was present across three estimates of gCBF ranging from values based on the highest activity voxels to those based on all voxels. The magnitude of the gCBF increase was related to the subject's duration of PD. It is not clear whether this CBF effect has a therapeutic role, but the impact of deep brain stimulation on cerebrovascular control warrants study from neuroscience, pathophysiological, and therapeutic perspectives.

The oxygen paradox of neurovascular coupling

PubMed Central

Leithner, Christoph; Royl, Georg

2014-01-01

The coupling of cerebral blood flow (CBF) to neuronal activity is well preserved during evolution. Upon changes in the neuronal activity, an incompletely understood coupling mechanism regulates diameter changes of supplying blood vessels, which adjust CBF within seconds. The physiologic brain tissue oxygen content would sustain unimpeded brain function for only 1 second if continuous oxygen supply would suddenly stop. This suggests that the CBF response has evolved to balance oxygen supply and demand. Surprisingly, CBF increases surpass the accompanying increases of cerebral metabolic rate of oxygen (CMRO2). However, a disproportionate CBF increase may be required to increase the concentration gradient from capillary to tissue that drives oxygen delivery. However, the brain tissue oxygen content is not zero, and tissue pO2 decreases could serve to increase oxygen delivery without a CBF increase. Experimental evidence suggests that CMRO2 can increase with constant CBF within limits and decreases of baseline CBF were observed with constant CMRO2. This conflicting evidence may be viewed as an oxygen paradox of neurovascular coupling. As a possible solution for this paradox, we hypothesize that the CBF response has evolved to safeguard brain function in situations of moderate pathophysiological interference with oxygen supply. PMID:24149931

Comparative evaluation of different methods for calculation of cerebral blood flow (CBF) in nonanesthetized rabbits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Angelini, G.; Lanza, E.; Rozza Dionigi, A.

1983-05-01

The measurement of cerebral blood flow (CBF) by the extracranial detection of the radioactivity of /sup 133/Xe injected into an internal carotid artery has proved to be of considerable value for the investigation of cerebral circulation in conscious rabbits. Methods are described for calculating CBF from the curves of clearance of /sup 133/Xe, and include exponential analysis (two-component model), initial slope, and stochastic method. The different methods of curve analysis were compared in order to evaluate the fitness with the theoretical model. The initial slope and stochastic methods, compared with the biexponential model, underestimate the CBF by 35% and 46%more » respectively. Furthermore, the validity of recording the clearance curve for 10 min was tested by comparing these CBF values with those obtained from the whole curve. CBF values calculated with the shortened procedure are overestimated by 17%. A correlation exists between the ''10 min'' CBF values and the CBF calculated from the whole curve; in spite of that, the values are not accurate for limited animal populations or for single animals. The extent of the two main compartments into which the CBF is divided was also measured. There is no correlation between CBF values and the extent of the relative compartment. This fact suggests that these two parameters correspond to different biological entities.« less

Resting state cerebral blood flow with arterial spin labeling MRI in developing human brains.

PubMed

Liu, Feng; Duan, Yunsuo; Peterson, Bradley S; Asllani, Iris; Zelaya, Fernando; Lythgoe, David; Kangarlu, Alayar

2018-07-01

The development of brain circuits is coupled with changes in neurovascular coupling, which refers to the close relationship between neural activity and cerebral blood flow (CBF). Studying the characteristics of CBF during resting state in developing brain can be a complementary way to understand the functional connectivity of the developing brain. Arterial spin labeling (ASL), as a noninvasive MR technique, is particularly attractive for studying cerebral perfusion in children and even newborns. We have collected pulsed ASL data in resting state for 47 healthy subjects from young children to adolescence (aged from 6 to 20 years old). In addition to studying the developmental change of static CBF maps during resting state, we also analyzed the CBF time series to reveal the dynamic characteristics of CBF in differing age groups. We used the seed-based correlation analysis to examine the temporal relationship of CBF time series between the selected ROIs and other brain regions. We have shown the developmental patterns in both static CBF maps and dynamic characteristics of CBF. While higher CBF of default mode network (DMN) in all age groups supports that DMN is the prominent active network during the resting state, the CBF connectivity patterns of some typical resting state networks show distinct patterns of metabolic activity during the resting state in the developing brains. Copyright © 2018 European Paediatric Neurology Society. All rights reserved.

Cerebral haemodynamics in patients with hydrocephalus after subarachnoid haemorrhage due to ruptured aneurysm.

PubMed

Chang, Chia-Cheng; Kuwana, Nobumasa; Ito, Susumu; Yokoyama, Takaakira; Kanno, Hiroshi; Yamamoto, Isao

2003-01-01

Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) may be reduced in patients with normal pressure hydrocephalus (NPH) after subarachnoid haemorrhage (SAH). However, little is known about brain circulation in asymptomatic patients with ventriculomegaly after SAH. This study investigated CBF and CVR in symptomatic and asymptomatic patients with ventriculomegaly to clarify the mechanism of NPH. CBF and CVR were investigated in 48 patients with ventriculomegaly after SAH due to ruptured aneurysm. Mean CBF of the whole brain was measured by first-pass radionuclide angiography using technetium-99m hexamethylpropylene amine oxime. CVR was measured as the percentage change from the baseline mean CBF value after administration of 500 mg acetazolamide. Thirty patients with NPH who responded to shunting had significantly ( P<0.01) reduced mean CBF and CVR compared with normal controls. Fourteen asymptomatic patients with ventriculomegaly showed significant ( P<0.01) reduction in CVR but no difference in mean CBF. Four symptomatic patients who did not respond to shunting showed significantly ( P<0.01) reduced mean CBF but had preserved CVR. Postoperative mean CBF and CVR increased significantly ( P<0.01) in 21 patients who responded to shunting, but showed no significant change in four symptomatic patients who did not respond to shunting. Reduction of CBF superimposed on pre-existing impairment of CVR may be an essential step in the mechanism responsible for the manifestation of symptoms of NPH.

Fluid-attenuated inversion recovery vascular hyperintensities in predicting cerebral hyperperfusion after intracranial arterial stenting.

PubMed

Wan, Chih-Cheng; Chen, David Yen-Ting; Tseng, Ying-Chi; Yan, Feng-Xian; Lee, Kun-Yu; Chiang, Chen-Hua; Chen, Chi-Jen

2017-08-01

No reliable imaging sign predicting cerebral hyperperfusion after intracranial arterial stenting (IAS) had been described in the literature. This study evaluated the effect of fluid-attenuated inversion recovery vascular hyperintensities (FVHs), also called hyperintense vessel sign on T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) MR images, in predicting significant increase in cerebral blood flow (CBF) defined by arterial spin labeling (ASL) after IAS. We reviewed ASL CBF images and T2-FLAIR MR images before (D0), 1 day after (D1), and 3 days after (D3) IAS of 16 patients. T1-weighted MR images were used as cerebral maps for calculating CBF. The changes in CBF values after IAS were calculated in and compared among stenting and nonstenting vascular territories. An increase more than 50% of CBF was considered as hyperperfusion. The effect of FVHs in predicting hyperperfusion was calculated. The D1 CBF value was significantly higher than the D0 CBF value in stenting vascular, contralateral anterior cerebral artery, contralateral middle cerebral artery, and contralateral posterior cerebral artery (PCA) territories (all P < .05). The D1 and D3 CBF values were significantly higher than the D0 CBF value in overall vascular (P < .001), overall nonstenting vascular (P < .001), and ipsilateral PCA (P < .05) territories. The rate of more than 50% increases in CBF was significantly higher in patients who exhibited asymmetric FVHs than in those who did not exhibit these findings. FVHs could be a critical predictor of a significant increase in CBF after IAS.

Cold Induction of Arabidopsis CBF Genes Involves Multiple ICE (Inducer of CBF Expression) Promoter Elements and a Cold-Regulatory Circuit That Is Desensitized by Low Temperature1

PubMed Central

Zarka, Daniel G.; Vogel, Jonathan T.; Cook, Daniel; Thomashow, Michael F.

2003-01-01

The Arabidopsis CBF1, 2, and 3 genes (also known as DREB1b, c, and a, respectively) encode transcriptional activators that have a central role in cold tolerance. CBF1-3 are rapidly induced upon exposing plants to low temperature, followed by expression of CBF-targeted genes, the CBF regulon, resulting in an increase in plant freezing tolerance. At present, little is known about the cold-sensing mechanism that controls CBF expression. Results presented here indicate that this mechanism does not require a cold shock to bring about the accumulation of CBF transcripts, but instead, absolute temperature is monitored with a greater degree of input, i.e. lower temperature, resulting in a greater output, i.e. higher levels of CBF transcripts. Temperature-shift experiments also indicate that the cold-sensing mechanism becomes desensitized to a given low temperature, such as 4°C, and that resensitization to that temperature requires between 8 and 24 h at warm temperature. Gene fusion experiments identified a 125-bp section of the CBF2 promoter that is sufficient to impart cold-responsive gene expression. Mutational analysis of this cold-responsive region identified two promoter segments that work in concert to impart robust cold-regulated gene expression. These sequences, designated ICEr1 and ICEr2 (induction of CBF expression region 1 or 2), were also shown to stimulate transcription in response to mechanical agitation and the protein synthesis inhibitor, cycloheximide. PMID:14500791

An ancient neurotrophin receptor code; a single Runx/Cbfβ complex determines somatosensory neuron fate specification in zebrafish

PubMed Central

Condon, Logan; Raible, David W.

2017-01-01

In terrestrial vertebrates such as birds and mammals, neurotrophin receptor expression is considered fundamental for the specification of distinct somatosensory neuron types where TrkA, TrkB and TrkC specify nociceptors, mechanoceptors and proprioceptors/mechanoceptors, respectively. In turn, Runx transcription factors promote neuronal fate specification by regulating neurotrophin receptor and sensory receptor expression where Runx1 mediates TrkA+ nociceptor diversification while Runx3 promotes a TrkC+ proprioceptive/mechanoceptive fate. Here, we report in zebrafish larvae that orthologs of the neurotrophin receptors in contrast to terrestrial vertebrates mark overlapping and distinct subsets of nociceptors suggesting that TrkA, TrkB and TrkC do not intrinsically promote nociceptor, mechanoceptor and proprioceptor/mechanoceptor neuronal fates, respectively. While we find that zebrafish Runx3 regulates nociceptors in contrast to terrestrial vertebrates, it shares a conserved regulatory mechanism found in terrestrial vertebrate proprioceptors/mechanoceptors in which it promotes TrkC expression and suppresses TrkB expression. We find that Cbfβ, which enhances Runx protein stability and affinity for DNA, serves as an obligate cofactor for Runx in neuronal fate determination. High levels of Runx can compensate for the loss of Cbfβ, indicating that in this context Cbfβ serves solely as a signal amplifier of Runx activity. Our data suggests an alteration/expansion of the neurotrophin receptor code of sensory neurons between larval teleost fish and terrestrial vertebrates, while the essential roles of Runx/Cbfβ in sensory neuron cell fate determination while also expanded are conserved. PMID:28708822

An ancient neurotrophin receptor code; a single Runx/Cbfβ complex determines somatosensory neuron fate specification in zebrafish.

PubMed

Gau, Philia; Curtright, Andrew; Condon, Logan; Raible, David W; Dhaka, Ajay

2017-07-01

In terrestrial vertebrates such as birds and mammals, neurotrophin receptor expression is considered fundamental for the specification of distinct somatosensory neuron types where TrkA, TrkB and TrkC specify nociceptors, mechanoceptors and proprioceptors/mechanoceptors, respectively. In turn, Runx transcription factors promote neuronal fate specification by regulating neurotrophin receptor and sensory receptor expression where Runx1 mediates TrkA+ nociceptor diversification while Runx3 promotes a TrkC+ proprioceptive/mechanoceptive fate. Here, we report in zebrafish larvae that orthologs of the neurotrophin receptors in contrast to terrestrial vertebrates mark overlapping and distinct subsets of nociceptors suggesting that TrkA, TrkB and TrkC do not intrinsically promote nociceptor, mechanoceptor and proprioceptor/mechanoceptor neuronal fates, respectively. While we find that zebrafish Runx3 regulates nociceptors in contrast to terrestrial vertebrates, it shares a conserved regulatory mechanism found in terrestrial vertebrate proprioceptors/mechanoceptors in which it promotes TrkC expression and suppresses TrkB expression. We find that Cbfβ, which enhances Runx protein stability and affinity for DNA, serves as an obligate cofactor for Runx in neuronal fate determination. High levels of Runx can compensate for the loss of Cbfβ, indicating that in this context Cbfβ serves solely as a signal amplifier of Runx activity. Our data suggests an alteration/expansion of the neurotrophin receptor code of sensory neurons between larval teleost fish and terrestrial vertebrates, while the essential roles of Runx/Cbfβ in sensory neuron cell fate determination while also expanded are conserved.

A novel class I Chitinase from Hippophae rhamnoides: Indications for participating in ICE-CBF cold stress signaling pathway.

PubMed

Kashyap, Prakriti; Deswal, Renu

2017-06-01

Plant chitinases are the members of PR (Pathogenesis related) proteins family and protect plants from biotic and abiotic stress. A novel chitinase HrCHI1 (Accession number JQ289153) of 954bp ORF encoding 317 amino acids protein was cloned, expressed and characterized from seabuckthorn, a cold/freeze tolerant shrub. The 3D structure (predicted with I-TASSER server) showed highest homology with Oryza sativa class I chitinase (PDB 2dkvA). Putative promoter region (obtained by genome walking) showed GCC box, E-boxes, the binding site for bHLH proteins and DRE elements, the CBF (C-repeat binding factor) binding site besides TATA and CAAT boxes. The gel shift assay with the nuclear extract indicated that the HrCHI1 might be participating in CBF/ERF dependent cold stress signaling pathway. The quantitative transcript profiling supported this observation as cold induced expression of HrCBF peaked earlier (at 1h) while HrCHI1 peaked latter (after 3h) indicating HrCHI1 expression might be induced by HrCBF. Further, HrCHI1 expression was methyl jasmonate (MeJa) dependent and salicylic acid (SA) independent. HrCHI1 was expressed in E. coli and purified using chitin affinity chromatography. It showed 512U/mg chitinase hydrolytic activity and resolved as a 34kDa spot with a slightly basic pI (8.5) on a 2-D gel. The E. coli cells containing recombinant chitinase showed higher rate of growth in cold in comparison with the cells containing the empty vector. In conclusion, we have isolated and characterized a cold responsive basic class I chitinase which is regulated by MeJa and seems to be functioning via CBF/ERF dependent cold stress signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Redox Signaling and CBF-Responsive Pathway Are Involved in Salicylic Acid-Improved Photosynthesis and Growth under Chilling Stress in Watermelon

PubMed Central

Cheng, Fei; Lu, Junyang; Gao, Min; Shi, Kai; Kong, Qiusheng; Huang, Yuan; Bie, Zhilong

2016-01-01

Salicylic acid (SA) plays an important role in plant response to abiotic stresses. This study investigated the potential role of SA in alleviating the adverse effects of chilling stress on photosynthesis and growth in watermelon (Citrullus lanatus). Chilling stress induced the simultaneous accumulation of free and conjugated SA in watermelon plants, and the chilling-induced SA production was attributed to the phenylalanine ammonia-lyase pathway. Applying SA at moderate concentrations induced chilling tolerance, whereas inhibition of SA biosynthesis by L-α-aminooxy-β-phenylpropionic acid (AOPP) increased the photooxidation of PS II under chilling stress in watermelon, resulting in reduced photosynthesis and growth. Chilling induced a transient increase in the ratios of reduced to oxidized glutathione and reduced ascorbate to dehydroascorbate. Then, the expression of antioxidant genes was upregulated, and the activities of antioxidant enzymes were enhanced. Furthermore, SA-induced chilling tolerance was associated with cellular glutathione and ascorbate homeostasis, which served as redox signals to regulate antioxidant metabolism under chilling stress. AOPP treatment stimulated the chilling-induced expression of cold-responsive genes, particularly via C-repeat binding factors CBF3 and CBF4. These results confirm the synergistic role of SA signaling and the CBF-dependent responsive pathway during chilling stress in watermelon. PMID:27777580

Exogenous application of molybdenum affects the expression of CBF14 and the development of frost tolerance in wheat.

PubMed

Al-Issawi, Mohammed; Rihan, Hail Z; Woldie, Wondwossen Abate; Burchett, Stephen; Fuller, Michael P

2013-02-01

Wheat is able to cold acclimate in response to low temperatures and thereby increase its frost tolerance and the extent of this acclimation is greater in winter genotypes compared to spring genotypes. Such up-regulation of frost tolerance is controlled by Cbf transcription factors. Molybdenum (Mo) application has been shown to enhance frost tolerance of wheat and this study aimed to investigate the effect of Mo on the development of frost tolerance in winter and spring wheat. Results showed that Mo treatment increased the expression of Cbf14 in wheat under non-acclimating condition but did not alter frost tolerance. However, when Mo was applied in conjunction with exposure of plants to low temperature, Mo increased the expression of Cbf14 and enhanced frost tolerance in both spring and winter genotypes but the effect was more pronounced in the winter genotype. It was concluded that the application of Mo could be useful in situations where enhanced frost resistance is required. Further studies are proposed to elucidate the effect of exogenous of applications of Mo on frost resistance in spring and winter wheat at different growth stages. Crown Copyright © 2012. Published by Elsevier Masson SAS. All rights reserved.

Transcriptomic and field evaluation of apple trees overexpressing a peach CBF gene

USDA-ARS?s Scientific Manuscript database

The role of CBF genes in cold response and acclimation has been well documented in both herbaceous and woody plants. Our initial research demonstrated that overexpression of a peach CBF gene (PpCBF1) in ‘M.26’ apple increases freezing tolerance of non-acclimated plants and unexpectedly also results...

Cochlear blood flow during occlusion and reperfusion of the anterior inferior cerebellar artery--effect of topical application of dexamethasone to the round window.

PubMed

Otake, Hironao; Yamamoto, Hiroshi; Teranishi, Masaaki; Sone, Michihiko; Nakashima, Tsutomu

2009-02-01

Topical application of dexamethasone may support autoregulation of cochlear blood flow (CBF), although it had no direct effect on CBF. Although intratympanic steroid therapy for patients with inner ear disorders is common, the mechanism by which steroids exert their effect is unclear. We investigated the response of CBF to topical application of dexamethasone onto the round window. Two concentrations of dexamethasone (3.3 mg/ml and 33 mg/ml dexamethasone in 0.5 microl saline) were applied to the round windows of rats, and CBF responses were measured using a laser Doppler flowmeter. The effects on CBF of a 2 h occlusion of the anterior inferior cerebellar artery (AICA) and subsequent release of the clamp with or without previous dexamethasone application were investigated. No significant change in CBF was observed after topical application of dexamethasone, and it did not affect the decrease in CBF caused by AICA occlusion. However, recovery of CBF after release of the AICA clamp was better in animals treated with dexamethasone than in those that did not receive dexamethasone.

Noninvasive MRI measurement of the absolute cerebral blood volume-cerebral blood flow relationship during visual stimulation in healthy humans.

PubMed

Ciris, Pelin Aksit; Qiu, Maolin; Constable, R Todd

2014-09-01

The relationship between cerebral blood volume (CBV) and cerebral blood flow (CBF) underlies blood oxygenation level-dependent functional MRI signal. This study investigates the potential for improved characterization of the CBV-CBF relationship in humans, and examines sex effects as well as spatial variations in the CBV-CBF relationship. Healthy subjects were imaged noninvasively at rest and during visual stimulation, constituting the first MRI measurement of the absolute CBV-CBF relationship in humans with complete coverage of the functional areas of interest. CBV and CBF estimates were consistent with the literature, and their relationship varied both spatially and with sex. In a region of interest with stimulus-induced activation in CBV and CBF at a significance level of the P < 0.05, a power function fit resulted in CBV = 2.1 CBF(0.32) across all subjects, CBV = 0.8 CBF(0.51) in females and CBV = 4.4 CBF(0.15) in males. Exponents decreased in both sexes as ROIs were expanded to include less significantly activated regions. Consideration for potential sex-related differences, as well as regional variations under a range of physiological states, may reconcile some of the variation across literature and advance our understanding of the underlying cerebrovascular physiology. Copyright © 2013 Wiley Periodicals, Inc.

Automated removal of spurious intermediate cerebral blood flow volumes improves image quality among older patients: A clinical arterial spin labeling investigation.

PubMed

Shirzadi, Zahra; Crane, David E; Robertson, Andrew D; Maralani, Pejman J; Aviv, Richard I; Chappell, Michael A; Goldstein, Benjamin I; Black, Sandra E; MacIntosh, Bradley J

2015-11-01

To evaluate the impact of rejecting intermediate cerebral blood flow (CBF) images that are adversely affected by head motion during an arterial spin labeling (ASL) acquisition. Eighty participants were recruited, representing a wide age range (14-90 years) and heterogeneous cerebrovascular health conditions including bipolar disorder, chronic stroke, and moderate to severe white matter hyperintensities of presumed vascular origin. Pseudocontinuous ASL and T1 -weigthed anatomical images were acquired on a 3T scanner. ASL intermediate CBF images were included based on their contribution to the mean estimate, with the goal to maximize CBF detectability in gray matter (GM). Simulations were conducted to evaluate the performance of the proposed optimization procedure relative to other ASL postprocessing approaches. Clinical CBF images were also assessed visually by two experienced neuroradiologists. Optimized CBF images (CBFopt ) had significantly greater agreement with a synthetic ground truth CBF image and greater CBF detectability relative to the other ASL analysis methods (P < 0.05). Moreover, empirical CBFopt images showed a significantly improved signal-to-noise ratio relative to CBF images obtained from other postprocessing approaches (mean: 12.6%; range 1% to 56%; P < 0.001), and this improvement was age-dependent (P = 0.03). Differences between CBF images from different analysis procedures were not perceptible by visual inspection, while there was a moderate agreement between the ratings (κ = 0.44, P < 0.001). This study developed an automated head motion threshold-free procedure to improve the detection of CBF in GM. The improvement in CBF image quality was larger when considering older participants. © 2015 Wiley Periodicals, Inc.

Use of O-15 water and C-11 butanol to measure cerebral blood flow (CBF) and water permeability with positron emission tomography (PET)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herscovitch, P.; Raichle, M.E.; Kilbourn, M.R.

1985-05-01

Tracers used to measure CBF with PET and the Kety autoradiographic approach should freely cross the blood-brain barrier. 0-15 water, which is not freely permeable, may underestimate CBF, especially at higher flows. The authors determined this under-estimation relative to flow measured with a freely diffusible tracer, C-11 butanol and used these data to calculate the extraction (E) and permeability surface area product (PS) for 0-15 water. Paired flow measurements were made with 0-15 water (CBF-wat) and C-11 butanol (CBF-but) in eight normal human subjects. Average CBF-but, 55.6 ml/(min . 100g) was significantly greater than CBF-water, 47.6 ml/(min . 100g). Themore » ratio of regional gray matter (GM) flow to white matter (WM) flow was significantly greater with C-11 butanol, indicating a greater underestimation of CBF with 0-15 water in the higher flow GM. Average E for water was 0.92 in WM and 0.82 in GM. The mean PS in GM, 148 ml/(min . 100g), was significantly greater than in WM, 94 ml/(min . 100g). Simulation studies demonstrated that a measurement error in CBF-wat or CBF-but causes an approximately equivalent error in E but a considerably larger error in PS due to the sensitivity of the equation, PS=-CBF . ln(1-E), to variations in E. Modest errors in E and PS result from tissue heterogeneity that occurs due to the limited spatial resolution of PET. The authors' measurements of E and PS for water are similar to data obtained by more invasive methods and demonstrate the ability of PET to measure brain water permeability.« less

Low-temperature conditioning induces chilling tolerance in stored mango fruit.

PubMed

Zhang, Zhengke; Zhu, Qinggang; Hu, Meijiao; Gao, Zhaoyin; An, Feng; Li, Min; Jiang, Yueming

2017-03-15

In this study, mango fruit were pre-treated with low-temperature conditioning (LTC) at 12°C for 24h, followed by refrigeration at 5°C for 25days before removal to ambient temperature (25°C) to investigate the effects and possible mechanisms of LTC on chilling injury (CI). The results showed that LTC effectively suppressed the development of CI in mango fruit, accelerated softening, and increased the soluble solids and proline content. Furthermore, LTC reduced electrolyte leakage, and levels of malondialdehyde, O 2 - and H 2 O 2 , maintaining membrane integrity. To reveal the molecular regulation of LTC on chilling tolerance in mango fruit, a C-repeat/dehydration-responsive element binding factor (CBF) gene, MiCBF1, was identified and its expression in response to LTC was examined using RT-qPCR. LTC resulted in a higher MiCBF1 expression. These findings suggest that LTC enhances chilling tolerance in mango fruit by inducing a series of physiological and molecular responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Increased hippocampal blood volume and normal blood flow in schizophrenia

PubMed Central

Talati, Pratik; Rane, Swati; Skinner, Jack; Gore, John; Heckers, Stephan

2015-01-01

Neuroimaging studies have provided compelling evidence for abnormal hippocampal activity in schizophrenia. Most studies made inferences about baseline hippocampal activity using a single hemodynamic parameter (e.g., blood volume or blood flow). Here we studied several hemodynamic measures in the same cohort to test the hypothesis of increased hippocampal activity in schizophrenia. We used dynamic susceptibility contrast- (DSC-) magnetic resonance imaging to assess blood volume, blood flow, and mean transit time in the hippocampus of 15 patients with chronic schizophrenia and 15 healthy controls. Left and right hippocampal measurements were combined for absolute measures of cerebral blood volume (CBV), blood flow (CBF), and mean transit time (MTT). We found significantly increased hippocampal CBV, but normal CBF and MTT, in schizophrenia. The uncoupling of CBV and CBF could be due to several factors, including antipsychotic medication, loss of cerebral perfusion pressure, or angiogenesis. Further studies need to incorporate several complementary imaging modalities to better characterize hippocampal dysfunction in schizophrenia. PMID:25896442

A novel Zea mays ssp. mexicana L. MYC-type ICE-like transcription factor gene ZmmICE1, enhances freezing tolerance in transgenic Arabidopsis thaliana.

PubMed

Lu, Xiang; Yang, Lei; Yu, Mengyuan; Lai, Jianbin; Wang, Chao; McNeil, David; Zhou, Meixue; Yang, Chengwei

2017-04-01

The annual Zea mays ssp. mexicana L., a member of the teosinte group, is a close wild relative of maize and thus can be effectively used in maize improvement. In this study, an ICE-like gene, ZmmICE1, was isolated from a cDNA library of RNA-Seq from cold-treated seedling tissues of Zea mays ssp. mexicana L. The deduced protein of ZmmICE1 contains a highly conserved basic helix-loop-helix (bHLH) domain and C-terminal region of ICE-like proteins. The ZmmICE1 protein localizes to the nucleus and shows sumoylation when expressed in an Escherichia coli reconstitution system. In addition, yeast one hybrid assays indicated that ZmmICE1 has transactivation activities. Moreover, ectopic expression of ZmmICE1 in the Arabidopsis ice1-2 mutant increased freezing tolerance. The ZmmICE1 overexpressed plants showed lower electrolyte leakage (EL), reduced contents of malondialdehyde (MDA). The expression of downstream cold related genes of Arabidopsis C-repeat-binding factors (AtCBF1, AtCBF2 and AtCBF3), cold-responsive genes (AtCOR15A and AtCOR47), kinesin-1 member gene (AtKIN1) and responsive to desiccation gene (AtRD29A) was significantly induced when compared with wild type under low temperature treatment. Taken together, these results indicated that ZmmICE1 is the homolog of Arabidopsis inducer of CBF expression genes (AtICE1/2) and plays an important role in the regulation of freezing stress response. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Cerebral hemodynamic changes and electroencephalography during carotid endarterectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Algotsson, L.; Messeter, K.; Rehncrona, S.

Some patients undergoing endarterectomy for occlusive carotid artery disease run a risk of brain ischemia during cross-clamping of the artery. The present study of 15 patients was undertaken to evaluate changes in cerebral blood flow (CBF), as measured with an intravenous (IV) tracer (133Xenon) technique, and to relate CBF changes to changes in the electroencephalogram (EEG). CBF was measured before and after induction of anesthesia, during cross-clamping of the carotid artery, after release of the clamps, and at 24 hours after the operation. All the patients were anesthetized with methohexitone, fentanyl, and nitrous oxide and oxygen. EEG was continuously recordedmore » during the operation. Carotid artery shunts were not used. In 8 patients, cross-clamping of the carotid artery did not influence the EEG. In this group of patients, induction of anesthesia caused a 38% decrease in CBF, which presumably reflects the normal reaction to the anesthetic agent given. There were no further changes in CBF during cross-clamping. In 7 patients, the EEG showed signs of deterioration during the intraoperative vascular occlusion. In these patients, anesthesia did not cause any CBF change, whereas cross-clamping the artery induced a 33% decrease in CBF. In individual patients, the severity of EEG changes correlated with the decrease in CBF. The absence of a change in CBF by anesthesia and a decrease due to cross-clamping of the carotid artery may be explained by the presence of a more advanced cerebrovascular disease and an insufficiency to maintain CBF during cross-clamping.« less

Static and dynamic characteristics of cerebral blood flow during the resting state in schizophrenia.

PubMed

Kindler, Jochen; Jann, Kay; Homan, Philipp; Hauf, Martinus; Walther, Sebastian; Strik, Werner; Dierks, Thomas; Hubl, Daniela

2015-01-01

The cerebral network that is active during rest and is deactivated during goal-oriented activity is called the default mode network (DMN). It appears to be involved in self-referential mental activity. Atypical functional connectivity in the DMN has been observed in schizophrenia. One hypothesis suggests that pathologically increased DMN connectivity in schizophrenia is linked with a main symptom of psychosis, namely, misattribution of thoughts. A resting-state pseudocontinuous arterial spin labeling (ASL) study was conducted to measure absolute cerebral blood flow (CBF) in 34 schizophrenia patients and 27 healthy controls. Using independent component analysis (ICA), the DMN was extracted from ASL data. Mean CBF and DMN connectivity were compared between groups using a 2-sample t test. Schizophrenia patients showed decreased mean CBF in the frontal and temporal regions (P < .001). ICA demonstrated significantly increased DMN connectivity in the precuneus (x/y/z = -16/-64/38) in patients than in controls (P < .001). CBF was not elevated in the respective regions. DMN connectivity in the precuneus was significantly correlated with the Positive and Negative Syndrome Scale scores (P < .01). In schizophrenia patients, the posterior hub--which is considered the strongest part of the DMN--showed increased DMN connectivity. We hypothesize that this increase hinders the deactivation of the DMN and, thus, the translation of cognitive processes from an internal to an external focus. This might explain symptoms related to defective self-monitoring, such as auditory verbal hallucinations or ego disturbances. © The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Tissue-Negative Transient Ischemic Attack: Is There a Role for Perfusion MRI?

PubMed

Grams, Raymond W; Kidwell, Chelsea S; Doshi, Amish H; Drake, Kendra; Becker, Jennifer; Coull, Bruce M; Nael, Kambiz

2016-07-01

Approximately 60% of patients with a clinical transient ischemic attack (TIA) do not have DWI evidence of cerebral ischemia. The purpose of this study was to assess the added diagnostic value of perfusion MRI in the evaluation of patients with TIA who have normal DWI findings. The inclusion criteria for this retrospective study were clinical presentation of TIA at admission with a discharge diagnosis of TIA confirmed by a stroke neurologist, MRI including both DWI and perfusion-weighted imaging within 48 hours of symptom onset, and no DWI lesion. Cerebral blood flow (CBF) and time to maximum of the residue function (Tmax) maps were evaluated independently by two observers. Multivariate analysis was used to assess perfusion findings; clinical variables; age, blood pressure, clinical symptoms, diabetes (ABCD2) score; duration of TIA; and time between MRI and onset and resolution of symptoms. Fifty-two patients (33 women, 19 men; age range, 20-95 years) met the inclusion criteria. A regional perfusion abnormality was identified on either Tmax or CBF maps of 12 of 52 (23%) patients. Seven (58%) of the patients with perfusion abnormalities had hypoperfused lesions best detected on Tmax maps; the other five had hyperperfusion best detected on CBF maps. In 11 of 12 (92%) patients with abnormal perfusion MRI findings, the regional perfusion deficit correlated with the initial neurologic deficits. Multivariable analysis revealed no significant difference in demographics, ABCD2 scores, or presentation characteristics between patients with and those without perfusion abnormalities. Perfusion MRI that includes Tmax and CBF parametric maps adds diagnostic value by depicting regions with delayed perfusion or postischemic hyperperfusion in approximately one-fourth of TIA patients who have normal DWI findings.

Sex Differences in the Neural Correlates of Autonomic Arousal: A Pilot PET Study

PubMed Central

Nugent, Allison C.; Bain, Earle E.; Thayer, Julian F.; Sollers, John J.; Drevets, Wayne C.

2011-01-01

Electrophysiology, behavioral, and neuroimaging studies have revealed sex-related differences in autonomic cardiac control, as reflected in measurements of heart rate variability (HRV). Imaging studies indicate that the neurobiological correlates of autonomic nervous system (ANS) function can be investigated by measuring indices of HRV during the performance of mildly strenuous motor tasks or mildly stressful cognitive tasks. In this preliminary study, fifteen male and seven female healthy subjects underwent H215O-positron emission tomography (PET) and electrocardiograph (ECG) recording while performing a handgrip motor task and an n-back task. Indices of HRV were calculated and correlated with regional cerebral blood flow (rCBF). We hypothesized that sex differences would be evident in brain regions known to participate in autonomic regulation: the anterior insula, the anterior cingulate cortex, the orbitofrontal cortex, and the amygdala. Our study found that associations between rCBF and parasympathetic indices differed significantly between female and male subjects in the amygdala. Females showed a positive correlation between rCBF and parasympathetic indices while males exhibited negative correlations. This differential correlation of amygdala rCBF and parasympathetic activity between males and females may reflect differences in parasympathetic/sympathetic balance between sexes, consistent with known sexual dimorphism in the amygdala and closely related structures such as the hypothalamus. These preliminary imaging results are consistent with earlier reports of significant correlation between brain activity and HRV, and extend these findings by demonstrating prominent sex differences in the neural control of the ANS. While the generalizability of our results was limited by the small size of the study samples, the relatively robust effect size of the differences found between groups encourages further work in larger samples to characterize sex differences in the neural correlates of autonomic arousal. PMID:21414364

Rho-kinase inhibition acutely augments blood flow in focal cerebral ischemia via endothelial mechanisms.

PubMed

Shin, Hwa Kyoung; Salomone, Salvatore; Potts, E Michelle; Lee, Sae-Won; Millican, Eric; Noma, Kensuke; Huang, Paul L; Boas, David A; Liao, James K; Moskowitz, Michael A; Ayata, Cenk

2007-05-01

Rho-kinase is a serine threonine kinase that increases vasomotor tone via its effects on both endothelium and smooth muscle. Rho-kinase inhibition reduces cerebral infarct size in wild type, but not endothelial nitric oxide synthase deficient (eNOS-/-) mice. The mechanism may be related to Rho-kinase activation under hypoxic/ischemic conditions and impaired vasodilation because of downregulation of eNOS activity. To further implicate Rho-kinase in impaired vascular relaxation during hypoxia/ischemia, we exposed isolated vessels from rat and mouse to 60 mins of hypoxia, and showed that hypoxia reversibly abolished acetylcholine-induced eNOS-dependent relaxation, and that Rho-kinase inhibitor hydroxyfasudil partially preserved this relaxation during hypoxia. We, therefore, hypothesized that if hypoxia-induced Rho-kinase activation acutely impairs vasodilation in ischemic cortex, in vivo, then Rho-kinase inhibitors would acutely augment cerebral blood flow (CBF) as a mechanism by which they reduce infarct size. To test this, we studied the acute cerebral hemodynamic effects of Rho-kinase inhibitors in ischemic core and penumbra during distal middle cerebral artery occlusion (dMCAO) in wild-type and eNOS-/- mice using laser speckle flowmetry. When administered 60 mins before or immediately after dMCAO, Rho-kinase inhibitors hydroxyfasudil and Y-27632 reduced the area of severely ischemic cortex. However, hydroxyfasudil did not reduce the area of CBF deficit in eNOS-/- mice, suggesting that its effect on CBF within the ischemic cortex is primarily endothelium-dependent, and not mediated by its direct vasodilator effect on vascular smooth muscle. Our results suggest that Rho-kinase negatively regulates eNOS activity in acutely ischemic brain, thereby worsening the CBF deficit. Therefore, rapid nontranscriptional upregulation of eNOS activity by small molecule inhibitors of Rho-kinase may be a viable therapeutic approach in acute stroke.

Overexpression of the Arabidopsis CBF3 Transcriptional Activator Mimics Multiple Biochemical Changes Associated with Cold Acclimation1

PubMed Central

Gilmour, Sarah J.; Sebolt, Audrey M.; Salazar, Maite P.; Everard, John D.; Thomashow, Michael F.

2000-01-01

We further investigated the role of the Arabidopsis CBF regulatory genes in cold acclimation, the process whereby certain plants increase in freezing tolerance upon exposure to low temperature. The CBF genes, which are rapidly induced in response to low temperature, encode transcriptional activators that control the expression of genes containing the C-repeat/dehydration responsive element DNA regulatory element in their promoters. Constitutive expression of either CBF1 or CBF3 (also known as DREB1b and DREB1a, respectively) in transgenic Arabidopsis plants has been shown to induce the expression of target COR (cold-regulated) genes and to enhance freezing tolerance in nonacclimated plants. Here we demonstrate that overexpression of CBF3 in Arabidopsis also increases the freezing tolerance of cold-acclimated plants. Moreover, we show that it results in multiple biochemical changes associated with cold acclimation: CBF3-expressing plants had elevated levels of proline (Pro) and total soluble sugars, including sucrose, raffinose, glucose, and fructose. Plants overexpressing CBF3 also had elevated P5CS transcript levels suggesting that the increase in Pro levels resulted, at least in part, from increased expression of the key Pro biosynthetic enzyme Δ1-pyrroline-5-carboxylate synthase. These results lead us to propose that CBF3 integrates the activation of multiple components of the cold acclimation response. PMID:11115899

Enduring disturbances in regional cerebral blood flow and brain oxygenation at 24 h after asphyxial cardiac arrest in developing rats.

PubMed

Foley, Lesley M; Clark, Robert S B; Vazquez, Alberto L; Hitchens, T Kevin; Alexander, Henry; Ho, Chien; Kochanek, Patrick M; Manole, Mioara D

2017-01-01

Disturbances in cerebral blood flow (CBF) and brain oxygenation (PbO 2 ) are present early after pediatric cardiac arrest (CA). CBF-targeted therapies improved neurological outcome in our CA model. To assess the therapeutic window for CBF- and PbO 2 -targeted therapies, we propose to determine if CBF and PbO 2 disturbances persist at 24 h after experimental pediatric CA. Regional CBF and PbO 2 were measured at 24 h after asphyxial CA in immature rats (n = 26, 6-8/group) using arterial spin label MRI and tissue electrodes, respectively. In all regions but the thalamus, CBF recovered to sham values by 24 h; thalamic CBF was >32% higher after CA vs. sham. PbO 2 values at 24 h after CA in the cortex and thalamus were similar to shams in rats who received supplemental oxygen, however, on room air, cortical PbO 2 was lower after CA vs. shams. CBF remains increased in the thalamus at 24 h after CA and PbO 2 is decreased to hypoxic levels in cortex at 24 h after CA in rats who do not receive supplemental oxygen. Given the enduring disturbances in this model and the lack of routine CBF or PbO 2 monitoring in patients, our data suggest the need for clinical correlation.

Stem Cell Modeling of Core Binding Factor Acute Myeloid Leukemia

PubMed Central

Mosna, Federico

2016-01-01

Even though clonally originated from a single cell, acute leukemia loses its homogeneity soon and presents at clinical diagnosis as a hierarchy of cells endowed with different functions, of which only a minority possesses the ability to recapitulate the disease. Due to their analogy to hematopoietic stem cells, these cells have been named “leukemia stem cells,” and are thought to be chiefly responsible for disease relapse and ultimate survival after chemotherapy. Core Binding Factor (CBF) Acute Myeloid Leukemia (AML) is cytogenetically characterized by either the t(8;21) or the inv(16)/t(16;16) chromosomal abnormalities, which, although being pathognomonic, are not sufficient per se to induce overt leukemia but rather determine a preclinical phase of disease when preleukemic subclones compete until the acquisition of clonal dominance by one of them. In this review we summarize the concepts regarding the application of the “leukemia stem cell” theory to the development of CBF AML; we will analyze the studies investigating the leukemogenetic role of t(8;21) and inv(16)/t(16;16), the proposed theories of its clonal evolution, and the role played by the hematopoietic niches in preserving the disease. Finally, we will discuss the clinical implications of stem cell modeling of CBF AML for the therapy of the disease. PMID:26880987

The Arabidopsis mediator complex subunits MED16, MED14, and MED2 regulate mediator and RNA polymerase II recruitment to CBF-responsive cold-regulated genes.

PubMed

Hemsley, Piers A; Hurst, Charlotte H; Kaliyadasa, Ewon; Lamb, Rebecca; Knight, Marc R; De Cothi, Elizabeth A; Steele, John F; Knight, Heather

2014-01-01

The Mediator16 (MED16; formerly termed SENSITIVE TO FREEZING6 [SFR6]) subunit of the plant Mediator transcriptional coactivator complex regulates cold-responsive gene expression in Arabidopsis thaliana, acting downstream of the C-repeat binding factor (CBF) transcription factors to recruit the core Mediator complex to cold-regulated genes. Here, we use loss-of-function mutants to show that RNA polymerase II recruitment to CBF-responsive cold-regulated genes requires MED16, MED2, and MED14 subunits. Transcription of genes known to be regulated via CBFs binding to the C-repeat motif/drought-responsive element promoter motif requires all three Mediator subunits, as does cold acclimation-induced freezing tolerance. In addition, these three subunits are required for low temperature-induced expression of some other, but not all, cold-responsive genes, including genes that are not known targets of CBFs. Genes inducible by darkness also required MED16 but required a different combination of Mediator subunits for their expression than the genes induced by cold. Together, our data illustrate that plants control transcription of specific genes through the action of subsets of Mediator subunits; the specific combination defined by the nature of the stimulus but also by the identity of the gene induced.

Neural predictors of emotional inertia in daily life.

PubMed

Waugh, Christian E; Shing, Elaine Z; Avery, Bradley M; Jung, Youngkyoo; Whitlow, Christopher T; Maldjian, Joseph A

2017-09-01

Assessing emotional dynamics in the brain offers insight into the fundamental neural and psychological mechanisms underlying emotion. One such dynamic is emotional inertia-the influence of one's emotional state at one time point on one's emotional state at a subsequent time point. Emotion inertia reflects emotional rigidity and poor emotion regulation as evidenced by its relationship to depression and neuroticism. In this study, we assessed changes in cerebral blood flow (CBF) from before to after an emotional task and used these changes to predict stress, positive and negative emotional inertia in daily life events. Cerebral blood flow changes in the lateral prefrontal cortex (lPFC) predicted decreased non-specific emotional inertia, suggesting that the lPFC may feature a general inhibitory mechanism responsible for limiting the impact that an emotional state from one event has on the emotional state of a subsequent event. CBF changes in the ventromedial prefrontal cortex and lateral occipital cortex were associated with positive emotional inertia and negative/stress inertia, respectively. These data advance the blossoming literature on the temporal dynamics of emotion in the brain and on the use of neural indices to predict mental health-relevant behavior in daily life. © The Author (2017). Published by Oxford University Press.

Neural predictors of emotional inertia in daily life

PubMed Central

Shing, Elaine Z.; Avery, Bradley M.; Jung, Youngkyoo; Whitlow, Christopher T.; Maldjian, Joseph A.

2017-01-01

Abstract Assessing emotional dynamics in the brain offers insight into the fundamental neural and psychological mechanisms underlying emotion. One such dynamic is emotional inertia—the influence of one’s emotional state at one time point on one’s emotional state at a subsequent time point. Emotion inertia reflects emotional rigidity and poor emotion regulation as evidenced by its relationship to depression and neuroticism. In this study, we assessed changes in cerebral blood flow (CBF) from before to after an emotional task and used these changes to predict stress, positive and negative emotional inertia in daily life events. Cerebral blood flow changes in the lateral prefrontal cortex (lPFC) predicted decreased non-specific emotional inertia, suggesting that the lPFC may feature a general inhibitory mechanism responsible for limiting the impact that an emotional state from one event has on the emotional state of a subsequent event. CBF changes in the ventromedial prefrontal cortex and lateral occipital cortex were associated with positive emotional inertia and negative/stress inertia, respectively. These data advance the blossoming literature on the temporal dynamics of emotion in the brain and on the use of neural indices to predict mental health-relevant behavior in daily life. PMID:28992272

Symptom correlates of cerebral blood flow following acute concussion.

PubMed

Churchill, Nathan W; Hutchison, Michael G; Graham, Simon J; Schweizer, Tom A

2017-01-01

Concussion is associated with significant symptoms within hours to days post-injury, including disturbances in physical function, cognition, sleep and emotion. However, little is known about how subjective impairments correlate with objective measures of cerebrovascular function following brain injury. This study examined the relationship between symptoms and cerebral blood flow (CBF) in individuals following sport-related concussion. Seventy university level athletes had CBF measured using Arterial Spin Labelling (ASL), including 35 with acute concussion and 35 matched controls and their symptoms were assessed using the Sport Concussion Assessment Tool 3 (SCAT3). For concussed athletes, greater total symptom severity was associated with elevated posterior cortical CBF, although mean CBF was not significantly different from matched controls ( p  = 0.46). Examining symptom clusters, athletes reporting greater cognitive symptoms also had lower frontal and subcortical CBF, relative to athletes with greater somatic symptoms. The "cognitive" and "somatic" subgroups also exhibited significant differences in CBF relative to controls ( p  ≤ 0.026). This study demonstrates objective CBF correlates of symptoms in recently concussed athletes and shows that specific symptom clusters may have distinct patterns of altered CBF, significantly extending our understanding of the neurobiology of concussion and traumatic brain injury.

CBF measured by Xe-CT: Approach to analysis and normal values

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yonas, H.; Darby, J.M.; Marks, E.C.

1991-09-01

Normal reference values and a practical approach to CBF analysis are needed for routine clinical analysis and interpretation of xenon-enhanced computed tomography (CT) CBF studies. The authors measured CBF in 67 normal individuals with the GE 9800 CT scanner adapted for CBF imaging with stable Xe. CBF values for vascular territories were systematically analyzed using the clustering of contiguous 2-cm circular regions of interest (ROIs) placed within the cortical mantle and basal ganglia. Mixed cortical flows averaged 51 {plus minus} 10ml.100g-1.min-1. High and low flow compartments, sampled by placing 5-mm circular ROIs in regions containing the highest and lowest flowmore » values in each hemisphere, averaged 84 {plus minus} 14 and 20 {plus minus} 5 ml.100 g-1.min-1, respectively. Mixed cortical flow values as well as values within the high flow compartment demonstrated significant decline with age; however, there were no significant age-related changes in the low flow compartment. The clustering of systematically placed cortical and subcortical ROIs has provided a normative data base for Xe-CT CBF and a flexible and uncomplicated method for the analysis of CBF maps generated by Xe-enhanced CT.« less

Changes in regional blood flow induced by unilateral subthalamic nucleus stimulation in patients with Parkinson's disease.

PubMed

Tanei, Takafumi; Kajita, Yasukazu; Nihashi, Takashi; Kaneoke, Yoshiki; Takebayashi, Shigenori; Nakatsubo, Daisuke; Wakabayashi, Toshihiko

2009-11-01

Changes in regional cerebral blood flow (rCBF) induced by unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) were investigated in 7 consecutive patients with Parkinson's disease, 4 men and 3 women (mean age 62.3 +/- 8.1 years), who underwent rCBF measurement by N-isopropyl-p-(iodine-123)-iodoamphetamine single photon emission computed tomography at rest before and after unilateral STN DBS preoperatively in the on-drug condition, and postoperatively in the on-drug and on-stimulation condition. Statistical parametric mapping was used to identify significant changes in rCBF from the preoperative to the postoperative conditions. rCBF was increased in the bilateral cingulate cortices and bilateral cerebellar hemispheres. rCBF was decreased in the bilateral medial frontal cortices and left superior temporal cortex. Unilateral STN DBS produced rCBF changes in the bilateral cingulate cortices, cerebellar hemispheres, and medial frontal cortices. These findings indicate that unilateral STN DBS affects rCBF in both hemispheres.

Quantifying cerebellum grey matter and white matter perfusion using pulsed arterial spin labeling.

PubMed

Li, Xiufeng; Sarkar, Subhendra N; Purdy, David E; Briggs, Richard W

2014-01-01

To facilitate quantification of cerebellum cerebral blood flow (CBF), studies were performed to systematically optimize arterial spin labeling (ASL) parameters for measuring cerebellum perfusion, segment cerebellum to obtain separate CBF values for grey matter (GM) and white matter (WM), and compare FAIR ASST to PICORE. Cerebellum GM and WM CBF were measured with optimized ASL parameters using FAIR ASST and PICORE in five subjects. Influence of volume averaging in voxels on cerebellar grey and white matter boundaries was minimized by high-probability threshold masks. Cerebellar CBF values determined by FAIR ASST were 43.8 ± 5.1 mL/100 g/min for GM and 27.6 ± 4.5 mL/100 g/min for WM. Quantitative perfusion studies indicated that CBF in cerebellum GM is 1.6 times greater than that in cerebellum WM. Compared to PICORE, FAIR ASST produced similar CBF estimations but less subtraction error and lower temporal, spatial, and intersubject variability. These are important advantages for detecting group and/or condition differences in CBF values.

Corticospinal excitability is associated with hypocapnia but not changes in cerebral blood flow

PubMed Central

Hartley, Geoffrey L.; Watson, Cody L.; Ainslie, Philip N.; Tokuno, Craig D.; Greenway, Matthew J.; Gabriel, David A.; O'Leary, Deborah D.

2016-01-01

Key points Reductions in cerebral blood flow (CBF) may be implicated in the development of neuromuscular fatigue; however, the contribution from hypocapnic‐induced reductions (i.e. P ETC O2) in CBF versus reductions in CBF per se has yet to be isolated.We assessed neuromuscular function while using indomethacin to selectively reduce CBF without changes in P ETC O2 and controlled hyperventilation‐induced hypocapnia to reduce both CBF and P ETC O2.Increased corticospinal excitability appears to be exclusive to reductions in P ETC O2 but not reductions in CBF, whereas sub‐optimal voluntary output from the motor cortex is moderately associated with decreased CBF independent of changes in P ETC O2.These findings suggest that changes in CBF and P ETC O2 have distinct roles in modulating neuromuscular function. Abstract Although reductions in cerebral blood flow (CBF) may be involved in central fatigue, the contribution from hypocapnia‐induced reductions in CBF versus reductions in CBF per se has not been isolated. This study examined whether reduced arterial PCO2 (P aC O2), independent of concomitant reductions in CBF, impairs neuromuscular function. Neuromuscular function, as indicated by motor‐evoked potentials (MEPs), maximal M‐wave (M max) and cortical voluntary activation (cVA) of the flexor carpi radialis muscle during isometric wrist flexion, was assessed in ten males (29 ± 10 years) during three separate conditions: (1) cyclooxygenase inhibition using indomethacin (Indomethacin, 1.2 mg kg−1) to selectively reduce CBF by 28.8 ± 10.3% (estimated using transcranial Doppler ultrasound) without changes in end‐tidal PCO2 (P ETC O2); (2) controlled iso‐oxic hyperventilation‐induced reductions in P aC O2 (Hypocapnia), P ETC O2  = 30.1 ± 4.5 mmHg with related reductions in CBF (21.7 ± 6.3%); and (3) isocapnic hyperventilation (Isocapnia) to examine the potential direct influence of hyperventilation‐mediated activation of respiratory control centres on CBF and changes in neuromuscular function. Change in MEP amplitude (%M max) from baseline was greater in Hypocapnia tha in Isocapnia (11.7 ± 9.8%, 95% confidence interval (CI) [2.6, 20.7], P = 0.01) and Indomethacin (13.3 ± 11.3%, 95% CI [2.8, 23.7], P = 0.01) with a large Cohen's effect size (d ≥ 1.17). Although not statistically significant, cVA was reduced with a moderate effect size in Indomethacin (d = 0.7) and Hypocapnia (d = 0.9) compared to Isocapnia. In summary, increased corticospinal excitability – as reflected by larger MEP amplitude – appears to be exclusive to reduced P aC O2, but not reductions in CBF per se. Sub‐optimal voluntary output from the motor cortex is moderately associated with decreased CBF, independent of reduced P aC O2. PMID:26836470

JunB is required for endothelial cell morphogenesis by regulating core-binding factor β

PubMed Central

Licht, Alexander H.; Pein, Oliver T.; Florin, Lore; Hartenstein, Bettina; Reuter, Hendrik; Arnold, Bernd; Lichter, Peter; Angel, Peter; Schorpp-Kistner, Marina

2006-01-01

The molecular mechanism triggering the organization of endothelial cells (ECs) in multicellular tubules is mechanistically still poorly understood. We demonstrate that cell-autonomous endothelial functions of the AP-1 subunit JunB are required for proper endothelial morphogenesis both in vivo in mouse embryos with endothelial-specific ablation of JunB and in in vitro angiogenesis models. By cDNA microarray analysis, we identified core-binding factor β (CBFβ), which together with the Runx proteins forms the heterodimeric core-binding transcription complex CBF, as a novel JunB target gene. In line with our findings, expression of the CBF target MMP-13 was impaired in JunB-deficient ECs. Reintroduction of CBFβ into JunB-deficient ECs rescued the tube formation defect and MMP-13 expression, indicating an important role for CBFβ in EC morphogenesis. PMID:17158955

Regulation of human airway ciliary beat frequency by intracellular pH

PubMed Central

Sutto, Zoltan; Conner, Gregory E; Salathe, Matthias

2004-01-01

pHi affects a number of cellular functions, but the influence of pHi on mammalian ciliary beat frequency (CBF) is not known. CBF and pHi of single human tracheobronchial epithelial cells in submerged culture were measured simultaneously using video microscopy (for CBF) and epifluorescence microscopy with the pH-sensitive dye BCECF. Baseline CBF and pHi values in bicarbonate-free medium were 7.2 ± 0.2 Hz and 7.49 ± 0.02, respectively (n = 63). Alkalization by ammonium pre-pulse to pHi 7.78 ± 0.02 resulted in a 2.2 ± 0.1 Hz CBF increase (P < 0.05). Following removal of NH4Cl, pHi decreased to 7.24 ± 0.02 and CBF to 5.8 ± 0.1 Hz (P < 0.05). Removal of extracellular CO2 to change pHi resulted in similar CBF changes. Pre-activation of cAMP-dependent protein kinase (10 μm forskolin), broad inhibition of protein kinases (100 μm H-7), inhibition of PKA (10 μm H-89), nor inhibition of phosphatases (10 μm cyclosporin + 1.5 μm okadaic acid) changed pHi-mediated changes in CBF, nor were they due to [Ca2+]i changes. CBF of basolaterally permeabilized human tracheobronchial cells, re-differentiated at the air–liquid interface, was 3.9 ± 0.3, 5.7 ± 0.4, 7.0 ± 0.3 and 7.3 ± 0.3 Hz at basolateral i.e., intracellular pH of 6.8, 7.2, 7.6 and 8.0, respectively (n = 18). Thus, intracellular alkalization stimulates, while intracellular acidification attenuates human airway CBF. Since phosphorylation and [Ca2+]i changes did not seem to mediate pHi-induced CBF changes, pHi may directly act on the ciliary motile machinery. PMID:15308676

Cerebral Blood Flow Autoregulation in Sepsis for the Intensivist: Why Its Monitoring May Be the Future of Individualized Care.

PubMed

Goodson, Carrie M; Rosenblatt, Kathryn; Rivera-Lara, Lucia; Nyquist, Paul; Hogue, Charles W

2018-02-01

Cerebral blood flow (CBF) autoregulation maintains consistent blood flow across a range of blood pressures (BPs). Sepsis is a common cause of systemic hypotension and cerebral dysfunction. Guidelines for BP management in sepsis are based on historical concepts of CBF autoregulation that have now evolved with the availability of more precise technology for its measurement. In this article, we provide a narrative review of methods of monitoring CBF autoregulation, the cerebral effects of sepsis, and the current knowledge of CBF autoregulation in sepsis. Current guidelines for BP management in sepsis are based on a goal of maintaining mean arterial pressure (MAP) above the lower limit of CBF autoregulation. Bedside tools are now available to monitor CBF autoregulation continuously. These data reveal that individual BP goals determined from CBF autoregulation monitoring are more variable than previously expected. In patients undergoing cardiac surgery with cardiopulmonary bypass, for example, the lower limit of autoregulation varied between a MAP of 40 to 90 mm Hg. Studies of CBF autoregulation in sepsis suggest patients frequently manifest impaired CBF autoregulation, possibly a result of BP below the lower limit of autoregulation, particularly in early sepsis or with sepsis-associated encephalopathy. This suggests that the present consensus guidelines for BP management in sepsis may expose some patients to both cerebral hypoperfusion and cerebral hyperperfusion, potentially resulting in damage to brain parenchyma. The future use of novel techniques to study and clinically monitor CBF autoregulation could provide insight into the cerebral pathophysiology of sepsis and offer more precise treatments that may improve functional and cognitive outcomes for survivors of sepsis.

A preliminary study on determining the time window of hypothermia cerebral protection in rat cortex by laser speckle flowmetry

NASA Astrophysics Data System (ADS)

Wang, Wenjia; Li, Qiang; Zeng, Shaoqun; Luo, Qingming; Li, Pengcheng

2007-02-01

Laser speckle imaging technique was used to characterize the spatiotemporal changes in cerebral blood flow (CBF) in rat cortex induced by the local ultraprofound hypothermia(0°C) with the duration time of 1 min, 2 min, 5 min, 7 min and 10 min. The experimental results showed significant difference of the spatiotemporal characteristics of changes in CBF between short term and long term of ultraprofound hypothermia. For the short duration of ultraprofound hypothermia (1 min, 2 min and 5 min), the hypothermia cause the CBF decrease firstly, and then the CBF increase rapidly when the temperature is recovered to 37°C, exceeding the baseline level and lasting 10+/-3 min, finally return to the baseline. This trend of changes in CBF is similar in the regions of artery, vein and parenchyma, but with different amplitude. For the duration time of 7 min, the changes in CBF also exhibit the similar decrease induced by ultraprofound hypothermia and the rapid increase induced by the temperature recovering, however the increase does not show the overshoot, but only reach around 75% of the baseline level. For the duration of 10 min of ultraprofound hypothermia, the CBF does not increase rapidly when the temperature is recovered to 37°C, but remains at the low level of CBF for 12+/-2 min, and then increases gradually at artery sites, or increases rapidly and then decrease slightly later at the vein and parenchyma sites. Similar as the case in the duration time of 7 min, the final CBF only recovers to about 75% of the baseline level. The experimental results suggest that the CBF can not recover to the baseline after a long duration of ultraprofound hypothermia longer than 7 min.

Long-term effects of boxing and judo-choking techniques on brain function.

PubMed

Rodriguez, G; Vitali, P; Nobili, F

1998-12-01

Regional cerebral blood flow (rCBF) was measured by 133-xenon inhalation in 24 amateur and 20 professional boxers, and in 10 judoka. Results were compared with those from age- and sex-matched healthy controls. Eighteen boxers (9 amateurs and 9 professionals) and all judoka also underwent electroencephalography (EEG). Mean rCBF values did not differ between either amateur boxers orjudoka and controls, whereas in professional boxers rCBF was significantly (p<.001) reduced in the whole brain, especially in the frontocentral regions. Healthy subjects, judoka, and amateur boxers showed a similar distribution of global CBF (gCBF, the mean of 32 probes) values, although 12.5% of amateurs had a significantly lower gCBF than controls. Among professional boxers, 25% showed a significantly low gCBF value; in the remaining 75%, gCBF was below the mean value of controls but did not reach statistical significance. Regional hypoperfusion, mainly in the frontocentral regions of both sides, was found in 35% of professional and in 29% of amateur boxers. A correlation between gCBF values and number of official matches was not found in boxers. EEG was normal in all judoka and amateur boxers, but it was abnormal in 3 professionals. This study shows the relevance of the neurophysiological assessment of athletes engaged in violent sports which can cause brain impairment. In fact, while professional boxers may show brain functional impairment in comparison to normal subjects, judoka do not. The lack of correlation between CBF values in boxers and the number of official matches points to the difficulty of taking into account variables, such as the number and the severity of matches during training.

Dissection of combinatorial control by the Met4 transcriptional complex.

PubMed

Lee, Traci A; Jorgensen, Paul; Bognar, Andrew L; Peyraud, Caroline; Thomas, Dominique; Tyers, Mike

2010-02-01

Met4 is the transcriptional activator of the sulfur metabolic network in Saccharomyces cerevisiae. Lacking DNA-binding ability, Met4 must interact with proteins called Met4 cofactors to target promoters for transcription. Two types of DNA-binding cofactors (Cbf1 and Met31/Met32) recruit Met4 to promoters and one cofactor (Met28) stabilizes the DNA-bound Met4 complexes. To dissect this combinatorial system, we systematically deleted each category of cofactor(s) and analyzed Met4-activated transcription on a genome-wide scale. We defined a core regulon for Met4, consisting of 45 target genes. Deletion of both Met31 and Met32 eliminated activation of the core regulon, whereas loss of Met28 or Cbf1 interfered with only a subset of targets that map to distinct sectors of the sulfur metabolic network. These transcriptional dependencies roughly correlated with the presence of Cbf1 promoter motifs. Quantitative analysis of in vivo promoter binding properties indicated varying levels of cooperativity and interdependency exists between members of this combinatorial system. Cbf1 was the only cofactor to remain fully bound to target promoters under all conditions, whereas other factors exhibited different degrees of regulated binding in a promoter-specific fashion. Taken together, Met4 cofactors use a variety of mechanisms to allow differential transcription of target genes in response to various cues.

Repeated measurements of cerebral blood flow in the left superior temporal gyrus reveal tonic hyperactivity in patients with auditory verbal hallucinations: a possible trait marker

PubMed Central

Homan, Philipp; Kindler, Jochen; Hauf, Martinus; Walther, Sebastian; Hubl, Daniela; Dierks, Thomas

2013-01-01

Background: The left superior temporal gyrus (STG) has been suggested to play a key role in auditory verbal hallucinations (AVH) in patients with schizophrenia. Methods: Eleven medicated subjects with schizophrenia and medication-resistant AVH and 19 healthy controls underwent perfusion magnetic resonance (MR) imaging with arterial spin labeling (ASL). Three additional repeated measurements were conducted in the patients. Patients underwent a treatment with transcranial magnetic stimulation (TMS) between the first 2 measurements. The main outcome measure was the pooled cerebral blood flow (CBF), which consisted of the regional CBF measurement in the left STG and the global CBF measurement in the whole brain. Results: Regional CBF in the left STG in patients was significantly higher compared to controls (p < 0.0001) and to the global CBF in patients (p < 0.004) at baseline. Regional CBF in the left STG remained significantly increased compared to the global CBF in patients across time (p < 0.0007), and it remained increased in patients after TMS compared to the baseline CBF in controls (p < 0.0001). After TMS, PANSS (p = 0.003) and PSYRATS (p = 0.01) scores decreased significantly in patients. Conclusions: This study demonstrated tonically increased regional CBF in the left STG in patients with schizophrenia and auditory hallucinations despite a decrease in symptoms after TMS. These findings were consistent with what has previously been termed a trait marker of AVH in schizophrenia. PMID:23805093

Quantitative assessment of cerebral blood flow in genetically confirmed spinocerebellar ataxia type 6.

PubMed

Honjo, Kie; Ohshita, Tomohiko; Kawakami, Hideshi; Naka, Hiromitsu; Imon, Yukari; Maruyama, Hirofumi; Mimori, Yasuyo; Matsumoto, Masayasu

2004-06-01

Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant cerebellar ataxia caused by CAG trinucleotide expansion. The characteristics of regional cerebral blood flow (rCBF) in SCA6 patients have not been established, whereas it has been reported that decreased rCBF in the cerebrum seems to be a remote effect of cerebellar impairment in other cerebellar disorders. To clarify the characteristics of rCBF, including cerebro-cerebellar relationship, and its correlation with clinical manifestations in patients with genetically confirmed SCA6 using quantitative assessment of rCBF by brain single-photon emission computed tomography (SPECT). Technetium Tc 99m ethyl cysteinate dimer SPECT study using a Patlak plot. Patients Hiroshima University Hospital, Hiroshima, Japan. Ten patients with SCA6 and 9 healthy controls. Main Outcome Measure The rCBF of the cerebellar vermis, cerebellar hemisphere, and frontal lobes. In SCA6 patients, rCBF was decreased only in the cerebellar vermis and hemisphere compared with healthy controls, and this was inversely correlated with duration of illness. The rCBF in the frontal lobes was slightly correlated with duration of illness without statistical significance. The rCBF in the vermis was inversely correlated with severity of dysarthria, but there was no significant correlation with CAG repeated expansions. Decrease in rCBF was found only in the cerebellum and was associated with duration of illness, dysarthria and ataxia, and cerebellar atrophy. No remote effect of cerebellar hypoperfusion was found in the SCA6 patients.

Cerebral white matter blood flow and energy metabolism in multiple sclerosis.

PubMed

Steen, Christel; D'haeseleer, Miguel; Hoogduin, Johannes M; Fierens, Yves; Cambron, Melissa; Mostert, Jop P; Heersema, Dorothea J; Koch, Marcus W; De Keyser, Jacques

2013-09-01

Cerebral blood flow (CBF) is reduced in normal-appearing white matter (NAWM) of subjects with multiple sclerosis (MS), but the underlying mechanism is unknown. The objective of this article is to assess the relationship between reduced NAWM CBF and both axonal mitochondrial metabolism and astrocytic phosphocreatine (PCr) metabolism. Ten healthy controls and 25 MS subjects were studied with 3 Tesla magnetic resonance imaging. CBF was measured using pseudo-continuous arterial spin labeling. N-acetylaspartate/creatine (NAA/Cr) ratios (axonal mitochondrial metabolism) were obtained using (1)H-MR spectroscopy and PCr/β-ATP ratios using (31)P-MR spectroscopy. In centrum semiovale NAWM, we assessed correlations between CBF and both NAA/Cr and PCr/β-ATP ratios. Subjects with MS had a widespread reduction in CBF of NAWM (centrum semiovale, periventricular, frontal and occipital), and gray matter (frontoparietal cortex and thalamus). Compared to controls, NAA/Cr in NAWM of the centrum semiovale of MS subjects was decreased, whereas PCr/β-ATP was increased. We found no correlations between CBF and PCr/β-ATP. CBF and NAA/Cr correlated in controls (p = 0.02), but not in MS subjects (p = 0.68). Our results suggest that in MS patients there is no relationship between reduced CBF in NAWM and impaired axonal mitochondrial metabolism or astrocytic PCr metabolism.

Response of cochlear blood flow to prostaglandin E1 applied topically to the round window.

PubMed

Tominaga, Mitsuo; Yamamoto, Hiroshi; Sone, Michihiko; Teranishi, Masa-aki; Nakashima, Tsutomu

2006-03-01

The increase in cochlear blood flow (CBF) after administration of prostaglandin E1 (PGE1) to the round window depends on increased blood flow through the anterior inferior cerebellar artery (AICA). To evaluate the response of CBF to PGE1 applied topically to the round window, and to investigate the origin of blood flow changes after this topical application. The response of CBF to topically applied PGE1 was measured by placing the tip of a laser Doppler probe on the bony wall of the basal turn of the cochlea after the middle ear mucosa over the cochlea had been removed in guinea pigs and rats. In rats, the CBF response to PGE1 administration was investigated after occlusion of the AICA or stapedial artery. CBF increased following PGE1 administration in both guinea pigs and rats. In rats, CBF increased from 100% to 132%+/-10% (mean+/-SD) after the topical application of 0.5 microl of a 0.014% PGE1 solution. CBF decreased after occlusion of the AICA or stapedial artery but did not increase after PGE1 administration during occlusion of the AICA. The CBF response to PGE1 administration was similar before and after occlusion of the stapedial artery.

Clinical application of arterial spin-labeling MR imaging in patients with carotid stenosis: quantitative comparative study with single-photon emission CT.

PubMed

Uchihashi, Y; Hosoda, K; Zimine, I; Fujita, A; Fujii, M; Sugimura, K; Kohmura, E

2011-09-01

Arterial spin-labeling is an emerging technique for noninvasive measurement of cerebral perfusion, but concerns remain regarding the reliability of CBF quantification and clinical applications. Recently, an ASL implementation called QUASAR was proposed, and it was shown to have good reproducibility of CBF assessment in healthy volunteers. This study aimed to determine the utility of QUASAR for CBF assessment in patients with cerebrovascular diseases. Twenty patients with carotid stenosis underwent CBF quantification by ASL (QUASAR) within 3 days of performance of (123)I-iodoamphetamine-SPECT. CVR to acetazolamide also was assessed by ASL and SPECT. In surgically treated patients, the respective scans before and after the procedures were compared. Regional CBF and CVR values measured by ASL were significantly correlated and agreed with those measured by SPECT (r(s) = 0.92 and 0.88, respectively). A Bland-Altman plot demonstrated good agreement between 2 methods in terms of CBF quantification. Furthermore, ASL could detect pathologic states such as hypoperfusion, impaired vasoreactivity, and postoperative hyperperfusion, equivalent to SPECT. However, ASL tended to overestimate CBF values especially in high-perfusion regions. ASL perfusion MR imaging is clinically applicable and can be an alternative method for CBF assessment in patients with cerebrovascular diseases.

Cerebral blood flow velocity in humans exposed to 24 h of head-down tilt

NASA Technical Reports Server (NTRS)

Kawai, Y.; Murthy, G.; Watenpaugh, D. E.; Breit, G. A.; Deroshia, C. W.; Hargens, A. R.

1993-01-01

This study investigates cerebral blood flow (CBF) velocity in humans before, during, and after 24 h of 6 deg head-down tilt (HDT), which is a currently accepted experimental model to simulate microgravity. CBF velocity was measured by use of the transcranial Doppler technique in the right middle cerebral artery of eight healthy male subjects. Mean CBF velocity increased from the pre-HDT upright seated baseline value of 55.5 +/- 3.7 (SE) cm/s to 61.5 +/- 3.3 cm/s at 0.5 h of HDT, reached a peak value of 63.2 +/- 4.1 cm/s at 3 h of HDT, and remained significantly above the pre-HDT baseline for over 6 h of HDT. During upright seated recovery, mean CBF velocity decreased to 87 percent of the pre-HDT baseline value. Mean CBF velocity correlated well with calculated intracranial arterial pressure (IAP). As analyzed by linear regression, mean CBF velocity = 29.6 + 0.32IAP. These results suggest that HDT increases CBF velocity by increasing IAP during several hours after the onset of microgravity. Importantly, the decrease in CBF velocity after HDT may be responsible, in part, for the increased risk of syncope observed in subjects after prolonged bed rest and also in astronauts returning to Earth.

Relationship between relative cerebral blood flow, relative cerebral blood volume, and relative cerebral metabolic rate of oxygen in the preterm neonatal brain.

PubMed

Nourhashemi, Mina; Kongolo, Guy; Mahmoudzadeh, Mahdi; Goudjil, Sabrina; Wallois, Fabrice

2017-04-01

The mechanisms responsible for coupling between relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative cerebral metabolic rate of oxygen ([Formula: see text]), an important function of the microcirculation in preterm infants, remain unclear. Identification of a causal relationship between rCBF-rCBV and [Formula: see text] in preterms may, therefore, help to elucidate the principles of cortical hemodynamics during development. We simultaneously recorded rCBF and rCBV and estimated [Formula: see text] by two independent acquisition systems: diffuse correlation spectroscopy and near-infrared spectroscopy, respectively, in 10 preterms aged between 28 and 35 weeks of gestational age. Transfer entropy was calculated in order to determine the directionality between rCBF-rCBV and [Formula: see text]. The surrogate method was applied to determine statistical significance. The results show that rCBV and [Formula: see text] have a predominant driving influence on rCBF at the resting state in the preterm neonatal brain. Statistical analysis robustly detected the correct directionality of rCBV on rCBF and [Formula: see text] on rCBF. This study helps to clarify the early organization of the rCBV-rCBF and [Formula: see text] inter-relationship in the immature cortex.

Quantifying Cerebellum Grey Matter and White Matter Perfusion Using Pulsed Arterial Spin Labeling

PubMed Central

Li, Xiufeng; Sarkar, Subhendra N.; Purdy, David E.; Briggs, Richard W.

2014-01-01

To facilitate quantification of cerebellum cerebral blood flow (CBF), studies were performed to systematically optimize arterial spin labeling (ASL) parameters for measuring cerebellum perfusion, segment cerebellum to obtain separate CBF values for grey matter (GM) and white matter (WM), and compare FAIR ASST to PICORE. Cerebellum GM and WM CBF were measured with optimized ASL parameters using FAIR ASST and PICORE in five subjects. Influence of volume averaging in voxels on cerebellar grey and white matter boundaries was minimized by high-probability threshold masks. Cerebellar CBF values determined by FAIR ASST were 43.8 ± 5.1 mL/100 g/min for GM and 27.6 ± 4.5 mL/100 g/min for WM. Quantitative perfusion studies indicated that CBF in cerebellum GM is 1.6 times greater than that in cerebellum WM. Compared to PICORE, FAIR ASST produced similar CBF estimations but less subtraction error and lower temporal, spatial, and intersubject variability. These are important advantages for detecting group and/or condition differences in CBF values. PMID:24949416

Resistance of Gerbil Auditory Function to Reversible Decrease in Cochlear Blood Flow.

PubMed

El Afia, Fahd; Giraudet, Fabrice; Gilain, Laurent; Mom, Thierry; Avan, Paul

2017-01-01

The objective was to design in gerbils a model of reversible decrease in cochlear blood flow (CBF) and analyze its influence on cochlear function. In Mongolian gerbils injected with ferromagnetic microbeads, a magnet placed near the porus acusticus allowed CBF to be manipulated. The cochlear microphonic potential (CM) from the basal cochlea was monitored by a round-window electrode. In 13 of the 20 successfully injected gerbils, stable CBF reduction was obtained for 11.5 min on average. The CM was affected only when CBF fell to less than 60% of its baseline, yet remained >40% of its initial level in about 2/3 of such cases. After CBF restoration, CM recovery was fast and usually complete. Reduced CM came with a 35- to 45-dB threshold elevation of neural responses determined by compound action potentials. This method allowing reversible changes of CBF confirms the robustness of cochlear function to decreased CBF. It can be used to study whether a hypovascularized cochlea is abnormally sensitive to stress. © 2017 S. Karger AG, Basel.

Genetics Home Reference: core binding factor acute myeloid leukemia

MedlinePlus

... the CBFB gene. One such rearrangement, called an inversion , involves breakage of a chromosome in two places; ... is reversed and reinserted into the chromosome. The inversion involved in CBF-AML (written as inv(16)) ...

Cerebral blood flow modulation by Basal forebrain or whisker stimulation can occur independently of large cytosolic Ca2+ signaling in astrocytes.

PubMed

Takata, Norio; Nagai, Terumi; Ozawa, Katsuya; Oe, Yuki; Mikoshiba, Katsuhiko; Hirase, Hajime

2013-01-01

We report that a brief electrical stimulation of the nucleus basalis of Meynert (NBM), the primary source of cholinergic projection to the cerebral cortex, induces a biphasic cerebral cortical blood flow (CBF) response in the somatosensory cortex of C57BL/6J mice. This CBF response, measured by laser Doppler flowmetry, was attenuated by the muscarinic type acetylcholine receptor antagonist atropine, suggesting a possible involvement of astrocytes in this type of CBF modulation. However, we find that IP3R2 knockout mice, which lack cytosolic Ca2+ surges in astrocytes, show similar CBF changes. Moreover, whisker stimulation resulted in similar degrees of CBF increase in IP3R2 knockout mice and the background strain C57BL/6J. Our results show that neural activity-driven CBF modulation could occur without large cytosolic increases of Ca2+ in astrocytes.

Intraoperative laser speckle contrast imaging improves the stability of rodent middle cerebral artery occlusion model

NASA Astrophysics Data System (ADS)

Yuan, Lu; Li, Yao; Li, Hangdao; Lu, Hongyang; Tong, Shanbao

2015-09-01

Rodent middle cerebral artery occlusion (MCAO) model is commonly used in stroke research. Creating a stable infarct volume has always been challenging for technicians due to the variances of animal anatomy and surgical operations. The depth of filament suture advancement strongly influences the infarct volume as well. We investigated the cerebral blood flow (CBF) changes in the affected cortex using laser speckle contrast imaging when advancing suture during MCAO surgery. The relative CBF drop area (CBF50, i.e., the percentage area with CBF less than 50% of the baseline) showed an increase from 20.9% to 69.1% when the insertion depth increased from 1.6 to 1.8 cm. Using the real-time CBF50 marker to guide suture insertion during the surgery, our animal experiments showed that intraoperative CBF-guided surgery could significantly improve the stability of MCAO with a more consistent infarct volume and less mortality.

Laser Speckle Imaging of Cerebral Blood Flow

NASA Astrophysics Data System (ADS)

Luo, Qingming; Jiang, Chao; Li, Pengcheng; Cheng, Haiying; Wang, Zhen; Wang, Zheng; Tuchin, Valery V.

Monitoring the spatio-temporal characteristics of cerebral blood flow (CBF) is crucial for studying the normal and pathophysiologic conditions of brain metabolism. By illuminating the cortex with laser light and imaging the resulting speckle pattern, relative CBF images with tens of microns spatial and millisecond temporal resolution can be obtained. In this chapter, a laser speckle imaging (LSI) method for monitoring dynamic, high-resolution CBF is introduced. To improve the spatial resolution of current LSI, a modified LSI method is proposed. To accelerate the speed of data processing, three LSI data processing frameworks based on graphics processing unit (GPU), digital signal processor (DSP), and field-programmable gate array (FPGA) are also presented. Applications for detecting the changes in local CBF induced by sensory stimulation and thermal stimulation, the influence of a chemical agent on CBF, and the influence of acute hyperglycemia following cortical spreading depression on CBF are given.

Localization of cortical areas activated by thinking.

PubMed

Roland, P E; Friberg, L

1985-05-01

These experiments were undertaken to demonstrate that pure mental activity, thinking, increases the cerebral blood flow and that different types of thinking increase the regional cerebral blood flow (rCBF) in different cortical areas. As a first approach, thinking was defined as brain work in the form of operations on internal information, done by an awake subject. The rCBF was measured in 254 cortical regions in 11 subjects with the intracarotid 133Xe injection technique. In normal man, changes in the regional cortical metabolic rate of O2 leads to proportional changes in rCBF. One control study was taken with the subjects at rest. Then the rCBF was measured during three different simple algorithm tasks, each consisting of retrieval of a specific memory followed by a simple operation on the retrieved information. Once started, the information processing went on in the brain without any communication with the outside world. In 50-3 thinking, the subjects started with 50 and then, in their minds only, continuously subtracted 3 from the result. In jingle thinking the subjects internally jumped every second word in a nine-word circular jingle. In route-finding thinking the subjects imagined that they started at their front door and then walked alternatively to the left or the right each time they reached a corner. The rCBF increased only in homotypical cortical areas during thinking. The areas in the superior prefrontal cortex increased their rCBF equivalently during the three types of thinking. In the remaining parts of the prefrontal cortex there were multifocal increases of rCBF. The localizations and intensities of these rCBF increases depended on the type of internal operation occurring. The rCBF increased bilaterally in the angular cortex during 50-3 thinking. The rCBF increased in the right midtemporal cortex exclusively during jingle thinking. The intermediate and remote visual association areas, the superior occipital, posterior inferior temporal, and posterior superior parietal cortex, increased their rCBF exclusively during route-finding thinking. We observed no decreases in rCBF. All rCBF increases extended over a few square centimeters of the cortex. The activation of the superior prefrontal cortex was attributed to the organization of thinking. The activation of the angular cortex in 50-3 thinking was attributed to the retrieval of the numerical memory and memory for subtractions. The activation of the right midtemporal cortex was attributed to the retrieval of the nonverbal auditory memory.(ABSTRACT TRUNCATED AT 400 WORDS)

An anisotropic diffusion method for denoising dynamic susceptibility contrast-enhanced magnetic resonance images

NASA Astrophysics Data System (ADS)

Murase, Kenya; Yamazaki, Youichi; Shinohara, Masaaki; Kawakami, Kazunori; Kikuchi, Keiichi; Miki, Hitoshi; Mochizuki, Teruhito; Ikezoe, Junpei

2001-10-01

The purpose of this study was to present an application of a novel denoising technique for improving the accuracy of cerebral blood flow (CBF) images generated from dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI). The method presented in this study was based on anisotropic diffusion (AD). The usefulness of this method was firstly investigated using computer simulations. We applied this method to patient data acquired using a 1.5 T MR system. After a bolus injection of Gd-DTPA, we obtained 40-50 dynamic images with a 1.32-2.08 s time resolution in 4-6 slices. The dynamic images were processed using the AD method, and then the CBF images were generated using pixel-by-pixel deconvolution analysis. For comparison, the CBF images were also generated with or without processing the dynamic images using a median or Gaussian filter. In simulation studies, the standard deviation of the CBF values obtained after processing by the AD method was smaller than that of the CBF values obtained without any processing, while the mean value agreed well with the true CBF value. Although the median and Gaussian filters also reduced image noise, the mean CBF values were considerably underestimated compared with the true values. Clinical studies also suggested that the AD method was capable of reducing the image noise while preserving the quantitative accuracy of CBF images. In conclusion, the AD method appears useful for denoising DSC-MRI, which will make the CBF images generated from DSC-MRI more reliable.

Threshold relationship between lesion extent of the cholinergic basal forebrain in the rat and working memory impairment in the radial maze.

PubMed

Wrenn, C C; Lappi, D A; Wiley, R G

1999-11-20

The cholinergic basal forebrain (CBF) degenerates in Alzheimer's Disease (AD), and the degree of this degeneration correlates with the degree of dementia. In the present study we have modeled this degeneration in the rat by injecting various doses of the highly selective immunotoxin 192 IgG-saporin (192-sap) into the ventricular system. The ability of 192-sap-treated rats to perform in a previously learned radial maze working memory task was then tested. We report here that 192-sap created lesions of the CBF and, to a lesser extent, cerebellar Purkinje cells in a dose-dependent fashion. Furthermore, we found that rats harboring lesions of the entire CBF greater than 75% had impaired spatial working memory in the radial maze. Correlational analysis of working memory impairment and lesion extent of the component parts of the CBF revealed that high-grade lesions of the hippocampal-projecting neurons of the CBF were not sufficient to impair working memory. Only rats with high-grade lesions of the hippocampal and cortical projecting neurons of the CBF had impaired working memory. These data are consistent with other 192-sap reports that found behavioral deficits only with high-grade CBF lesions and indicate that the relationship between CBF lesion extent and working memory impairment is a threshold relationship in which a high degree of neuronal loss can be tolerated without detectable consequences. Additionally, the data suggest that the CBF modulates spatial working memory via its connections to both the hippocampus and cortex.

Electrodeposition of Polypyrrole and Reduced Graphene Oxide onto Carbon Bundle Fibre as Electrode for Supercapacitor.

PubMed

Abdul Bashid, Hamra Assyaima; Lim, Hong Ngee; Kamaruzaman, Sazlinda; Abdul Rashid, Suraya; Yunus, Robiah; Huang, Nay Ming; Yin, Chun Yang; Rahman, Mohammad Mahbubur; Altarawneh, Mohammednoor; Jiang, Zhong Tao; Alagarsamy, Pandikumar

2017-12-01

A nanocomposite comprising of polypyrrole and reduced graphene oxide was electrodeposited onto a carbon bundle fibre (CBF) through a two-step approach (CBF/PPy-rGO-2). The CBF/PPy-rGO-2 had a highly porous structure compared to a nanocomposite of polypyrrole and reduced graphene oxide that was electrodeposited onto a CBF in a one-step approach (CBF/PPy-rGO), as observed through a field emission scanning electron microscope. An X-ray photoelectron spectroscopic analysis revealed the presence of hydrogen bond between the oxide functional groups of rGO and the amine groups of PPy in PPy-rGO-2 nanocomposite. The fabricated CBF/PPy-rGO-2 nanocomposite material was used as an electrode material in a symmetrical solid-state supercapacitor, and the device yielded a specific capacitance, energy density and power density of 96.16 F g - 1 , 13.35 Wh kg - 1 and of 322.85 W kg - 1 , respectively. Moreover, the CBF/PPy-rGO-2 showed the capacitance retention of 71% after 500 consecutive charge/discharge cycles at a current density of 1 A g - 1 . The existence of a high degree of porosity in CBF/PPy-rGO-2 significantly improved the conductivity and facilitated the ionic penetration. The CBF/PPy-rGO-2-based symmetrical solid-state supercapacitor device demonstrated outstanding pliability because the cyclic voltammetric curves remained the same upon bending at various angles. Carbon bundle fibre modified with porous polypyrrole/reduced graphene oxide nanocomposite for flexible miniature solid-state supercapacitor.

Assessment of Alzheimer's disease risk with functional magnetic resonance imaging: an arterial spin labeling study.

PubMed

Bangen, Katherine J; Restom, Khaled; Liu, Thomas T; Wierenga, Christina E; Jak, Amy J; Salmon, David P; Bondi, Mark W

2012-01-01

Functional magnetic resonance imaging (fMRI) of older adults at risk for Alzheimer's disease (AD) by virtue of their cognitive (i.e., mild cognitive impairment [MCI]) and/or genetic (i.e., apolipoprotein E [APOE] ε4 allele) status demonstrate divergent brain response patterns during memory encoding across studies. Using arterial spin labeling MRI, we examined the influence of AD risk on resting cerebral blood flow (CBF) as well as the CBF and blood oxygenation level dependent (BOLD) signal response to memory encoding in the medial temporal lobes (MTL) in 45 older adults (29 cognitively normal [14 APOE ε4 carriers and 15 noncarriers]; 16 MCI [8 APOE ε4 carriers, 8 noncarriers]). Risk groups were comparable in terms of mean age, years of education, gender distribution, and vascular risk burden. Individuals at genetic risk for AD by virtue of the APOE ε4 allele demonstrated increased MTL resting state CBF relative to ε4 noncarriers, whereas individuals characterized as MCI showed decreased MTL resting state CBF relative to their cognitively normal peers. For percent change CBF, there was a trend toward a cognitive status by genotype interaction. In the cognitively normal group, there was no difference in percent change CBF based on APOE genotype. In contrast, in the MCI group, APOE ε4 carriers demonstrated significantly greater percent change in CBF relative to ε4 noncarriers. No group differences were found for BOLD response. Findings suggest that abnormal resting state CBF and CBF response to memory encoding may be early indicators of brain dysfunction in individuals at risk for developing AD.

An animal model for the analysis of cochlear blood flow [corrected] disturbance and hearing threshold in vivo.

PubMed

Canis, Martin; Arpornchayanon, Warangkana; Messmer, Catalina; Suckfuell, Markus; Olzowy, Bernhard; Strieth, Sebastian

2010-02-01

Impairment of cochlear blood flow (CBF) is considered to be important in inner ear pathology. However, direct measurement of CBF is difficult and has not been investigated in combination with hearing function. Six guinea pigs were used to show feasibility of an animal model for the analysis of cochlear microcirculation by intravital microscopy in combination with investigation of the hearing threshold by brainstem response audiometry (ABR). By the application of sodium nitroprusside (SNP), CBF was increased over 30 min. Reproducibility of measurements was shown by retest measurements. Mean baseline velocity of CBF was 109 +/- 19 mum/s. Vessel diameters had a mean value of 9.4 +/- 2.7 mum. Mean hearing threshold was 19 +/- 6 dB. In response to SNP, CBF velocity increased significantly to 161 +/- 26 mum/s. Mean arterial pressure decreased significantly to 36 +/- 11 mmHg. After the end of the application, CBF velocity recovered to a minimum of 123 +/- 17 microm/s. Within the retest, CBF velocity significantly increased to a maximum of 160 +/- 31 microm/s. Second recovery of CBF velocity was 125 +/- 14 mum/s. Within the second retest, CBF increased significantly to 157 +/- 25 microm/s. ABR thresholds did not change significantly. The increase in blood flow velocity occurred in spite of substantial hypotension as induced by a vasodilator. This may explain the fact that ABR threshold remained unchanged reflecting a maintained blood supply in this part of the brain. This technique can be used to evaluate effects of treatments aimed at cochlear microcirculation in inner ear pathologies.

Effects of smoking marijuana on brain perfusion and cognition.

PubMed

O'Leary, Daniel S; Block, Robert I; Koeppel, Julie A; Flaum, Michael; Schultz, Susan K; Andreasen, Nancy C; Ponto, Laura Boles; Watkins, G Leonard; Hurtig, Richard R; Hichwa, Richard D

2002-06-01

The effects of smoking marijuana on regional cerebral blood flow (rCBF) and cognitive performance were assessed in 12 recreational users in a double-blinded, placebo-controlled study. PET with [(15)Oxygen]-labeled water ([(15)O]H(2)O) was used to measure rCBF before and after smoking of marijuana and placebo cigarettes, as subjects repeatedly performed an auditory attention task. Smoking marijuana resulted in intoxication, as assessed by a behavioral rating scale, but did not significantly alter mean behavioral performance on the attention task. Heart rate and blood pressure increased dramatically following smoking of marijuana but not placebo cigarettes. However, mean global CBF did not change significantly. Increased rCBF was observed in orbital and mesial frontal lobes, insula, temporal poles, anterior cingulate, as well as in the cerebellum. The increases in rCBF in anterior brain regions were predominantly in "paralimbic" regions and may be related to marijuana's mood-related effects. Reduced rCBF was observed in temporal lobe auditory regions, in visual cortex, and in brain regions that may be part of an attentional network (parietal lobe, frontal lobe and thalamus). These rCBF decreases may be the neural basis of perceptual and cognitive alterations that occur with acute marijuana intoxication. There was no significant rCBF change in the nucleus accumbens or other reward-related brain regions, nor in basal ganglia or hippocampus, which have a high density of cannabinoid receptors.

Effects of smoking marijuana on focal attention and brain blood flow.

PubMed

O'Leary, Daniel S; Block, Robert I; Koeppel, Julie A; Schultz, Susan K; Magnotta, Vincent A; Ponto, Laura Boles; Watkins, G Leonard; Hichwa, Richard D

2007-04-01

Using an attention task to control cognitive state, we previously found that smoking marijuana changes regional cerebral blood flow (rCBF). The present study measured rCBF during tasks requiring attention to left and right ears in different conditions. Twelve occasional marijuana users (mean age 23.5 years) were imaged with PET using [15O]water after smoking marijuana or placebo cigarettes as they performed a reaction time (RT) baseline task, and a dichotic listening task with attend-right- and attend-left-ear instructions. Smoking marijuana, but not placebo, resulted in increased normalized rCBF in orbital frontal cortex, anterior cingulate, temporal pole, insula, and cerebellum. RCBF was reduced in visual and auditory cortices. These changes occurred in all three tasks and replicated our earlier studies. They appear to reflect the direct effects of marijuana on the brain. Smoking marijuana lowered rCBF in auditory cortices compared to placebo but did not alter the normal pattern of attention-related rCBF asymmetry (i.e., greater rCBF in the temporal lobe contralateral to the direction of attention) that was also observed after placebo. These data indicate that marijuana has dramatic direct effects on rCBF, but causes relatively little change in the normal pattern of task-related rCBF on this auditory focused attention task. Copyright 2007 John Wiley & Sons, Ltd.

Quantitative measurement of cerebral blood flow in a juvenile porcine model by depth-resolved near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Elliott, Jonathan T.; Diop, Mamadou; Tichauer, Kenneth M.; Lee, Ting-Yim; Lawrence, Keith St.

2010-05-01

Nearly half a million children and young adults are affected by traumatic brain injury each year in the United States. Although adequate cerebral blood flow (CBF) is essential to recovery, complications that disrupt blood flow to the brain and exacerbate neurological injury often go undetected because no adequate bedside measure of CBF exists. In this study we validate a depth-resolved, near-infrared spectroscopy (NIRS) technique that provides quantitative CBF measurement despite significant signal contamination from skull and scalp tissue. The respiration rates of eight anesthetized pigs (weight: 16.2+/-0.5 kg, age: 1 to 2 months old) are modulated to achieve a range of CBF levels. Concomitant CBF measurements are performed with NIRS and CT perfusion. A significant correlation between CBF measurements from the two techniques is demonstrated (r2=0.714, slope=0.92, p<0.001), and the bias between the two techniques is -2.83 mL.min-1.100 g-1 (CI0.95: -19.63 mL.min-1.100 g-1-13.9 mL.min-1.100 g-1). This study demonstrates that accurate measurements of CBF can be achieved with depth-resolved NIRS despite significant signal contamination from scalp and skull. The ability to measure CBF at the bedside provides a means of detecting, and thereby preventing, secondary ischemia during neurointensive care.

Relationships between Cerebral Blood Flow and IQ in Typically Developing Children and Adolescents.

PubMed

Kilroy, Emily; Liu, Collin Y; Yan, Lirong; Kim, Yoon Chun; Dapretto, Mirella; Mendez, Mario F; Wang, Danny J J

2011-01-01

The objective of this study was to explore the relationships between IQ and cerebral blood flow (CBF) measured by arterial spin labeling (ASL) in children and adolescents. ASL was used to collect perfusion MRI data on 39 healthy participants aged 7 to 17. The Wechsler Abbreviated Intelligence Scale was administered to determine IQ scores. Multivariate regression was applied to reveal correlations between CBF and IQ scores, accounting for age, sex and global mean CBF. Voxel Based Morphometry (VBM) analysis, which measures regional cortical volume, was performed as a control. Regression analyses were further performed on CBF data with adjustment of regional gray matter density (GMD). A positive correlation between CBF and IQ scores was primarily seen in the subgenual/anterior cingulate, right orbitofrontal, superior temporal and right inferior parietal regions. An inverse relationship between CBF and IQ was mainly observed in bilateral posterior temporal regions. After adjusting for regional GMD, the correlations between CBF and IQ in the subgenual/anterior cingulate cortex, right orbitofrontal, superior temporal regions and left insula remained significant. These findings support the Parieto-Frontal Integration Theory of intelligence, especially the role of the subgenual/anterior cingulate cortex in the neural networks associated with intelligence. The present study also demonstrates the unique value of CBF in assessing brain-behavior relationships, in addition to structural morphometric measures.

Serodiagnosis of sporotrichosis infection in cats by enzyme-linked immunosorbent assay using a specific antigen, SsCBF, and crude exoantigens.

PubMed

Fernandes, Geisa Ferreira; Lopes-Bezerra, Leila Maria; Bernardes-Engemann, Andréa Reis; Schubach, Tânia Maria Pacheco; Dias, Maria Adelaide Galvão; Pereira, Sandro Antonio; de Camargo, Zoilo Pires

2011-01-27

The main objective of this study is to standardize an ELISA for the diagnosis of feline sporotrichosis. Sporothrix schenckii is the etiological agent of human and animal sporotrichosis. Cats may act as reservoirs for S. schenckii and can transmit the infection to humans by a bite or scratch. There are few methods for the serological diagnosis of fungal diseases in animals. In this paper, an ELISA test for the diagnosis of cat sporotrichosis is proposed, which detects S. schenckii-specific antibodies in feline sera. Two different kinds of antigens were used: "SsCBF", a specific molecule from S. schenckii that consists of a Con A-binding fraction derived from a peptido-rhamnomannan component of the cell wall, and a S. schenckii crude exoantigen preparation. The ELISA was developed, optimized, and evaluated using sera from 30 cats with proven sporotrichosis (by culture isolation); 22 sera from healthy feral cats from a zoonosis center were used as negative controls. SsCBF showed 90% sensitivity and 96% specificity in ELISA; while crude exoantigens demonstrated 96% sensitivity and 98% specificity. The ELISA assay described here would be a valuable screening tool for the detection of specific S. schenckii antibodies in cats with sporotrichosis. The assay is inexpensive, quick to perform, easy to interpret, and permits the diagnosis of feline sporotrichosis. Copyright © 2010 Elsevier B.V. All rights reserved.

Discrimination between patients with mild Alzheimer's disease and healthy subjects based on cerebral blood flow images of the lateral views in xenon-enhanced computed tomography.

PubMed

Sase, Shigeru; Yamamoto, Homaro; Kawashima, Ena; Tan, Xin; Sawa, Yutaka

2018-01-01

Quantitative cerebral blood flow (CBF) measurement is expected to help early detection of functional abnormalities caused by Alzheimer's disease (AD) and enable AD treatment to begin in its early stages. Recently, a technique of layer analysis was reported that allowed CBF to be analyzed from the outer to inner layers of the brain. The aim of this work was to develop methods for discriminating between patients with mild AD and healthy subjects based on CBF images of the lateral views created with the layer analysis technique in xenon-enhanced computed tomography. Xenon-enhanced computed tomography using a wide-volume CT was performed on 17 patients with mild AD aged 75 or older and on 15 healthy age-matched volunteers. For each subject, we created CBF images of the right and left lateral views with a depth of 10-15 mm from the surface of the brain. Ten circular regions of interest (ROI) were placed on each image, and CBF was calculated for each ROI. We determined discriminant ROI that had CBF that could be used to differentiate between the AD and volunteer groups. AD patients' CBF range (mean - SD to mean + SD) and healthy volunteers' CBF range (mean - SD to mean + SD) were obtained for each ROI. Receiver-operator curves were created to identify patients with AD for each of the discriminant ROI and for the AD patients' and healthy volunteers' CBF ranges. We selected an ROI on both the right and left temporal lobes as the discriminant ROI. Areas under the receiver-operator curve were 93.3% using the ROI on the right temporal lobe, 95.3% using the ROI on the left temporal lobe, and 92.4% using the AD patients' and healthy volunteers' CBF ranges. We could effectively discriminate between patients with mild AD and healthy subjects using ROI placed on CBF images of the lateral views in xenon-enhanced computed tomography. © 2017 Japanese Psychogeriatric Society.

Vascular cognitive impairment, dementia, aging and energy demand. A vicious cycle.

PubMed

Popa-Wagner, A; Buga, Ana-Maria; Popescu, B; Muresanu, D

2015-08-01

To a great extent, cognitive health depends on cerebrovascular health and a deeper understanding of the subtle interactions between cerebrovascular function and cognition is needed to protect humans from one of the most devastating affliction, dementia. However, the underlying biological mechanisms are still not completely clear. Many studies demonstrated that the neurovascular unit is compromised in cerebrovascular diseases and also in other types of dementia. The hemodynamic neurovascular coupling ensures a strong increase of the cerebral blood flow (CBF) and an acute increase in neuronal glucose uptake upon increased neural activity. Dysfunction of cerebral autoregulation with increasing age along with age-related structural and functional alterations in cerebral blood vessels including accumulation of amyloid-beta (Aβ) in the media of cortical arterioles, neurovascular uncoupling due to astrocyte endfeet retraction, impairs the CBF and increases the neuronal degeneration and susceptibility to hypoxia and ischemia. A decreased cerebral glucose metabolism is an early event in Alzheimer's disease (AD) pathology and may precede the neuropathological Aβ deposition associated with AD. Aβ accumulation in turn leads to further decreases in the CBF closing the vicious cycle. Alzheimer, aging and diabetes are also influenced by insulin/insulin-like growth factor-1 signaling, and accumulated evidence indicates sporadic AD is associated with disturbed brain insulin metabolism. Understanding how vascular and metabolic factors interfere with progressive loss of functional neuronal networks becomes essential to develop efficient drugs to prevent cognitive decline in elderly.

Induction of Dormancy in Arabidopsis Summer Annuals Requires Parallel Regulation of DOG1 and Hormone Metabolism by Low Temperature and CBF Transcription Factors[W][OA

PubMed Central

Kendall, Sarah L.; Hellwege, Anja; Marriot, Poppy; Whalley, Celina; Graham, Ian A.; Penfield, Steven

2011-01-01

Summer annuals overwinter as seeds in the soil seed bank. This is facilitated by a cold-induced increase in dormancy during seed maturation followed by a switch to a state during seed imbibition in which cold instead promotes germination. Here, we show that the seed maturation transcriptome in Arabidopsis thaliana is highly temperature sensitive and reveal that low temperature during seed maturation induces several genes associated with dormancy, including DELAY OF GERMINATION1 (DOG1), and influences gibberellin and abscisic acid levels in mature seeds. Mutants lacking DOG1, or with altered gibberellin or abscisic acid synthesis or signaling, in turn show reduced ability to enter the deeply dormant states in response to low seed maturation temperatures. In addition, we find that DOG1 promotes gibberellin catabolism during maturation. We show that C-REPEAT BINDING FACTORS (CBFs) are necessary for regulation of dormancy and of GA2OX6 and DOG1 expression caused by low temperatures. However, the temperature sensitivity of CBF transcription is markedly reduced in seeds and is absent in imbibed seeds. Our data demonstrate that inhibition of CBF expression is likely a critical feature allowing cold to promote rather than inhibit germination and support a model in which CBFs act in parallel to a low-temperature signaling pathway in the regulation of dormancy. PMID:21803937

Crenolanib is a type I tyrosine kinase inhibitor that inhibits mutant KIT D816 isoforms prevalent in systemic mastocytosis and core binding factor leukemia.

PubMed

Kampa-Schittenhelm, Kerstin Maria; Frey, Julia; Haeusser, Lara A; Illing, Barbara; Pavlovsky, Ashly A; Blumenstock, Gunnar; Schittenhelm, Marcus Matthias

2017-10-10

Activating D816 mutations of the class III receptor tyrosine kinase KIT are associated with the majority of patients with systemic mastocytosis (SM), but also core binding factor (CBF) AML, making KIT mutations attractive therapeutic targets for the treatment of these cancers. Crenolanib is a potent and selective inhibitor of wild-type as well as mutant isoforms of the class III receptor tyrosine kinases FLT3 and PDGFRα/β. Notably, crenolanib inhibits constitutively active mutant-FLT3 isoforms resulting from amino acid substitutions of aspartic acid at codon 835, which is homologous to codon 816 in the KIT gene - suggesting sensitivity against mutant-KIT D816 isoforms as well. Here we demonstrate that crenolanib targets KIT D816 in SM and CBF AML models: crenolanib inhibits cellular proliferation and initiates apoptosis of mastocytosis cell lines expressing these mutations. Target-specificity was confirmed using an isogenic cell model. In addition, we demonstrate that KIT D816 mutations are targetable with clinically achievable doses of crenolanib. Further, a rationale to combine cladribine (2-CDA), the therapeutic standard in SM, with crenolanib is provided. In conclusion, we demonstrate that crenolanib is an inhibitor of mutant-KIT D816 isoforms at clinically achievable concentrations, and thus may be a potential treatment for SM and CBF AML as a monotherapy or in combination approaches.

The Arabidopsis Mediator Complex Subunits MED16, MED14, and MED2 Regulate Mediator and RNA Polymerase II Recruitment to CBF-Responsive Cold-Regulated Genes[C][W][OPEN

PubMed Central

Hemsley, Piers A.; Hurst, Charlotte H.; Kaliyadasa, Ewon; Lamb, Rebecca; Knight, Marc R.; De Cothi, Elizabeth A.; Steele, John F.; Knight, Heather

2014-01-01

The Mediator16 (MED16; formerly termed SENSITIVE TO FREEZING6 [SFR6]) subunit of the plant Mediator transcriptional coactivator complex regulates cold-responsive gene expression in Arabidopsis thaliana, acting downstream of the C-repeat binding factor (CBF) transcription factors to recruit the core Mediator complex to cold-regulated genes. Here, we use loss-of-function mutants to show that RNA polymerase II recruitment to CBF-responsive cold-regulated genes requires MED16, MED2, and MED14 subunits. Transcription of genes known to be regulated via CBFs binding to the C-repeat motif/drought-responsive element promoter motif requires all three Mediator subunits, as does cold acclimation–induced freezing tolerance. In addition, these three subunits are required for low temperature–induced expression of some other, but not all, cold-responsive genes, including genes that are not known targets of CBFs. Genes inducible by darkness also required MED16 but required a different combination of Mediator subunits for their expression than the genes induced by cold. Together, our data illustrate that plants control transcription of specific genes through the action of subsets of Mediator subunits; the specific combination defined by the nature of the stimulus but also by the identity of the gene induced. PMID:24415770

Increased resting cerebral blood flow in adult Fabry disease: MRI arterial spin labeling study.

PubMed

Phyu, Po; Merwick, Aine; Davagnanam, Indran; Bolsover, Fay; Jichi, Fatima; Wheeler-Kingshott, Claudia; Golay, Xavier; Hughes, Deralynn; Cipolotti, Lisa; Murphy, Elaine; Lachmann, Robin H; Werring, David John

2018-04-17

To assess resting cerebral blood flow (CBF) in the whole-brain and cerebral white matter (WM) and gray matter (GM) of adults with Fabry disease (FD), using arterial spin labeling (ASL) MRI, and to investigate CBF correlations with WM hyperintensity (WMH) volume and the circulating biomarker lyso-Gb3. This cross-sectional, case-control study included 25 patients with genetically confirmed FD and 18 age-matched healthy controls. We quantified resting CBF using Quantitative Signal Targeting With Alternating Radiofrequency Labeling of Arterial Regions (QUASAR) ASL MRI. We measured WMH volume using semiautomated software. We measured CBF in regions of interest in whole-brain, WM, and deep GM, and assessed correlations with WMH volume and plasma lyso-Gb3. The mean age (% male) for FD and healthy controls was 42.2 years (44%) and 37.1 years (50%). Mean whole-brain CBF was 27.56 mL/100 mL/min (95% confidence interval [CI] 23.78-31.34) for FD vs 22.39 mL/100 mL/min (95% CI 20.08-24.70) for healthy controls, p = 0.03. In WM, CBF was higher in FD (22.42 mL/100 mL/min [95% CI 17.72-27.12] vs 16.25 mL/100 mL/min [95% CI 14.03-18.48], p = 0.05). In deep GM, CBF was similar between groups (40.41 mL/100 mL/min [95% CI 36.85-43.97] for FD vs 37.46 mL/100 mL/min [95% CI 32.57-42.35], p = 0.38). In patients with FD with WMH (n = 20), whole-brain CBF correlated with WMH volume ( r = 0.59, p = 0.006), not with plasma lyso-Gb3. In FD, resting CBF is increased in WM but not deep GM. In FD, CBF correlates with WMH, suggesting that cerebral perfusion changes might contribute to, or result from, WM injury. © 2018 American Academy of Neurology.

Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease.

PubMed

Karimi, M; Golchin, N; Tabbal, S D; Hershey, T; Videen, T O; Wu, J; Usche, J W M; Revilla, F J; Hartlein, J M; Wernle, A R; Mink, J W; Perlmutter, J S

2008-10-01

Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (r(s) = -0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (r(s) = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (r(s) = -0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease.

Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease

PubMed Central

Karimi, M.; Golchin, N.; Tabbal, S. D.; Hershey, T.; Videen, T. O.; Wu, J.; Usche, J. W. M.; Revilla, F. J.; Hartlein, J. M.; Wernle, A. R.; Mink, J. W.

2008-01-01

Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (rs = –0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (rs = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (rs = –0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor signs of Parkinson's disease. PMID:18697909

Changes of cerebral blood flow during the secondary expansion of a cortical contusion assessed by 14C-iodoantipyrine autoradiography in mice using a non-invasive protocol.

PubMed

Engel, Doortje C; Mies, Günter; Terpolilli, Nicole A; Trabold, Raimund; Loch, Alexander; De Zeeuw, Chris I; Weber, John T; Maas, Andrew I R; Plesnila, Nikolaus

2008-07-01

Although changes of cerebral blood flow (CBF) in and around traumatic contusions are well documented, the role of CBF for the delayed death of neuronal cells in the traumatic penumbra ultimately resulting in secondary contusion expansion remains unclear. The aim of the current study was therefore to investigate the relationship between changes of CBF and progressive peri-contusional cell death following traumatic brain injury (TBI). CBF and contusion size were measured in C57Bl6 mice under continuous on-line monitoring of (ETp)CO2 before, and at 15 min and 24 h following controlled cortical impact by 14C-iodoantipyrine autoradiography (IAP-AR; n = 5-6 per group) and by Nissl staining, respectively. Contused and ischemic (CBF < 10%) tissue volumes were calculated and compared over time. Cortical CBF in not injured mice varied between 69 and 93 mL/100mg/min depending on the anatomical location. Fifteen minutes after trauma, CBF decreased in the whole brain by approximately 50% (39 +/- 18 mL/100mg/min; p < 0.05), except in contused tissue where it fell by more than 90% (3 +/- 2 mL/100mg/min; p < 0.001). Within 24 h after TBI, CBF recovered to normal values in all brain areas except the contusion where it remained reduced by more than 90% (p < 0.001). Contusion volume expanded from 24.9 to 35.5 mm3 (p < 0.01) from 15 min to 24 h after trauma (+43%), whereas the area of severe ischemia (CBF < 10%) showed only a minimal (+13%) and not significant increase (22.3 to 25.1 mm3). The current data therefore suggest that the delayed secondary expansion of a cortical contusion following traumatic brain injury may not be caused by a reduction of CBF alone.

Cerebral cortical blood flow maps are reorganized in MAOB-deficient mice

PubMed Central

Scremin, Oscar U.; Holschneider, Daniel P.; Chen, Kevin; Li, Mingen G.; Shih, Jean C.

2014-01-01

Cerebral cortical blood flow (CBF) was measured autoradiographically in conscious mice without the monoamine oxidase B (MAOB) gene (KO, n = 11) and the corresponding wild-type animals (WILD, n = 11). Subgroups of animals of each genotype received a continuous intravenous infusion over 30 min of phenylethylamine (PEA), an endogenous substrate of MAOB, (8 nmol g−1 min−1 in normal saline at a volume rate of 0.11 μl g−1 min−1) or saline at the same volume rate. Maps of relative CBF distribution showed predominance of midline motor and sensory area CBF in KO mice over WILD mice that received saline. PEA enhanced CBF in lateral frontal and piriform cortex in both KO and WILD mice. These changes may reflect a differential activation due to chronic and acute PEA elevations on motor and olfactory function, as well as on the anxiogenic effects of this amine. In addition to its effects on regional CBF distribution, PEA decreased CBF globally in KO mice (range −31% to −41% decrease from control levels) with a lesser effect in WILD mice. It is concluded that MAOB may normally regulate CBF distribution and its response to blood PEA. PMID:10095040

Altered Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity in Schizophrenia.

PubMed

Zhu, Jiajia; Zhuo, Chuanjun; Xu, Lixue; Liu, Feng; Qin, Wen; Yu, Chunshui

2017-10-21

Respective changes in resting-state cerebral blood flow (CBF) and functional connectivity in schizophrenia have been reported. However, their coupling alterations in schizophrenia remain largely unknown. 89 schizophrenia patients and 90 sex- and age-matched healthy controls underwent resting-state functional MRI to calculate functional connectivity strength (FCS) and arterial spin labeling imaging to compute CBF. The CBF-FCS coupling of the whole gray matter and the CBF/FCS ratio (the amount of blood supply per unit of connectivity strength) of each voxel were compared between the 2 groups. Whole gray matter CBF-FCS coupling was decreased in schizophrenia patients relative to healthy controls. In schizophrenia patients, the decreased CBF/FCS ratio was predominantly located in cognitive- and emotional-related brain regions, including the dorsolateral prefrontal cortex, insula, hippocampus and thalamus, whereas an increased CBF/FCS ratio was mainly identified in the sensorimotor regions, including the putamen, and sensorimotor, mid-cingulate and visual cortices. These findings suggest that the neurovascular decoupling in the brain may be a possible neuropathological mechanism of schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

Regional cerebral blood flow and cerebrovascular reactivity in Alzheimer's disease and vascular dementia assessed by arterial spinlabeling magnetic resonance imaging.

PubMed

Gao, Yong-Zhe; Zhang, Jun-Jian; Liu, Hui; Wu, Guang-Yao; Xiong, Li; Shu, Min

2013-02-01

Hemodynamic disturbance in cerebral blood flow (CBF) is common in both Alzheimer's disease (AD) and vascular dementia (VaD).The aim of this study is to investigate the different patterns of regional cerebral blood flow (rCBF) change and cerebrovascular reactivity (CVR) in these two types of dementia. Mean flow velocity (MFV) of middle cerebral artery and rCBF were measured by Transcranial Doppler ultrasound (TCD) and arterial spin-labeling (ASL) magnetic resonance, separately. CVR was evaluated by MFV or rCBF change in response to 5% CO2 inhalation. The ASL results showed that, rCBF was significantly lower in both the bilateral frontal and temporal lobes in AD group and lower in left frontal and temporal white matter in patients with VaD. CVR calculated by rCBF was impaired more severely in bilateral frontal cortices in AD. Conversely, TCD tests failed to demonstrate significant difference in MFV and CVR between the two groups. It is concluded that the different patterns detected by ASL in resting rCBF change and cerebrovascular reactivity in response to carbogen inhalation may serve as a potential marker to distinguish AD and VaD.

Altered Cerebral Blood Flow Covariance Network in Schizophrenia.

PubMed

Liu, Feng; Zhuo, Chuanjun; Yu, Chunshui

2016-01-01

Many studies have shown abnormal cerebral blood flow (CBF) in schizophrenia; however, it remains unclear how topological properties of CBF network are altered in this disorder. Here, arterial spin labeling (ASL) MRI was employed to measure resting-state CBF in 96 schizophrenia patients and 91 healthy controls. CBF covariance network of each group was constructed by calculating across-subject CBF covariance between 90 brain regions. Graph theory was used to compare intergroup differences in global and nodal topological measures of the network. Both schizophrenia patients and healthy controls had small-world topology in CBF covariance networks, implying an optimal balance between functional segregation and integration. Compared with healthy controls, schizophrenia patients showed reduced small-worldness, normalized clustering coefficient and local efficiency of the network, suggesting a shift toward randomized network topology in schizophrenia. Furthermore, schizophrenia patients exhibited altered nodal centrality in the perceptual-, affective-, language-, and spatial-related regions, indicating functional disturbance of these systems in schizophrenia. This study demonstrated for the first time that schizophrenia patients have disrupted topological properties in CBF covariance network, which provides a new perspective (efficiency of blood flow distribution between brain regions) for understanding neural mechanisms of schizophrenia.

PmRunt regulated by Pm-miR-183 participates in nacre formation possibly through promoting the expression of collagen VI-like and Nacrein in pearl oyster Pinctada martensii.

PubMed

Zheng, Zhe; Du, Xiaodong; Xiong, Xinwei; Jiao, Yu; Deng, Yuewen; Wang, Qingheng; Huang, Ronglian

2017-01-01

Heterodimeric PEBP2/CBFs are key regulators in diverse biological processes, such as haematopoietic stem-cell generation, bone formation and cancers. In this work, we cloned runt-like transcriptional factor (designated as PmRunt) and CBF β (designated as PmCBF) gene, which comprise the heterodimeric transcriptional factor in Pinctada martensii. PmRunt was identified with an open reading frame that encodes 545 amino acids and has typical Runt domain. Phylogenetic analysis results speculated that runt-like transcriptional factors (RDs) in vertebrates and invertebrates are separated into two branches. In molluscs, PmRunt and other RDs are clustered in one of these branches. Direct interaction between PmRunt and PmCBF was evidenced by yeast two-hybrid assay results. Gene repression by RNA interference decreased the expression level of PmRunt, and subsequent observation of the inner surface of the nacre by scanning electron microscopy demonstrated disordered growth. The luciferase activities of reporters that contain promoter regions of Collagen VI-like (PmColVI) and PmNacrein were enhanced by PmRunt. Meanwhile, Pm-miR-183 apparently inhibited the relative luciferase activity of reporters containing the 3'-UTR of PmRunt. The expression level of PmRunt was repressed after Pm-miR-183 was overexpressed in the mantle tissue. Therefore, we proposed that PmRunt could be targeted by Pm-miR-183 and regulate the transcription of PmColVI and PmNacrein by increasing their transcriptional activity, thereby governing nacre formation.

Nitric oxide synthase inhibition depresses the height of the cerebral blood flow-pressure autoregulation curve during moderate hypotension.

PubMed

Jones, Stephen C; Easley, Kirk A; Radinsky, Carol R; Chyatte, Douglas; Furlan, Anthony J; Perez-Trepichio, Alejandro D

2003-09-01

Variations in the height of the CBF response to hypotension have been described recently in normal animals. The authors evaluated the effects of nitric oxide synthase (NOS) inhibition on these variations in height using laser Doppler flowmetry in 42 anesthetized (halothane and N2O) male Sprague-Dawley rats prepared with a superfused closed cranial window. In four groups (time control, enantiomer control, NOS inhibition, and reinfusion control) exsanguination to MABPs from 100 to 40 mm Hg was used to produce autoregulatory curves. For each curve the lower limit of autoregulation (the MABP at the first decrease in CBF) was identified; the pattern of autoregulation was classified as "peak" (15% increase in %CBF), "classic" (plateau with a decrease at the lower limit of autoregulation), or "none" (15% decrease in %CBF); and the autoregulatory height as the %CBF at 70 mm Hg (%CBF(70)) was determined. NOS inhibition decreased %CBF(70) in the NOS inhibition group (P = 0.014), in the control (combined time and enantiomer control) group (P = 0.015), and in the reinfusion control group (P = 0.025). NOS inhibition via superfusion depressed the autoregulatory pattern (P = 0.02, McNemar test on changes in autoregulatory pattern) compared with control (P = 0.375). Analysis of covariance showed that changes induced by NOS inhibition in the parameters of autoregulatory height are not related to changes in the lower limit, but are strongly (P < 0.001) related to each other. NOS inhibition depressed the autoregulatory pattern, decreasing the seemingly paradoxical increase in CBF as blood pressure decreases. These results suggest that nitric oxide increases CBF near the lower limit and augments the hypotensive portion of the autoregulatory curve.

Variation of Ciliary Beat Pattern in Three Different Beating Planes in Healthy Subjects.

PubMed

Kempeneers, Celine; Seaton, Claire; Chilvers, Mark A

2017-05-01

Digital high-speed video microscopy (DHSV) allows analysis of ciliary beat frequency (CBF) and ciliary beat pattern (CBP) of respiratory cilia in three planes. Normal reference data use a sideways edge to evaluate ciliary dyskinesia and calculate CBF using the time needed for a cilium to complete 10 beat cycles. Variability in CBF within the respiratory epithelium has been described, but data concerning variation of CBP is limited in healthy epithelium. This study aimed to document variability of CBP in normal samples, to compare ciliary function in three profiles, and to compare CBF calculated over five or 10 beat cycles. Nasal brushing samples from 13 healthy subjects were recorded using DHSV in three profiles. CBP and CBF over a 10-beat cycle were evaluated in all profiles, and CBF was reevaluated over five-beat cycles in the sideways edges. A uniform CBP was seen in 82.1% of edges. In the sideways profile, uniformity within the edge was lower (uniform normal CBP, 69.1% [sideways profile]; 97.1% [toward the observer], 92.0% [from above]), and dyskinesia was higher. Interobserver agreement for dyskinesia was poor. CBF was not different between profiles (P = .8097) or between 10 and five beat cycles (P = .1126). Our study demonstrates a lack of uniformity and consistency in manual CBP analysis of samples from healthy subjects, emphasizing the risk of automated CBP analysis in limited regions of interest and of single and limited manual CBP analysis. The toward the observer and from above profiles may be used to calculate CBF but may be less sensitive for evaluation of ciliary dyskinesia and CBP. CBF can be measured reliably by evaluation of only five-beat cycles. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Effect of K+ATP channel and adenosine receptor blockade during rest and exercise in congestive heart failure.

PubMed

Traverse, Jay H; Chen, YingJie; Hou, MingXiao; Li, Yunfang; Bache, Robert J

2007-06-08

K(+)(ATP) channels are important metabolic regulators of coronary blood flow (CBF) that are activated in the setting of reduced levels of ATP or perfusion pressure. In the normal heart, blockade of K(+)(ATP) channels results in a approximately 20% reduction in resting CBF but does not impair the increase in CBF that occurs during exercise. In contrast, adenosine receptor blockade fails to alter CBF or myocardial oxygen consumption (MVO(2)) in the normal heart but contributes to the increase in CBF during exercise when vascular K(+)(ATP) channels are blocked. Congestive heart failure (CHF) is associated with a decrease in CBF that is matched to a decrease in MVO(2) suggesting downregulation of myocardial energy utilization. Because myocardial ATP levels and coronary perfusion pressure are reduced in CHF, this study was undertaken to examine the role of K(+)(ATP) channels and adenosine in dogs with pacing-induced CHF. Myocardial blood flow (MBF) and MVO(2) were measured during rest and treadmill exercise before and after K(+)(ATP) channel blockade with glibenclamide (50 microg/kg/min ic) or adenosine receptor blockade with 8-phenyltheophylline (8-PT; 5 mg/kg iv). Inhibition of K(+)(ATP) channels resulted in a decrease in CBF and MVO(2) at rest and during exercise without a change in the relationship between CBF and MVO(2). In contrast, adenosine receptor blockade caused a significant increase in CBF that occurred secondary to an increase of MVO(2). These findings demonstrate that coronary K(+)(ATP) channel activity contribute to the regulation of resting MBF in CHF, and that endogenous adenosine may act to inhibit MVO(2) in the failing heart.

Resting-state regional cerebral blood flow during adolescence: associations with initiation of substance use and prediction of future use disorders.

PubMed

Ramage, Amy E; Lin, Ai-Ling; Olvera, Rene L; Fox, Peter T; Williamson, Douglas E

2015-04-01

Adolescence is a period of developmental flux when brain systems are vulnerable to influences of early substance use, which in turn relays increased risk for substance use disorders. Our study intent was to assess adolescent regional cerebral blood flow (rCBF) as it relates to current and future alcohol use. The aim was to identify brain-based predictors for initiation of alcohol use and onset of future substance use disorders. Quantitative rCBF was assessed in 100 adolescents (age 12-15). Prospective behavioral assessments were conducted annually over a three-year follow-up period to characterize onset of alcohol initiation, future drinking patterns and use disorders. Comparisons amongst use groups (i.e., current-, future-, and non-alcohol using adolescents) identified rCBF associated with initiation of alcohol use. Regression by future drinking patterns identified rCBF predictive of heavier drinking. Survival analysis determined whether or not baseline rCBF predicted later development of use disorders. Baseline rCBF was decreased to the parietal cortex and increased to mesolimbic regions in adolescents currently using alcohol as well as those who would use alcohol in the future. Higher baseline rCBF to the left fusiform gyrus and lower rCBF to the right inferior parietal cortex and left cerebellum was associated with future drinking patterns as well as predicted the onset of alcohol and substance use disorders in this cohort. Variations in resting rCBF to regions within reward and default mode or control networks appear to represent trait markers of alcohol use initiation and are predictive of future development of use disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Distinct genetic alteration profiles of acute myeloid leukemia between Caucasian and Eastern Asian population.

PubMed

Wei, Hui; Wang, Ying; Zhou, Chunlin; Lin, Dong; Liu, Bingcheng; Liu, Kaiqi; Qiu, Shaowei; Gong, Benfa; Li, Yan; Zhang, Guangji; Wei, Shuning; Gong, Xiaoyuan; Liu, Yuntao; Zhao, Xingli; Gu, Runxia; Mi, Yingchang; Wang, Jianxiang

2018-02-10

Racial and ethnic disparities in malignancies attract extensive attention. To investigate whether there are racial and ethnic disparities in genetic alteration between Caucasian and Eastern Asian population, data from several prospective AML trials were retrospectively analyzed in this study. We found that there were more patients with core binding factor (CBF) leukemia in Eastern Asian cohorts and there were different CBF leukemia constitutions between them. The ratios of CBF leukemia are 27.7, 22.1, 21.1, and 23.4%, respectively, in our (ChiCTR-TRC-10001202), another Chinese, Korean, and Japanese Eastern Asian cohorts, which are significantly higher than those in ECOG1900, MRC AML15, UK NCRI AML17, HOVON/SAKK AML-42, and German AML2003 (15.5, 12.5, 9.3, 10.2, and 12%, respectively). And CBFbeta-MYH11 occurred more prevalently in HOVON/SAKK AML- 42 and ECOG1900 trials (50.0 and 54.3% of CBF leukemia, respectively) than in Chinese and Japanese trials (20.1 and 20.8%, respectively). The proportion of FLT3-ITD mutation is 11.2% in our cohort, which is lower than that in MRC AML15 and UK NCRI AML17 (24.6 and 17.9%, respectively). Even after excluding the age bias, there are still different incidence rates of mutation between Caucasian and Eastern Asian population. These data suggest that there are racial and ethnic disparities in genetic alteration between Caucasian and Eastern Asian population.

Regional cerebral blood flow in Parkinson disease with nonpsychotic visual hallucinations.

PubMed

Oishi, N; Udaka, F; Kameyama, M; Sawamoto, N; Hashikawa, K; Fukuyama, H

2005-12-13

Patients with Parkinson disease (PD) often experience visual hallucinations (VH) with retained insight (nonpsychotic) but the precise mechanism remains unclear. To clarify which neural substrates participate in nonpsychotic VH in PD, the authors evaluated regional cerebral blood flow (rCBF) changes in patients with PD and VH. The authors compared 24 patients with PD who had nonpsychotic VH (hallucinators) and 41 patients with PD who had never experienced VH (non-hallucinators) using SPECT images with N-isopropyl-p-[(123)I]iodoamphetamine. There were no significant differences in age, sex, duration of disease, doses of PD medications, Hoehn and Yahr scale, or Mini-Mental State Examination (MMSE) scores between the two groups. The rCBF data were analyzed using statistical parametric mapping (SPM). The rCBF in the right fusiform gyrus was lower in the hallucinators than in the non-hallucinators (corrected p < 0.05 at cluster levels). The hallucinators revealed higher rCBF in the right superior and middle temporal gyri than the non-hallucinators (uncorrected p < 0.001). These significant differences were demonstrated after MMSE scores and duration of disease, which are the relevant factors associated with VH, were covariated out. Nonpsychotic visual hallucinations in Parkinson disease (PD) may be associated with hypoperfusion in the right fusiform gyrus and hyperperfusion in the right superior and middle temporal gyri. These temporal regions are important for visual object recognition and these regional cerebral blood flow changes are associated with inappropriate visual processing and are responsible for nonpsychotic visual hallucinations in PD.

Enhancement of automated blood flow estimates (ENABLE) from arterial spin-labeled MRI.

PubMed

Shirzadi, Zahra; Stefanovic, Bojana; Chappell, Michael A; Ramirez, Joel; Schwindt, Graeme; Masellis, Mario; Black, Sandra E; MacIntosh, Bradley J

2018-03-01

To validate a multiparametric automated algorithm-ENhancement of Automated Blood fLow Estimates (ENABLE)-that identifies useful and poor arterial spin-labeled (ASL) difference images in multiple postlabeling delay (PLD) acquisitions and thereby improve clinical ASL. ENABLE is a sort/check algorithm that uses a linear combination of ASL quality features. ENABLE uses simulations to determine quality weighting factors based on an unconstrained nonlinear optimization. We acquired a set of 6-PLD ASL images with 1.5T or 3.0T systems among 98 healthy elderly and adults with mild cognitive impairment or dementia. We contrasted signal-to-noise ratio (SNR) of cerebral blood flow (CBF) images obtained with ENABLE vs. conventional ASL analysis. In a subgroup, we validated our CBF estimates with single-photon emission computed tomography (SPECT) CBF images. ENABLE produced significantly increased SNR compared to a conventional ASL analysis (Wilcoxon signed-rank test, P < 0.0001). We also found the similarity between ASL and SPECT was greater when using ENABLE vs. conventional ASL analysis (n = 51, Wilcoxon signed-rank test, P < 0.0001) and this similarity was strongly related to ASL SNR (t = 24, P < 0.0001). These findings suggest that ENABLE improves CBF image quality from multiple PLD ASL in dementia cohorts at either 1.5T or 3.0T, achieved by multiparametric quality features that guided postprocessing of dementia ASL. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:647-655. © 2017 International Society for Magnetic Resonance in Medicine.

Decreased cerebral blood flow of the right anterior cingulate cortex in long-term and short-term abstinent methamphetamine users.

PubMed

Hwang, Jaeuk; Lyoo, In Kyoon; Kim, Seog Ju; Sung, Young Hoon; Bae, Soojeong; Cho, Sung-Nam; Lee, Ho Young; Lee, Dong Soo; Renshaw, Perry F

2006-04-28

The aim of the current study was to explore changes of relative regional cerebral blood flow (rCBF) in short-term and long-term abstinent methamphetamine (MA) users. Relative rCBF in 40 abstinent MA users and 23 healthy comparison subjects was compared by the technetium-99m-hexamethyl-propylene amine oxime ((99m)Tc-HMPAO) single photon emission computed tomography (SPECT). Relative rCBF in areas that were found to differ significantly was also compared in groups of MA users with short-term (<6 months) and long-term (>or=6 months) abstinence. MA users showed decreased relative rCBF in the right anterior cingulate cortex (Brodmann area 32) relative to healthy comparison subjects. Long-term abstinent MA users had significantly greater rCBF than short-term abstinent MA users. We report that abstinent MA users have decreased rCBF in the anterior cingulate cortex with smaller relative decreases in subjects with prolonged abstinence.

Assessment of cerebral blood flow autoregulation (CBF AR) with rheoencephalography (REG): studies in animals

NASA Astrophysics Data System (ADS)

Popovic, Djordje; Bodo, Michael; Pearce, Frederick; van Albert, Stephen; Garcia, Alison; Settle, Tim; Armonda, Rocco

2013-04-01

The ability of cerebral vasculature to regulate cerebral blood flow (CBF) in the face of changes in arterial blood pressure (SAP) or intracranial pressure (ICP) is an important guard against secondary ischemia in acute brain injuries, and official guidelines recommend that therapeutic decisions be guided by continuous monitoring of CBF autoregulation (AR). The common method for CBF AR monitoring, which rests on real-time derivation of the correlation coefficient (PRx) between slow oscillations in SAP and ICP is, however, rarely used in clinical practice because it requires invasive ICP measurements. This study investigated whether the correlation coefficient between SAP and the pulsatile component of the non-invasive transcranial bioimpedance signal (rheoencephalography, REG) could be used to assess the state and lower limit of CBF AR. The results from pigs and rhesus macaques affirm the utility of REG; however, additional animal and clinical studies are warranted to assess selectivity of automatic REG-based evaluation of CBF AR.

Aberrant Cerebral Blood Flow in Response to Hunger and Satiety in Women Remitted from Anorexia Nervosa

PubMed Central

Wierenga, Christina E.; Bischoff-Grethe, Amanda; Rasmusson, Grace; Bailer, Ursula F.; Berner, Laura A.; Liu, Thomas T.; Kaye, Walter H.

2017-01-01

The etiology of pathological eating in anorexia nervosa (AN) remains poorly understood. Cerebral blood flow (CBF) is an indirect marker of neuronal function. In healthy adults, fasting increases CBF, reflecting increased delivery of oxygen and glucose to support brain metabolism. This study investigated whether women remitted from restricting-type AN (RAN) have altered CBF in response to hunger that may indicate homeostatic dysregulation contributing to their ability to restrict food. We compared resting CBF measured with pulsed arterial spin labeling in 21 RAN and 16 healthy comparison women (CW) when hungry (after a 16-h fast) and after a meal. Only remitted subjects were examined to avoid the confounding effects of malnutrition on brain function. Compared to CW, RAN demonstrated a reduced difference in the Hungry − Fed CBF contrast in the right ventral striatum, right subgenual anterior cingulate cortex (pcorr < 0.05) and left posterior insula (punc < 0.05); RAN had decreased CBF when hungry versus fed, whereas CW had increased CBF when hungry versus fed. Moreover, decreased CBF when hungry in the left insula was associated with greater hunger ratings on the fasted day for RAN. This represents the first study to show that women remitted from AN have aberrant resting neurovascular function in homeostatic neural circuitry in response to hunger. Regions involved in homeostatic regulation showed group differences in the Hungry − Fed contrast, suggesting altered cellular energy metabolism in this circuitry that may reduce motivation to eat. PMID:28770207

Aberrant Cerebral Blood Flow in Response to Hunger and Satiety in Women Remitted from Anorexia Nervosa.

PubMed

Wierenga, Christina E; Bischoff-Grethe, Amanda; Rasmusson, Grace; Bailer, Ursula F; Berner, Laura A; Liu, Thomas T; Kaye, Walter H

2017-01-01

The etiology of pathological eating in anorexia nervosa (AN) remains poorly understood. Cerebral blood flow (CBF) is an indirect marker of neuronal function. In healthy adults, fasting increases CBF, reflecting increased delivery of oxygen and glucose to support brain metabolism. This study investigated whether women remitted from restricting-type AN (RAN) have altered CBF in response to hunger that may indicate homeostatic dysregulation contributing to their ability to restrict food. We compared resting CBF measured with pulsed arterial spin labeling in 21 RAN and 16 healthy comparison women (CW) when hungry (after a 16-h fast) and after a meal. Only remitted subjects were examined to avoid the confounding effects of malnutrition on brain function. Compared to CW, RAN demonstrated a reduced difference in the Hungry - Fed CBF contrast in the right ventral striatum, right subgenual anterior cingulate cortex ( p corr  < 0.05) and left posterior insula ( p unc  < 0.05); RAN had decreased CBF when hungry versus fed, whereas CW had increased CBF when hungry versus fed. Moreover, decreased CBF when hungry in the left insula was associated with greater hunger ratings on the fasted day for RAN. This represents the first study to show that women remitted from AN have aberrant resting neurovascular function in homeostatic neural circuitry in response to hunger. Regions involved in homeostatic regulation showed group differences in the Hungry - Fed contrast, suggesting altered cellular energy metabolism in this circuitry that may reduce motivation to eat.

Fiber optic laser light scattering measurement of ciliary function of the fallopian tube

NASA Astrophysics Data System (ADS)

Halbert, Sheridan A.; Lim, Kap; Lee, Wylie I.

1990-07-01

A fiber-optic laser light-scattering system (FLS) for measuring ciliary function was evaluated by means of three sets of in vitro experiments. First, FLS performance was compared to that of a previously proven benchtop laser system (BLS). Using tissue excised from rabbit fallopian tubes, ciliary beat frequency (CBF) of each sample was measured with FLS and BLS. Paired CBF measurements showed excellent correlation between the two systems (r =0.93). Second, the FLS was used to evaluate the dependency of CBF on temperature (T) by using tissue sampies of rabbit oviductal fimbna. Regression analysis of CBF vs T showed a linear relationship over the range of 18-37°C for both individual samples (r =0.98) and pooled data from all experiments (r = 0.84). Fmally, the relalionship between CBF and ciliary ovum transport rate (TR) was tested by using T to modulate CBF of rabbit fimbria, in vitro. The relationship was linear over the range of CBF from 10 to 30 Hz (r2 = 0.83). At 37°C, CBF = 31+/-1 Hz, and TR = O.12+/-.02 mm/sec. equal to ovum transport rate in situ. The FLS is a valuable tool for characterizing ciliary activity and thus ovum transport function. Owing to the fact that ciliary dyskinesia resulting from disease of the fallopian tube is associated with infeitility, the FLS may be useful to acquire data important to the clinical evaluation of fallopian tube function and female infertility.

Exercise intensity modulates the change in cerebral blood flow following aerobic exercise in chronic stroke.

PubMed

Robertson, Andrew D; Crane, David E; Rajab, A Saeed; Swardfager, Walter; Marzolini, Susan; Shirzadi, Zahra; Middleton, Laura E; MacIntosh, Bradley J

2015-08-01

The mechanisms supporting functional improvement by aerobic exercise following stroke remain incompletely understood. This study investigated how cycling intensity and aerobic fitness influence cerebral blood flow (CBF) following a single exercise session. Thirteen community-living stroke survivors performed 20 min of semi-recumbent cycling at low and moderate intensities (40-50 and 60-70 % of heart rate reserve, respectively) as determined from an exercise stress test. CBF was quantified by arterial spin labeling MRI at baseline, as well as 30 and 50 min post-exercise. An intensity-dependent effect was observed in the right post-central and supramarginal gyri up to 50 min after exercise (uncorrected p < 0.005, cluster size ≥10). Regional CBF was increased 18 ± 17 % and reduced 8 ± 12 % following moderate- and low-intensity cycling, respectively. In contrast, CBF changes were similar between sessions in the right lentiform nucleus and mid-frontal gyrus, as well as the left temporal and parietal gyri. Aerobic fitness was directly related to posterior cingulate and thalamic CBF, and inversely related to precuneal CBF at rest (R (2) ≥ 0.75); however, no relationship between fitness and the post-exercise change in CBF was observed. Divergent changes in regional CBF were observed in the right parietal cortex following low- and moderate-intensity exercise, which suggests that intensity of prescribed exercise may be useful in optimizing rehabilitation.

Preoperative regional cerebral blood flow and postoperative clinical improvement in patients with Parkinson's disease undergoing subthalamic nucleus deep brain stimulation.

PubMed

Nagai, Toshiya; Kajita, Yasukazu; Maesawa, Satoshi; Nakatsubo, Daisuke; Yoshida, Kota; Kato, Katsuhiko; Wakabayashi, Toshihiko

2012-01-01

Preoperative regional cerebral blood flow (rCBF) was measured in 92 patients with Parkinson's disease (PD) by iodine-123 N-isopropyl-p-iodoamphetamine single-photon emission computed tomography. Quantitative mapping of rCBF was performed using the stereotactic extraction estimation method. The clinical features of the patients were assessed according to the Unified Parkinson Disease Rating Scale (UPDRS). The correlation between rCBF and improvement in the UPDRS score following surgery was examined. rCBF in the fusiform gyrus, superior and inferior parietal gyri, middle occipital gyrus, superior frontal gyrus, and middle temporal gyrus of the Talairach Daemon Level 3 was significantly correlated with UPDRS part II (off stage) and III (on stage) scores (p < 0.05). rCBF in the middle temporal gyrus (p = 0.00147), medial frontal gyrus (p = 0.00713), and cerebellum (p = 0.048) of the Talairach Daemon Level 3 was significantly greater in 47 patients with >60% improvement of UPDRS part III (off stage) score than in 37 patients with 40-60% improvement. The cutoff value of rCBF, which indicated that >40% improvement in the surgical outcome could be expected, was 38.8 ± 6.2 ml/100 g/min in the frontal lobe. This study indicated that rCBF in patients with PD might be related to their clinical features, suggesting that quantitative mapping of rCBF may be useful for predicting surgical outcome.

Priming within and across modalities: exploring the nature of rCBF increases and decreases.

PubMed

Badgaiyan, R D; Schacter, D L; Alpert, N M

2001-02-01

Neuroimaging studies suggest that within-modality priming is associated with reduced regional cerebral blood flow (rCBF) in the extrastriate area, whereas cross-modality priming is associated with increased rCBF in prefrontal cortex. To characterize the nature of rCBF changes in within- and cross-modality priming, we conducted two neuroimaging experiments using positron emission tomography (PET). In experiment 1, rCBF changes in within-modality auditory priming on a word stem completion task were observed under same- and different-voice conditions. Both conditions were associated with decreased rCBF in extrastriate cortex. In the different-voice condition there were additional rCBF changes in the middle temporal gyrus and prefrontal cortex. Results suggest that the extrastriate involvement in within-modality priming is sensitive to a change in sensory modality of target stimuli between study and test, but not to a change in the feature of a stimulus within the same modality. In experiment 2, we studied cross-modality priming on a visual stem completion test after encoding under full- and divided-attention conditions. Increased rCBF in the anterior prefrontal cortex was observed in the full- but not in the divided-attention condition. Because explicit retrieval is compromised after encoding under the divided-attention condition, prefrontal involvement in cross-modality priming indicates recruitment of an aspect of explicit retrieval mechanism. The aspect of explicit retrieval that is most likely to be involved in cross-modality priming is the familiarity effect. Copyright 2001 Academic Press.

Cerebral blood flow in normal and abnormal sleep and dreaming

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, J.S.; Ishikawa, Y.; Hata, T.

Measurements of regional or local cerebral blood flow (CBF) by the xenon-133 inhalation method and stable xenon computerized tomography CBF (CTCBF) method were made during relaxed wakefulness and different stages of REM and non-REM sleep in normal age-matched volunteers, narcoleptics, and sleep apneics. In the awake state, CBF values were reduced in both narcoleptics and sleep apneics in the brainstem and cerebellar regions. During sleep onset, whether REM or stage I-II, CBF values were paradoxically increased in narcoleptics but decreased severely in sleep apneics, while in normal volunteers they became diffusely but more moderately decreased. In REM sleep and dreamingmore » CBF values greatly increased, particularly in right temporo-parietal regions in subjects experiencing both visual and auditory dreaming.« less

Acute marijuana effects on rCBF and cognition: a PET study.

PubMed

O'Leary, D S; Block, R I; Flaum, M; Schultz, S K; Boles Ponto, L L; Watkins, G L; Hurtig, R R; Andreasen, N C; Hichwa, R D

2000-11-27

The effects of smoking marijuana on cognition and brain function were assessed with PET using H2(15)O. Regional cerebral blood flow (rCBF) was measured in five recreational users before and after smoking a marijuana cigarette, as they repeatedly performed an auditory attention task. Blood flow increased following smoking in a number of paralimbic brain regions (e.g. orbital frontal lobes, insula, temporal poles) and in anterior cingulate and cerebellum. Large reductions in rCBF were observed in temporal lobe regions that are sensitive to auditory attention effects. Brain regions showing increased rCBF may mediate the intoxicating and mood-related effects of smoking marijuana, whereas reduction of task-related rCBF in temporal lobe cortices may account for the impaired cognitive functions associated with acute intoxication.

The effects of poststroke captopril and losartan treatment on cerebral blood flow autoregulation in SHRsp with hemorrhagic stroke.

PubMed

Smeda, John S; Daneshtalab, Noriko

2011-02-01

The ability of captopril and losartan treatment to restore cerebral blood flow (CBF) autoregulation after intracerebral hemorrhagic stroke (HS) was assessed in Kyoto-Wistar stroke-prone hypertensive rats (SHRsp). Laser Doppler techniques assessed CBF autoregulation in the middle cerebral artery (MCA) perfusion domain and a pressure myograph was used to measure pressure-dependent constriction (PDC) in isolated MCAs before and after stroke and after 13, 33, and 63 days of poststroke captopril or losartan treatment. The treatments did not lower blood pressure (BP) and equally suppressed plasma aldosterone after HS. The HS development was associated with the loss of CBF autoregulation, high CBF, increased CBF conductance to elevations in BP, and the loss of PDC in the MCAs. Both treatments restored these functions to prestroke levels within 13 days. The PDC and CBF autoregulation subsequently deteriorated after 63 days of captopril treatment while being maintained at prestroke levels over all durations of losartan treatment. The SHRsp subjected to 35 days of poststroke losartan treatment exhibited less blood-brain barrier (BBB) disruption and brain herniation than captopril-treated SHRsp. The superior ability of losartan to restore CBF autoregulation and myogenic function may have contributed to the more effective attenuation of cerebral damage after HS.

The effects of poststroke captopril and losartan treatment on cerebral blood flow autoregulation in SHRsp with hemorrhagic stroke

PubMed Central

Smeda, John S; Daneshtalab, Noriko

2011-01-01

The ability of captopril and losartan treatment to restore cerebral blood flow (CBF) autoregulation after intracerebral hemorrhagic stroke (HS) was assessed in Kyoto–Wistar stroke-prone hypertensive rats (SHRsp). Laser Doppler techniques assessed CBF autoregulation in the middle cerebral artery (MCA) perfusion domain and a pressure myograph was used to measure pressure-dependent constriction (PDC) in isolated MCAs before and after stroke and after 13, 33, and 63 days of poststroke captopril or losartan treatment. The treatments did not lower blood pressure (BP) and equally suppressed plasma aldosterone after HS. The HS development was associated with the loss of CBF autoregulation, high CBF, increased CBF conductance to elevations in BP, and the loss of PDC in the MCAs. Both treatments restored these functions to prestroke levels within 13 days. The PDC and CBF autoregulation subsequently deteriorated after 63 days of captopril treatment while being maintained at prestroke levels over all durations of losartan treatment. The SHRsp subjected to 35 days of poststroke losartan treatment exhibited less blood–brain barrier (BBB) disruption and brain herniation than captopril-treated SHRsp. The superior ability of losartan to restore CBF autoregulation and myogenic function may have contributed to the more effective attenuation of cerebral damage after HS. PMID:20648036

Automatic and Reproducible Positioning of Phase-Contrast MRI for the Quantification of Global Cerebral Blood Flow

PubMed Central

Liu, Peiying; Lu, Hanzhang; Filbey, Francesca M.; Pinkham, Amy E.; McAdams, Carrie J.; Adinoff, Bryon; Daliparthi, Vamsi; Cao, Yan

2014-01-01

Phase-Contrast MRI (PC-MRI) is a noninvasive technique to measure blood flow. In particular, global but highly quantitative cerebral blood flow (CBF) measurement using PC-MRI complements several other CBF mapping methods such as arterial spin labeling and dynamic susceptibility contrast MRI by providing a calibration factor. The ability to estimate blood supply in physiological units also lays a foundation for assessment of brain metabolic rate. However, a major obstacle before wider applications of this method is that the slice positioning of the scan, ideally placed perpendicular to the feeding arteries, requires considerable expertise and can present a burden to the operator. In the present work, we proposed that the majority of PC-MRI scans can be positioned using an automatic algorithm, leaving only a small fraction of arteries requiring manual positioning. We implemented and evaluated an algorithm for this purpose based on feature extraction of a survey angiogram, which is of minimal operator dependence. In a comparative test-retest study with 7 subjects, the blood flow measurement using this algorithm showed an inter-session coefficient of variation (CoV) of . The Bland-Altman method showed that the automatic method differs from the manual method by between and , for of the CBF measurements. This is comparable to the variance in CBF measurement using manually-positioned PC MRI alone. In a further application of this algorithm to 157 consecutive subjects from typical clinical cohorts, the algorithm provided successful positioning in 89.7% of the arteries. In 79.6% of the subjects, all four arteries could be planned using the algorithm. Chi-square tests of independence showed that the success rate was not dependent on the age or gender, but the patients showed a trend of lower success rate (p = 0.14) compared to healthy controls. In conclusion, this automatic positioning algorithm could improve the application of PC-MRI in CBF quantification. PMID:24787742

Activation of anterior paralimbic structures during guilt-related script-driven imagery.

PubMed

Shin, L M; Dougherty, D D; Orr, S P; Pitman, R K; Lasko, M; Macklin, M L; Alpert, N M; Fischman, A J; Rauch, S L

2000-07-01

Several recent neuroimaging studies have examined the neuroanatomical correlates of normal emotional states, such as happiness, sadness, fear, anger, anxiety, and disgust; however, no previous study has examined the emotional state of guilt. In the current study, we used positron emission tomography and the script-driven imagery paradigm to study regional cerebral blood flow (rCBF) during the transient emotional experience of guilt in eight healthy male participants. In the Guilt condition, participants recalled and imagined participating in a personal event involving the most guilt they had ever experienced. In the Neutral condition, participants recalled and imagined participating in an emotionally neutral personal event. In the Guilt versus Neutral comparison, rCBF increases occurred in anterior paralimbic regions of the brain: bilateral anterior temporal poles, anterior cingulate gyrus, and left anterior insular cortex/inferior frontal gyrus. These results, along with those of previous studies, are consistent with the notion that anterior paralimbic regions of the brain mediate negative emotional states in healthy individuals.

Complementation of Human Papillomavirus Type 16 E6 and E7 by Jagged1-Specific Notch1-Phosphatidylinositol 3-Kinase Signaling Involves Pleiotropic Oncogenic Functions Independent of CBF1;Su(H);Lag-1 Activation†

PubMed Central

Veeraraghavalu, Karthikeyan; Subbaiah, Vanitha K.; Srivastava, Sweta; Chakrabarti, Oishee; Syal, Ruchi; Krishna, Sudhir

2005-01-01

We have analyzed the induction and role of phosphatidylinositol 3-kinase (PI3K) by Notch signaling in human papillomavirus (HPV)-derived cancers. Jagged1, in contrast to Delta1, is preferentially upregulated in human cervical tumors. Jagged1 and not Delta1 expression sustained in vivo tumors by HPV16 oncogenes in HaCaT cells. Further, Jagged1 expression correlates with the rapid induction of PI3K-mediated epithelial-mesenchymal transition in both HaCaT cells and a human cervical tumor-derived cell line, suggestive of Delta1;Serrate/Jagged;Lag2 ligand-specific roles. Microarray analysis and dominant-negatives reveal that Notch-PI3K oncogenic functions can be independent of CBF1;Su(H);Lag-1 activation and instead relies on Deltex1, an alternative Notch effector. PMID:15919944

Resistance Training Augments Cerebral Blood Flow Pulsatility: Cross-Sectional Study.

PubMed

Nakamura, Nobuhiro; Muraoka, Isao

2018-06-11

Increased central arterial stiffness and/or decreased compliance reduces buffer function and increases cerebral blood flow (CBF) pulsatility, which leads to increased cerebral microvascular damage, resulting in the augmentation of the risk of cerebrovascular diseases. Resistance-trained men showed higher central arterial stiffness and lower arterial compliance than age-matched, sedentary men. This study examined the effect of increased central arterial stiffness and/or decreased arterial compliance on CBF pulsatility. The study participants included 31 young healthy men (15 resistance-trained men, aged 21 ± 1 years; and 16 controls, aged 23 ± 1 years). β-Stiffness index and arterial compliance were measured in the right carotid artery as index of central arterial stiffness and compliance, respectively. The pulsatility index (PI) was measured in the middle cerebral artery as index of CBF pulsatility. β-Stiffness index and PI were significantly higher in the resistance-trained group than in the control group (β-stiffness index: 5.3 ± 0.3 vs. 3.5 ± 0.3 a.u., P < 0.05, PI: 0.80 ± 0.02 vs. 0.70 ± 0.02, P < 0.05). The resistance-trained group showed significantly lower arterial compliance than the control group (0.16 ± 0.01 vs. 0.23 ± 0.01 mm2/mm Hg, P < 0.05). Positive and negative correlations were observed between β-stiffness index and PI (r = 0.39, P < 0.05), and between arterial compliance and PI (r = -0.59, P < 0.05), respectively. The resistance-trained group showed higher central arterial stiffness and PI and lower arterial compliance. Central arterial stiffness and arterial compliance were associated with PI. Increased arterial stiffness and decreased arterial compliance with resistance training impair buffer function, resulting in increased CBF pulsatility. Trial Number UMIN000023816 URL: http://www.umin.ac.jp/icdr/index.html Official scientific title of the study: effect of increase arterial stiffness by resistance training on cerebral hemodynamic.

Effects of head-down-tilt bed rest on cerebral hemodynamics during orthostatic stress

NASA Technical Reports Server (NTRS)

Zhang, R.; Zuckerman, J. H.; Pawelczyk, J. A.; Levine, B. D.; Blomqvist, C. G. (Principal Investigator)

1997-01-01

Our aim was to determine whether the adaptation to simulated microgravity (microG) impairs regulation of cerebral blood flow (CBF) during orthostatic stress and contributes to orthostatic intolerance. Twelve healthy subjects (aged 24 +/- 5 yr) underwent 2 wk of -6 degrees head-down-tilt (HDT) bed rest to simulate hemodynamic changes that occur when humans are exposed to microG. CBF velocity in the middle cerebral artery (transcranial Doppler), blood pressure, cardiac output (acetylene rebreathing), and forearm blood flow were measured at each level of a ramped protocol of lower body negative pressure (LBNP; -15, -30, and -40 mmHg x 5 min, -50 mmHg x 3 min, then -10 mmHg every 3 min to presyncope) before and after bed rest. Orthostatic tolerance was assessed by using the cumulative stress index (CSI; mmHg x minutes) for the LBNP protocol. After bed rest, each individual's orthostatic tolerance was reduced, with the group CSI decreased by 24% associated with greater decreases in cardiac output and greater increases in systemic vascular resistance at each level of LBNP. Before bed rest, mean CBF velocity decreased by 14, 10, and 45% at -40 mmHg, -50 mmHg, and maximal LBNP, respectively. After bed rest, mean velocity decreased by 16% at -30 mmHg and by 21, 35, and 39% at -40 mmHg, -50 mmHg, and maximal LBNP, respectively. Compared with pre-bed rest, post-bed-rest mean velocity was less by 11, 10, and 21% at -30, -40, and -50 mmHg, respectively. However, there was no significant difference at maximal LBNP. We conclude that cerebral autoregulation during orthostatic stress is impaired by adaptation to simulated microG as evidenced by an earlier and greater fall in CBF velocity during LBNP. We speculate that impairment of cerebral autoregulation may contribute to the reduced orthostatic tolerance after bed rest.

Low nocturnal blood pressure is associated with reduced cerebral blood flow in the cohort “Men born in 1914”

PubMed Central

Reinprecht, Faina; Axelsson, Johan; Siennicki-Lantz, Arkadiusz; Elmståhl, Sölve

2008-01-01

BACKGROUND: “Men born in 1914” is a population-based cohort study of the epidemiology of cardiovascular and cerebral disease. Little is known about how diurnal variation in blood pressure (BP) levels influence cerebral perfusion in very elderly populations. OBJECTIVES: To study the association between systolic (SBP) and diastolic BP (DBP) levels, during the day and at night, expressed through 24 h ambulatory BP monitoring (ABPM) and regional cerebral blood flow (rCBF) disturbances. METHODS: A cross-sectional study from a population-based cohort of 108 men 81 years of age (born in 1914) was performed in an out-patient university clinic. Cerebral blood flow measurements using 99mTc-hexamethylpropyleneamine oxime single photon emission computed tomography and 24 h ABPM were performed. Eleven men were excluded due to incomplete ABPM data. RESULTS: Mean DBP at night for each tertile was correlated to rCBF for the medial temporal right (P=0.012) and left (P=0.039) regions. Also, DBP during the day was correlated to the medial temporal right region (P=0.025). When analyses were stratified for DBP during the day, subjects with high DBP during the day (greater than 70 mmHg) showed a stronger association between low medial temporal right rCBF and low mean DBP at night (r=0.32, P=0.009) compared with subjects who had a lower daytime DBP. A corresponding positive correlation was noted for the medial temporal left region and daytime SBP, whereas a negative correlation was noted for frontal left region blood flow and SBP at night. CONCLUSIONS: A significant association was seen between low BP levels, especially at night, and rCBF in subjects with otherwise normal daytime DBP that may indicate a risk for nocturnal cerebral ischemia. PMID:22477391

Multimodal MRI-based imputation of the Aβ+ in early mild cognitive impairment

PubMed Central

Tosun, Duygu; Joshi, Sarang; Weiner, Michael W; for the Alzheimer's Disease Neuroimaging Initiative

2014-01-01

Objective The primary goal of this study was to identify brain atrophy from structural MRI (magnetic resonance imaging) and cerebral blood flow (CBF) patterns from arterial spin labeling perfusion MRI that are best predictors of the Aβ-burden, measured as composite 18F-AV45-PET (positron emission tomography) uptake, in individuals with early mild cognitive impairment (MCI). Furthermore, another objective was to assess the relative importance of imaging modalities in classification of Aβ+/Aβ− early MCI. Methods Sixty-seven Alzheimer's Disease Neuroimaging Initiative (ADNI)-GO/2 participants with early MCI were included. Voxel-wise anatomical shape variation measures were computed by estimating the initial diffeomorphic mapping momenta from an unbiased control template. CBF measures normalized to average motor cortex CBF were mapped onto the template space. Using partial least squares regression, we identified the structural and CBF signatures of Aβ after accounting for normal cofounding effects of age, gender, and education. Results 18F-AV45-positive early MCIs could be identified with 83% classification accuracy, 87% positive predictive value, and 84% negative predictive value by multidisciplinary classifiers combining demographics data, ApoE ε4-genotype, and a multimodal MRI-based Aβ score. Interpretation Multimodal MRI can be used to predict the amyloid status of early-MCI individuals. MRI is a very attractive candidate for the identification of inexpensive and noninvasive surrogate biomarkers of Aβ deposition. Our approach is expected to have value for the identification of individuals likely to be Aβ+ in circumstances where cost or logistical problems prevent Aβ detection using cerebrospinal fluid analysis or Aβ-PET. This can also be used in clinical settings and clinical trials, aiding subject recruitment and evaluation of treatment efficacy. Imputation of the Aβ-positivity status could also complement Aβ-PET by identifying individuals who would benefit the most from this assessment. PMID:24729983

Absolute Cerebral Blood Flow Infarction Threshold for 3-Hour Ischemia Time Determined with CT Perfusion and 18F-FFMZ-PET Imaging in a Porcine Model of Cerebral Ischemia

PubMed Central

Cockburn, Neil; Kovacs, Michael

2016-01-01

CT Perfusion (CTP) derived cerebral blood flow (CBF) thresholds have been proposed as the optimal parameter for distinguishing the infarct core prior to reperfusion. Previous threshold-derivation studies have been limited by uncertainties introduced by infarct expansion between the acute phase of stroke and follow-up imaging, or DWI lesion reversibility. In this study a model is proposed for determining infarction CBF thresholds at 3hr ischemia time by comparing contemporaneously acquired CTP derived CBF maps to 18F-FFMZ-PET imaging, with the objective of deriving a CBF threshold for infarction after 3 hours of ischemia. Endothelin-1 (ET-1) was injected into the brain of Duroc-Cross pigs (n = 11) through a burr hole in the skull. CTP images were acquired 10 and 30 minutes post ET-1 injection and then every 30 minutes for 150 minutes. 370 MBq of 18F-FFMZ was injected ~120 minutes post ET-1 injection and PET images were acquired for 25 minutes starting ~155–180 minutes post ET-1 injection. CBF maps from each CTP acquisition were co-registered and converted into a median CBF map. The median CBF map was co-registered to blood volume maps for vessel exclusion, an average CT image for grey/white matter segmentation, and 18F-FFMZ-PET images for infarct delineation. Logistic regression and ROC analysis were performed on infarcted and non-infarcted pixel CBF values for each animal that developed infarct. Six of the eleven animals developed infarction. The mean CBF value corresponding to the optimal operating point of the ROC curves for the 6 animals was 12.6 ± 2.8 mL·min-1·100g-1 for infarction after 3 hours of ischemia. The porcine ET-1 model of cerebral ischemia is easier to implement then other large animal models of stroke, and performs similarly as long as CBF is monitored using CTP to prevent reperfusion. PMID:27347877

The cathelicidin-BF Lys16 mutant Cbf-K16 selectively inhibits non-small cell lung cancer proliferation in vitro.

PubMed

Tian, Yuwei; Wang, Hui; Li, Bing; Ke, Mengyun; Wang, Jing; Dou, Jie; Zhou, Changlin

2013-11-01

The 30-amino acid antimicrobial peptide Cbf-K16 is a cathelicidin-BF (BF-30) Lys16 mutant derived from the snake venom of Bungarus fasciatus. Our previous study found that BF-30 selectively inhibited the proliferation of the metastatic melanoma cell line B16F10 in vitro and in vivo, but had a negligible effect on human lung cells. In the present study, it was demonstrated for the first time that Cbf-K16 selectively inhibits the proliferation of lung carcinoma cells in vitro, with low toxicity to normal cells. The half-maximal inhibitory concentrations (IC50) of Cbf-K16 against H460 human non-small cell lung carcinoma cells and mouse Lewis lung cancer cells were only 16.5 and 10.5 µM, respectively, which were much less compared to that of BF-30 (45 and 40.3 µM). Data using a transmission electron microscope (TEM) assay showed that, at 20 and 40 µM, Cbf-K16 induced the rupture of the cytoplasmic membrane, which was consistent with data obtained from lactate dehydrogenase (LDH) release assays. The LDH release increased from 17.8 to 52.9% as the duration and dosage of Cbf-K16 increased. Annexin V-fluorescein and propidium iodide staining assays indicated that there were no obvious apoptotic effects at the different dosages and times tested. In H460 cells, the rate of genomic DNA binding increased from 51.9 to 86.8% as the concentration of Cbf-K16 increased from 5 to 10 µM. These data indicate that Cbf-K16 selectively inhibits the proliferation of lung carcinoma cells via cytoplasmic membrane permeabilization and DNA binding, rather than apoptosis. Although Cbf-K16 displayed significant cytotoxic activity (40 µM) against tumor cells, in splenocytes no significant inhibitory effect was observed and hemolysis was only 5.6%. These results suggest that Cbf-K16 is a low-toxicity anti-lung cancer drug candidate.

Arterial spin labeling reveals relationships between resting cerebral perfusion and motor learning in Parkinson's disease.

PubMed

Barzgari, Amy; Sojkova, Jitka; Maritza Dowling, N; Pozorski, Vincent; Okonkwo, Ozioma C; Starks, Erika J; Oh, Jennifer; Thiesen, Frances; Wey, Alexandra; Nicholas, Christopher R; Johnson, Sterling; Gallagher, Catherine L

2018-05-09

Parkinson's disease (PD) is an age-related neurodegenerative disease that produces changes in movement, cognition, sleep, and autonomic function. Motor learning involves acquisition of new motor skills through practice, and is affected by PD. The purpose of the present study was to evaluate regional differences in resting cerebral blood flow (rCBF), measured using arterial spin labeling (ASL) MRI, during a finger-typing task of motor skill acquisition in PD patients compared to age- and gender-matched controls. Voxel-wise multiple linear regression models were used to examine the relationship between rCBF and several task variables, including initial speed, proficiency gain, and accuracy. In these models, a task-by-disease group interaction term was included to investigate where the relationship between rCBF and task performance was influenced by PD. At baseline, perfusion was lower in PD subjects than controls in the right occipital cortex. The task-by-disease group interaction for initial speed was significantly related to rCBF (p < 0.05, corrected) in several brain regions involved in motor learning, including the occipital, parietal, and temporal cortices, cerebellum, anterior cingulate, and the superior and middle frontal gyri. In these regions, PD patients showed higher rCBF, and controls lower rCBF, with improved performance. Within the control group, proficiency gain over 12 typing trials was related to greater rCBF in cerebellar, occipital, and temporal cortices. These results suggest that higher rCBF within networks involved in motor learning enable PD patients to compensate for disease-related deficits.

Autoregulation after ischaemic stroke

PubMed Central

Powers, William J.; Videen, Tom O.; Diringer, Michael N.; Aiyagari, Venkatesh; Zazulia, Allyson R.

2010-01-01

Objectives Absent outcome data from randomized clinical trials, management of hypertension in acute ischaemic stroke remains controversial. Data from human participants have failed to resolve the question whether cerebral blood flow (CBF) in the peri-infarct region will decrease due to impaired autoregulation when systemic mean arterial pressure (MAP) is rapidly reduced. Methods Nine participants, 1–11 days after hemispheric ischaemic stroke, with systolic blood pressure more than 145 mmHg, underwent baseline PET measurements of regional CBF. Intravenous nicardipine infusion was then used to rapidly reduce mean arterial pressure 16 ± 7 mmHg and CBF measurement was repeated. Results Compared with the contralateral hemisphere, there were no significant differences in the percent change in CBF in the infarct (P = 0.43), peri-infarct region (P = 1.00) or remainder of the ipsilateral hemisphere (P = 0.50). Two participants showed CBF reductions of greater than 19% in both hemispheres. Conclusion In this study, selective regional impairment of CBF autoregulation in the infarcted hemisohere to reduced systemic blood pressure was not a characteristic of acute cerebral infarction. Reductions in CBF did occur in some individuals, but it was bihemispheric phenomenon that likely was due to an upward shift of the autoregulatory curve as a consequence of chronic hypertension. These results indicate individual monitoring of changes in global CBF, such as with bedside transcranial Doppler, may be useful to determine individual safe limits when MAP is lowered in the setting of acute ischaemic stroke. The benefit of such an approach can only be demonstrated by clinical trials demonstrating improved patient outcome. PMID:19644387

Results of Prospective Cohort Study on Symptomatic Cerebrovascular Occlusive Disease Showing Mild Hemodynamic Compromise [Japanese Extracranial-Intracranial Bypass Trial (JET)-2 Study

PubMed Central

KATAOKA, Hiroharu; MIYAMOTO, Susumu; OGASAWARA, Kuniaki; IIHARA, Koji; TAKAHASHI, Jun C.; NAKAGAWARA, Jyoji; INOUE, Tooru; MORI, Etsuro; OGAWA, Akira

The purpose of this study is to determine the true threshold of cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) for subsequent ischemic stroke without extracranial-intracranial (EC-IC) bypass surgery in patients with hemodynamic ischemia due to symptomatic major cerebral arterial occlusive diseases. Patients were categorized based on rest CBF and CVR into four subgroups as follows: Group A, 80% < CBF < 90% and CVR < 10%; Group B, CBF < 80% and 10% < CVR < 20%; Group C, 80% < CBF < 90% and 10% < CVR < 20%; and Group D, CBF < 90% and 20% < CVR < 30%. Patients were followed up for 2 years under best medical treatment by the stroke neurologists. Primary and secondary end points were defined as all adverse events and ipsilateral stroke recurrence respectively. A total of 132 patients were enrolled. All adverse events were observed in 9 patients (3.5%/year) and ipsilateral stroke recurrence was observed only in 2 patients (0.8%/year). There was no significant difference among the four subgroups in terms of the rate of both primary and secondary end points. Compared with the medical arm of the Japanese EC-IC bypass trial (JET) study including patients with CBF < 80% and CVR < 10% as a historical control, the incidence of ipsilateral stroke recurrence was significantly lower in the present study. Patients with symptomatic major cerebral arterial occlusive diseases and mild hemodynamic compromise have a good prognosis under medical treatment. EC-IC bypass surgery is unlikely to benefit patients with CBF > 80% or CVR > 10%. PMID:26041628

Bedside Xenon-CT Shows Lower CBF in SAH Patients with Impaired CBF Pressure Autoregulation as Defined by Pressure Reactivity Index (PRx).

PubMed

Johnson, Ulf; Engquist, Henrik; Howells, Tim; Nilsson, Pelle; Ronne-Engström, Elisabeth; Lewén, Anders; Rostami, Elham; Enblad, Per

2016-08-01

Subarachnoid hemorrhage (SAH) is a disease with a high rate of unfavorable outcome, often related to delayed cerebral ischemia (DCI), i.e., ischemic injury that develops days-weeks after onset, with a multifactorial etiology. Disturbances in cerebral pressure autoregulation, the ability to maintain a steady cerebral blood flow (CBF), despite fluctuations in systemic blood pressure, have been suggested to play a role in the development of DCI. Pressure reactivity index (PRx) is a well-established measure of cerebral pressure autoregulation that has been used to study traumatic brain injury, but not extensively in SAH. To study the relation between PRx and CBF in SAH patients, and to examine if PRx can be used to predict DCI. Retrospective analysis of prospectively collected data. PRx was calculated as the correlation coefficient between mean arterial blood pressure (MABP) and intracranial pressure (ICP) in a 5 min moving window. CBF was measured using bedside Xenon-CT (Xe-CT). DCI was diagnosed clinically. 47 poor-grade mechanically ventilated patients were studied. Patients with disturbed pressure autoregulation (high PRx values) had lower CBF, as measured by bedside Xe-CT; both in the early (day 0-3) and late (day 4-14) acute phase of the disease. PRx did not differ significantly between patients who developed DCI or not. In mechanically ventilated and sedated SAH patients, high PRx (more disturbed CBF pressure autoregulation) is associated with low CBF, both day 0-3 and day 4-14 after onset. The role of PRx as a monitoring tool in SAH patients needs further studying.

Middle cerebral artery blood velocity and cerebral blood flow and O2 uptake during dynamic exercise.

PubMed

Madsen, P L; Sperling, B K; Warming, T; Schmidt, J F; Secher, N H; Wildschiødtz, G; Holm, S; Lassen, N A

1993-01-01

Results obtained by the 133Xe clearance method with external detectors and by transcranial Doppler sonography (TCD) suggest that dynamic exercise causes an increase of global average cerebral blood flow (CBF). These data are contradicted by earlier data obtained during less-well-defined conditions. To investigate this controversy, we applied the Kety-Schmidt technique to measure the global average levels of CBF and cerebral metabolic rate of oxygen (CMRO2) during rest and dynamic exercise. Simultaneously with the determination of CBF and CMRO2, we used TCD to determine mean maximal flow velocity in the middle cerebral artery (MCA Vmean). For values of CBF and MCA Vmean a correction for an observed small drop in arterial PCO2 was carried out. Baseline values for global CBF and CMRO2 were 50.7 and 3.63 ml.100 g-1.min-1, respectively. The same values were found during dynamic exercise, whereas a 22% (P < 0.0001) increase in MCA Vmean was observed. Hence, the exercise-induced increase in MCA Vmean is not a reflection of a proportional increase in CBF.

beta. -Receptor-mediated increase in cerebral blood flow during hypoglycemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hollinger, B.R.; Bryan, R.M.

1987-10-01

The authors tested the hypothesis that {beta}-adrenergic receptor stimulation is involved with the increase in regional cerebral blood flow (rCBF) during hypoglycemia. Rats were surgically prepared with the use of halothane-nitrous oxide anesthesia. A plaster restraining cast was placed around the hindquarters, and anesthesia was discontinued. Hypoglycemia was produced by an intravenous injection of insulin; normoglycemic control rates were given saline. Propranolol was administered to some control and some hypoglycemic rats to block the {beta}-adrenergic receptors. Regional CBF was measured using 4-(N-methyl-{sup 14}C)iodoantipyrine. Regional CBF increased during hypoglycemia in rats that were not treated with propranolol. The increase varied frommore » {approximately}60 to 200% depending on the brain region. During hypoglycemia, propranolol abolished the increase in rCBF in the hypothalamus, cerebellum, and pyramidal tract. In other regions the increase in rCBF was only 33-65% of the increase in hypoglycemic rats that were not treated with propranolol. They conclude that {beta}-receptor stimulation plays a major role in the increase in rCBF during hypoglycemia.« less

Intraoperative cerebral blood flow imaging of rodents

NASA Astrophysics Data System (ADS)

Li, Hangdao; Li, Yao; Yuan, Lu; Wu, Caihong; Lu, Hongyang; Tong, Shanbao

2014-09-01

Intraoperative monitoring of cerebral blood flow (CBF) is of interest to neuroscience researchers, which offers the assessment of hemodynamic responses throughout the process of neurosurgery and provides an early biomarker for surgical guidance. However, intraoperative CBF imaging has been challenging due to animal's motion and position change during the surgery. In this paper, we presented a design of an operation bench integrated with laser speckle contrast imager which enables monitoring of the CBF intraoperatively. With a specially designed stereotaxic frame and imager, we were able to monitor the CBF changes in both hemispheres during the rodent surgery. The rotatable design of the operation plate and implementation of online image registration allow the technician to move the animal without disturbing the CBF imaging during surgery. The performance of the system was tested by middle cerebral artery occlusion model of rats.

Prognostic Importance of C-KIT Mutations in Core Binding Factor Acute Myeloid Leukemia: A Systematic Review.

PubMed

Ayatollahi, Hossein; Shajiei, Arezoo; Sadeghian, Mohammad Hadi; Sheikhi, Maryam; Yazdandoust, Ehsan; Ghazanfarpour, Masumeh; Shams, Seyyede Fatemeh; Shakeri, Sepideh

2017-03-01

Acute myeloid leukemia (AML) is defined as leukemic blast reproduction in bone marrow. Chromosomal abnormalities form different subgroups with joint clinical specifications and results. t(8;21)(q22;q22) and inv(16)(p13;q22) form core binding factor-AML (CBF-AML). c-kit mutation activation occurs in 12.8-46.1% of adults with CBF leukemia. These mutations occur in 20-25% of t(8;21) and 30% of inv(16) cases. In this systematic review, we searched different databases, including PubMed, Scopus, and Embase. Selected articles were measured based on the inclusion criteria of this study and initially compared in terms of titles or abstracts. Finally, articles relevant to the subject of this review were retrieved in full text. Twenty-two articles matched the inclusion criteria and were selected for this review. In this study, c-kit mutations were associated with poor prognosis in AML patients with t(8;21) and inv(16). In addition, these mutations had better prognostic effects on AML patients with inv(16) compared with those with t(8;21). According to the results of this study, c-kit mutations have intense, harmful effects on the relapse and white blood cell increase in CBF-AML adults. However, these mutations have no significant prognostic effects on patients. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

Quantitative measurement of cerebral blood flow during hypothermia with a time-resolved near-infrared technique

NASA Astrophysics Data System (ADS)

Fazel Bakhsheshi, Mohammad; Diop, Mamadou; St Lawrence, Keith; Lee, Ting-Yim

2012-02-01

Hypothermia, in which the brain is cooled to 32-33 °C, has been shown to be neuroprotective for brain injury caused by hypoxia-ischemia, head trauma, or neonatal asphyxia. Neuroprotective effect of Hypothermia is partly due to suppression of brain metabolism and cerebral blood flow (CBF). The ability to measure CBF at the bedside provides a means of detecting, and thereby preventing, secondary ischemia during neuro intensive care before brain injury occurs. The purpose of the present study is to investigate the ability of a time-resolved near-infrared (TR-NIR) bolus-tracking method using indocyanine green as an intravascular flow tracer to measure CBF during cooling in a newborn animal model. For validation, CBF was independently measured by computed tomography (CT) perfusion. The results show a good agreement between CBF obtained with the two methods (R2 ~ 0.84, Δ ~ 5.84 ml. min -1.100 g -1, 32-38.5 °C), demonstrating the ability of the TR-NIR technique to non-invasively measure absolute CBF in-vivo during dynamic hypothermia. The TR-NIR technique reveals that CBF decreases from 54.3 +/- 5.4 ml. min -1.100 g -1, at normothermia (Tbrain of 38.5 °C), to 33.8 +/- 0.9 ml. min -1.100 g -1 at Tbrain of 32 °C during the hypothermia treatment.

Reduced Dynamic Coupling Between Spontaneous BOLD-CBF Fluctuations in Older Adults: A Dual-Echo pCASL Study.

PubMed

Chiacchiaretta, Piero; Cerritelli, Francesco; Bubbico, Giovanna; Perrucci, Mauro Gianni; Ferretti, Antonio

2018-01-01

Measurement of the dynamic coupling between spontaneous Blood Oxygenation Level Dependent (BOLD) and cerebral blood flow (CBF) fluctuations has been recently proposed as a method to probe resting-state brain physiology. Here we investigated how the dynamic BOLD-CBF coupling during resting-state is affected by aging. Fifteen young subjects and 17 healthy elderlies were studied using a dual-echo pCASL sequence. We found that the dynamic BOLD-CBF coupling was markedly reduced in elderlies, in particular in the left supramarginal gyrus, an area known to be involved in verbal working memory and episodic memory. Moreover, correcting for temporal shift between BOLD and CBF timecourses resulted in an increased correlation of the two signals for both groups, but with a larger increase for elderlies. However, even after temporal shift correction, a significantly decreased correlation was still observed for elderlies in the left supramarginal gyrus, indicating that the age-related dynamic BOLD-CBF uncoupling in this region is more pronounced and can be only partially explained with a simple time-shift between the two signals. Interestingly, these results were observed in a group of elderlies with normal cognitive functions, suggesting that the study of dynamic BOLD-CBF coupling during resting-state is a promising technique, potentially able to provide early biomarkers of functional changes in the aging brain.

Regional reduction in cortical blood flow among cognitively impaired adults with relapsing-remitting multiple sclerosis patients

PubMed Central

Hojjat, Seyed-Parsa; Cantrell, Charles Grady; Vitorino, Rita; Feinstein, Anthony; Shirzadi, Zahra; MacIntosh, Bradley J.; Crane, David E.; Zhang, Lying; Morrow, Sarah A; Lee, Liesly; O’Connor, Paul; Carroll, Timothy J.; Aviv, Richard I.

2015-01-01

Purpose Detection of cortical abnormalities in relapsing-remitting multiple sclerosis (RRMS) remains elusive. Structural MRI measures of cortical integrity are limited, although functional techniques such as pseudocontinuous Arterial Spin Labeling (pCASL) show promise as a surrogate marker of disease severity. We sought to determine the utility of pCASL to assess cortical cerebral blood flow (CBF) in RRMS patients with (RRMS-I) and without (RRMS-NI) cognitive impairment. Methods 19 age-matched healthy controls and 39 RRMS patients were prospectively recruited. Cognition was assessed using the MACFIMS battery. Cortical CBF was compared between groups using a mass univariate voxel-based morphometric analysis accounting for demographic and structural variable covariates. Results Cognitive impairment was present in 51.3% of patients. Significant CBF reduction was present in the RRMS-I compared to other groups in left frontal and right superior frontal cortex. Compared to healthy controls, RRMS-I displayed reduced CBF in the frontal, limbic, parietal and temporal cortex and putamen/thalamus. RRMS-I demonstrated reduced left superior frontal lobe cortical CBF compared to RRMS-NI. No significant cortical CBF differences were present between healthy controls and RRMS-NI. Conclusion Significant cortical CBF reduction occurs in RRMS-I compared to healthy controls and RRMS-NI in anatomically significant regions after controlling for structural and demographic differences. PMID:26754799

Hypoperfusion induces overexpression of beta-amyloid precursor protein mRNA in a focal ischemic rodent model.

PubMed

Shi, J; Yang, S H; Stubley, L; Day, A L; Simpkins, J W

2000-01-17

Silent stroke is one of the risk factors of dementia. In the present study, we used a novel focal ischemic animal model to investigate the effects of comparatively small changes of cerebral blood flow (CBF) on the expression of beta-amyloid precursor protein (APP) mRNA. Focal ischemia was achieved by introducing a 4-0 monofilament to the bifurcation of anterior and middle cerebral arteries. Brain samples were harvested from ischemic core and penumbra of cortices at 1, 4 and 7 days following ischemia. The expression of APP mRNA was assessed by RT-PCR. The CBF was decreased to 50% for 1 day after stroke and recovered to 90% at the fourth day after stroke. The changes of CBF were accompanied by an increase in the expression of APP mRNA. APP mRNA increased to 208% and 152% in the penumbra and core ischemic regions, respectively, on the fourth day after MCAO and remained high through the seventh day of ischemia. This study suggests brain hypoperfusion enhances APP mRNA expression and may contribute to the progression of cognitive impairment after silent stroke.

Plasma Membrane CRPK1-Mediated Phosphorylation of 14-3-3 Proteins Induces Their Nuclear Import to Fine-Tune CBF Signaling during Cold Response.

PubMed

Liu, Ziyan; Jia, Yuxin; Ding, Yanglin; Shi, Yiting; Li, Zhen; Guo, Yan; Gong, Zhizhong; Yang, Shuhua

2017-04-06

In plant cells, changes in fluidity of the plasma membrane may serve as the primary sensor of cold stress; however, the precise mechanism and how the cell transduces and fine-tunes cold signals remain elusive. Here we show that the cold-activated plasma membrane protein cold-responsive protein kinase 1 (CRPK1) phosphorylates 14-3-3 proteins. The phosphorylated 14-3-3 proteins shuttle from the cytosol to the nucleus, where they interact with and destabilize the key cold-responsive C-repeat-binding factor (CBF) proteins. Consistent with this, the crpk1 and 14-3-3κλ mutants show enhanced freezing tolerance, and transgenic plants overexpressing 14-3-3λ show reduced freezing tolerance. Further study shows that CRPK1 is essential for the nuclear translocation of 14-3-3 proteins and for 14-3-3 function in freezing tolerance. Thus, our study reveals that the CRPK1-14-3-3 module transduces the cold signal from the plasma membrane to the nucleus to modulate CBF stability, which ensures a faithfully adjusted response to cold stress of plants. Copyright © 2017 Elsevier Inc. All rights reserved.

The effect of acetyl-L-carnitine and R-alpha-lipoic acid treatment in ApoE4 mouse as a model of human Alzheimer's disease.

PubMed

Shenk, Justin C; Liu, Jiankang; Fischbach, Kathryn; Xu, Kui; Puchowicz, Michel; Obrenovich, Mark E; Gasimov, Eldar; Alvarez, Ludis Morales; Ames, Bruce N; Lamanna, Joseph C; Aliev, Gjumrakch

2009-08-15

We measured age-dependent effects of human ApoE4 on cerebral blood flow (CBF) using ApoE4 transgenic mice compared to age-matched wild-type (WT) mice by use of [(14)C] iodoantipyrene autoradiography. ApoE4 associated factors reduce CBF gradually to create brain hypoperfusion when compared to WT, and the differences in CBF are greatest as animals age from 6-weeks to 12-months. Transmission electron microscopy with colloidal gold immunocytochemistry showed structural damage in young and aged microvessel endothelium of ApoE4 animals extended to the cytoplasm of perivascular cells, perivascular nerve terminals and hippocampal neurons and glial cells. These abnormalities coexist with mitochondrial structural alteration and mitochondrial DNA overproliferation and/or deletion in all brain cellular compartments. Spatial memory and temporal memory tests showed a trend in improving cognitive function in ApoE4 mice fed selective mitochondrial antioxidants acetyl-l-carnitine and R-alpha-lipoic acid. Our findings indicate that ApoE4 genotype-induced mitochondrial changes and associated structural damage may explain age-dependent pathology seen in AD, indicating potential for novel treatment strategies in the near future.

Prognostic Markers in Core-Binding Factor AML and Improved Survival with Multiple Consolidation Cycles of Intermediate/High-dose Cytarabine.

PubMed

Prabahran, Ashvind; Tacey, Mark; Fleming, Shaun; Wei, Andrew; Tate, Courtney; Marlton, Paula; Wight, Joel; Grigg, Andrew; Tuckfield, Annabel; Szer, Jeff; Ritchie, David; Chee, Lynette

2018-05-02

Core-binding factor acute myeloid leukaemia (CBF AML) defined by t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) has a favourable prognosis, however 30-40% of patients still relapse after chemotherapy. We sought to evaluate risk factors for relapse in a de novo CBF AML cohort. A retrospective review of patients from 4 Australian tertiary centres from 2001-2012, comprising 40 t(8;21) and 30 inv(16) AMLs. Multivariate analysis identified age (p=0.032) and WCC>40 (p=0.025) as significant predictors for inferior OS and relapse respectively. Relapse risk was higher in the inv(16) group vs the t(8;21) group (57% vs 18%, HR 4.31, 95% CI: 1.78-10.42, p=0.001). Induction therapy had no bearing on OS or relapse free survival (RFS) however, consolidation treatment with >3 cycles of intermediate/high dose cytarabine improved OS (p=0.035) and relapse-free survival (RFS) (p=0.063). 5 patients demonstrated post-treatment stable q PCR positivity without relapse. (1)>3 consolidation cycles of intermediate/ high-dose cytarabine improves patient outcomes. (2)Age and inv(16) CBF AML subtype are predictors of inferior OS and RFS respectively. (3)Stable low-level MRD by qPCR does not predict relapse. (4)Similar OS in the inv(16) cohort compared to the t(8;21) cohort, despite a higher relapse rate, confirms salvageability of relapsed disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Tumor Necrosis Factor-induced Decrease of Cochlear Blood Flow Can Be Reversed by Etanercept or JTE-013.

PubMed

Sharaf, Kariem; Ihler, Friedrich; Bertlich, Mattis; Reichel, Christoph A; Berghaus, Alexander; Canis, Martin

2016-08-01

This study aimed to quantify the effects of tumor necrosis factor (TNF) inhibitor Etanercept and sphingosine-1-phosphate receptor 2 antagonist JTE-013 on cochlear blood flow in guinea pigs after TNF-induced decrease. Sudden sensorineural hearing loss is a common cause for disability and reduced quality of life. Good understanding of the pathophysiology and strong evidence-based therapy concepts are still missing. In various inner ear disorders, inflammation and impairment of cochlear blood flow (CBF) have been considered factors in the pathophysiology. A central mediator of inflammation and microcirculation in the cochlea is TNF. S1P acts downstream in one TNF pathway. Cochlea lateral wall vessels were exposed surgically and assessed by intravital microscopy in guinea pigs in vivo. Twenty-eight animals were randomly distributed into four groups of seven each. Exposed vessels were superfused by TNF (5.0 ng/ml) and afterward repeatedly either by Etanercept (1.0 μg/ml), JTE-013 (10 μmol/L), or vehicle (0.9 % NaCl solution or ethanol: phosphate-buffered saline buffer, respectively). After decreasing CBF with TNF (p <0.001, two-way RM ANOVA), both treatments reversed CBF, compared with vehicle (p <0.001, two-way RM ANOVA). The comparison of the vehicle groups showed no difference (p = 0.969, two-way RM ANOVA), while there was also no difference between the treatment groups (p = 0.850, two-way RM ANOVA). Both Etanercept and JTE-013 reverse the decreasing effect of TNF on cochlear blood flow and, therefore, TNF and the S1P-signalling pathway might be targets for treatment of microcirculation-related hearing loss.

Radial extracorporeal shock wave therapy improves cerebral blood flow and neurological function in a rat model of cerebral ischemia.

PubMed

Kang, Nan; Zhang, Jing; Yu, Xiaotong; Ma, Yuewen

2017-01-01

We performed middle cerebral artery occlusion (MCAO) in rats to investigate the effect and some of the underlying mechanisms of radial extracorporeal shock wave therapy (rESWT) in cerebral ischemia rats. We measured neurological function and cerebral blood flow (CBF) using a full-field laser perfusion imager and brain infarct volume on days 3, 12, and 30. Immunofluorescence, western blot, and real-time polymerase chain reaction (PCR) techniques were used to detect the expression of vascular endothelial growth factor (VEGF), neuron-specific enolase (NSE), nestin, Wnt3a, and β-catenin in the ischemic hemisphere. The dose of rESWT used on the head revealed remarkable advantages over sham rESWT, as demonstrated by improved neurological function scores, increased CBF, and reduced brain infarct volume. Furthermore, applying rESWT to the head and limbs enhanced short-term neurological function. Our results confirmed that rESWT can induce VEGF expression over an extended period with a profound effect, which may be the primary reason for CBF recovery. High NSE and nestin expression levels suggest that rESWT enhanced the number of neurons and neural stem cells (NSCs). Wnt3a and β-catenin expression were up-regulated in the ischemic hemisphere, indicating that rESWT promoted NSC proliferation and differentiation via the Wnt/β-catenin pathway. Overall, our findings suggest that an appropriate rESWT dose delivered to the head of rats helps restore neurological function and CBF, and additional application of rESWT to the limbs is more effective than treating the head alone.

Association of freezing tolerance to LpCBFIIIb and LpCBFIIIc gene polymorphism in perennial ryegrass accessions

USDA-ARS?s Scientific Manuscript database

CBF/DREB related genes are considered important genes for regulation of abiotic stress in plants. In this study, CBF/DREB genes in perennial ryegrass (Lolium perenne L.), also known as LpCBF genes, were resequenced from several cultivated and landrace plants from a worldwide collection. The same pla...

Effect of nicergoline on cerebral blood flow

PubMed Central

Iliff, L. D.; Boulay, G. H. Du; Marshall, John; Russell, R. W. Ross; Symon, Lindsay

1977-01-01

Cerebral blood flow (CBF) was measured before and after intravenous injection of the cerebral vasodilator nicergoline in 13 patients with cerebrovascular disease. CBF increased in seven. The possibility that the effect of the drug in the remainder may have been masked by a fall of CBF which occurs during sequential measurement of patients at rest is discussed. PMID:925694

Effect of simulated weightlessness on the expression of Cbfα1 induced by fluid shear stress in MG-63 osteosarcoma cells.

NASA Astrophysics Data System (ADS)

Yang, Z.; Zhang, S.; Wang, B.; Sun, X. Q.

Objective The role of mechanical load in the functional regulation of osteoblasts becomes an emphasis in osseous biomechanical researches recently This study was aim to explore the effect of flow shear stress on the expression of Cbf alpha 1 in human osteosarcoma cells and to survey its functional alteration in simulated weightlessness Method After cultured for 72 h in two different gravitational environments i e 1G terrestrial gravitational condition and simulated weightlessness condition human osteosarcoma cells MG-63 were treated with 0 5 Pa or 1 5 Pa fluid shear stress FSS in a flow chamber for 15 30 60 min respectively The total RNA in cells was isolated Transcription PCR analysis was made to examine the gene expression of Cbf alpha 1 And the total protein of cells was extracted and the expression of Cbf alpha 1 protein was detected by means of Western Blotting Results MG-63 cultured in 1G condition reacted to FSS treatment with an enhanced expression of Cbf alpha 1 Compared with no FSS control group Cbf alpha 1 mRNA and protein expression increased significantly at 30 and 60 min with the treatment of FSS P 0 01 And there was remarkable difference on the Cbf alpha 1 mRNA and protein expression between the treatments of 0 5 Pa and 1 5 Pa FSS at 30 min or 60 min P 0 01 As to the osteoblasts cultured in simulated weightlessness by using clinostat the expression of Cbf alpha 1 was significantly different between 1G and simulated weightlessness conditions at each test time P 0 05 Compared with no FSS

Apparent CBF decrease with normal aging due to partial volume effects: MR-based partial volume correction on CBF SPECT.

PubMed

Inoue, Kentaro; Ito, Hiroshi; Goto, Ryoi; Nakagawa, Manabu; Kinomura, Shigeo; Sato, Tachio; Sato, Kazunori; Fukuda, Hiroshi

2005-06-01

Several studies using single photon emission tomography (SPECT) have shown changes in cerebral blood flow (CBF) with age, which were associated with partial volume effects by some authors. Some studies have also demonstrated gender-related differences in CBF. The present study aimed to examine age and gender effects on CBF SPECT images obtained using the 99mTc-ethyl cysteinate dimer and a SPECT scanner, before and after partial volume correction (PVC) using magnetic resonance (MR) imaging. Forty-four healthy subjects (29 males and 15 females; age range, 27-64 y; mean age, 50.0 +/- 9.8 y) participated. Each MR image was segmented to yield grey and white matter images and coregistered to a corresponding SPECT image, followed by convolution to approximate the SPECT spatial resolution. PVC-SPECT images were produced using the convoluted grey matter MR (GM-MR) and white matter MR images. The age and gender effects were assessed using SPM99. Decreases with age were detected in the anterolateral prefrontal cortex and in areas along the lateral sulcus and the lateral ventricle, bilaterally, in the GM-MR images and the SPECT images. In the PVC-SPECT images, decreases in CBF in the lateral prefrontal cortex lost their statistical significance. Decreases in CBF with age found along the lateral sulcus and the lateral ventricle, on the other hand, remained statistically significant, but observation of the spatially normalized MR images suggests that these findings are associated with the dilatation of the lateral sulcus and lateral ventricle, which was not completely compensated for by the spatial normalization procedure. Our present study demonstrated that age effects on CBF in healthy subjects could reflect morphological differences with age in grey matter.

Blood flow and vascular reactivity during attacks of classic migraine--limitations of the Xe-133 intraarterial technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skyhoj Olsen, T.; Lassen, N.A.

1989-01-01

The present study reports cerebral blood flow (CBF) measurements in 11 patients during attacks of classic migraine (CM)--migraine with aura. In 6 and 7 patients, respectively, cerebral vascular reactivity to increased blood pressure and to hypocapnia was also investigated during the CM attacks. The Xenon-133 intraarterial injection technique was used to measure CBF. In this study, based in part on previously published data, methodological limitations, in particular caused by scattered radiation (Compton scatter), are critically analysed. Based on this analysis and the results of the CBF studies it is concluded: During CM attacks CBF appears to decrease focally in themore » posterior part of the brain to a level around 20 ml/100 g/min which is consistent with a mild degree of ischemia. Changes of CBF in focal low flow areas are difficult to evaluate accurately with the Xe-133 technique. In most cases true CBF may change 50% or more in the low flow areas without giving rise to significantly measurable changes of CBF. This analysis suggests that the autoregulation response cannot be evaluated in the low flow areas with the technique used while the observations are compatible with the concept that a vasoconstrictive state, unresponsive to hypocapnia, prevails in the low flow areas during CM attacks. The gradual increase in size of the low flow area seen in several cases may be interpreted in two different ways. A spreading process may actually exist. However, due to Compton scatter, a gradual decrease of CBF in a territory that does not increase in size will also appear as a gradually spreading low flow area when studied with the Xe-133 intracarotid technique.« less

Cerebral autoregulation and flow/metabolism coupling during cardiopulmonary bypass: the influence of PaCO/sub 2/

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murkin, J.M.; Farrar, J.K.; Tweed, W.A.

Measurement of /sup 133/Xe clearance and effluent cerebral venous blood sampling were used in 38 patients to determine the effects of cardiopulmonary bypass, and of maintaining temperature corrected or noncorrected PaCO/sub 2/ at 40 mm Hg on regulation of cerebral blood flow (CBF) and flow/metabolism coupling. After induction of anesthesia with diazepam and fentanyl, mean CBF was 25 ml X 100 g-1 X min-1 and cerebral oxygen consumption, 1.67 ml X 100 g-1 X min-1. Cerebral oxygen consumption during nonpulsatile cardiopulmonary bypass at 26 degrees C was reduced to 0.42 ml X 100 g-1 X min-1 in both groups. CBFmore » was reduced to 14-15 ml X 100 g-1 X min-1 in the non-temperature-corrected group (n = 21), was independent of cerebral perfusion pressure over the range of 20-100 mm Hg, but correlated with cerebral oxygen consumption. In the temperature-corrected group (n = 17), CBF varied from 22 to 32 ml X 100 g-1 X min-1, and flow/metabolism coupling was not maintained (i.e., CBF and cerebral oxygen consumption varied independently). However, variation in CBF correlated significantly with cerebral perfusion pressure over the pressure range of 15-95 mm Hg. This study demonstrates a profound reduction in cerebral oxygen consumption during hypothermic nonpulsatile cardiopulmonary bypass. When a non-temperature-corrected PaCO/sub 2/ of approximately 40 mm Hg was maintained, CBF was lower, and analysis of pooled data suggested that CBF regulation was better preserved, i.e., CBF was independent of pressure changes and dependent upon cerebral oxygen consumption.« less

Task Related Cerebral Blood Flow Changes of Patients with Chronic Fatigue Syndrome: An Arterial Spin Labeling Study.

PubMed

Staud, Roland; Boissoneault, Jeff; Craggs, Jason G; Lai, Song; Robinson, Michael E

2018-01-01

One hallmark of chronic fatigue syndrome (ME/CFS) is task related worsening of fatigue. Global brain hypoperfusion, abnormal regional activation, and altered functional connectivity of brain areas associated with cognition and memory have been reported but remain controversial. We enrolled 17 female participants fulfilling the CDC Criteria for ME/CFS and 16 matched healthy controls (HC). Using a 3T-Phillips Achieva MRI-scanner, pseudo-continuous arterial spin-labeling (pCASL), was used to study the dynamics of regional cerebral blood flow (rCBF) and their relationship to mental fatigue in ME/CFS patients and HC during a demanding cognitive task, i.e. modified Paced-Auditory-Serial-Addition-Testing (PASAT). ME/CFS subjects reported more fatigue than HC at baseline (p < .01). Global brain perfusion of ME/CFS and HC subjects was similar at rest. The PASAT resulted in significantly increased fatigue in ME/CFS participants and HC. Although not different between groups, overall CBF significantly increased over the first 3 min of the PASAT and then decreased thereafter. Regional CBF (rCBF) changes were significantly different between groups during the post-task recovery period. Whereas improvement of fatigue of ME/CFS subjects was associated with decreased rCBF in both superior temporal gyri (STG), precuneus, and fusiform gyrus, it was associated with increased rCBF in the same areas in HC. Our results suggest that ME/CFS is associated with normal global CBF at rest and during a strenuous task (PASAT); however rCBF of several brain regions associated with memory, goal-oriented attention, and visual function was differentially associated with recovery from fatigue in ME/CFS patients and HC.

Task Related Cerebral Blood Flow Changes of Patients with Chronic Fatigue Syndrome: An Arterial Spin Labeling Study

PubMed Central

Staud, Roland; Boissoneault, Jeff; Craggs, Jason G.; Lai, Song; Robinson, Michael E.

2018-01-01

Purpose One hallmark of chronic fatigue syndrome (ME/CFS) is task related worsening of fatigue. Global brain hypoperfusion, abnormal regional activation, and altered functional connectivity of brain areas associated with cognition and memory have been reported but remain controversial. Methods We enrolled 17 female participants fulfilling the CDC Criteria for ME/CFS and 16 matched healthy controls (HC). Using a 3T-Phillips Achieva MRI-scanner, pseudo-continuous arterial spin-labeling (pCASL), was used to study the dynamics of regional cerebral blood flow (rCBF) and their relationship to mental fatigue in ME/CFS patients and HC during a demanding cognitive task, i.e. modified Paced-Auditory-Serial-Addition-Testing (PASAT). Results ME/CFS subjects reported more fatigue than HC at baseline (p < .01). Global brain perfusion of ME/CFS and HC subjects was similar at rest. The PASAT resulted in significantly increased fatigue in ME/CFS participants and HC. Although not different between groups, overall CBF significantly increased over the first 3 min of the PASAT and then decreased thereafter. Regional CBF (rCBF) changes were significantly different between groups during the post-task recovery period. Whereas improvement of fatigue of ME/CFS subjects was associated with decreased rCBF in both superior temporal gyri (STG), precuneus, and fusiform gyrus, it was associated with increased rCBF in the same areas in HC. Conclusions Our results suggest that ME/CFS is associated with normal global CBF at rest and during a strenuous task (PASAT); however rCBF of several brain regions associated with memory, goal-oriented attention, and visual function was differentially associated with recovery from fatigue in ME/CFS patients and HC. PMID:29707427

Cerebral hyperperfusion and decreased cerebrovascular reactivity correlate with neurologic disease severity in MELAS.

PubMed

Rodan, L H; Poublanc, J; Fisher, J A; Sobczyk, O; Wong, T; Hlasny, E; Mikulis, D; Tein, I

2015-05-01

To study the mechanisms underlying stroke-like episodes (SLEs) in MELAS syndrome. We performed a case control study in 3 siblings with MELAS syndrome (m.3243A>G tRNA(Leu(UUR))) with variable % mutant mtDNA in blood (35 to 59%) to evaluate regional cerebral blood flow (CBF) and arterial cerebrovascular reactivity (CVR) compared to age- and sex-matched healthy study controls and a healthy control population. Subjects were studied at 3T MRI using arterial spin labeling (ASL) to measure CBF; CVR was measured as a change in % Blood Oxygen Level Dependent signal (as a surrogate of CBF) to repeated 10 mmHg step increase in arterial partial pressure of CO2 (PaCO2). MELAS siblings had decreased CVR (p ≤ 0.002) and increased CBF (p < 0.0026) compared to controls; changes correlated with disease severity and % mutant mtDNA (inversely for CVR: r = -0.82 frontal, r = -0.91 occipital cortex; directly for CBF: r = +0.85 frontal, not for occipital infarct penumbra). Mean CVR was reduced more in frontal (p < 0.001) versus occipital cortex (p = 0.002); mean CBF was increased more in occipital (p = 0.001) than frontal (p = 0.0026) cortices compared to controls. CBF correlated inversely with CVR (r = -0.99 in frontal; not in occipital infarct penumbra) suggesting that increased frontal resting flows are at the expense of flow reserve. MELAS disease severity and mutation load were inversely correlated with Interictal CVR and directly correlated with frontal CBF. These metrics offer further insight into the cerebrovascular hemodynamics in MELAS syndrome and may serve as noninvasive prognostic markers to stratify risk for SLEs. Class III. Copyright © 2015 © Elsevier B.V. and Mitochondria Research Society. Published by Elsevier B.V. All rights reserved.

Post traumatic brain perfusion SPECT analysis using reconstructed ROI maps of radioactive microsphere derived cerebral blood flow and statistical parametric mapping

PubMed Central

McGoron, Anthony J; Capille, Michael; Georgiou, Michael F; Sanchez, Pablo; Solano, Juan; Gonzalez-Brito, Manuel; Kuluz, John W

2008-01-01

Background Assessment of cerebral blood flow (CBF) by SPECT could be important in the management of patients with severe traumatic brain injury (TBI) because changes in regional CBF can affect outcome by promoting edema formation and intracranial pressure elevation (with cerebral hyperemia), or by causing secondary ischemic injury including post-traumatic stroke. The purpose of this study was to establish an improved method for evaluating regional CBF changes after TBI in piglets. Methods The focal effects of moderate traumatic brain injury (TBI) on cerebral blood flow (CBF) by SPECT cerebral blood perfusion (CBP) imaging in an animal model were investigated by parallelized statistical techniques. Regional CBF was measured by radioactive microspheres and by SPECT 2 hours after injury in sham-operated piglets versus those receiving severe TBI by fluid-percussion injury to the left parietal lobe. Qualitative SPECT CBP accuracy was assessed against reference radioactive microsphere regional CBF measurements by map reconstruction, registration and smoothing. Cerebral hypoperfusion in the test group was identified at the voxel level using statistical parametric mapping (SPM). Results A significant area of hypoperfusion (P < 0.01) was found as a response to the TBI. Statistical mapping of the reference microsphere CBF data confirms a focal decrease found with SPECT and SPM. Conclusion The suitability of SPM for application to the experimental model and ability to provide insight into CBF changes in response to traumatic injury was validated by the SPECT SPM result of a decrease in CBP at the left parietal region injury area of the test group. Further study and correlation of this characteristic lesion with long-term outcomes and auxiliary diagnostic modalities is critical to developing more effective critical care treatment guidelines and automated medical imaging processing techniques. PMID:18312639

Post traumatic brain perfusion SPECT analysis using reconstructed ROI maps of radioactive microsphere derived cerebral blood flow and statistical parametric mapping.

PubMed

McGoron, Anthony J; Capille, Michael; Georgiou, Michael F; Sanchez, Pablo; Solano, Juan; Gonzalez-Brito, Manuel; Kuluz, John W

2008-02-29

Assessment of cerebral blood flow (CBF) by SPECT could be important in the management of patients with severe traumatic brain injury (TBI) because changes in regional CBF can affect outcome by promoting edema formation and intracranial pressure elevation (with cerebral hyperemia), or by causing secondary ischemic injury including post-traumatic stroke. The purpose of this study was to establish an improved method for evaluating regional CBF changes after TBI in piglets. The focal effects of moderate traumatic brain injury (TBI) on cerebral blood flow (CBF) by SPECT cerebral blood perfusion (CBP) imaging in an animal model were investigated by parallelized statistical techniques. Regional CBF was measured by radioactive microspheres and by SPECT 2 hours after injury in sham-operated piglets versus those receiving severe TBI by fluid-percussion injury to the left parietal lobe. Qualitative SPECT CBP accuracy was assessed against reference radioactive microsphere regional CBF measurements by map reconstruction, registration and smoothing. Cerebral hypoperfusion in the test group was identified at the voxel level using statistical parametric mapping (SPM). A significant area of hypoperfusion (P < 0.01) was found as a response to the TBI. Statistical mapping of the reference microsphere CBF data confirms a focal decrease found with SPECT and SPM. The suitability of SPM for application to the experimental model and ability to provide insight into CBF changes in response to traumatic injury was validated by the SPECT SPM result of a decrease in CBP at the left parietal region injury area of the test group. Further study and correlation of this characteristic lesion with long-term outcomes and auxiliary diagnostic modalities is critical to developing more effective critical care treatment guidelines and automated medical imaging processing techniques.

Positron emission tomography/magnetic resonance hybrid scanner imaging of cerebral blood flow using 15O-water positron emission tomography and arterial spin labeling magnetic resonance imaging in newborn piglets

PubMed Central

Andersen, Julie B; Henning, William S; Lindberg, Ulrich; Ladefoged, Claes N; Højgaard, Liselotte; Greisen, Gorm; Law, Ian

2015-01-01

Abnormality in cerebral blood flow (CBF) distribution can lead to hypoxic–ischemic cerebral damage in newborn infants. The aim of the study was to investigate minimally invasive approaches to measure CBF by comparing simultaneous 15O-water positron emission tomography (PET) and single TI pulsed arterial spin labeling (ASL) magnetic resonance imaging (MR) on a hybrid PET/MR in seven newborn piglets. Positron emission tomography was performed with IV injections of 20 MBq and 100 MBq 15O-water to confirm CBF reliability at low activity. Cerebral blood flow was quantified using a one-tissue-compartment-model using two input functions: an arterial input function (AIF) or an image-derived input function (IDIF). The mean global CBF (95% CI) PET-AIF, PET-IDIF, and ASL at baseline were 27 (23; 32), 34 (31; 37), and 27 (22; 32) mL/100 g per minute, respectively. At acetazolamide stimulus, PET-AIF, PET-IDIF, and ASL were 64 (55; 74), 76 (70; 83) and 79 (67; 92) mL/100 g per minute, respectively. At baseline, differences between PET-AIF, PET-IDIF, and ASL were 22% (P<0.0001) and −0.7% (P=0.9). At acetazolamide, differences between PET-AIF, PET-IDIF, and ASL were 19% (P=0.001) and 24% (P=0.0003). In conclusion, PET-IDIF overestimated CBF. Injected activity of 20 MBq 15O-water had acceptable concordance with 100 MBq, without compromising image quality. Single TI ASL was questionable for regional CBF measurements. Global ASL CBF and PET CBF were congruent during baseline but not during hyperperfusion. PMID:26058699

An Automated Measurement of Ciliary Beating Frequency using a Combined Optical Flow and Peak Detection.

PubMed

Kim, Woojae; Han, Tae Hwa; Kim, Hyun Jun; Park, Man Young; Kim, Ku Sang; Park, Rae Woong

2011-06-01

The mucociliary transport system is a major defense mechanism of the respiratory tract. The performance of mucous transportation in the nasal cavity can be represented by a ciliary beating frequency (CBF). This study proposes a novel method to measure CBF by using optical flow. To obtain objective estimates of CBF from video images, an automated computer-based image processing technique is developed. This study proposes a new method based on optical flow for image processing and peak detection for signal processing. We compare the measuring accuracy of the method in various combinations of image processing (optical flow versus difference image) and signal processing (fast Fourier transform [FFT] vs. peak detection [PD]). The digital high-speed video method with a manual count of CBF in slow motion video play, is the gold-standard in CBF measurement. We obtained a total of fifty recorded ciliated sinonasal epithelium images to measure CBF from the Department of Otolaryngology. The ciliated sinonasal epithelium images were recorded at 50-100 frames per second using a charge coupled device camera with an inverted microscope at a magnification of ×1,000. The mean square errors and variance for each method were 1.24, 0.84 Hz; 11.8, 2.63 Hz; 3.22, 1.46 Hz; and 3.82, 1.53 Hz for optical flow (OF) + PD, OF + FFT, difference image [DI] + PD, and DI + FFT, respectively. Of the four methods, PD using optical flow showed the best performance for measuring the CBF of nasal mucosa. The proposed method was able to measure CBF more objectively and efficiently than what is currently possible.

Changes in cerebral blood flow and vasoreactivity in response to acetazolamide in patients with transient global amnesia

PubMed Central

Sakashita, Y.; Kanai, M.; Sugimoto, T.; Taki, S.; Takamori, M.

1997-01-01

OBJECTIVE—Previous reports about changes in cerebral blood flow (CBF) in transient global amnesia disclosed decreased flow in some parts of the brain. However, CBF analyses in most reports were qualitative but not quantitative. The purpose of this study was to determine changes in CBF in transient global amnesia.
METHODS—The CBF was measured and the vasoreactive response to acetazolamide was evaluated in six patients with transient global amnesia using technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT). The CBF was measured during an attack in two patients and soon after an attack in the other four. About one month later, CBF was re-evaluated in each patient.
RESULTS—Two patients examined during an attack and one patient examined five hours after an attack had increased blood flow in the occipital cortex and cerebellum. Three patients examined at six to 10 hours after an attack had decreased blood flow in the thalamus, cerebellum, or putamen. These abnormalities of blood flow almost disappeared in all patients one month after onset. The vasodilatory response to acetazolamide, which was evaluated initially using SPECT, was poor in areas of increased blood flow. By the second evaluation of CBF with acetazolamide, the vasodilatory response had returned to normal.
CONCLUSIONS—In a patient with transient global amnesia, CBF increased in the vertebrobasilar territory during the attack and decreased afterwards. The vasodilatory response to acetazolamide may be impaired in the parts of the brain with increased blood flow. It is suggested that transient global amnesia is distinct from migraine but may share the same underlying mechanism.

 PMID:9408101

Environmental heat stress enhances mental fatigue during sustained attention task performing: evidence from an ASL perfusion study.

PubMed

Qian, Shaowen; Li, Min; Li, Guoying; Liu, Kai; Li, Bo; Jiang, Qingjun; Li, Li; Yang, Zhen; Sun, Gang

2015-03-01

This study was to investigate the potential enhancing effect of heat stress on mental fatigue progression during sustained attention task using arterial spin labeling (ASL) imaging. Twenty participants underwent two thermal exposures in an environmental chamber: normothermic (NT) condition (25°C, 1h) and hyperthermic (HT) condition (50°C, 1h). After thermal exposure, they performed a twenty-minute psychomotor vigilance test (PVT) in the scanner. Behavioral analysis revealed progressively increasing subjective fatigue ratings and reaction time as PVT progressed. Moreover, heat stress caused worse performance. Perfusion imaging analyses showed significant resting-state cerebral blood flow (CBF) alterations after heat exposure. Specifically, increased CBF mainly gathered in thalamic-brainstem area while decreased CBF predominantly located in fronto-parietal areas, anterior cingulate cortex, posterior cingulate cortex, and medial frontal cortex. More importantly, diverse CBF distributions and trend of changes between both conditions were observed as the fatigue level progressed during subsequent PVT task. Specifically, higher CBF and enhanced rising trend were presented in superior parietal lobe, precuneus, posterior cingulate cortex and anterior cingulate cortex, while lower CBF or inhibited rising trend was found in dorsolateral frontal cortex, medial frontal cortex, inferior parietal lobe and thalamic-brainstem areas. Furthermore, the decrease of post-heat resting-state CBF in fronto-parietal cortex was correlated with subsequent slower reaction time, suggesting prior disturbed resting-state CBF might be indicator of performance potential and fatigue level in following task. These findings may provide proof for such a view: heat stress has a potential fatigue-enhancing effect when individual is performing highly cognition-demanding attention task. Copyright © 2014 Elsevier B.V. All rights reserved.

Cerebral Perfusion Changes in Post-Concussion Syndrome: A Prospective Controlled Cohort Study

PubMed Central

Marcil, Lorenzo D.; Dewey, Deborah; Carlson, Helen L.; MacMaster, Frank P.; Brooks, Brian L.; Lebel, R. Marc

2017-01-01

Abstract The biology of post-concussive symptoms is unclear. Symptoms are often increased during activities, and have been linked to decreased cerebrovascular reactivity and perfusion. The aim of this study was to examine cerebral blood flow (CBF) in children with different clinical recovery patterns following mild traumatic brain injury (mTBI). This was a prospective controlled cohort study of children with mTBI (ages 8 to 18 years) who were symptomatic with post-concussive symptoms at one month post-injury (symptomatic, n = 27) and children who had recovered quickly (asymptomatic, n = 24). Pseudo continuous arterial spin labeling magnetic resonance imaging (MRI) was used to quantify CBF. The mTBI groups were imaged at 40 days post-injury. Global and regional CBF were compared with healthy controls of similar age and sex but without a history of mTBI (n = 21). Seventy-two participants (mean age: 14.1 years) underwent neuroimaging. Significant differences in CBF were found: global CBF was higher in the symptomatic group and lower in the asymptomatic group compared with controls, (F(2,69) 9.734; p < 0.001). Post-injury symptom score could be predicted by pre-injury symptoms and CBF in presence of mTBI (adjusted R2 = 0.424; p < 0.001). Altered patterns of cerebral perfusion are seen following mTBI and are associated with the recovery trajectory. Symptomatic children have higher CBF. Children who “recovered” quickly, have decreased CBF suggesting that clinical recovery precedes the cerebral recovery. Further longitudinal studies are required to determine if these perfusion patterns continue to change over time. PMID:27554429

Brain Tissue Oxygen: In Vivo Monitoring with Carbon Paste Electrodes

PubMed Central

Bolger, Fiachra B.; Lowry, John P.

2005-01-01

In this communication we review selected experiments involving the use of carbon paste electrodes (CPEs) to monitor and measure brain tissue O2 levels in awake freely-moving animals. Simultaneous measurements of rCBF were performed using the H2 clearance technique. Voltammetric techniques used include both differential pulse (O2) and constant potential amperometry (rCBF). Mild hypoxia and hyperoxia produced rapid changes (decrease and increase respectively) in the in vivo O2 signal. Neuronal activation (tail pinch and stimulated grooming) produced similar increases in both O2and rCBF indicating that CPE O2currents provide an index of increases in rCBF when such increases exceed O2 utilization. Saline injection produced a transient increase in the O2 signal while chloral hydrate produced slower more long-lasting changes that accompanied the behavioral changes associated with anaesthesia. Acetazolamide increased O2 levels through an increase in rCBF.

CEREBRAL BLOOD FLOW AND METABOLISM IN ANXIETY AND ANXIETY DISORDERS

PubMed Central

Mathew, Roy J.

1994-01-01

Anxiety disorders are some of the commonest psychiatric disorders and anxiety commonly co-exists with other psychiatric conditions. Anxiety can also be a normal emotion. Thus, study of the neurobiological effects of anxiety is of considerable significance. In the normal brain, cerebral blood flow (CBF) and metabolism (CMR) serve as indices of brain function. CBF/CMR research is expected to provide new insight into alterations in brain function in anxiety disorders and other psychiatric disorders. Possible associations between stress I anxiety I panic and cerebral ischemia I stroke give additional significance to the effects of anxiety on CBF. With the advent of non-invasive techniques, study of CBF/CMR in anxiety disorders became easier. A large numbers of research reports are available on the effects of stress, anxiety and panic on CBF/CMR in normals and anxiety disorder patients. This article reviews the available human research on this topic. PMID:21743685

Combination of volume and perfusion parameters reveals different types of grey matter changes in schizophrenia.

PubMed

Xu, Lixue; Qin, Wen; Zhuo, Chuanjun; Liu, Huaigui; Zhu, Jiajia; Yu, Chunshui

2017-03-27

Diverse brain structural and functional changes have been reported in schizophrenia. Identifying different types of brain changes may help to understand the neural mechanisms and to develop reliable biomarkers in schizophrenia. We aimed to categorize different grey matter changes in schizophrenia based on grey matter volume (GMV) and cerebral blood flow (CBF). Structural and perfusion magnetic resonance imaging data were acquired in 100 schizophrenia patients and 95 healthy comparison subjects. Voxel-based GMV comparison was used to show structural changes, CBF analysis was used to demonstrate functional changes. We identified three types of grey matter changes in schizophrenia: structural and functional impairments in the anterior cingulate cortex and insular cortex, displaying reduction in both GMV and CBF; structural impairment with preserved function in the frontal and temporal cortices, demonstrating decreased GMV with normal CBF; pure functional abnormality in the anterior cingulate cortex and lateral prefrontal cortex and putamen, showing altered CBF with normal GMV. By combination of GMV and CBF, we identified three types of grey matter changes in schizophrenia. These findings may help to understand the complex manifestations and to develop reliable biomarkers in schizophrenia.

Changes in cerebral blood flow after cognitive behavior therapy in patients with panic disorder: a SPECT study

PubMed Central

Seo, Ho-Jun; Choi, Young Hee; Chung, Yong-An; Rho, Wangku; Chae, Jeong-Ho

2014-01-01

Aim Inconsistent results continue to be reported in studies that examine the neural correlates of cognitive behavioral therapy (CBT) in patients with panic disorder. We examined the changes in regional cerebral blood flow (rCBF) associated with the alleviation of anxiety by CBT in panic patients. Methods The change in rCBF and clinical symptoms before and after CBT were assessed using single photon emission computed tomography and various clinical measures were analyzed. Results Fourteen subjects who completed CBT showed significant improvements in symptoms on clinical measures, including the Panic and Agoraphobic Scale and the Anxiety Sensitivity Index-Revised. After CBT, increased rCBF was detected in the left postcentral gyrus (BA 43), left precentral gyrus (BA 4), and left inferior frontal gyrus (BA 9 and BA 47), whereas decreased rCBF was detected in the left pons. Correlation analysis of the association between the changes in rCBF and changes in each clinical measure did not show significant results. Conclusion We found changes in the rCBF associated with the successful completion of CBT. The present findings may help clarify the effects of CBT on changes in brain activity in panic disorder. PMID:24790449

Vertigo-related cerebral blood flow changes on magnetic resonance imaging.

PubMed

Chang, Feiyan; Li, Zhongshi; Xie, Sheng; Liu, Hui; Wang, Wu

2014-11-01

A prospective study using magnetic resonance imaging on a consecutive cohort of patients with cervical vertigo. To quantitatively investigate the cerebral blood flow (CBF) changes associated with cervical vertigo by using 3-dimensional pseudocontinuous arterial spin labeling. Previous studies reported blood flow velocity reduction in posterior circulation during vertigo. However, the detailed information of CBF related to cervical vertigo has not been provided. A total of 33 patients with cervical vertigo and 14 healthy volunteers were recruited in this study. Three-dimensional pseudocontinuous arterial spin labeling was performed on each subject to evaluate the CBF before and after the cervical hyperextension-hyperflexion movement tests, which was used to induce cervical vertigo. Repeated-measures analysis of variance was conducted to assess the effect of subjects and tests. There were time effects of CBF in the territory of bilateral superior cerebellar artery, bilateral posterior cerebral artery, bilateral middle cerebral artery, and right anterior cerebral artery, but no group effect was observed. The analysis of CBF revealed a significant main effect of tests (P=0.024) and participants (P=0.038) in the dorsal pons. Cervical vertigo onset may be related to CBF reduction in the dorsal pons, which sequentially evokes the vestibular nuclei. 2.

Cerebral blood flow associated with creative performance: a comparative study.

PubMed

Chávez-Eakle, Rosa Aurora; Graff-Guerrero, Ariel; García-Reyna, Juan-Carlos; Vaugier, Víctor; Cruz-Fuentes, Carlos

2007-11-15

Creativity is important for social survival and individual wellbeing; science, art, philosophy and technology have been enriched and expanded by this trait. To our knowledge this is the first study probing differences in brain cerebral blood flow (CBF) between highly creative individuals (scientists and/or artists socially recognized for their contributions to their fields with creativity indexes corresponding to the 99% percentile) and average control subjects while performing a verbal task from the Torrance Tests of Creative Thinking. Additionally, we correlated CBF with creativity dimensions such as fluency, originality and flexibility. Subjects with a high creative performance showed greater CBF activity in right precentral gyrus, right culmen, left and right middle frontal gyrus, right frontal rectal gyrus, left frontal orbital gyrus, and left inferior gyrus (BA 6, 10, 11, 47, 20), and cerebellum; confirming bilateral cerebral contribution. These structures have been involved in cognition, emotion, working memory, and novelty response. The score on the three creativity dimensions--fluency, originality, and flexibility--correlated with CBF activation in right middle frontal gyrus and right rectal gyrus (Brodmann Area 6, 11). Moreover, fluency and flexibility strongly correlated with CBF in left inferior frontal gyrus and originality correlated with CBF in left superior temporal gyrus and cerebellar tonsil. These findings suggest an integration of perceptual, volitional, cognitive and emotional processes in creativity. The higher CBF found in particular brain regions of highly creative individuals during the performance of a creative task provides evidence of a specific neural network related to the creative process.

Measurement of ciliary beat frequency using ultra-high resolution optical coherence tomography

NASA Astrophysics Data System (ADS)

Chen, Jason J.; Jing, Joseph C.; Su, Erica; Badger, Christopher; Coughlan, Carolyn A.; Chen, Zhongping; Wong, Brian J. F.

2016-02-01

Ciliated epithelial cells populate up to 80% of the surface area of the human airway and are responsible for mucociliary transport, which is the key protective mechanism that provides the first line of defense in the respiratory tract. Cilia beat in a rhythmic pattern and may be easily affected by allergens, pollutants, and pathogens, altering ciliary beat frequency (CBF) subsequently. Diseases including cystic fibrosis, chronic obstructive pulmonary disease, and primary ciliary dyskinesia may also decrease CBF. CBF is therefore a critical component of respiratory health. The current clinical method of measuring CBF is phase-contrast microscopy, which involves a tissue biopsy obtained via brushing of the nasal cavity. While this method is minimally invasive, the tissue sample must be oriented to display its profile view, making the visualization of a single layer of cilia challenging. In addition, the conventional method requires subjective analysis of CBF, e.g., manually counting by visual inspection. On the contrary, optical coherence tomography (OCT) has been used to study the retina in ophthalmology as well as vasculature in cardiology, and offers higher resolution than conventional computed tomography and magnetic resonance imaging. Based on this technology, our lab specifically developed an ultra-high resolution OCT system to image the microstructure of the ciliated epithelial cells. Doppler analysis was also performed to determine CBF. Lastly, we also developed a program that utilizes fast Fourier transform to determine CBF under phase-contrast microscopy, providing a more objective method compared to the current method.

Distinct pattern of cerebral blood flow alterations specific to schizophrenics experiencing auditory verbal hallucinations with and without insight: a pilot study.

PubMed

Jing, Rixing; Huang, Jiangjie; Jiang, Deguo; Lin, Xiaodong; Ma, Xiaolei; Tian, Hongjun; Li, Jie; Zhuo, Chuanjun

2018-01-23

Schizophrenia is associated with widespread and complex cerebral blood flow (CBF) disturbance. Auditory verbal hallucinations (AVH) and insight are the core symptoms of schizophrenia. However, to the best of our knowledge, very few studies have assessed the CBF characteristics of the AVH suffered by schizophrenic patients with and without insight. Based on our previous findings, Using a 3D pseudo-continuous ASL (pcASL) technique, we investigated the differences in AVH-related CBF alterations in schizophrenia patients with and without insight. We used statistical parametric mapping (SPM8) and statistical non-parametric mapping (SnPM13) to perform the fMRI analysis. We found that AVH-schizophrenia patients without insight showed an increased CBF in the left temporal pole and a decreased CBF in the right middle frontal gyrus when compared to AVH-schizophrenia patients with insight. Our novel findings suggest that AVH-schizophrenia patients without insight possess a more complex CBF disturbance. Simultaneously, our findings also incline to support the idea that the CBF aberrant in some specific brain regions may be the common neural basis of insight and AVH. Our findings support the mostly current hypotheses regarding AVH to some extent. Although our findings come from a small sample, it provide the evidence that indicate us to conduct a larger study to thoroughly explore the mechanisms of schizophrenia, especially the core symptoms of AVHs and insight.

Relationship of 133Xe cerebral blood flow to middle cerebral arterial flow velocity in men at rest

NASA Technical Reports Server (NTRS)

Clark, J. M.; Skolnick, B. E.; Gelfand, R.; Farber, R. E.; Stierheim, M.; Stevens, W. C.; Beck, G. Jr; Lambertsen, C. J.

1996-01-01

Cerebral blood flow (CBF) was measured by 133Xe clearance simultaneously with the velocity of blood flow through the left middle cerebral artery (MCA) over a wide range of arterial PCO2 in eight normal men. Average arterial PCO2, which was varied by giving 4% and 6% CO2 in O2 and by controlled hyperventilation on O2, ranged from 25.3 to 49.9 mm Hg. Corresponding average values of global CBF15 were 27.2 and 65.0 ml 100 g min-1, respectively, whereas MCA blood-flow velocity ranged from 42.8 to 94.2 cm/s. The relationship of CBF to MCA blood-flow velocity over the imposed range of arterial PCO2 was described analytically by a parabola with the equation: CBF = 22.8 - 0.17 x velocity + 0.006 x velocity2 The observed data indicate that MCA blood-flow velocity is a useful index of CBF response to change in arterial PCO2 during O2 breathing at rest. With respect to baseline values measured while breathing 100% O2 spontaneously, percent changes in velocity were significantly smaller than corresponding percent changes in CBF at increased levels of arterial PCO2 and larger than CBF changes at the lower arterial PCO2. These observed relative changes are consistent with MCA vasodilation at the site of measurement during exposure to progressive hypercapnia and also during extreme hyperventilation hypocapnia.

Comparing cerebrovascular reactivity measured using BOLD and cerebral blood flow MRI: The effect of basal vascular tension on vasodilatory and vasoconstrictive reactivity

PubMed Central

Halani, Sheliza; Kwinta, Jonathan B.; Golestani, Ali M.; Khatamian, Yasha B.; Chen, J. Jean

2016-01-01

Cerebrovascular reactivity (CVR) is an important metric of cerebrovascular health. While the BOLD fMRI method in conjunction with carbon-dioxide (CO2) based vascular manipulation has been the most commonly used, the BOLD signal is not a direct measure of vascular changes, and the use of arterial-spin labeling (ASL) cerebral blood flow (CBF) imaging is increasingly advocated. Nonetheless, given the differing dependencies of BOLD and CBF on vascular baseline conditions and the diverse CO2 manipulation types currently used in the literature, knowledge of potential biases introduced by each technique is critical for the interpretation of CVR measurements. In this work, we use simultaneous BOLD-CBF acquisitions during both vasodilatory (hypercapnic) and vasoconstrictive (hypocapnic) stimuli to measure CVR. We further imposed different levels of baseline vascular tension by inducing hypercapnic and hypocapnic baselines, separately from normocapnia by 4 mm Hg. We saw significant and diverse dependencies on vascular stimulus and baseline condition in both BOLD and CBF CVR measurements: (i) BOLD-based CVR is more sensitive to basal vascular tension than CBF-based CVR; (ii) the use of a combination of vasodilatory and vasoconstrictive stimuli maximizes the sensitivity of CBF-based CVR to vascular tension changes; (iii) the BOLD and CBF vascular response delays are both significantly lengthened at predilated baseline. As vascular tension can often be altered by potential pathology, our findings are important considerations when interpreting CVR measurements in health and disease. PMID:25655446

Functional PET Evaluation of the Photosensitive Baboon

PubMed Central

Szabó, C. Ákos; Salinas, Felipe S; Narayana, Shalini

2011-01-01

The baboon provides a unique, natural model of epilepsy in nonhuman primates. Additionally, photosensitivity of the epileptic baboon provides an important window into the mechanism of human idiopathic generalized epilepsies. In order to better understand the networks underlying this model, our group utilized functional positron emission tomography (PET) to compare cerebral blood flow (CBF) changes occurring during intermittent light stimulation (ILS) and rest between baboons photosensitive, epileptic (PS) and asymptomatic, control (CTL) animals. Our studies utilized subtraction and covariance analyses to evaluate CBF changes occurring during ILS across activation and resting states, but also evaluated CBF correlations with ketamine doses and interictal epileptic discharge (IED) rate during the resting state. Furthermore, our group also assessed the CBF responses related to variation of ILS in PS and CTL animals. CBF changes in the subtraction and covariance analyses reveal the physiological response and visual connectivity in CTL animals and pathophysiological networks underlying responses associated with the activation of ictal and interictal epileptic discharges in PS animals. The correlation with ketamine dose is essential to understanding differences in CBF responses between both groups, and correlations with IED rate provides an insight into an epileptic network independent of visual activation. Finally, the ILS frequency dependent changes can help develop a framework to study not only spatial connectivity but also the temporal sequence of regional activations and deactivations related to ILS. The maps generated by the CBF analyses will be used to target specific nodes in the epileptic network for electrophysiological evaluation using intracranial electrodes. PMID:22276085

Reduced Perfusion in Broca’s Area in Developmental Stuttering

PubMed Central

Desai, Jay; Huo, Yuankai; Wang, Zhishun; Bansal, Ravi; Williams, Steven C. R.; Lythgoe, David; Zelaya, Fernando O.; Peterson, Bradley S.

2016-01-01

Objective To study resting cerebral blood flow in children and adults with developmental stuttering. Methods We acquired pulsed arterial spin labeling magnetic resonance imaging data in 26 participants with stuttering and 36 healthy, fluent controls. While covarying for age, sex, and IQ, we compared perfusion values voxel-wise across diagnostic groups and assessed correlations of perfusion with stuttering severity within the stuttering group and with measures of motor speed in both groups. Results We detected lower regional Cerebral Blood Flow (rCBF) at rest in the stuttering group compared to healthy controls in Broca’s area bilaterally and the superior frontal gyrus. rCBF values in Broca’s area bilaterally correlated inversely with the severity of stuttering and extended posteriorly into other portions of the language loop. We also found increased rCBF in cerebellar nuclei and parietal cortex in the stuttering group compared to healthy controls. Findings were unchanged in child-only analyses and when excluding participants with comorbid illnesses or those taking medication. Conclusions rCBF is reduced in Broca’s region in persons who stutter. More severe stuttering is associated with even greater reductions in rCBF to Broca’s region, additive to the underlying putative trait reduction in rCBF relative to control values. Moreover, a greater abnormality in rCBF in the posterior language loop is associated with more severe symptoms, suggesting that a common pathophysiology throughout the language loop likely contributes to stuttering severity. PMID:28035724

Carbofuran removal in continuous-photocatalytic reactor: Reactor optimization, rate-constant determination and carbofuran degradation pathway analysis.

PubMed

Vishnuganth, M A; Remya, Neelancherry; Kumar, Mathava; Selvaraju, N

2017-05-04

Carbofuran (CBF) removal in a continuous-flow photocatalytic reactor with granular activated carbon supported titanium dioxide (GAC-TiO 2 ) catalyst was investigated. The effects of feed flow rate, TiO 2 concentration and addition of supplementary oxidants on CBF removal were investigated. The central composite design (CCD) was used to design the experiments and to estimate the effects of feed flow rate and TiO 2 concentration on CBF removal. The outcome of CCD experiments demonstrated that reactor performance was influenced mainly by feed flow rate compared to TiO 2 concentration. A second-order polynomial model developed based on CCD experiments fitted the experimental data with good correlation (R 2 ∼ 0.964). The addition of 1 mL min -1 hydrogen peroxide has shown complete CBF degradation and 76% chemical oxygen demand removal under the following operating conditions of CBF ∼50 mg L -1 , TiO 2 ∼5 mg L -1 and feed flow rate ∼82.5 mL min -1 . Rate constant of the photodegradation process was also calculated by applying the kinetic data in pseudo-first-order kinetics. Four major degradation intermediates of CBF were identified using GC-MS analysis. As a whole, the reactor system and GAC-TiO 2 catalyst used could be constructive in cost-effective CBF removal with no impact to receiving environment through getaway of photocatalyst.

Reduced perfusion in Broca's area in developmental stuttering.

PubMed

Desai, Jay; Huo, Yuankai; Wang, Zhishun; Bansal, Ravi; Williams, Steven C R; Lythgoe, David; Zelaya, Fernando O; Peterson, Bradley S

2017-04-01

To study resting cerebral blood flow in children and adults with developmental stuttering. We acquired pulsed arterial spin labeling magnetic resonance imaging data in 26 participants with stuttering and 36 healthy, fluent controls. While covarying for age, sex, and IQ, we compared perfusion values voxel-wise across diagnostic groups and assessed correlations of perfusion with stuttering severity within the stuttering group and with measures of motor speed in both groups. We detected lower regional Cerebral Blood Flow (rCBF) at rest in the stuttering group compared with healthy controls in Broca's area bilaterally and the superior frontal gyrus. rCBF values in Broca's area bilaterally correlated inversely with the severity of stuttering and extended posteriorly into other portions of the language loop. We also found increased rCBF in cerebellar nuclei and parietal cortex in the stuttering group compared with healthy controls. Findings were unchanged in child-only analyses and when excluding participants with comorbid illnesses or those taking medication. rCBF is reduced in Broca's region in persons who stutter. More severe stuttering is associated with even greater reductions in rCBF to Broca's region, additive to the underlying putative trait reduction in rCBF relative to control values. Moreover, a greater abnormality in rCBF in the posterior language loop is associated with more severe symptoms, suggesting that a common pathophysiology throughout the language loop likely contributes to stuttering severity. Hum Brain Mapp 38:1865-1874, 2017. © 2017 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Facial nerve stimulation in normal pigs and healthy human volunteers: transitional development of a medical device for the emergency treatment of ischemic stroke.

PubMed

Sanchez, Olivia; García, Andrea; Castro-Prado, Fernando; Perez, Miriam; Lara-Estrada, Rafael; Ramirez-Meza, Martin; Godinez, Montserrat; Coco, Michael L; Azpiroz, Joaquín; Borsody, Mark K; Sacristán, Emilio

2018-02-15

Magnetic stimulation of the facial nerve has been tested in preclinical studies as a new, non-invasive emergency treatment of ischemic stroke that acts by increasing cerebral blood flow (CBF). The objective of the studies reported herein was to identify minimal stimulation parameters that increase CBF in large animals and then test those stimulation parameters in healthy volunteers for safety, tolerability, and effectiveness at increasing CBF. This translational research is necessary preparation for clinical studies in ischemic stroke patients. Initial experiments in anesthetized Yorkshire pigs were undertaken in order to identify the lowest stimulus power and duration that increase CBF. A full 3 × 3 factorial design was used to evaluate magnetic stimulation of the facial nerve at various stimulation powers (1.3, 1.6, and 1.9 Tesla field strength at coil surface) and for various durations (2, 3.5, and 5 min). CBF was measured with contrast MRI perfusion imaging and the internal carotid arteries were assessed with MR angiography. Magnetic facial nerve stimulation with parameters identified in the pig study was then applied to 35 healthy volunteers. Safety was assessed with adverse event reports and by medical examination. Tolerability was defined as each volunteer's ability to withstand at least 2 min of stimulation. Volunteers could determine the maximum power of stimulation they received during a ramp-up period. In pigs, unilateral facial nerve stimulation increased CBF by as much as 77% over pre-stimulation baseline when administered across a range of 1.3-1.9 Tesla power and for 2- to 5-min duration. No clear dose-response relationship could be observed across this range, but lower powers and durations than these were markedly less effective. The effect of a single stimulation lasted 90 min. A second stimulation delivered 100 min after the first stimulation sustained the increased CBF without evidence of tachyphylaxis. In human, bilateral facial nerve stimulation caused only non-serious adverse events that were limited to the 2-min stimulation period. Tolerability was greatly improved by gentle encouragement from the study staff, which enabled most volunteers to tolerate 1.6-1.8 Tesla of stimulation power. CBF measures taken approximately 10 min after stimulation demonstrated on average a 32 ± 6% increase in CBF, with ≥ 25% increases in CBF occurring in 10 of the 31 volunteers who had adequate CBF measurements. The minimal effective stimulation parameters defined by increased CBF, as identified in the pig study, translated into safe, tolerable, and effective stimulation of healthy volunteers. These results support the future development and evaluation of non-invasive facial nerve stimulation for the emergency treatment of ischemic stroke. Trial Registration retrospectively registered with clinicaltrials.gov NRV_P1_01_15 on June 6, 2017.

Decrease of oxygen difference between arterial blood and cerebrospinal fluid after intravenous injection of sodium bicarbonate in hyperoxic patients, anaesthetized, paralyzed and artificially ventilated.

PubMed

Ryba, M; Pokorski, M

1981-01-01

In the subjects being prepared to neurosurgical treatment an i.v. injection of NaHCO3 (2 mEq/kg) elicited a significant increase in PCSFO2 from 69 +/- 6.4 (SEM) Torr to 75.5 +/- 3.9 (SEM) Torr. This change ws accompanied by a significant drop of PaO2 from 150.5 +/- 6.0 Torr to 138.0 +/- 5.8 Torr. Metabolic alkalosis (pH 7.54 +/- 0.02 SEM) elicited by bicarbonate administration was accompanied by arterial blood hyperoxia. Both these factors reduce the cerebral flow (CBF). We suppose that changes in the blood--CSF oxygen relationship reflect the presence of a mechanism which might protect the CNS against a decrease in CBF.

Caffeine and human cerebral blood flow: A positron emission tomography study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cameron, O.G.; Modell, J.G.; Hariharan, M.

1990-01-01

Positron emission tomography (PET) was used to quantify the effect of caffeine on whole brain and regional cerebral blood flow (CBF) in humans. A mean dose of 250 mg of caffeine produced approximately a 30% decrease in whole brain CBF; regional differences in caffeine effect were not observed. Pre-caffeine CBF strongly influenced the magnitude of the caffeine-induced decrease. Caffeine decreased p{sub a}CO{sub 2} and increased systolic blood pressure significantly; the change in p{sub a}CO{sub 2} did not account for the change in CBF. Smaller increases in diastolic blood pressure, heart rate, plasma epinephrine and norepinephrine, and subjectively reported anxiety weremore » also observed.« less

Cerebral blood flow asymmetries in headache-free migraineurs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levine, S.R.; Welch, K.M.; Ewing, J.R.

1987-11-01

Regional cerebral blood flow (rCBF) asymmetries were studied in controls and patients with common and classic/complicated migraine using /sup 133/Xe inhalation with 8 homologously situated external collimators over each cerebral hemisphere. Migraine patients as a group more frequently had posterior rCBF asymmetries than controls (p less than 0.03). Although there were no differences in the number of anterior rCBF asymmetries, migraine patients had 2 or more asymmetric probe pairs more often than controls (p less than 0.02). The posterior rCBF asymmetries, consistent with the site of activation of many migraine attacks, may be related to more labile control of themore » cerebral circulation.« less

The Cbf5-Nop10 Complex is a Molecular Bracket that Organizes Box H/ACA RNPs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamma, Tomoko; Reichow, Steve L.; Varani, Gabriele

2005-12-01

Box H/ACA ribonucleoprotein particles (RNPs) catalyze RNA pseudouridylation and direct processing of ribosomal RNA, and are essential architectural components of vertebrate telomerases. H/ACA RNPs comprise four proteins and a multihelical RNA. Two proteins, Cbf5 and Nop10, suffice for basal enzymatic activity in an archaeal in vitro system. We now report their cocrystal structure at 1.95-A resolution. We find that archaeal Cbf5 can assemble with yeast Nop10 and with human telomerase RNA, consistent with the high sequence identity of the RNP componenets between archaea and eukarya. Thus, the Cbf5-Nop10 architecture is phylogenetically conserved. The structure shows how Nop10 buttresses the activemore » site of Cbf5, and it reveals two basic troughs that bidirectionally extend the active site cleft. Mutagenesis results implicate an adjacent basic patch in RNA binding. This tripartite RNA-binding surface may function as a molecular bracket that organizes the multihelical H/ACA and telomerase RNAs.« less

Effect of ethanol on cerebral blood flow (CBF) and metabolism (CMRO2) in conscious sheep

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krasney, J.A.; Zubkov, B.; Iwamoto, J.

1991-03-11

A moderate dose of ethanol severely depresses CBF and CMRO2 in the awake sheep fetus. However, the effects of ethanol on CBF and CMRO2 in the adult are unclear. The same dose of ethanol was infused for 2 hr in 5 ewes instrumented with aortic, left ventricular and sagittal sinus catheters. Ethanol caused ataxia accompanied by early modest and variable increases of total and regional CBF and CMRO2, followed by later modest and variable decreases of total and regional CBF (cerebellum) and CMRO2. Ethanol caused a cerebral transcapillary fluid shift as indicated by significant increases of the arterial-cerebral venous differencesmore » for hematocrit and hemoglobin. Brain wet-dry ratios increased by 10% above control levels. However, cerebral venous pressures were unchanged. The authors conclude that the adult cerebral response to ethanol differs quantitatively from that of the fetus. The functional significance of the cerebral fluid shift is unclear.« less

Neurovascular unit impairment in early Alzheimer's disease measured with magnetic resonance imaging.

PubMed

van de Haar, Harm J; Jansen, Jacobus F A; van Osch, Matthias J P; van Buchem, Mark A; Muller, Majon; Wong, Sau May; Hofman, Paul A M; Burgmans, Saartje; Verhey, Frans R J; Backes, Walter H

2016-09-01

The neurovascular unit, which protects neuronal cells and supplies them with essential molecules, plays an important role in the pathophysiology of Alzheimer's Disease (AD). The aim of this study was to noninvasively investigate 2 linked functional elements of the neurovascular unit, blood-brain barrier (BBB) permeability and cerebral blood flow (CBF), in patients with early AD and healthy controls. Therefore, both dynamic contrast-enhanced magnetic resonance imaging and arterial spin labeling magnetic resonance imaging were applied to measure BBB permeability and CBF, respectively. The patients with early AD showed significantly lower CBF and local blood volume in the gray matter, compared with controls. In the patients, we also found that a reduction in CBF is correlated with an increase in leakage rate. This finding supports the hypothesis that neurovascular damage, and in particular impairment of the neurovascular unit constitutes the pathophysiological link between CBF reduction and BBB impairment in AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Cerebral blood flow and red cell delivery in normal subjects and in multiple sclerosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swank, R.L.; Roth, J.G.; Woody, D.C. Jr.

1983-01-01

Regional cerebral blood flow (rCBF) was determined in 77 normal females and 53 normal males of different ages and in 26 men and 45 women with multiple sclerosis by the inhalation of radioactive Xe133 method. In the normal subjects the CBF was relatively high in the teens and fell, at first rapidly and then slowly in both sexes with age. During adult life the flow in females was significantly higher than in males. The delivery of packed red cells (RCD) was determined by multiplying the CBF by the percentage concentration of red cells (HCT). The RCD for both sexes wasmore » nearly the same. In the patients with multiple sclerosis there occurred a progressive generalized decrease in CBF and in RCD with age which was significantly greater than observed in normal subjects. The rate of decrease in CBF and RCD correlated directly with the rate of progress of the disease.« less

Hypothyroidism Is Associated With Coronary Endothelial Dysfunction in Women

PubMed Central

Sara, Jaskanwal D; Zhang, Ming; Gharib, Hossein; Lerman, Lilach O; Lerman, Amir

2015-01-01

Background Hypothyroidism is associated with an increased risk of coronary artery disease, beyond that which can be explained by its association with conventional cardiovascular risk factors. Coronary endothelial dysfunction precedes atherosclerosis, has been linked to adverse cardiovascular events, and may account for some of the increased risk in patients with hypothyroidism. The aim of this study was to determine whether there is an association between epicardial and microvascular coronary endothelial dysfunction and hypothyroidism. Methods and Results In 1388 patients (mean age 50.5 [12.3] years, 34% male) presenting with stable chest pain to Mayo Clinic, Rochester, MN for diagnostic coronary angiography, and who were found to have nonobstructive coronary artery disease (<40% stenosis), we invasively assessed coronary artery endothelial-dependent microvascular and epicardial function by evaluating changes in coronary blood flow (% Δ CBF Ach) and diameter (% Δ CAD Ach), respectively, in response to intracoronary infusions of acetylcholine. Patients were divided into 2 groups: hypothyroidism, defined as a documented history of hypothyroidism or a thyroid-stimulating hormone (TSH) >10.0 mU/mL, n=188, and euthyroidism, defined as an absence of a history of hypothyroidism in the clinical record and/or 0.3

Arterial spin labelling reveals prolonged arterial arrival time in idiopathic Parkinson's disease.

PubMed

Al-Bachari, Sarah; Parkes, Laura M; Vidyasagar, Rishma; Hanby, Martha F; Tharaken, Vivek; Leroi, Iracema; Emsley, Hedley C A

2014-01-01

Idiopathic Parkinson's disease (IPD) is the second most common neurodegenerative disease, yet effective disease modifying treatments are still lacking. Neurodegeneration involves multiple interacting pathological pathways. The extent to which neurovascular mechanisms are involved is not well defined in IPD. We aimed to determine whether novel magnetic resonance imaging (MRI) techniques, including arterial spin labelling (ASL) quantification of cerebral perfusion, can reveal altered neurovascular status (NVS) in IPD. Fourteen participants with IPD (mean ± SD age 65.1 ± 5.9 years) and 14 age and cardiovascular risk factor matched control participants (mean ± SD age 64.6 ± 4.2 years) underwent a 3T MRI scan protocol. ASL images were collected before, during and after a 6 minute hypercapnic challenge. FLAIR images were used to determine white matter lesion score. Quantitative images of cerebral blood flow (CBF) and arterial arrival time (AAT) were calculated from the ASL data both at rest and during hypercapnia. Cerebrovascular reactivity (CVR) images were calculated, depicting the change in CBF and AAT relative to the change in end-tidal CO2. A significant (p = 0.005) increase in whole brain averaged baseline AAT was observed in IPD participants (mean ± SD age 1532 ± 138 ms) compared to controls (mean ± SD age 1335 ± 165 ms). Voxel-wise analysis revealed this to be widespread across the brain. However, there were no statistically significant differences in white matter lesion score, CBF, or CVR between patients and controls. Regional CBF, but not AAT, in the IPD group was found to correlate positively with Montreal cognitive assessment (MoCA) scores. These findings provide further evidence of alterations in NVS in IPD.

Exercise-induced decrease in insular cortex rCBF during postexercise hypotension.

PubMed

Lamb, Kala; Gallagher, Kevin; McColl, Roderick; Mathews, Dana; Querry, Ross; Williamson, Jon W

2007-04-01

The insular cortex (IC), a region of the brain involved in blood pressure (BP) modulation, shows decreases in regional cerebral blood flow (rCBF) during postexercise hypotension (PEH). To determine whether changes in IC neural activity were caused by prior exercise or by changes in BP, this investigation compared patterns of rCBF during periods of hypotension, which was induced by prior exercise (i.e., PEH) and sodium nitroprusside (SNP) infusion and a cold pressor (CP), to restore BP. Ten subjects were studied on three different days with randomly assigned conditions: i) resting baseline; ii) PEH; and iii) SNP-induced hypotension (matched to the PEH BP decrease). Data were collected for heart rate (HR) and mean BP, and rCBF was assessed using single-photon emission computed tomography (SPECT) as an index of brain activation. Using ANOVA across conditions, there were differences (P<0.05; mean +/- SD) from baseline during PEH for HR (+12 +/- 3 bpm) and mean BP (-8 +/- 2 mm Hg) and during SNP-induced hypotension (HR = +15 +/- 4 bpm; MBP = -9 +/- 2 mm Hg), with no differences between PEH and SNP. After exercise, there were decreases (P<0.05) in the leg sensorimotor area, anterior cingulate, and the right and left inferior thalamus, right inferior insula, and left anterior insular regions. During SNP-induced hypotension, there were significant increases in the right and left inferior thalamus and the right and left inferior anterior IC. CP during PEH increased BP and IC activity. Data show that reductions in IC neural activity are not caused by acute BP decreases. Findings suggest that exercise can lead to a temporary decrease in IC neural activity, which may be a significant neural factor contributing to PEH.

The effect of black tea and caffeine on regional cerebral blood flow measured with arterial spin labeling

PubMed Central

Vidyasagar, Rishma; Greyling, Arno; Draijer, Richard; Corfield, Douglas R; Parkes, Laura M

2013-01-01

Black tea consumption has been shown to improve peripheral vascular function. Its effect on brain vasculature is unknown, though tea contains small amounts of caffeine, a psychoactive substance known to influence cerebral blood flow (CBF). We investigated the effects on CBF due to the intake of tea components in 20 healthy men in a double-blinded, randomized, placebo-controlled study. On separate days, subjects received a single dose of 184 mg caffeine (equivalent to one strong espresso coffee), 2,820 mg black tea solids containing 184 mg caffeine (equivalent to 6 cups of tea), 2,820 mg decaffeinated black tea solids, or placebo. The CBF and cerebrovascular reactivity (CVR) to hypercapnia were measured with arterial spin labeled magnetic resonance imaging (MRI) before and 2 hours after administration. We found a significant global reduction with caffeine (20%) and tea (21%) in gray matter CBF, with no effect of decaffeinated tea, suggesting that only caffeine influences CBF acutely. Voxelwise analysis revealed the effect of caffeine to be regionally specific. None of the interventions had an effect on CVR. Additional research is required to conclude on the physiologic relevance of these findings and the chronic effects of caffeine and tea intake on CBF. PMID:23486295

Interindividual variations of cerebral blood flow, oxygen delivery, and metabolism in relation to hemoglobin concentration measured by positron emission tomography in humans.

PubMed

Ibaraki, Masanobu; Shinohara, Yuki; Nakamura, Kazuhiro; Miura, Shuichi; Kinoshita, Fumiko; Kinoshita, Toshibumi

2010-07-01

Regional cerebral blood flow (CBF) and oxygen metabolism can be measured by positron emission tomography (PET) with (15)O-labeled compounds. Hemoglobin (Hb) concentration of blood, a primary determinant of arterial oxygen content (C(a)O(2)), influences cerebral circulation. We investigated interindividual variations of CBF, cerebral blood volume (CBV), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO(2)) in relation to Hb concentration in healthy human volunteers (n=17) and in patients with unilateral steno-occlusive disease (n=44). For the patients, data obtained only from the contralateral hemisphere (normal side) were analyzed. The CBF and OEF were inversely correlated with Hb concentration, but CMRO(2) was independent of Hb concentration. Oxygen delivery defined as a product of C(a)O(2) and CBF (C(a)O(2) CBF) increased with a rise of Hb concentration. The analysis with a simple oxygen model showed that oxygen diffusion parameter (L) was constant over the range of Hb concentration, indicating that a homeostatic mechanism controlling CBF is necessary to maintain CMRO(2). The current findings provide important knowledge to understand the control mechanism of cerebral circulation and to interpret the (15)O PET data in clinical practice.

The severity of anaemia depletes cerebrovascular dilatory reserve in children with sickle cell disease: a quantitative magnetic resonance imaging study.

PubMed

Kosinski, Przemyslaw D; Croal, Paula L; Leung, Jackie; Williams, Suzan; Odame, Isaac; Hare, Gregory M T; Shroff, Manohar; Kassner, Andrea

2017-01-01

Overt ischaemic stroke is one of the most devastating complications in children with sickle cell disease (SCD). The compensatory response to anaemia in SCD includes an increase in cerebral blood flow (CBF) by accessing cerebrovascular dilatory reserve. Exhaustion of dilatory reserve secondary to anaemic stress may lead to cerebral ischaemia. The purpose of this study was to investigate CBF and cerebrovascular reactivity (CVR) using magnetic resonance imaging (MRI) in children with SCD and to correlate these with haematological markers of anaemia. Baseline CBF was measured using arterial spin labelling. Blood-oxygen level-dependent MRI in response to a CO 2 stimulus was used to acquire CVR. In total, 28 children with SCD (23 not on any disease-modifying treatment, 5 on chronic transfusion) and 22 healthy controls were imaged using MRI. Transfusion patients were imaged at two time points to assess the effect of changes in haematocrit after a transfusion cycle. In children with SCD, CBF was significantly elevated compared to healthy controls, while CVR was significantly reduced. Both measures were significantly correlated with haematocrit. For transfusion patients, CBF decreased and CVR increased following a transfusion cycle. Lastly, a significant correlation was observed between CBF and CVR in both children with SCD and healthy controls. © 2016 John Wiley & Sons Ltd.

Characterizing Resting-State Brain Function Using Arterial Spin Labeling

PubMed Central

Jann, Kay; Wang, Danny J.J.

2015-01-01

Abstract Arterial spin labeling (ASL) is an increasingly established magnetic resonance imaging (MRI) technique that is finding broader applications in studying the healthy and diseased brain. This review addresses the use of ASL to assess brain function in the resting state. Following a brief technical description, we discuss the use of ASL in the following main categories: (1) resting-state functional connectivity (FC) measurement: the use of ASL-based cerebral blood flow (CBF) measurements as an alternative to the blood oxygen level-dependent (BOLD) technique to assess resting-state FC; (2) the link between network CBF and FC measurements: the use of network CBF as a surrogate of the metabolic activity within corresponding networks; and (3) the study of resting-state dynamic CBF-BOLD coupling and cerebral metabolism: the use of dynamic CBF information obtained using ASL to assess dynamic CBF-BOLD coupling and oxidative metabolism in the resting state. In addition, we summarize some future challenges and interesting research directions for ASL, including slice-accelerated (multiband) imaging as well as the effects of motion and other physiological confounds on perfusion-based FC measurement. In summary, this work reviews the state-of-the-art of ASL and establishes it as an increasingly viable MRI technique with high translational value in studying resting-state brain function. PMID:26106930

Neutral endopeptidase inhibitor potentiates the tachykinin-induced increase in ciliary beat frequency in rabbit trachea.

PubMed

Kondo, M; Tamaoki, J; Takizawa, T

1990-08-01

We used cultured rabbit tracheal epithelium to determine the effect of mammalian-derived tachykinin on airway ciliary activity and its modulation by neutral endopeptidase EC 3.4.24.11 (NEP). Neurokinin A (NKA) caused dose-dependent increases in ciliary beat frequency (CBF), as measured by a photoelectric method, with the maximal increase from the baseline 15.7 +/- 1.7% (mean +/- SEM, p less than 0.01), whereas substance P (SP) had no effect. The NKA-induced increase in CBF was not inhibited by phentolamine, propranolol, or atropine, but it was abolished by the tachykinin antagonist [D-Pro2, D-Trp7,9]SP. Pretreatment of tissue with thiorphan (10(-5) M), a NEP inhibitor, had little effect on CBF responses to NKA; however, it significantly potentiated the responses to SP (14.9 +/- 3.0%, p less than 0.01). Other peptidase inhibitors, including captopril, bestatin, and leupeptin, did not alter the tachykinin-induced CBF response, suggesting that angiotensin converting enzyme, aminopeptidases, and serine proteinases do not modulate ciliary activity in response to tachykinins. These results suggest that NKA increases CBF by acting directly on tachykinin receptors and that NEP may play a role in modulating the tachykinin-induced stimulatory effects on CBF.

Cerebral blood flow during paroxysmal EEG activation induced by sleep in patients with complex partial seizures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gozukirmizi, E.; Meyer, J.S.; Okabe, T.

1982-01-01

Cerebral blood flow (CBF) measurements were combined with sleep polysomnography in nine patients with complex partial seizures. Two methods were used: the 133Xe method for measuring regional (rCBF) and the stable xenon CT method for local (LCBF). Compared to nonepileptic subjects, who show diffuse CBF decreases during stages I-II, non-REM sleep onset, patients with complex partial seizures show statistically significant increases in CBF which are maximal in regions where the EEG focus is localized and are predominantly seen in one temporal region but are also propagated to other cerebral areas. Both CBF methods gave comparable results, but greater statistical significancemore » was achieved by stable xenon CT methodology. CBF increases are more diffuse than predicted by EEG paroxysmal activity recorded from scalp electrodes. An advantage of the 133Xe inhalation method was achievement of reliable data despite movement of the head. This was attributed to the use of a helmet which maintained the probes approximated to the scalp. Disadvantages were poor resolution (7 cm3) and two-dimensional information. The advantage of stable xenon CT method is excellent resolution (80 mm3) in three dimensions, but a disadvantage is that movement of the head in patients with seizure disorders may limit satisfactory measurements.« less

The roles of cerebral blood flow, capillary transit time heterogeneity, and oxygen tension in brain oxygenation and metabolism

PubMed Central

Jespersen, Sune N; Østergaard, Leif

2012-01-01

Normal brain function depends critically on moment-to-moment regulation of oxygen supply by the bloodstream to meet changing metabolic needs. Neurovascular coupling, a range of mechanisms that converge on arterioles to adjust local cerebral blood flow (CBF), represents our current framework for understanding this regulation. We modeled the combined effects of CBF and capillary transit time heterogeneity (CTTH) on the maximum oxygen extraction fraction (OEFmax) and metabolic rate of oxygen that can biophysically be supported, for a given tissue oxygen tension. Red blood cell velocity recordings in rat brain support close hemodynamic–metabolic coupling by means of CBF and CTTH across a range of physiological conditions. The CTTH reduction improves tissue oxygenation by counteracting inherent reductions in OEFmax as CBF increases, and seemingly secures sufficient oxygenation during episodes of hyperemia resulting from cortical activation or hypoxemia. In hypoperfusion and states of blocked CBF, both lower oxygen tension and CTTH may secure tissue oxygenation. Our model predicts that disturbed capillary flows may cause a condition of malignant CTTH, in which states of higher CBF display lower oxygen availability. We propose that conditions with altered capillary morphology, such as amyloid, diabetic or hypertensive microangiopathy, and ischemia–reperfusion, may disturb CTTH and thereby flow-metabolism coupling and cerebral oxygen metabolism. PMID:22044867

Cerebral Blood Flow and Cerebral Edema in Rats With Diabetic Ketoacidosis

PubMed Central

Yuen, Natalie; Anderson, Steven E.; Glaser, Nicole; Tancredi, Daniel J.; O'Donnell, Martha E.

2008-01-01

OBJECTIVE— Cerebral edema (CE) is a potentially life-threatening complication of diabetic ketoacidosis (DKA) in children. Osmotic fluctuations during DKA treatment have been considered responsible, but recent data instead suggest that cerebral hypoperfusion may be involved and that activation of cerebral ion transporters may occur. Diminished cerebral blood flow (CBF) during DKA, however, has not been previously demonstrated. We investigated CBF and edema formation in a rat model of DKA and determined the effects of bumetanide, an inhibitor of Na-K-Cl cotransport. RESEARCH DESIGN AND METHODS— Juvenile rats with streptozotocin-induced DKA were treated with intravenous saline and insulin, similar to human treatment protocols. CBF was determined by magnetic resonance (MR) perfusion–weighted imaging before and during treatment, and CE was assessed by determining apparent diffusion coefficients (ADCs) using MR diffusion–weighted imaging. RESULTS— CBF was significantly reduced in DKA and was responsive to alterations in pCO2. ADC values were reduced, consistent with cell swelling. The reduction in ADCs correlated with dehydration, as reflected in blood urea nitrogen concentrations. Bumetanide caused a rapid rise in ADCs of DKA rats without significantly changing CBF, while saline/insulin caused a rapid rise in CBF and a gradual rise in ADCs. DKA rats treated with bumetanide plus saline/insulin showed a trend toward more rapid rise in cortical ADCs and a larger rise in striatal CBF than those observed with saline/insulin alone. CONCLUSIONS— These data demonstrate that CE in DKA is accompanied by cerebral hypoperfusion before treatment and suggest that blocking Na-K-Cl cotransport may reduce cerebral cell swelling. PMID:18633109

Effects of antidepressant treatment with rTMS and fluoxetine on brain perfusion in PD.

PubMed

Fregni, F; Ono, C R; Santos, C M; Bermpohl, F; Buchpiguel, C; Barbosa, E R; Marcolin, M A; Pascual-Leone, A; Valente, K D

2006-06-13

Although depression is highly prevalent in Parkinson disease (PD), little is known about the neural correlates associated with depression and antidepressant treatment in PD. To examine the effects of fluoxetine and repetitive transcranial magnetic stimulation (rTMS) on regional cerebral blood flow (rCBF) using SPECT in patients with PD and depression. Twenty-six patients were enrolled into two groups: One received active rTMS and placebo medication and the other sham rTMS and fluoxetine 20 mg/day. Brain SPECT was performed at baseline and after 2 and 8 weeks. Changes in rCBF were compared across timepoints and correlated with clinical scores. In addition, baseline rCBF of these patients was compared with that of 29 healthy, age-matched subjects. At baseline, patients with PD and depression showed significantly lower rCBF in the left prefrontal cortex, posterior cingulate gyrus, left insula, and right parietal cortex when compared with healthy controls. Both treatments induced significant clinical improvement and increases in rCBF in the posterior cingulate gyrus and decreases in rCBF in the right medial frontal gyrus. These changes were significantly correlated to the clinical outcome. Furthermore, the comparison between these two treatments revealed that whereas rTMS treatment was associated with an increased perfusion in the right and left prefrontal cortex, fluoxetine treatment was associated with a relative rCBF increase in the occipital lobe. Depression in patients with Parkinson disease is correlated with a dysfunction of the frontal-limbic network that can be modulated by two different antidepressant therapies.

Cerebral oxygen metabolism in patients with early Parkinson's disease.

PubMed

Borghammer, Per; Cumming, Paul; Østergaard, Karen; Gjedde, Albert; Rodell, Anders; Bailey, Christopher J; Vafaee, Manoucher S

2012-02-15

Decreased activity of the mitochondrial electron transport chain (ETC) has been implicated in the pathogenesis of Parkinson's disease (PD). This model would most likely predict a decrease in the rate of cerebral oxygen consumption (CMRO(2)). To test this hypothesis, we compared CMRO(2) and cerebral blood flow (CBF) PET scans from PD patients and healthy controls. Nine early-stage PD patients and 15 healthy age-matched controls underwent PET scans for quantitative mapping of CMRO(2) and CBF. Between-group differences were evaluated for absolute data and intensity-normalized values. No group differences were detected in regional magnitudes of CMRO(2) or CBF. Upon normalization using the reference cluster method, significant relative CMRO(2) decreases were evident in widespread prefrontal, parieto-occipital, and lateral temporal regions. Sensory-motor and subcortical regions, brainstem, and the cerebellum were spared. A similar pattern was evident in normalized CBF data, as described previously. While the data did not reveal substantially altered absolute CMRO(2) in brain of PD patients, employing data-driven intensity normalization revealed widespread relative CMRO(2) decreases in cerebral cortex. The detected pattern was very similar to that reported in earlier CBF and CMRglc studies of PD, and in the CBF images from the same subjects. Thus, the present results are consistent with the occurrence of parallel declines in CMRO(2), CBF, and CMRglc in spatially contiguous cortical regions in early PD, and support the hypothesis that ETC dysfunction could be a primary pathogenic mechanism in early PD. Copyright © 2011 Elsevier B.V. All rights reserved.

Abnormal regional cerebral blood flow in systemic lupus erythematosus patients with psychiatric symptoms.

PubMed

Oda, Kenji; Matsushima, Eisuke; Okubo, Yoshiro; Ohta, Katsuya; Murata, Yuji; Koike, Ryuji; Miyasaka, Nobuyuki; Kato, Motoichiro

2005-07-01

Single-photon emission computed tomography (SPECT) studies have demonstrated decreased regional cerebral blood flow (rCBF) in systemic lupus erythematosus (SLE) patients. However, no study has done voxel-based analysis using statistical parametric mapping (SPM) that can evaluate rCBF objectively, and the relationship between rCBF and psychiatric symptoms has not been well investigated. Using L,L-ethyl cysteinate dimer (99mTc ECD) SPECT and SPM, we aimed to clarify the association of rCBF changes with psychiatric symptoms in SLE patients whose magnetic resonance imaging (MRI) showed no morphological abnormalities. Twenty SLE patients and 19 healthy volunteers underwent 99mTc ECD SPECT. Data were collected from August 2000 to March 2003. SLE was diagnosed according to American College of Rheumatology criteria, and psychiatric symptoms were diagnosed according to ICD-10 criteria. On the basis of the modified Carbotte, Denburg, and Denburg method, the patients were classified into 3 groups: a group with major psychiatric symptoms (hallucinosis, delusional disorder, and mood disorder), a group with minor psychiatric symptoms (anxiety disorder, dissociative disorder, and emotionally labile disorder), and a group without psychiatric symptoms. Gross organic lesions were ruled out by brain MRI. Group comparisons of rCBF were performed with analysis using SPM99. SLE patients without MRI lesions showed decreased rCBF in the posterior cingulate gyrus and thalamus. The reduction in rCBF was overt in patients with major psychiatric symptoms. Our study indicated that SLE patients may have dysfunction in the posterior cingulate gyrus and thalamus and that this may be associated with the severity of psychiatric symptoms.

Moderate hyperventilation during intravenous anesthesia increases net cerebral lactate efflux.

PubMed

Grüne, Frank; Kazmaier, Stephan; Sonntag, Hans; Stolker, Robert Jan; Weyland, Andreas

2014-02-01

Hyperventilation is known to decrease cerebral blood flow (CBF) and to impair cerebral metabolism, but the threshold in patients undergoing intravenous anesthesia is unknown. The authors hypothesized that reduced CBF associated with moderate hyperventilation might impair cerebral aerobic metabolism in patients undergoing intravenous anesthesia. Thirty male patients scheduled for coronary surgery were included in a prospective, controlled crossover trial. Measurements were performed under fentanyl-midazolam anesthesia in a randomized sequence aiming at partial pressures of carbon dioxide of 30 and 50 mmHg. Endpoints were CBF, blood flow velocity in the middle cerebral artery, and cerebral metabolic rates for oxygen, glucose, and lactate. Global CBF was measured using a modified Kety-Schmidt technique with argon as inert gas tracer. CBF velocity of the middle cerebral artery was recorded by transcranial Doppler sonography. Data were presented as mean (SD). Two-sided paired t tests and one-way ANOVA for repeated measures were used for statistical analysis. Moderate hyperventilation significantly decreased CBF by 60%, blood flow velocity by 41%, cerebral oxygen delivery by 58%, and partial pressure of oxygen of the jugular venous bulb by 45%. Cerebral metabolic rates for oxygen and glucose remained unchanged; however, net cerebral lactate efflux significantly increased from -0.38 (2.18) to -2.41(2.43) µmol min 100 g. Moderate hyperventilation, when compared with moderate hypoventilation, in patients with cardiovascular disease undergoing intravenous anesthesia increased net cerebral lactate efflux and markedly reduced CBF and partial pressure of oxygen of the jugular venous bulb, suggesting partial impairment of cerebral aerobic metabolism at clinically relevant levels of hypocapnia.

Recruitment of prefrontal-striatal circuit in response to skilled motor challenge.

PubMed

Guo, Yumei; Wang, Zhuo; Prathap, Sandhya; Holschneider, Daniel P

2017-12-13

A variety of physical fitness regimens have been shown to improve cognition, including executive function, yet our understanding of which parameters of motor training are important in optimizing outcomes remains limited. We used functional brain mapping to compare the ability of two motor challenges to acutely recruit the prefrontal-striatal circuit. The two motor tasks - walking in a complex running wheel with irregularly spaced rungs or walking in a running wheel with a smooth internal surface - differed only in the extent of skill required for their execution. Cerebral perfusion was mapped in rats by intravenous injection of [C]-iodoantipyrine during walking in either a motorized complex wheel or in a simple wheel. Regional cerebral blood flow (rCBF) was quantified by whole-brain autoradiography and analyzed in three-dimensional reconstructed brains by statistical parametric mapping and seed-based functional connectivity. Skilled or simple walking compared with rest, increased rCBF in regions of the motor circuit, somatosensory and visual cortex, as well as the hippocampus. Significantly greater rCBF increases were noted during skilled walking than for simple walking. Skilled walking, unlike simple walking or the resting condition, was associated with a significant positive functional connectivity in the prefrontal-striatal circuit (prelimbic cortex-dorsomedial striatum) and greater negative functional connectivity in the prefrontal-hippocampal circuit. Our findings suggest that the level of skill of a motor training task determines the extent of functional recruitment of the prefrontal-corticostriatal circuit, with implications for a new approach in neurorehabilitation that uses circuit-specific neuroplasticity to improve motor and cognitive functions.

A Conserved Region in the F2 Subunit of Paramyxovirus Fusion Proteins Is Involved In Fusion Regulation▿

PubMed Central

Gardner, Amanda E.; Dutch, Rebecca E.

2007-01-01

Paramyxoviruses utilize both an attachment protein and a fusion (F) protein to drive virus-cell and cell-cell fusion. F exists functionally as a trimer of two disulfide-linked subunits: F1 and F2. Alignment and analysis of a set of paramyxovirus F protein sequences identified three conserved blocks (CB): one in the fusion peptide/heptad repeat A domain, known to play important roles in fusion promotion, one in the region between the heptad repeats of F1 (CBF1) (A. E. Gardner, K. L. Martin, and R. E. Dutch, Biochemistry 46:5094-5105, 2007), and one in the F2 subunit (CBF2). To analyze the functions of CBF2, alanine substitutions at conserved positions were created in both the simian virus 5 (SV5) and Hendra virus F proteins. A number of the CBF2 mutations resulted in folding and expression defects. However, the CBF2 mutants that were properly expressed and trafficked had altered fusion promotion activity. The Hendra virus CBF2 Y79A and P89A mutants showed significantly decreased levels of fusion, whereas the SV5 CBF2 I49A mutant exhibited greatly increased cell-cell fusion relative to that for wild-type F. Additional substitutions at SV5 F I49 suggest that both side chain volume and hydrophobicity at this position are important in the folding of the metastable, prefusion state and the subsequent triggering of membrane fusion. The recently published prefusogenic structure of parainfluenza virus 5/SV5 F (H. S. Yin et al., Nature 439:38-44, 2006) places CBF2 in direct contact with heptad repeat A. Our data therefore indicate that this conserved region plays a critical role in stabilizing the prefusion state, likely through interactions with heptad repeat A, and in triggering membrane fusion. PMID:17507474

Cerebrovascular response to the cold pressor test - the critical role of carbon dioxide.

PubMed

Tymko, Michael M; Kerstens, Thijs P; Wildfong, Kevin W; Ainslie, Philip N

2017-12-01

What is the central question of this study? What is the role of carbon dioxide in the cerebral blood flow (CBF) response to the cold pressor test (CPT)? What is the main finding and its importance? The CBF response was elevated during the isocapnic (controlled CO 2 ) CPT in the middle cerebral artery and the internal carotid artery compared with the poikilocapnic (uncontrolled CO 2 ) CPT, owing to ventilation-associated reductions in end-tidal CO 2 . Furthermore, the common carotid artery vasodilated to a greater extent during the isocapnic compared with the poikilocapnic CPT, whereas the internal carotid artery vasoconstricted during both CPTs. Our data highlight the importance of CO 2 control when investigating the CBF response to the CPT. In addition to increasing sympathetic nervous activity, blood pressure and cerebral blood flow (CBF), the cold pressor test (CPT) stimulates pain receptors, which may increase ventilation above metabolic demand; this response is likely to reduce the partial pressure of end-tidal carbon dioxide (P ET ,CO2) and will attenuate elevations in CBF. Our hypotheses were as follows: (i) the CPT will elicit hyperventilation, effectively lowering P ET ,CO2; (ii) the CBF response will be elevated during an isocapnic (controlled P ET ,CO2) compared with a poikilocapnic CPT (uncontrolled P ET ,CO2); and (iii) in response to the CPT, the common carotid artery (CCA) will vasodilate, while the internal carotid artery (ICA) will remain unchanged to help regulate CBF. Using a new, randomized experimental design, we measured the cerebrovascular response in the middle cerebral artery (MCA), CCA and internal carotid artery (ICA), during an isocapnic and poikilocapnic CPT in 15 participants. Blood pressure and cardiac output (finger photoplethysmography), heart rate (ECG), MCA mean velocity (transcranial Doppler ultrasound) and CCA and ICA CBF (Duplex ultrasound) were recorded during both CPT trials. Our findings were as follows: (i) ventilation increased, which reduced P ET ,CO2 (-5.3 ± 6.4 mmHg) during the poikilocapnic compared with the isocapnic CPT; (ii) the CBF response was elevated during the isocapnic compared with the poikilocapnic CPT in the MCA and ICA, but not in the CCA; and (iii) the CCA dilated to a greater extent during the isocapnic compared with the poikilocapnic CPT, and the ICA vasoconstricted during both trials. Our data emphasize the importance of P ET ,CO2 control in the CBF response to the CPT and in the differential vasomotor regulation between the CCA and ICA. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Effects of Fructose vs Glucose on Regional Cerebral Blood Flow in Brain Regions Involved With Appetite and Reward Pathways

PubMed Central

Page, Kathleen A.; Chan, Owen; Arora, Jagriti; Belfort-DeAguiar, Renata; Dzuira, James; Roehmholdt, Brian; Cline, Gary W.; Naik, Sarita; Sinha, Rajita; Constable, R. Todd; Sherwin, Robert S.

2014-01-01

Importance Increases in fructose consumption have paralleled the increasing prevalence of obesity, and high-fructose diets are thought to promote weight gain and insulin resistance. Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion, and central administration of fructose provokes feeding in rodents, whereas centrally administered glucose promotes satiety. Objective To study neurophysiological factors that might underlie associations between fructose consumption and weight gain. Design, Setting, and Participants Twenty healthy adult volunteers underwent 2 magnetic resonance imaging sessions at Yale University in conjunction with fructose or glucose drink ingestion in a blinded, random-order, crossover design. Main Outcome Measures Relative changes in hypothalamic regional cerebral blood flow (CBF) after glucose or fructose ingestion. Secondary outcomes included whole-brain analyses to explore regional CBF changes, functional connectivity analysis to investigate correlations between the hypothalamus and other brain region responses, and hormone responses to fructose and glucose ingestion. Results There was a significantly greater reduction in hypothalamic CBF after glucose vs fructose ingestion (–5.45 vs 2.84 mL/g per minute, respectively; mean difference, 8.3 mL/g per minute [95% CI of mean difference, 1.87-14.70]; P=.01). Glucose ingestion (compared with baseline) increased functional connectivity between the hypothalamus and the thalamus and striatum. Fructose increased connectivity between the hypothalamus and thalamus but not the striatum. Regional CBF within the hypothalamus, thalamus, insula, anterior cingulate, and striatum (appetite and reward regions) was reduced after glucose ingestion compared with baseline (P<.05 significance threshold, family-wise error [FWE] whole-brain corrected). In contrast, fructose reduced regional CBF in the thalamus, hippocampus, posterior cingulate cortex, fusiform, and visual cortex (P<.05 significance threshold, FWE whole-brain corrected). In whole-brain voxel-level analyses, there were no significant differences between direct comparisons of fructose vs glucose sessions following correction for multiple comparisons. Fructose vs glucose ingestion resulted in lower peak levels of serum glucose (mean difference, 41.0 mg/dL [95% CI, 27.7-54.5]; P<.001), insulin (mean difference, 49.6 μU/mL [95% CI, 38.2-61.1]; P<.001), and glucagon-like polypep-tide 1 (mean difference, 2.1 pmol/L [95% CI, 0.9-3.2]; P=.01). Conclusion and Relevance In a series of exploratory analyses, consumption of fructose compared with glucose resulted in a distinct pattern of regional CBF and a smaller increase in systemic glucose, insulin, and glucagon-like polypeptide 1 levels. PMID:23280226

Accurate placement of substrate RNA by Gar1 in H/ACA RNA-guided pseudouridylation.

PubMed

Wang, Peng; Yang, Lijiang; Gao, Yi Qin; Zhao, Xin Sheng

2015-09-03

H/ACA RNA-guided ribonucleoprotein particle (RNP), the most complicated RNA pseudouridylase so far known, uses H/ACA guide RNA for substrate capture and four proteins (Cbf5, Nop10, L7Ae and Gar1) for pseudouridylation. Although it was shown that Gar1 not only facilitates the product release, but also enhances the catalytic activity, the chemical role that Gar1 plays in this complicated machinery is largely unknown. Kinetics measurement on Pyrococcus furiosus RNPs at different temperatures making use of fluorescence anisotropy showed that Gar1 reduces the catalytic barrier through affecting the activation entropy instead of enthalpy. Site-directed mutagenesis combined with molecular dynamics simulations demonstrated that V149 in the thumb loop of Cbf5 is critical in placing the target uridine to the right position toward catalytic D85 of Cbf5. The enzyme elegantly aligns the position of uridine in the catalytic site with the help of Gar1. In addition, conversion of uridine to pseudouridine results in a rigid syn configuration of the target nucleotide in the active site and causes Gar1 to pull out the thumb. Both factors guarantee the efficient release of the product. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Chronic cocaine disrupts neurovascular networks and cerebral function: optical imaging studies in rodents

NASA Astrophysics Data System (ADS)

Zhang, Qiujia; You, Jiang; Volkow, Nora D.; Choi, Jeonghun; Yin, Wei; Wang, Wei; Pan, Yingtian; Du, Congwu

2016-02-01

Cocaine abuse can lead to cerebral strokes and hemorrhages secondary to cocaine's cerebrovascular effects, which are poorly understood. We assessed cocaine's effects on cerebrovascular anatomy and function in the somatosensory cortex of the rat's brain. Optical coherence tomography was used for in vivo imaging of three-dimensional cerebral blood flow (CBF) networks and to quantify CBF velocities (CBFv), and multiwavelength laser-speckle-imaging was used to simultaneously measure changes in CBFv, oxygenated (Δ[HbO2]) and deoxygenated hemoglobin (Δ[HbR]) concentrations prior to and after an acute cocaine challenge in chronically cocaine exposed rats. Immunofluorescence techniques on brain slices were used to quantify microvasculature density and levels of vascular endothelial growth factor (VEGF). After chronic cocaine (2 and 4 weeks), CBFv in small vessels decreased, whereas vasculature density and VEGF levels increased. Acute cocaine further reduced CBFv and decreased Δ[HbO2] and this decline was larger and longer lasting in 4 weeks than 2 weeks cocaine-exposed rats, which indicates that risk for ischemia is heightened during intoxication and that it increases with chronic exposures. These results provide evidence of cocaine-induced angiogenesis in cortex. The CBF reduction after chronic cocaine exposure, despite the increases in vessel density, indicate that angiogenesis was insufficient to compensate for cocaine-induced disruption of cerebrovascular function.

Cerebral amyloid angiopathy increases susceptibility to infarction after focal cerebral ischemia in Tg2576 mice.

PubMed

Milner, Eric; Zhou, Meng-Liang; Johnson, Andrew W; Vellimana, Ananth K; Greenberg, Jacob K; Holtzman, David M; Han, Byung Hee; Zipfel, Gregory J

2014-10-01

We and others have shown that soluble amyloid β-peptide (Aβ) and cerebral amyloid angiopathy (CAA) cause significant cerebrovascular dysfunction in mutant amyloid precursor protein (APP) mice, and that these deficits are greater in aged APP mice having CAA compared with young APP mice lacking CAA. Amyloid β-peptide in young APP mice also increases infarction after focal cerebral ischemia, but the impact of CAA on ischemic brain injury is unknown. To determine this, we assessed cerebrovascular reactivity, cerebral blood flow (CBF), and extent of infarction and neurological deficits after transient middle cerebral artery occlusion in aged APP mice having extensive CAA versus young APP mice lacking CAA (and aged-matched littermate controls). We found that aged APP mice have more severe cerebrovascular dysfunction that is CAA dependent, have greater CBF compromise during and immediately after middle cerebral artery occlusion, and develop larger infarctions after middle cerebral artery occlusion. These data indicate CAA induces a more severe form of cerebrovascular dysfunction than amyloid β-peptide alone, leading to intra- and postischemic CBF deficits that ultimately exacerbate cerebral infarction. Our results shed mechanistic light on human studies identifying CAA as an independent risk factor for ischemic brain injury. © 2014 American Heart Association, Inc.

Physiologic underpinnings of negative BOLD cerebrovascular reactivity in brain ventricles.

PubMed

Thomas, Binu P; Liu, Peiying; Aslan, Sina; King, Kevin S; van Osch, Matthias J P; Lu, Hanzhang

2013-12-01

With a growing need for specific biomarkers in vascular diseases, there has been a surging interest in mapping cerebrovascular reactivity (CVR) of the brain. This index can be measured by conducting a hypercapnia challenge while acquiring blood-oxygenation-level-dependent (BOLD) signals. A BOLD signal increase with hypercapnia is the expected outcome and represents the majority of literature reports; in this work we report an intriguing observation of an apparently negative BOLD CVR response at 3T, during inhalation of 5% CO2 with balance medical air. These "negative-CVR" clusters were specifically located in the ventricular regions of the brain, where CSF is abundant and results in an intense baseline signal. The amplitude of the CVR response was -0.51±0.44% (N=14, age 26±4 years). We hypothesized that this observation might not be due to a decrease in oxygenation but rather a volume effect in which bright CSF signal is replaced by a less intensive blood signal as a result of vasodilation. To test this, we performed an inversion-recovery (IR) experiment to suppress the CSF signal (N=10, age 27±5 years). This maneuver in imaging sequence reversed the sign of the signal response (to 0.66±0.25%), suggesting that the volume change was the predominant reason for the apparently negative CVR in the BOLD experiment. Further support of this hypothesis was provided by a BOLD hyperoxia experiment, in which no voxels showed a negative response, presumably because vasodilation is not usually associated with this challenge. Absolute CBF response to hypercapnia was measured in a new group of subjects (N=8, age 29±7 years) and it was found that CBF in ventricular regions increased by 48% upon CO2 inhalation, suggesting that blood oxygenation most likely increased rather than decreased. The findings from this study suggest that CO2 inhalation results in the dilation of ventricular vessels accompanied by shrinkage in CSF space, which is responsible for the apparently negative CVR in brain ventricles. © 2013.

Effects of intra-aortic balloon pump on cerebral blood flow during peripheral venoarterial extracorporeal membrane oxygenation support

PubMed Central

2014-01-01

Background The addition of an intra-aortic balloon pump (IABP) during peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO) support has been shown to improve coronary bypass graft flows and cardiac function in refractory cardiogenic shock after cardiac surgery. The purpose of this study was to evaluate the impact of additional IABP support on the cerebral blood flow (CBF) in patients with peripheral VA ECMO following cardiac procedures. Methods Twelve patients (mean age 60.40 ± 9.80 years) received VA ECMO combined with IABP support for postcardiotomy cardiogenic shock after coronary artery bypass grafting. The mean CBF in the bilateral middle cerebral arteries was measured with and without IABP counterpulsation by transcranial Doppler. The patients provided their control values. The mean CBF data were divided into two groups (pulsatile pressure greater than 10 mmHg, P group; pulsatile pressure less than 10 mmHg, N group) based on whether the patients experienced cardiac stun. The mean cerebral blood flow in VA ECMO (IABP turned off) alone and VA ECMO with IABP support were compared using the paired t test. Results All of the patients were successfully weaned from VA ECMO, and eight patients survived to discharge. The addition of IABP to VA ECMO did not change the mean CBF (251.47 ± 79.28 ml/min vs. 251.30 ± 79.47 ml/min, P = 0.96). The mean CBF was higher in VA ECMO alone than in VA ECMO combined with IABP support in the N group (257.68 ± 97.21 ml/min vs. 239.47 ± 95.60, P = 0.00). The addition of IABP to VA ECMO support increased the mean CBF values significantly compared with VA ECMO alone (261.68 ± 82.45 ml/min vs. 244.43 ± 45.85 ml/min, P = 0.00) in the P group. Conclusion These results demonstrate that an IABP significantly changes the CBF during peripheral VA ECMO, depending on the antegrade blood flow by spontaneous cardiac function. The addition of an IABP to VA ECMO support decreased the CBF during cardiac stun, and it increased CBF without cardiac stun. PMID:24766774

Analyses of Magnetic Resonance Imaging of Cerebrospinal Fluid Dynamics Pre and Post Short and Long-Duration Space Flights

NASA Technical Reports Server (NTRS)

Alperin, Noam; Barr, Yael; Lee, Sang H.; Mason,Sara; Bagci, Ahmet M.

2015-01-01

Preliminary results are based on analyses of data from 17 crewmembers. The initial analysis compares pre to post-flight changes in total cerebral blood flow (CBF) and craniospinal CSF flow volume. Total CBF is obtained by summation of the mean flow rates through the 4 blood vessels supplying the brain (right and left internal carotid and vertebral arteries). Volumetric flow rates were obtained using an automated lumen segmentation technique shown to have 3-4-fold improved reproducibility and accuracy over manual lumen segmentation (6). Two cohorts, 5 short-duration and 8 long-duration crewmembers, who were scanned within 3 to 8 days post landing were included (4 short-duration crewmembers with MRI scans occurring beyond 10 days post flight were excluded). The VIIP Clinical Practice Guideline (CPG) classification is being used initially as a measure for VIIP syndrome severity. Median CPG scores of the short and long-duration cohorts were similar, 2. Mean preflight total CBF for the short and long-duration cohorts were similar, 863+/-144 and 747+/-119 mL/min, respectively. Percentage CBF changes for all short duration crewmembers were 11% or lower, within the range of normal physiological fluctuations in healthy individuals. In contrast, in 4 of the 8 long-duration crewmembers, the change in CBF exceeded the range of normal physiological fluctuation. In 3 of the 4 subjects an increase in CBF was measured. Large pre to post-flight changes in the craniospinal CSF flow volume were found in 6 of the 8 long-duration crewmembers. Box-Whisker plots of the CPG and the percent CBF and CSF flow changes for the two cohorts are shown in Figure 4. Examples of CSF flow waveforms for a short and two long-duration (CPG 0 and 3) are shown in Figure 5. Changes in CBF and CSF flow dynamics larger than normal physiological fluctuations were observed in the long-duration crewmembers. Changes in CSF flow were more pronounced than changes in CBF. Decreased CSF flow dynamics were observed in a subject with VIIP signs. Study limitations include a slightly longer landing-to-MRI scan period for the short-duration cohort and limited sensitivity of the subjective discrete ordinal CPG scale. This limitation can be overcome by using imaging based parametric measures of VIIP severity such as globe deformation measures.

Deactivation of the left dorsolateral prefrontal cortex in Prader-Willi syndrome after meal consumption

PubMed Central

Reinhardt, Martin; Parigi, Angelo Del; Chen, Kewei; Reiman, Eric M.; Thiyyagura, Pradeep; Krakoff, Jonathan; Hohenadel, Maximilian G.; Le, Duc Son N.T.; Weise, Christopher M.

2016-01-01

Background/Objectives Prader-Willi syndrome (PWS) a type of human genetic obesity may inform us about the physiology of non-syndromic obesity. Objective of this study was to investigate the functional correlates of hunger and satiety in individuals with PWS in comparison to healthy controls with obesity, hypothesizing that we would see significant differences in activation in the left dorsolateral prefrontal cortex (DLPFC) based on prior findings. Subjects/Methods This study compared the central effects of food consumption in 9 individuals with PWS (7 men, 2 women; body fat 35.3%±10.0) and 7 controls (7 men; body fat 28.8%±7.6), matched for percentage body fat. H215O PET scans were performed before and after consumption of a standardized liquid meal to obtain quantitative measures of regional cerebral blood flow (rCBF), a marker of neuronal activity. Results Compared with obese controls, PWS showed altered (p<0.05 FWE cluster-level corrected; voxelwise p<0.001) rCBF before and after meal consumption in multiple brain regions. There was a significant differential rCBF response within the left DLPFC after meal ingestion with decreases in DLPFC rCBF in PWS; in controls DLPFC rCBF tended to remain unchanged. In more liberal analyses (voxelwise p<0.005) rCBF of the right orbitofrontal cortex (OFC) increased in PWS and decreased in controls. In PWS, ΔrCBF of the right OFC was associated with changes in appetite ratings. Conclusion The pathophysiology of eating behavior in PWS is characterized by a paradoxical meal induced deactivation of the left DLPFC and activation in the right OFC, brain regions implicated in the central regulation of eating behavior. PMID:27121248

Degradation of selected agrochemicals by the white rot fungus Trametes versicolor.

PubMed

Mir-Tutusaus, Josep Anton; Masís-Mora, Mario; Corcellas, Cayo; Eljarrat, Ethel; Barceló, Damià; Sarrà, Montserrat; Caminal, Glòria; Vicent, Teresa; Rodríguez-Rodríguez, Carlos E

2014-12-01

Use of agrochemicals is a worldwide practice that exerts an important effect on the environment; therefore the search of approaches for the elimination of such pollutants should be encouraged. The degradation of the insecticides imiprothrin (IP) and cypermethrin (CP), the insecticide/nematicide carbofuran (CBF) and the antibiotic of agricultural use oxytetracycline (OTC) were assayed with the white rot fungus Trametes versicolor. Experiments with fungal pellets demonstrated extensive degradation of the four tested agrochemicals, at rates that followed the pattern IP>OTC>CP>CBF. In vitro assays with laccase-mediator systems showed that this extracellular enzyme participates in the transformation of IP but not in the cases of CBF and OTC. On the other hand, in vivo studies with inhibitors of cytochrome P450 revealed that this intracellular system plays an important role in the degradation of IP, OTC and CBF, but not for CP. The compounds 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCCA) and 3-phenoxybenzoic acid (PBA) were detected as transformation products of CP, as a result of the breakdown of the molecule. Meanwhile, 3-hydroxycarbofuran was detected as a transformation product of CBF; this metabolite tended to accumulate during the process, nonetheless, the toxicity of the system was effectively reduced. Simultaneous degradation of CBF and OTC showed a reduction in toxicity; similarly, when successive additions of OTC were done during the slower degradation of CBF, the fungal pellets were able to degrade both compounds. The simultaneous degradation of the four compounds successfully took place with minimal inhibition of fungal activity and resulted in the reduction of the global toxicity, thus supporting the potential use of T. versicolor for the treatment of diverse agrochemicals. Copyright © 2014 Elsevier B.V. All rights reserved.

Does helmet CPAP reduce cerebral blood flow and volume by comparison with Infant Flow driver CPAP in preterm neonates?

PubMed

Zaramella, Patrizia; Freato, Federica; Grazzina, Nicoletta; Saraceni, Elisabetta; Vianello, Andrea; Chiandetti, Lino

2006-10-01

We compared neonatal helmet continuous positive airway pressure (CPAP) and the conventional nasal Infant Flow driver (IFD) CPAP in the noninvasive assessment of absolute cerebral blood flow (CBF) and relative cerebral blood volume changes (DeltaCBV) by near-infrared spectroscopy. A randomized crossover study in a tertiary referral NICU. Assessment of CBF and DeltaCBV in 17 very low birth weight infants with respiratory distress (median age 5 days) treated with two CPAP devices at a continuous distending pressure of 4 mbar. Neonates were studied for two consecutive 60-min periods with helmet CPAP and with IFD CPAP. Basal chromophore traces enabled DeltaCBV changes to be calculated. CBF was calculated in milliliters per 100 grams per minute from the saturation rise integral and rate of rise O(2)Hb-HHb. Median (range) CBF with helmet CPAP was 27.37 (9.47-48.20) vs. IFD CBF 34.74 (13.59-60.10)(p=0.049) and DeltaCBV 0.15 (0.09-0.28) with IFD and 0.13 (0.07-0.27) with helmet CPAP (NS). Using helmet and IFD CPAP, the neonates showed no difference in mean physiological parameters (transcutaneous carbon dioxide and oxygen tension, pulse oximetry saturation, heart rate, breathing rate, mean arterial blood pressure, desaturation rate, axillary temperature). Assessing CBF and DeltaCBV measured by near-infrared spectroscopy with two CPAP devices revealed no differences in relative blood volume, but CBF was lower with helmet CPAP. Greater active vasoconstriction and/or passive capillary and/or venous vessel compression seem the most likely reason, due to a positive pressure around the head, neck, and shoulders by comparison with the airway pressure.

Early postoperative changes in cerebral oxygen metabolism following neonatal cardiac surgery: Effects of surgical duration

PubMed Central

Buckley, Erin M.; Lynch, Jennifer M.; Goff, Donna A.; Schwab, Peter J.; Baker, Wesley B.; Durduran, Turgut; Busch, David R.; Nicolson, Susan C.; Montenegro, Lisa M.; Naim, Maryam Y.; Xiao, Rui; Spray, Thomas L.; Yodh, A. G.; Gaynor, J. William; Licht, Daniel J.

2013-01-01

Objective The early postoperative period following neonatal cardiac surgery is a time of increased risk for brain injury, yet the mechanisms underlying this risk are unknown. To understand these risks more completely, we quantified changes in postoperative cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood flow (CBF) compared with preoperative levels by using noninvasive optical modalities. Methods Diffuse optical spectroscopy and diffuse correlation spectroscopy were used concurrently to derive cerebral blood flow and oxygen utilization postoperatively for 12 hours. Relative changes in CMRO2, OEF, and CBF were quantified with reference to preoperative data. A mixed-effect model was used to investigate the influence of total support time and deep hypothermic circulatory arrest duration on relative changes in CMRO2, OEF, and CBF. Results Relative changes in CMRO2, OEF, and CBF were assessed in 36 patients, 21 with single-ventricle defects and 15 with 2-ventricle defects. Among patients with single-ventricle lesions, deep hypothermic circulatory arrest duration did not affect relative changes in CMRO2, CBF, or OEF (P > .05). Among 2-ventricle patients, total support time was not a significant predictor of relative changes in CMRO2 or CBF (P > .05), although longer total support time was associated significantly with greater increases in relative change of postoperative OEF (P = .008). Conclusions Noninvasive diffuse optical techniques were used to quantify postoperative relative changes in CMRO2, CBF, and OEF for the first time in this observational pilot study. Pilot data suggest that surgical duration does not account for observed variability in the relative change in CMRO2, and that more comprehensive clinical studies using the new technology are feasible and warranted to elucidate these issues further. PMID:23111021

Assessment of cerebral blood flow with magnetic resonance imaging in children with sickle cell disease: A quantitative comparison with transcranial Doppler ultrasonography.

PubMed

Croal, Paula L; Leung, Jackie; Kosinski, Przemyslaw; Shroff, Manohar; Odame, Isaac; Kassner, Andrea

2017-11-01

Transcranial Doppler ultrasonography (TCD) is a clinical tool for stratifying ischemic stroke risk by identifying abnormal elevations in blood flow velocity (BFV) in the middle cerebral artery (MCA). However, TCD is not effective at screening for subtle neurologic injury such as silent cerebral infarcts. To better understand this disparity, we compared TCD measures of BFV with tissue-level cerebral blood flow (CBF) using arterial spin-labeling MRI in children with and without sickle cell disease, and correlated these measurements against clinical hematologic measures of disease severity. TCD and MRI assessment were performed in 13 pediatric sickle cell disease patients and eight age-matched controls. Using MRI measures of MCA diameter and territory weight, TCD measures of BFV in the MCA [cm/s] were converted into units of CBF [ml min -1 100 g -1 ] for comparison. There was no significant association between TCD measures of BFV in the MCA and corresponding MRI measures of CBF in patients ( r  =   .28, p  =   .39) or controls ( r  =   .10, p  =   .81). After conversion from BFV into units of CBF, a strong association was observed between TCD and MRI measures ( r  =   .67, p  =   .017 in patients, r  =   .86, p  =   .006 in controls). While BFV in the MCA showed a lack of correlation with arterial oxygen content, an inverse association was observed for CBF measurements. This study demonstrates that BFV in the MCA cannot be used as a surrogate marker for tissue-level CBF in children with sickle cell disease. Therefore, TCD alone may not be sufficient for understanding and predicting subtle pathophysiology in this population, highlighting the potential clinical value of tissue-level CBF.

Measurement of ciliary beat frequency using Doppler optical coherence tomography.

PubMed

Lemieux, Bryan T; Chen, Jason J; Jing, Joseph; Chen, Zhongping; Wong, Brian J F

2015-11-01

Measuring ciliary beat frequency (CBF) is a technical challenge and difficult to perform in vivo. Doppler optical coherence tomography (D-OCT) is a mesoscopic noncontact imaging modality that provides high-resolution tomographic images and detects micromotion simultaneously in living tissues. In this work we used D-OCT to measure CBF in ex vivo tissue as the first step toward translating this technology to clinical use. Fresh ex vivo samples of rabbit tracheal mucosa were imaged using both D-OCT and phase-contrast microscopy (n = 5). The D-OCT system was designed and built to specification in our lab (1310-nm swept source vertical-cavity surface-emitting laser [VCSEL], 6-μm axial resolution). The samples were placed in culture and incubated at 37°C. A fast Fourier transform was performed on the D-OCT signal recorded on the surface of the samples to gauge CBF. High-speed digital video of the epithelium recorded via phase-contrast microscopy was analyzed to confirm the CBF measurements. The D-OCT system detected Doppler signal at the epithelial layer of ex vivo rabbit tracheal samples suggestive of ciliary motion. CBF was measured at 9.36 ± 1.22 Hz using D-OCT and 9.08 ± 0.48 Hz using phase-contrast microscopy. No significant differences were found between the 2 methods (p > 0.05). D-OCT allows for the quantitative measurement of CBF without the need to resolve individual cilia. Furthermore, D-OCT technology can be incorporated into endoscopic platforms that allow clinicians to readily measure CBF in the office and provide a direct measurement of mucosal health. © 2015 ARS-AAOA, LLC.

Regional Cerebral Blood Flow during Wakeful Rest in Older Subjects with Mild to Severe Obstructive Sleep Apnea.

PubMed

Baril, Andrée-Ann; Gagnon, Katia; Arbour, Caroline; Soucy, Jean-Paul; Montplaisir, Jacques; Gagnon, Jean-François; Gosselin, Nadia

2015-09-01

To evaluate changes in regional cerebral blood flow (rCBF) during wakeful rest in older subjects with mild to severe obstructive sleep apnea (OSA) and healthy controls, and to identify markers of OSA severity that predict altered rCBF. High-resolution (99m)Tc-HMPAO SPECT imaging during wakeful rest. Research sleep laboratory affiliated with a University hospital. Fifty untreated OSA patients aged between 55 and 85 years, divided into mild, moderate, and severe OSA, and 20 age-matched healthy controls. N/A. Using statistical parametric mapping, rCBF was compared between groups and correlated with clinical, respiratory, and sleep variables. Whereas no rCBF change was observed in mild and moderate groups, participants with severe OSA had reduced rCBF compared to controls in the left parietal lobules, left precentral gyrus, bilateral postcentral gyri, and right precuneus. Reduced rCBF in these regions and in areas of the bilateral frontal and left temporal cortex was associated with more hypopneas, snoring, hypoxemia, and sleepiness. Higher apnea, microarousal, and body mass indexes were correlated to increased rCBF in the basal ganglia, insula, and limbic system. While older individuals with severe obstructive sleep apnea (OSA) had hypoperfusion in the sensorimotor and parietal areas, respiratory variables and subjective sleepiness were correlated with extended regions of hypoperfusion in the lateral cortex. Interestingly, OSA severity, sleep fragmentation, and obesity correlated with increased perfusion in subcortical and medial cortical regions. Anomalies with such a distribution could result in cognitive deficits and reflect impaired vascular regulation, altered neuronal integrity, and/or undergoing neurodegenerative processes. © 2015 Associated Professional Sleep Societies, LLC.

A Low-Cost Method of Ciliary Beat Frequency Measurement Using iPhone and MATLAB: Rabbit Study.

PubMed

Chen, Jason J; Lemieux, Bryan T; Wong, Brian J F

2016-08-01

(1) To determine ciliary beat frequency (CBF) using a consumer-grade cellphone camera and MATLAB and (2) to evaluate the effectiveness and accuracy of the proposed method. Prospective animal study. Academic otolaryngology department research laboratory. Five ex vivo tracheal samples were extracted from 3 freshly euthanized (<3 hours postmortem) New Zealand white rabbits and incubated for 30 minutes in buffer at 23°C, buffer at 37°C, or 10% formalin at 23°C. Samples were sectioned transversely and observed under a phase-contrast microscope. Cilia movement was recorded through the eyepiece using an iPhone 6 at 240 frames per second (fps). Through MATLAB programming, the video of the 23°C sample was downsampled to 120, 60, and 30 fps, and Fourier analysis was performed on videos of all frame rates and conditions to determine CBF. CBF of the 23°C sample was also calculated manually frame by frame for verification. Recorded at 240 fps, the CBF at 23°C was 5.03 ± 0.4 Hz, and the CBF at 37°C was 9.08 ± 0.49 Hz (P < .001). The sample with 10% formalin did not display any data beyond DC noise. Compared with 240 fps, the means of other frame rates/methods (120, 60, 30 fps; manual counting) at 23°C all showed no statistical difference (P > .05). There is no significant difference between CBF measured via visual inspection and that analyzed by the developed program. Furthermore, all tested acquisition rates are shown to be effective, providing a fast and inexpensive alternative to current CBF measurement protocols. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Cerebral Blood Flow Response to Hypercapnia in Children with Obstructive Sleep Apnea Syndrome.

PubMed

Busch, David R; Lynch, Jennifer M; Winters, Madeline E; McCarthy, Ann L; Newland, John J; Ko, Tiffany; Cornaglia, Mary Anne; Radcliffe, Jerilynn; McDonough, Joseph M; Samuel, John; Matthews, Edward; Xiao, Rui; Yodh, Arjun G; Marcus, Carole L; Licht, Daniel J; Tapia, Ignacio E

2016-01-01

Children with obstructive sleep apnea syndrome (OSAS) often experience periods of hypercapnia during sleep, a potent stimulator of cerebral blood flow (CBF). Considering this hypercapnia exposure during sleep, it is possible that children with OSAS have abnormal CBF responses to hypercapnia even during wakefulness. Therefore, we hypothesized that children with OSAS have blunted CBF response to hypercapnia during wakefulness, compared to snorers and controls. CBF changes during hypercapnic ventilatory response (HCVR) were tested in children with OSAS, snorers, and healthy controls using diffuse correlation spectroscopy (DCS). Peak CBF changes with respect to pre-hypercapnic baseline were measured for each group. The study was conducted at an academic pediatric sleep center. Twelve children with OSAS (aged 10.1 ± 2.5 [mean ± standard deviation] y, obstructive apnea hypopnea index [AHI] = 9.4 [5.1-15.4] [median, interquartile range] events/hour), eight snorers (11 ± 3 y, 0.5 [0-1.3] events/hour), and 10 controls (11.4 ± 2.6 y, 0.3 [0.2-0.4] events/hour) were studied. The fractional CBF change during hypercapnia, normalized to the change in end-tidal carbon dioxide, was significantly higher in controls (9 ± 1.8 %/mmHg) compared to OSAS (7.1 ± 1.5, P = 0.023) and snorers (6.7 ± 1.9, P = 0.025). Children with OSAS and snorers have blunted CBF response to hypercapnia during wakefulness compared to controls. Noninvasive DCS blood flow measurements of hypercapnic reactivity offer insights into physiopathology of OSAS in children, which could lead to further understanding about the central nervous system complications of OSAS. © 2016 Associated Professional Sleep Societies, LLC.

Prefrontal Recruitment Mitigates Risk-Taking Behavior in Human Immunodeficiency Virus-Infected Young Adults.

PubMed

Smith, Robert X; Guha, Anika; Vaida, Florin; Paul, Robert H; Ances, Beau

2018-05-02

Human immunodeficiency virus (HIV)-infected (HIV+) young adults often engage in risk-taking behavior. However, the disruptive effects of HIV on the neurobiological underpinnings of risky decision making are not well understood. Risky decision making, measured via the Iowa Gambling Task (IGT), was compared voxel-wise to resting cerebral blood flow (rCBF) acquired via arterial spin labeling. Separate topographical maps were obtained for HIV-uninfected (HIV-; n = 62) and HIV+ (n = 41) young adults (18-24 years old) and were compared to the full cohort of participants. For the HIV+ group, rCBF was compared to recent and nadir CD4. IGT performance was supported by rCBF in 3 distinct brain regions: regions I, II, and III. The relationship between IGT performance and rCBF in HIV+ individuals was most robust in region I, the ventromedial prefrontal and insular cortices. Region II contained strong relationships for both HIV- and HIV+. Region III, dorsolateral prefrontal and posterior cingulate cortices, contained relationships that were strongest for HIV- controls. IGT performance was intact among HIV+ participants with higher rCBF in either region I or region III. By contrast, performance was worse among HIV+ individuals with lower rCBF in both regions I and III when compared to HIV- controls (P = .01). rCBF in region III was reduced in HIV+ compared with HIV- individuals (P = .04), and positively associated with nadir CD4 cell count (P = .02). Recruitment of executive systems (region III) mitigates risk-taking behavior in HIV+ and HIV- individuals. Recruitment of reward systems (region I) mitigates risk-taking behavior when region III is disrupted due to immunological compromise. Identifying individual recruitment patterns may aid anatomically directed therapeutics or psychosocial interventions.

Differential effects of gaseous versus injectable anesthetics on changes in regional cerebral blood flow and metabolism induced by l-DOPA in a rat model of Parkinson's disease.

PubMed

Bimpisidis, Zisis; Öberg, Carl M; Maslava, Natallia; Cenci, M Angela; Lundblad, Cornelia

2017-06-01

Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [ 14 C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [ 14 C]-2-deoxyglucose) with a highly sensitive autoradiographic method. The two types of anesthetics had quite distinct effects on l-DOPA-induced changes in rCBF and rCMR. Isoflurane did not affect either the absolute rCBF values or the increases in rCBF in the basal ganglia after l-DOPA administration. On the contrary, rats anesthetized with ketamine/xylazine showed lower absolute rCBF values, and the rCBF increases induced by l-DOPA were masked. We developed a novel improved model to calculate rCMR, and found lower metabolic activities in rats anesthetized with isoflurane compared to animals anesthetized with ketamine/xylazine. Both anesthetics prevented changes in rCMR upon l-DOPA administration. Pharmacological challenges in isoflurane-anesthetized rats indicated that drugs mimicking the actions of ketamine/xylazine on adrenergic or glutamate receptors reproduced distinct effects of the injectable anesthetics on rCBF and rCMR. Our results highlight the importance of anesthesia in studies of cerebral flow and metabolism, and provide novel insights into mechanisms mediating abnormal neurovascular responses to l-DOPA in Parkinson's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Age-associated patterns in gray matter volume, cerebral perfusion and BOLD oscillations in children and adolescents.

PubMed

Bray, Signe

2017-05-01

Healthy brain development involves changes in brain structure and function that are believed to support cognitive maturation. However, understanding how structural changes such as grey matter thinning relate to functional changes is challenging. To gain insight into structure-function relationships in development, the present study took a data driven approach to define age-related patterns of variation in gray matter volume (GMV), cerebral blood flow (CBF) and blood-oxygen level dependent (BOLD) signal variation (fractional amplitude of low-frequency fluctuations; fALFF) in 59 healthy children aged 7-18 years, and examined relationships between modalities. Principal components analysis (PCA) was applied to each modality in parallel, and participant scores for the top components were assessed for age associations. We found that decompositions of CBF, GMV and fALFF all included components for which scores were significantly associated with age. The dominant patterns in GMV and CBF showed significant (GMV) or trend level (CBF) associations with age and a strong spatial overlap, driven by increased signal intensity in default mode network (DMN) regions. GMV, CBF and fALFF additionally showed components accounting for 3-5% of variability with significant age associations. However, these patterns were relatively spatially independent, with small-to-moderate overlap between modalities. Independence of age effects was further demonstrated by correlating individual subject maps between modalities: CBF was significantly less correlated with GMV and fALFF in older children relative to younger. These spatially independent effects of age suggest that the parallel decline observed in global GMV and CBF may not reflect spatially synchronized processes. Hum Brain Mapp 38:2398-2407, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Deactivation of the left dorsolateral prefrontal cortex in Prader-Willi syndrome after meal consumption.

PubMed

Reinhardt, M; Parigi, A D; Chen, K; Reiman, E M; Thiyyagura, P; Krakoff, J; Hohenadel, M G; Le, D S N T; Weise, C M

2016-09-01

Prader-Willi syndrome (PWS) is a type of human genetic obesity that may give us information regarding the physiology of non-syndromic obesity. The objective of this study was to investigate the functional correlates of hunger and satiety in individuals with PWS in comparison with healthy controls with obesity, hypothesizing that we would see significant differences in activation in the left dorsolateral prefrontal cortex (DLPFC) based on prior findings. This study compared the central effects of food consumption in nine individuals with PWS (7 men, 2 women; body fat 35.3±10.0%) and seven controls (7 men; body fat 28.8±7.6%), matched for percentage body fat. H2(15)O-PET (positron emission tomography) scans were performed before and after consumption of a standardized liquid meal to obtain quantitative measures of regional cerebral blood flow (rCBF), a marker of neuronal activity. Compared with obese controls, PWS showed altered (P<0.05 family-wise error cluster-level corrected; voxelwise P<0.001) rCBF before and after meal consumption in multiple brain regions. There was a significant differential rCBF response within the left DLPFC after meal ingestion with decreases in DLPFC rCBF in PWS; in controls, DLPFC rCBF tended to remain unchanged. In more liberal analyses (P<0.05 family-wise error cluster-level corrected; voxelwise P<0.005), rCBF of the right orbitofrontal cortex (OFC) increased in PWS and decreased in controls. In PWS, ΔrCBF of the right OFC was associated with changes in appetite ratings. The pathophysiology of eating behavior in PWS is characterized by a paradoxical meal-induced deactivation of the left DLPFC and activation in the right OFC, brain regions implicated in the central regulation of eating behavior.

Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice

PubMed Central

Drouin, Annick; Bolduc, Virginie; Thorin-Trescases, Nathalie; Bélanger, Élisabeth; Fernandes, Priscilla; Baraghis, Edward; Lesage, Frédéric; Gillis, Marc-Antoine; Villeneuve, Louis; Hamel, Edith; Ferland, Guylaine; Thorin, Eric

2013-01-01

Severe dyslipidemia and the associated oxidative stress could accelerate the age-related decline in cerebrovascular endothelial function and cerebral blood flow (CBF), leading to neuronal loss and impaired learning abilities. We hypothesized that a chronic treatment with the polyphenol catechin would prevent endothelial dysfunction, maintain CBF responses, and protect learning abilities in atherosclerotic (ATX) mice. We treated ATX (C57Bl/6-LDLR−/− hApoB+/+; 3 mo old) mice with catechin (30 mg·kg−1·day−1) for 3 mo, and C57Bl/6 [wild type (WT), 3 and 6 mo old] mice were used as controls. ACh- and flow-mediated dilations (FMD) were recorded in pressurized cerebral arteries. Basal CBF and increases in CBF induced by whisker stimulation were measured by optical coherence tomography and Doppler, respectively. Learning capacities were evaluated with the Morris water maze test. Compared with 6-mo-old WT mice, cerebral arteries from 6-mo-old ATX mice displayed a higher myogenic tone, lower responses to ACh and FMD, and were insensitive to NOS inhibition (P < 0.05), suggesting endothelial dysfunction. Basal and increases in CBF were lower in 6-mo-old ATX than WT mice (P < 0.05). A decline in the learning capabilities was also observed in ATX mice (P < 0.05). Catechin 1) reduced cerebral superoxide staining (P < 0.05) in ATX mice, 2) restored endothelial function by reducing myogenic tone, improving ACh- and FMD and restoring the sensitivity to nitric oxide synthase inhibition (P < 0.05), 3) increased the changes in CBF during stimulation but not basal CBF, and 4) prevented the decline in learning abilities (P < 0.05). In conclusion, catechin treatment of ATX mice prevents cerebrovascular dysfunctions and the associated decline in learning capacities. PMID:21186270

Chronic kidney disease, cerebral blood flow, and white matter volume in hypertensive adults.

PubMed

Tamura, Manjula Kurella; Pajewski, Nicholas M; Bryan, R Nick; Weiner, Daniel E; Diamond, Matthew; Van Buren, Peter; Taylor, Addison; Beddhu, Srinivasan; Rosendorff, Clive; Jahanian, Hesamoddin; Zaharchuk, Greg

2016-03-29

To determine the relation between markers of kidney disease-estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR)-with cerebral blood flow (CBF) and white matter volume (WMV) in hypertensive adults. We used baseline data collected from 665 nondiabetic hypertensive adults aged ≥50 years participating in the Systolic Blood Pressure Intervention Trial (SPRINT). We used arterial spin labeling to measure CBF and structural 3T images to segment tissue into normal and abnormal WMV. We used quantile regression to estimate the association between eGFR and UACR with CBF and abnormal WMV, adjusting for sociodemographic and clinical characteristics. There were 218 participants (33%) with eGFR <60 mL/min/1.73 m(2) and 146 participants (22%) with UACR ≥30 mg/g. Reduced eGFR was independently associated with higher adjusted median CBF, but not with abnormal WMV. Conversely, in adjusted analyses, there was a linear independent association between UACR and larger abnormal WMV, but not with CBF. Compared to participants with neither marker of CKD (eGFR ≥60 mL/min/1.73 m(2) and UACR <30 mg/g), median CBF was 5.03 mL/100 g/min higher (95% confidence interval [CI] 0.78, 9.29) and abnormal WMV was 0.63 cm(3) larger (95% CI 0.08, 1.17) among participants with both markers of CKD (eGFR <60 mL/min/1.73 m(2) and UACR ≥30 mg/g). Among nondiabetic hypertensive adults, reduced eGFR was associated with higher CBF and higher UACR was associated with larger abnormal WMV. © 2016 American Academy of Neurology.

Linearization correction of /sup 99m/Tc-labeled hexamethyl-propylene amine oxime (HM-PAO) image in terms of regional CBF distribution: comparison to C VO2 inhalation steady-state method measured by positron emission tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inugami, A.; Kanno, I.; Uemura, K.

1988-12-01

The radioisotope distribution following intravenous injection of 99mTc-labeled hexamethylpropyleneamine oxime (HM-PAO) in the brain was measured by single photon emission computed tomography (SPECT) and corrected for the nonlinearity caused by differences in net extraction. The linearization correction was based on a three compartment model, and it required a region of reference to normalize the SPECT image in terms of regional cerebral blood flow distribution. Two different regions of reference, the cerebellum and the whole brain, were tested. The uncorrected and corrected HM-PAO images were compared with cerebral blood flow (CBF) image measured by the C VO2 inhalation steady state methodmore » and positron emission tomography (PET). The relationship between uncorrected HM-PAO and PET-CBF showed a correlation coefficient of 0.85 but tended to saturate at high CBF values, whereas it was improved to 0.93 after the linearization correction. The whole-brain normalization worked just as well as normalization using the cerebellum. This study constitutes a validation of the linearization correction and it suggests that after linearization the HM-PAO image may be scaled to absolute CBF by employing a global hemispheric CBF value as measured by the nontomographic TTXe clearance method.« less

Lower cerebral blood flow in subjects with Alzheimer's dementia, mild cognitive impairment, and subjective cognitive decline using two-dimensional phase-contrast magnetic resonance imaging.

PubMed

Leijenaar, Jolien F; van Maurik, Ingrid S; Kuijer, Joost P A; van der Flier, Wiesje M; Scheltens, Philip; Barkhof, Frederik; Prins, Niels D

2017-01-01

In this cross-sectional study, we aimed to detect differences in cerebral blood flow (CBF) between subjects with Alzheimer's disease (AD), mild cognitive impairment (MCI), and subjective cognitive decline (SCD), using two-dimensional phase-contrast magnetic resonance imaging. We included 74 AD patients (67 years, 51% female), 36 MCI patients (66 years, 33% female), and 62 patients with SCD (60 years, 32% female) from the Amsterdam Dementia Cohort. Patients with SCD are those who visited the memory clinic with subjective cognitive complaints without objective cognitive impairment. Whole-brain CBF (mL/100 g/min) was calculated using total volume flow measured with two-dimensional phase-contrast magnetic resonance imaging and normalized for brain volume. Mean CBF values (SD) were lower in AD compared to SCD (age and sex adjusted 70 ± 26 vs. 82 ± 24 mL/100 g/min, P  < .05). Mean CBF values of MCI were comparable to AD. Across clinical groups, lower CBF was associated with lower scores on the Mini-Mental State Examination (age and sex adjusted stβ = 0.19 per mL/100 g/min; P  = .02). Lower whole-brain CBF is seen in AD patients compared to SCD patients and is associated with worse cognitive function.

Altered cerebral blood flow and neurocognitive correlates in adolescent cannabis users

PubMed Central

Jacobus, Joanna; Goldenberg, Diane; Wierenga, Christina E.; Tolentino, Neil J.; Liu, Thomas T.

2012-01-01

Rationale The effects of adolescent marijuana use on the developing brain remain unclear, despite its prevalence. Arterial spin labeling (ASL) is a noninvasive imaging technique that characterizes neurovascular status and cerebral blood flow (CBF), potentially revealing contributors to neuropathological alterations. No studies to date have looked at CBF in adolescent marijuana users. Objectives This study examined CBF in adolescent marijuana users and matched healthy controls at baseline and after 4 weeks of monitored abstinence. Methods Heavy adolescent marijuana users (n=23, >200 lifetime marijuana use days) and demographically matched controls (n=23) with limited substance exposure underwent an ASL brain scan at an initial session and after 4 weeks of sequential urine toxicology to confirm abstinence. Results Marijuana users showed reduced CBF in four cortical regions including the left superior and middle temporal gyri, left insula, left and right medial frontal gyrus, and left supramarginal gyrus at baseline; users showed increased CBF in the right precuneus at baseline, as compared to controls (corrected p values<0.05). No between group differences were found at follow-up. Conclusions Marijuana use may influence CBF in otherwise healthy adolescents acutely; however, group differences were not observed after several weeks of abstinence. Neurovascular alterations may contribute to or underlie changes in brain activation, neuropsychological performance, and mood observed in young cannabis users with less than a month of abstinence. PMID:22395430

Accuracy and precision of pseudo-continuous arterial spin labeling perfusion during baseline and hypercapnia: a head-to-head comparison with ¹⁵O H₂O positron emission tomography.

PubMed

Heijtel, D F R; Mutsaerts, H J M M; Bakker, E; Schober, P; Stevens, M F; Petersen, E T; van Berckel, B N M; Majoie, C B L M; Booij, J; van Osch, M J P; Vanbavel, E; Boellaard, R; Lammertsma, A A; Nederveen, A J

2014-05-15

Measurements of the cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) provide useful information about cerebrovascular condition and regional metabolism. Pseudo-continuous arterial spin labeling (pCASL) is a promising non-invasive MRI technique to quantitatively measure the CBF, whereas additional hypercapnic pCASL measurements are currently showing great promise to quantitatively assess the CVR. However, the introduction of pCASL at a larger scale awaits further evaluation of the exact accuracy and precision compared to the gold standard. (15)O H₂O positron emission tomography (PET) is currently regarded as the most accurate and precise method to quantitatively measure both CBF and CVR, though it is one of the more invasive methods as well. In this study we therefore assessed the accuracy and precision of quantitative pCASL-based CBF and CVR measurements by performing a head-to-head comparison with (15)O H₂O PET, based on quantitative CBF measurements during baseline and hypercapnia. We demonstrate that pCASL CBF imaging is accurate during both baseline and hypercapnia with respect to (15)O H₂O PET with a comparable precision. These results pave the way for quantitative usage of pCASL MRI in both clinical and research settings. Copyright © 2014 Elsevier Inc. All rights reserved.

The relationship between depression and regional cerebral blood flow in Parkinson's disease and the effect of selegiline treatment.

PubMed

Imamura, K; Okayasu, N; Nagatsu, T

2011-07-01

We examined the relationship between severity of depression in Parkinson's disease (PD) and regional cerebral blood flow (rCBF) using single photon emission computed tomography (SPECT) and the reaction to levodopa-selegiline combination therapy. We evaluated 52 patients with PD and nine age-matched controls with SPECT and the Unified Parkinson's Disease Rating Scale (UPDRS) part III, Mini-Mental State Examination (MMSE), and Beck Depression Inventory (BDI) to evaluate depression severity and its connection with rCBF. Furthermore, we examined rCBF in patients with PD treated with levodopa with or without selegiline. A significant fall in rCBF was observed in the bilateral posterior cingulate, hippocampus, and cuneus and the superior parietal and primary visual areas in PD patients with minor depression and in all regions in those with major depression. Elevations in UPDRS part III and BDI scores and falls in MMSE scores were of significantly lower magnitude in the levodopa-selegiline group than in the levodopa group. Whole brain rCBF fell significantly less in the levodopa-selegiline group than in the levodopa group. These results indicate that selegiline controlled not only worsening of motor function and cognitive function in PD but also aggravation of minor depression, and restrained a fall in whole brain rCBF. © 2010 John Wiley & Sons A/S.

A hybrid personalized data recommendation approach for geoscience data sharing

NASA Astrophysics Data System (ADS)

WANG, M.; Wang, J.

2016-12-01

Recommender systems are effective tools helping Internet users overcome information overloading. The two most widely used recommendation algorithms are collaborating filtering (CF) and content-based filtering (CBF). A number of recommender systems based on those two algorithms were developed for multimedia, online sells, and other domains. Each of the two algorithms has its advantages and shortcomings. Hybrid approaches that combine these two algorithms are better choices in many cases. In geoscience data sharing domain, where the items (datasets) are more informative (in space and time) and domain-specific, no recommender system is specialized for data users. This paper reports a dynamic weighted hybrid recommendation algorithm that combines CF and CBF for geoscience data sharing portal. We first derive users' ratings on items with their historical visiting time by Jenks Natural Break. In the CBF part, we incorporate the space, time, and subject information of geoscience datasets to compute item similarity. Predicted ratings were computed with k-NN method separately using CBF and CF, and then combined with weights. With training dataset we attempted to find the best model describing ideal weights and users' co-rating numbers. A logarithmic function was confirmed to be the best model. The model was then used to tune the weights of CF and CBF on user-item basis with test dataset. Evaluation results show that the dynamic weighted approach outperforms either solo CF or CBF approach in terms of Precision and Recall.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yonas, H.; Steed, D.L.; Latchaw, R.E.

Operative intervention remains controversial for patients with transient nonhemispheric symptoms with occlusive disease of both the anterior and posterior cerebral circulations. In addition to the standard evaluation of these patients, we have used stable xenon-enhanced computed tomographic mapping of cerebral blood flow (Xe/CT CBF). This relatively new and potentially widely available CBF methodology, by measuring approximately 30,000 CBF values within each of three CT levels, provides a readily interpretable means of evaluating extremes of hemodynamic compromise within any or all vascular territories. In the past 30 months, Xe/CT CBF studies in 300 patients with occlusive vascular disease have identified ninemore » patients with global low flow and nonhemispheric symptoms (vertigo, lightheadedness, and/or blurred vision). Blood pressures determined by ocular pneumoplethysmography of Gee were markedly abnormal with reduced ocular/brachial ratios. Each patient had a combination of both segmental carotid and vertebrobasilar occlusive disease. Each patient had a flow-augmenting procedure performed on the anterior circulation in an attempt to improve global flow: carotid endarterectomy (two patients), subclavian-external carotid bypass (one patient), and superficial temporal artery-middle cerebral artery bypass (six patients). In each case disabling transient symptoms were relieved. There were no operative deaths, but one stroke occurred, probably as a result of a brief period of postoperative hypotension. Postoperative Xe/CT CBF studies show a long-term improved global CBF in all patients.« less

Meta-analysis of the effect of overexpression of dehydration-responsive element binding family genes on temperature stress tolerance and related responses

USDA-ARS?s Scientific Manuscript database

C-repeat/dehydration-responsive element binding proteins are transcription factors that play a critical role in plant response to temperature stress. Over-expression of CBF/DREB genes has been demonstrated to enhance temperature stress tolerance. A series of physiological and biochemical modificat...

Operation Brain Trauma Therapy

DTIC Science & Technology

2011-10-01

Nicotinamide Choline Atorvastatin FK 506 Minocycline Lithium Rolipram Aniracetam Pentostatin...possible effects on CBF and trophic factor production. They confer benefit in experimental TBI.24,25 Atorvastatin , simvastatin, and lovastatin all show...promise after TBI in rats. Impressive benefit was seen with atorvastatin therapy by Wang et al.24 where improved perfor- mance on rotarod and Morris

Effect of angiotensin converting enzyme inhibitor on chronic ischemic patients.

PubMed

Kawakami, N; Yamashita, T; Nakano, S; Ishihara, H; Kitahara, T; Nakashima, K; Kashiwagi, S; Ito, H

1996-01-01

Most of patients with cerebrovascular disease are associated with hypertension. Hypertension induces progressive atheromatous changes in cerebral arteries, and often causes steno-occlusive lesions of cerebral arteries. Angiotensin converting enzyme (ACE) inhibitor cilazapril is one of the antihypertensive drugs. It was reported that cilazapril improved resting cerebral blood flow (CBF) and cerebrovascular reserve capacity (CRC) in experimental studies. In this clinical study, the authors investigated whether long-term treatment with cilazapril could improve CBF and CRC in patients with steno-occlusive lesions of the major cerebral arterial trunk, measured by stable xenon computerized tomography (Xe-CT) with acetazolamide challenge. On the other hand, CBF and CRC in the calcium blocker-treated patients were measured in the same way. CBF did not change after long-term treatment with both cilazapril and calcium blocker. In the cilazapril-treated group, CRC was increased significantly (p < 0.05). However, CRC did not change in the calcium blocker-treated group. It was recognized that long-term treatment with cilazapril did not decrease CBF and improved CRC in patients with occlusive lesions of the major cerebral arterial trunk.

Controlled study on the effect of pentoxifylline and an ergot alkaloid derivative on regional cerebral blood flow in patients with chronic cerebrovascular disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartmann, A.; Tsuda, Y.

Regional cerebral blood flow (rCBF) in 90 patients with CBF decreased due to vascular diseases was studied by using the xenon 133 inhalation technique and a 32-detector setup. Whereas 30 patients received their standard basic therapy only and were regarded as controls, 30 others received 3 x 2 mg/day of an ergot alkaloid (co-dergocrine mesylate), and 30 others received 3 x 400 mg pentoxifylline (slow-release formulation)/day orally. Therapy was performed for eight weeks and CBF measured before start of treatment, after a four-week treatment period, and at the end of the study. CBF did not change significantly in the controlmore » group; both the pentoxifylline and the ergot alkaloid group presented with a significant increase in the CBF. This positive effect was significantly more pronounced in the pentoxifylline group and affected more ischemic than other brain tissues. In addition, symptoms like sleep disturbances, vertigo, and tinnitus improved significantly during the pentoxifylline observation period.« less

Cerebral blood flow and autoregulation: current measurement techniques and prospects for noninvasive optical methods

PubMed Central

Fantini, Sergio; Sassaroli, Angelo; Tgavalekos, Kristen T.; Kornbluth, Joshua

2016-01-01

Abstract. Cerebral blood flow (CBF) and cerebral autoregulation (CA) are critically important to maintain proper brain perfusion and supply the brain with the necessary oxygen and energy substrates. Adequate brain perfusion is required to support normal brain function, to achieve successful aging, and to navigate acute and chronic medical conditions. We review the general principles of CBF measurements and the current techniques to measure CBF based on direct intravascular measurements, nuclear medicine, X-ray imaging, magnetic resonance imaging, ultrasound techniques, thermal diffusion, and optical methods. We also review techniques for arterial blood pressure measurements as well as theoretical and experimental methods for the assessment of CA, including recent approaches based on optical techniques. The assessment of cerebral perfusion in the clinical practice is also presented. The comprehensive description of principles, methods, and clinical requirements of CBF and CA measurements highlights the potentially important role that noninvasive optical methods can play in the assessment of neurovascular health. In fact, optical techniques have the ability to provide a noninvasive, quantitative, and continuous monitor of CBF and autoregulation. PMID:27403447

Platelet activating factor induces transient blood-brain barrier opening to facilitate edaravone penetration into the brain.

PubMed

Fang, Weirong; Zhang, Rui; Sha, Lan; Lv, Peng; Shang, Erxin; Han, Dan; Wei, Jie; Geng, Xiaohan; Yang, Qichuan; Li, Yunman

2014-03-01

The blood-brain barrier (BBB) greatly limits the efficacy of many neuroprotective drugs' delivery to the brain, so improving drug penetration through the BBB has been an important focus of research. Here we report that platelet activating factor (PAF) transiently opened BBB and facilitated neuroprotectant edaravone penetration into the brain. Intravenous infusion with PAF induced a transient BBB opening in rats, reflected by increased Evans blue leakage and mild edema formation, which ceased within 6 h. Furthermore, rat regional cerebral blood flow (rCBF) declined acutely during PAF infusion, but recovered slowly. More importantly, this transient BBB opening significantly increased the penetration of edaravone into the brain, evidenced by increased edaravone concentrations in tissue interstitial fluid collected by microdialysis and analyzed by Ultra-performance liquid chromatograph combined with a hybrid quadrupole time-of-flight mass spectrometer (UPLC-MS/MS). Similarly, incubation of rat brain microvessel endothelial cells monolayer with 1 μM PAF for 1 h significantly increased monolayer permeability to (125)I-albumin, which recovered 1 h after PAF elimination. However, PAF incubation with rat brain microvessel endothelial cells for 1 h did not cause detectable cytotoxicity, and did not regulate intercellular adhesion molecule-1, matrix-metalloproteinase-9 and P-glycoprotein expression. In conclusion, PAF could induce transient and reversible BBB opening through abrupt rCBF decline, which significantly improved edaravone penetration into the brain. Platelet activating factor (PAF) transiently induces BBB dysfunction and increases BBB permeability, which may be due to vessel contraction and a temporary decline of regional cerebral blood flow (rCBF) triggered by PAF. More importantly, the PAF induced transient BBB opening facilitates neuroprotectant edaravone penetration into brain. The results of this study may provide a new approach to improve drug delivery into the brain. © 2013 International Society for Neurochemistry.

Impact of Competing Risk of Mortality on Association of Weight Loss with Risk of Central Body Fractures in Older Men: A Prospective Cohort Study

PubMed Central

Ensrud, Kristine E.; Harrison, Stephanie L.; Cauley, Jane A.; Langsetmo, Lisa; Schousboe, John T.; Kado, Deborah M.; Gourlay, Margaret L.; Lyons, Jennifer G.; Fredman, Lisa; Napoli, Nicolas; Crandall, Carolyn J.; Lewis, Cora E.; Orwoll, Eric S.; Stefanick, Marcia L.; Cawthon, Peggy M.

2017-01-01

To determine the association of weight loss with risk of clinical fractures at the hip, spine and pelvis (central body fractures [CBF]) in older men with and without accounting for the competing risk of mortality, we used data from 4,523 men (mean age 77.5 years). Weight change between baseline and follow-up (mean 4.5 years between examinations) was categorized as moderate loss (loss ≥10%), mild loss (loss 5% to <10%), stable (<5% change) or gain (gain ≥5%). Participants were contacted every 4 months after the follow-up examination to ascertain vital status (deaths verified by death certificates) and ask about fractures (confirmed by radiographic reports). Absolute probability of CBF by weight change category was estimated using traditional Kaplan-Meier method and cumulative incidence function accounting for competing mortality risk. Risk of CBF by weight change category was determined using conventional Cox proportional hazards regression and subdistribution hazards models with death as a competing risk. During an average of 8 years, 337 men (7.5%) experienced CBF and 1,569 (34.7%) died before experiencing this outcome. Among men with moderate weight loss, CBF probability was 6.8% at 5 years and 16.9% at 10 years using Kaplan-Meier vs. 5.7% at 5 years and 10.2% at 10 years using a competing risk approach. Men with moderate weight loss compared with those with stable weight had a 1.6-fold higher adjusted risk of CBF (HR 1.59, 95% CI 1.06–2.38) using Cox models that was substantially attenuated in models accounting for competing mortality risk and no longer significant (subdistribution HR 1.16, 95% CI 0.77–1.75). Results were similar in analyses substituting hip fracture for CBF. Older men with weight loss who survive are at increased risk of CBF, including hip fracture. However, ignoring the competing mortality risk among men with weight loss substantially overestimates their longterm fracture probability and relative fracture risk. PMID:27739103

Comparison of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Ciliary Beat Frequency Activation by the CFTR Modulators Genistein, VRT-532, and UCCF-152 in Primary Sinonasal Epithelial Cultures

PubMed Central

Conger, Bryant T.; Zhang, Shaoyan; Skinner, Daniel; Hicks, Stephen B.; Sorscher, Eric J.; Rowe, Steven M.; Woodworth, Bradford A.

2014-01-01

IMPORTANCE Pharmacologic activation of mucociliary clearance (MCC) represents an emerging therapeutic strategy for patients with chronic rhinosinusitis, even in the absence of congenital mutations of the CFTR gene. Drug discovery efforts have identified small molecules that activate the cystic fibrosis transmembrane conductance regulator (CFTR), including potentiators under development for treatment of cystic fibrosis. OBJECTIVE To evaluate the properties of CFTR modulators and their effects on ciliary beat frequency (CBF) in human sinonasal epithelium (HSNE). DESIGN Primary HSNE cultures (wild type and F508del/F508del) were used to compare stimulation of CFTR-mediated Cl− conductance and CBF by the CFTR modulators genistein, VRT-532, and UCCF-152. MAIN OUTCOMES AND MEASURES Increase in CFTR-dependent anion transport and CBF. RESULTS HSNE cultures were analyzed using pharmacologic manipulation of ion transport (change in short-circuit current [ΔISC]) and high-speed digital imaging (CBF). Activation of CFTR-dependent anion transport was significantly different among agonists (P < .001), with genistein exerting the greatest effect (mean [SD] ΔISC, genistein, 23.1 [1.8] µA/cm2 > VRT-532, 8.1 [1.0] µA/cm2 > UCCF-152, 3.4 [1.4] µA/cm2 > control, 0.7 [0.2] µA/cm2; Tukey-Kramer P < .05) in the absence of forskolin. Genistein and UCCF-152 augmented CBF (under submerged conditions) significantly better (Tukey-Kramer P < .05) than cells treated with VRT-532 or dimethyl sulfoxide vehicle control (mean [SD] fold change over baseline, genistein, 1.63 [0.06]; UCCF-152, 1.56 [0.06]; VRT-532, 1.38 [0.08]; control, 1.27 [0.02]). Activation of CBF was blunted in F508del/F508del HSNE cultures. CONCLUSIONS AND RELEVANCE The degree of CBF stimulation was not dependent on the magnitude of Cl− secretion, suggesting that different mechanisms of action may underlie MCC activation by these small molecule potentiators. Agents that activate both CFTR-dependent ISC and CBF are particularly attractive as therapeutics because they may address 2 independent pathways that contribute to deficient MCC in chronic rhinosinusitis. PMID:23949358

Comparison of cystic fibrosis transmembrane conductance regulator (CFTR) and ciliary beat frequency activation by the CFTR Modulators Genistein, VRT-532, and UCCF-152 in primary sinonasal epithelial cultures.

PubMed

Conger, Bryant T; Zhang, Shaoyan; Skinner, Daniel; Hicks, Stephen B; Sorscher, Eric J; Rowe, Steven M; Woodworth, Bradford A

2013-08-01

Pharmacologic activation of mucociliary clearance (MCC) represents an emerging therapeutic strategy for patients with chronic rhinosinusitis, even in the absence of congenital mutations of the CFTR gene. Drug discovery efforts have identified small molecules that activate the cystic fibrosis transmembrane conductance regulator (CFTR), including potentiators under development for treatment of cystic fibrosis. To evaluate the properties of CFTR modulators and their effects on ciliary beat frequency (CBF) in human sinonasal epithelium (HSNE). Primary HSNE cultures (wild type and F508del/F508del) were used to compare stimulation of CFTR-mediated Cl- conductance and CBF by the CFTR modulators genistein, VRT-532, and UCCF-152. Increase in CFTR-dependent anion transport and CBF. HSNE cultures were analyzed using pharmacologic manipulation of ion transport (change in short-circuit current [∆ISC]) and high-speed digital imaging (CBF). Activation of CFTR-dependent anion transport was significantly different among agonists (P < .001), with genistein exerting the greatest effect (mean [SD] ∆ISC, genistein, 23.1 [1.8] μA/cm2² > VRT-532, 8.1 [1.0] μA/cm² > UCCF-152, 3.4 [1.4] μA/cm² > control, 0.7 [0.2] μA/cm²; Tukey-Kramer P < .05) in the absence of forskolin. Genistein and UCCF-152 augmented CBF (under submerged conditions) significantly better (Tukey-Kramer P < .05) than cells treated with VRT-532 or dimethyl sulfoxide vehicle control (mean [SD] fold change over baseline, genistein, 1.63 [0.06]; UCCF-152, 1.56 [0.06]; VRT-532, 1.38 [0.08]; control, 1.27 [0.02]). Activation of CBF was blunted in F508del/F508del HSNE cultures. The degree of CBF stimulation was not dependent on the magnitude of Cl- secretion, suggesting that different mechanisms of action may underlie MCC activation by these small molecule potentiators. Agents that activate both CFTR-dependent ISC and CBF are particularly attractive as therapeutics because they may address 2 independent pathways that contribute to deficient MCC in chronic rhinosinusitis.

Contribution of oxygen-sensitive neurons of the rostral ventrolateral medulla to hypoxic cerebral vasodilatation in the rat

NASA Technical Reports Server (NTRS)

Golanov, E. V.; Reis, D. J.

1996-01-01

1. We sought to determine whether hypoxic stimulation of neurons of the rostral ventrolateral reticular nucleus (RVL) would elevate regional cerebral blood flow (rCBF) in anaesthetized paralysed rats. 2. Microinjection of sodium cyanide (NaCN; 150-450 pmol) into the RVL rapidly (within 1-2 s), transiently, dose-dependently and site-specifically elevated rCBF1 measured by laser Doppler flowmetry, by 61.3 +/- 22.1% (P < 0.01), increased arterial pressure (AP; +30 +/- 8 mmHg; P < 0.01)1 and triggered a synchronized 6 Hz rhythm of EEG activity. 3. Following cervical spinal cord transection, NaCN and also dinitrophenol (DNP) significantly (P < 0.05) elevated rCBF and synchronized the EEG but did not elevate AP; the response to NaCN was attenuated by hyperoxia and deepening of anaesthesia. 4. Electrical stimulation of NaCN-sensitive sites in the RVL in spinalized rats increased rCBF measured autoradiographically with 14C iodoantipyrine (Kety method) in the mid-line thalamus (by 182.3 +/- 17.2%; P < 0.05) and cerebral cortex (by 172.6 +/- 15.6%; P < 0.05) regions, respectively, directly or indirectly innervated by RVL neurons, and in the remainder of the brain. In contrast regional cerebral glucose utilization (rCGU), measured autoradiographically with 14C-2-deoxyglucose (Sokoloff method), was increased in proportion to rCBF in the mid-line thalamus (165.6 +/- 17.8%, P < 0.05) but was unchanged in the cortex. 5. Bilateral electrolytic lesions of NaCN sensitive sites of RVL, while not altering resting rCBF or the elevation elicited by hypercarbia (arterial CO2 pressure, Pa,CO2, approximately 69 mmHg), reduced the vasodilatation elicited by normocapnic hypoxaemia (arterial O2 pressure, Pa,O2, approximately 27 mmHg) by 67% (P < 0.01) and flattened the slope of the Pa,O2-rCBF response curve. 6. We conclude that the elevation of rCBF produced in the cerebral cortex by hypoxaemia is in large measure neurogenic, mediated trans-synaptically over intrinsic neuronal pathways, and initiated by excitation of oxygen sensitive neurons in the RVL.

Exploratory Analysis of Carbon Dioxide Levels, Ultrasound and Optical Coherence Tomography Measures of the Eye During ISS Missions

NASA Technical Reports Server (NTRS)

Schaefer, C.; Coble, C.; Mason, S.; Young, M.; Wear, M. L.; Sargsyan, A.; Garcia, K.; Patel, N.; Gibson, C.; Alexander, D.;

Heat stress redistributes blood flow in arteries of the brain during dynamic exercise.

PubMed

Sato, Kohei; Oue, Anna; Yoneya, Marina; Sadamoto, Tomoko; Ogoh, Shigehiko

2016-04-01

We hypothesized that heat stress would decrease anterior and posterior cerebral blood flow (CBF) during exercise, and the reduction in anterior CBF would be partly associated with large increase in extracranial blood flow (BF). Nine subjects performed 40 min of semirecumbent cycling at 60% of the peak oxygen uptake in hot (35°C; Heat) and thermoneutral environments (25°C; Control). We evaluated BF and conductance (COND) in the external carotid artery (ECA), internal carotid artery (ICA), and vertebral artery (VA) using ultrasonography. During the Heat condition, ICA and VA BF were significantly increased 10 min after the start of exercise (P < 0.05) and thereafter gradually decreased. ICA COND was significantly decreased (P < 0.05), whereas VA COND remained unchanged throughout Heat. Compared with the Control, either BF or COND of ICA and VA at the end of Heat tended to be lower, but not significantly. In contrast, ECA BF and COND at the end of Heat were both higher than levels in the Control condition (P < 0.01). During Heat, a reduction in ICA BF appears to be associated with a decline in end-tidal CO2 tension (r = 0.84), whereas VA BF appears to be affected by a change in cardiac output (r = 0.87). In addition, a change in ECA BF during Heat was negatively correlated with a change in ICA BF (r = -0.75). Heat stress resulted in modification of the vascular response of head and brain arteries to exercise, which resulted in an alteration in the distribution of cardiac output. Moreover, a hyperthermia-induced increase in extracranial BF might compromise anterior CBF during exercise with heat stress. Copyright © 2016 the American Physiological Society.

Consideration of the Intracranial Pressure Threshold Value for the Initiation of Traumatic Brain Injury Treatment: A Xenon CT and Perfusion CT Study.

PubMed

Honda, Mitsuru; Ichibayashi, Ryo; Suzuki, Ginga; Yokomuro, Hiroki; Seiki, Yoshikatsu; Sase, Shigeru; Kishi, Taichi

2017-12-01

Monitoring of intracranial pressure (ICP) is considered to be fundamental for the care of patients with severe traumatic brain injury (TBI) and is routinely used to direct medical and surgical therapy. Accordingly, some guidelines for the management of severe TBI recommend that treatment be initiated for ICP values >20 mmHg. However, it remained to be accounted whether there is a scientific basis to this instruction. The purpose of the present study was to clarify whether the basis of ICP values >20 mmHg is appropriate. We retrospectively reviewed 25 patients with severe TBI who underwent neuroimaging during ICP monitoring within the first 7 days. We measured cerebral blood flow (CBF), mean transit time (MTT), cerebral blood volume (CBV), and ICP 71 times within the first 7 days. Although the CBF, MTT, and CBV values were not correlated with the ICP value at ICP values ≤20 mmHg, the CBF value was significantly negatively correlated with the ICP value (r = -0.381, P < 0.05) at ICP values >20 mmHg. The MTT value was also significantly positively correlated with the ICP value (r = 0.638, P < 0.05) at ICP values >20 mmHg. The cerebral circulation disturbance increased with the ICP value. We demonstrated the cerebral circulation disturbance at ICP values >20 mmHg. This study suggests that an ICP >20 mmHg is the threshold to initiate treatments. An active treatment intervention would be required for severe TBI when the ICP was >20 mmHg.

A comparative analysis of the dependences of the hemodynamic parameters on changes in ROI's position in perfusion CT scans

NASA Astrophysics Data System (ADS)

Choi, Yong-Seok; Cho, Jae-Hwan; Namgung, Jang-Sun; Kim, Hyo-Jin; Yoon, Dae-Young; Lee, Han-Joo

2013-05-01

This study performed a comparative analysis of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and mean time-to-peak (TTP) obtained by changing the region of interest's (ROI) anatomical positions, during CT brain perfusion. We acquired axial source images of perfusion CT from 20 patients undergoing CT perfusion exams due to brain trauma. Subsequently, the CBV, CBF, MTT, and TTP values were calculated through data-processing of the perfusion CT images. The color scales for the CBV, CBF, MTT, and TTP maps were obtained using the image data. Anterior cerebral artery (ACA) was taken as the standard ROI for the calculations of the perfusion values. Differences in the hemodynamic average values were compared in a quantitative analysis by placing ROI and the dividing axial images into proximal, middle, and distal segments anatomically. By performing the qualitative analysis using a blind test, we observed changes in the sensory characteristics by using the color scales of the CBV, CBF, and MTT maps in the proximal, middle, and distal segments. According to the qualitative analysis, no differences were found in CBV, CBF, MTT, and TTP values of the proximal, middle, and distal segments and no changes were detected in the color scales of the the CBV, CBF, MTT, and TTP maps in the proximal, middle, and distal segments. We anticipate that the results of the study will useful in assessing brain trauma patients using by perfusion imaging.

Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling

PubMed Central

Schiffner, René; Bischoff, Sabine Juliane; Lehmann, Thomas; Rakers, Florian; Rupprecht, Sven; Reiche, Juliane; Matziolis, Georg; Schubert, Harald; Schwab, Matthias; Huber, Otmar; Schmidt, Martin

2017-01-01

Background: Maintenance of brain circulation during shock is sufficient to prevent subcortical injury but the cerebral cortex is not spared. This suggests area-specific regulation of cerebral blood flow (CBF) during hemorrhage. Methods: Cortical and subcortical CBF were continuously measured during blood loss (≤50%) and subsequent reperfusion using laser Doppler flowmetry. Blood gases, mean arterial blood pressure (MABP), heart rate and renal blood flow were also monitored. Urapidil was used for α1A-adrenergic receptor blockade in dosages, which did not modify the MABP-response to blood loss. Western blot and quantitative reverse transcription polymerase chain reactions were used to determine adrenergic receptor expression in brain arterioles. Results: During hypovolemia subcortical CBF was maintained at 81 ± 6% of baseline, whereas cortical CBF decreased to 40 ± 4% (p < 0.001). Reperfusion led to peak CBFs of about 70% above baseline in both brain regions. α1A-Adrenergic blockade massively reduced subcortical CBF during hemorrhage and reperfusion, and prevented hyperperfusion during reperfusion in the cortex. α1A-mRNA expression was significantly higher in the cortex, whereas α1D-mRNA expression was higher in the subcortex (p < 0.001). Conclusions: α1-Adrenergic receptors are critical for perfusion redistribution: activity of the α1A-receptor subtype is a prerequisite for redistribution of CBF, whereas the α1D-receptor subtype may determine the magnitude of redistribution responses. PMID:28492488

Redistribution of Cerebral Blood Flow during Severe Hypovolemia and Reperfusion in a Sheep Model: Critical Role of α1-Adrenergic Signaling.

PubMed

Schiffner, René; Bischoff, Sabine Juliane; Lehmann, Thomas; Rakers, Florian; Rupprecht, Sven; Reiche, Juliane; Matziolis, Georg; Schubert, Harald; Schwab, Matthias; Huber, Otmar; Schmidt, Martin

2017-05-11

Maintenance of brain circulation during shock is sufficient to prevent subcortical injury but the cerebral cortex is not spared. This suggests area-specific regulation of cerebral blood flow (CBF) during hemorrhage. Cortical and subcortical CBF were continuously measured during blood loss (≤50%) and subsequent reperfusion using laser Doppler flowmetry. Blood gases, mean arterial blood pressure (MABP), heart rate and renal blood flow were also monitored. Urapidil was used for α1A-adrenergic receptor blockade in dosages, which did not modify the MABP-response to blood loss. Western blot and quantitative reverse transcription polymerase chain reactions were used to determine adrenergic receptor expression in brain arterioles. During hypovolemia subcortical CBF was maintained at 81 ± 6% of baseline, whereas cortical CBF decreased to 40 ± 4% ( p < 0.001). Reperfusion led to peak CBFs of about 70% above baseline in both brain regions. α1A-Adrenergic blockade massively reduced subcortical CBF during hemorrhage and reperfusion, and prevented hyperperfusion during reperfusion in the cortex. α1A-mRNA expression was significantly higher in the cortex, whereas α1D-mRNA expression was higher in the subcortex ( p < 0.001). α1-Adrenergic receptors are critical for perfusion redistribution: activity of the α1A-receptor subtype is a prerequisite for redistribution of CBF, whereas the α1D-receptor subtype may determine the magnitude of redistribution responses.

A broadband continuous-wave multichannel near-infrared system for measuring regional cerebral blood flow and oxygen consumption in newborn piglets

NASA Astrophysics Data System (ADS)

Diop, Mamadou; Elliott, Jonathan T.; Tichauer, Kenneth M.; Lee, Ting-Yim; St. Lawrence, Keith

2009-05-01

Near-infrared spectroscopy (NIRS) is a promising technique for assessing brain function in newborns, particularly due to its portability and sensitivity to cerebral hemodynamics and oxygenation. Methods for measuring cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) have been developed based on broadband continuous-wave NIRS. However, broadband NIRS apparatus typically have only one detection channel, which limits their applicability to measuring regional CBF and CMRO2. In this study, a relatively simple multiplexing approach based on electronically controlled mechanical shutters is proposed to expand the detection capabilities from one to eight channels. The tradeoff is an increase in the sampling interval; however, this has negligible effects on CBF measurements for intervals less than or equal to 1 s. The ability of the system to detect focal brain injury was demonstrated in piglets by injecting endothelin-1 (ET-1) into the cerebral cortex. For validation, CBF was independently measured by computed tomography (CT) perfusion. The average reduction in CBF from the source-detector pair that interrogated the injured region was 51%±9%, which was in good agreement with the CBF reduction measured by CT perfusion (55%±5%). No significant changes in regional CMRO2 were observed. The average regional differential pathlength prior to ET-1 injection was 8.4±0.2 cm (range of 7.1-9.6 cm) and did not significantly change after the injury.

Integrative regulation of human brain blood flow

PubMed Central

Willie, Christopher K; Tzeng, Yu-Chieh; Fisher, Joseph A; Ainslie, Philip N

2014-01-01

Herein, we review mechanisms regulating cerebral blood flow (CBF), with specific focus on humans. We revisit important concepts from the older literature and describe the interaction of various mechanisms of cerebrovascular control. We amalgamate this broad scope of information into a brief review, rather than detailing any one mechanism or area of research. The relationship between regulatory mechanisms is emphasized, but the following three broad categories of control are explicated: (1) the effect of blood gases and neuronal metabolism on CBF; (2) buffering of CBF with changes in blood pressure, termed cerebral autoregulation; and (3) the role of the autonomic nervous system in CBF regulation. With respect to these control mechanisms, we provide evidence against several canonized paradigms of CBF control. Specifically, we corroborate the following four key theses: (1) that cerebral autoregulation does not maintain constant perfusion through a mean arterial pressure range of 60–150 mmHg; (2) that there is important stimulatory synergism and regulatory interdependence of arterial blood gases and blood pressure on CBF regulation; (3) that cerebral autoregulation and cerebrovascular sensitivity to changes in arterial blood gases are not modulated solely at the pial arterioles; and (4) that neurogenic control of the cerebral vasculature is an important player in autoregulatory function and, crucially, acts to buffer surges in perfusion pressure. Finally, we summarize the state of our knowledge with respect to these areas, outline important gaps in the literature and suggest avenues for future research. PMID:24396059

Influence of essential and fatty oils on ciliary beat frequency of human nasal epithelial cells.

PubMed

Neher, Andreas; Gstöttner, Michaela; Thaurer, Michael; Augustijns, Patrick; Reinelt, Monika; Schobersberger, Wolfgang

2008-01-01

In alternative and complementary medicine, the use of essential and fatty oils has become more and more popular. In addition to conventional medical therapies, self-medication is showing increasing popularity, using agents with unclear compounds and poorly controlled dosages. Among other disorders, these alternative treatments are used in bronchitis and rhinitis, including some topical applications. Thus, the influence on ciliated epithelia should be evaluated, because a disturbance of the ciliary function can lead to recurrent sinusitis and chronic rhinosinusitis. The aim of this study was to test the influence of fatty and essential oils on the ciliary beat frequency (CBF) of nasal mucosa in vivo. The influence of sesame oil, soy oil, peanut oil, Miglyol 840, thyme oil, lavender oil, eucalyptus oil, and menthol on the ciliary activity of nasal brushings was evaluated by digital high-speed imaging. The presence of most fatty oils resulted in an increase in CBF, the effect being highest for peanut oil. Miglyol 840 had no significant influence on CBF. The essential oils were tested at a concentration of 0.2 and 2%. Thyme oil did not affect CBF, whereas the presence of all other essentials oils resulted in an increase in CBF; the effect was higher at 0.2% than at 2%. Except thyme oil and Miglyol 840, all tested oils caused an increase in CBF. Interestingly, the 0.2% concentrations of essential oils resulted in stronger effects when compared with the 2% concentrations.

Neuroimaging Assessment of Cerebrovascular Reactivity in Concussion: Current Concepts, Methodological Considerations, and Review of the Literature

PubMed Central

Ellis, Michael J.; Ryner, Lawrence N.; Sobczyk, Olivia; Fierstra, Jorn; Mikulis, David J.; Fisher, Joseph A.; Duffin, James; Mutch, W. Alan C.

2016-01-01

Concussion is a form of traumatic brain injury (TBI) that presents with a wide spectrum of subjective symptoms and few objective clinical findings. Emerging research suggests that one of the processes that may contribute to concussion pathophysiology is dysregulation of cerebral blood flow (CBF) leading to a mismatch between CBF delivery and the metabolic needs of the injured brain. Cerebrovascular reactivity (CVR) is defined as the change in CBF in response to a measured vasoactive stimulus. Several magnetic resonance imaging (MRI) techniques can be used as a surrogate measure of CBF in clinical and laboratory studies. In order to provide an accurate assessment of CVR, these sequences must be combined with a reliable, reproducible vasoactive stimulus that can manipulate CBF. Although CVR imaging currently plays a crucial role in the diagnosis and management of many cerebrovascular diseases, only recently have studies begun to apply this assessment tool in patients with concussion. In order to evaluate the quality, reliability, and relevance of CVR studies in concussion, it is important that clinicians and researchers have a strong foundational understanding of the role of CBF regulation in health, concussion, and more severe forms of TBI, and an awareness of the advantages and limitations of currently available CVR measurement techniques. Accordingly, in this review, we (1) discuss the role of CVR in TBI and concussion, (2) examine methodological considerations for MRI-based measurement of CVR, and (3) provide an overview of published CVR studies in concussion patients. PMID:27199885

A comparison of the effects of citalopram and moclobemide on resting brain perfusion in social anxiety disorder.

PubMed

Warwick, J M; Carey, P; Van der Linden, G; Prinsloo, C; Niehaus, D; Seedat, S; Dupont, P; Stein, D J

2006-09-01

The serotonin specific reuptake inhibitor (SSRI) citalopram and the reversible mono-amine oxidase-A inhibitor (RIMA) moclobemide have both been used successfully for the treatment of social anxiety disorder (SAD). In this study we investigate the effects of these compounds on resting brain function using single photon emission computed tomography (SPECT). Subjects meeting DSM-IV criteria for SAD underwent regional cerebral blood flow (rCBF) SPECT using Tc-HMPAO at baseline and after 8 weeks of treatment with either citalopram or moclobemide. Using statistical parametric mapping brain SPECT studies were analysed to determine the effects of treatment on rCBF, to compare the effects of citalopram and moclobemide, and to detect correlations between changes in rCBF and clinical response. Subjects received citalopram (n=17) or moclobemide (n=14) as therapy. Subjects in both treatment groups demonstrated a significant improvement of SAD symptoms as measured by the Liebowitz Social Anxiety Scale total score. All subjects demonstrated a decrease in rCBF in the insulae post therapy. Subjects receiving citalopram had decreased superior cingulate rCBF after therapy compared to those receiving moclobemide. Both SSRI's and RIMA's decreased rCBF in the insulae during treatment of SAD; an effect that may be consistent with the role of these regions in processing internal somatic cues evoked by emotional stimuli. Citalopram had a greater effect on superior cingulate perfusion, an effect that is consistent with evidence of high levels of 5-HT transporters in this region.

FAIR exempting separate T (1) measurement (FAIREST): a novel technique for online quantitative perfusion imaging and multi-contrast fMRI.

PubMed

Lai, S; Wang, J; Jahng, G H

2001-01-01

A new pulse sequence, dubbed FAIR exempting separate T(1) measurement (FAIREST) in which a slice-selective saturation recovery acquisition is added in addition to the standard FAIR (flow-sensitive alternating inversion recovery) scheme, was developed for quantitative perfusion imaging and multi-contrast fMRI. The technique allows for clean separation between and thus simultaneous assessment of BOLD and perfusion effects, whereas quantitative cerebral blood flow (CBF) and tissue T(1) values are monitored online. Online CBF maps were obtained using the FAIREST technique and the measured CBF values were consistent with the off-line CBF maps obtained from using the FAIR technique in combination with a separate sequence for T(1) measurement. Finger tapping activation studies were carried out to demonstrate the applicability of the FAIREST technique in a typical fMRI setting for multi-contrast fMRI. The relative CBF and BOLD changes induced by finger-tapping were 75.1 +/- 18.3 and 1.8 +/- 0.4%, respectively, and the relative oxygen consumption rate change was 2.5 +/- 7.7%. The results from correlation of the T(1) maps with the activation images on a pixel-by-pixel basis show that the mean T(1) value of the CBF activation pixels is close to the T(1) of gray matter while the mean T(1) value of the BOLD activation pixels is close to the T(1) range of blood and cerebrospinal fluid. Copyright 2001 John Wiley & Sons, Ltd.

Changes in Cerebral Blood Flow during an Alteration in Glycemic State in a Large Non-human Primate (Papio hamadryas sp.).

PubMed

Kochunov, Peter; Wey, Hsiao-Ying; Fox, Peter T; Lancaster, Jack L; Davis, Michael D; Wang, Danny J J; Lin, Ai-Ling; Bastarrachea, Raul A; Andrade, Marcia C R; Mattern, Vicki; Frost, Patrice; Higgins, Paul B; Comuzzie, Anthony G; Voruganti, Venkata S

2017-01-01

Changes in cerebral blood flow (CBF) during a hyperglycemic challenge were mapped, using perfusion-weighted MRI, in a group of non-human primates. Seven female baboons were fasted for 16 h prior to 1-h imaging experiment, performed under general anesthesia, that consisted of a 20-min baseline, followed by a bolus infusion of glucose (500 mg/kg). CBF maps were collected every 7 s and blood glucose and insulin levels were sampled at regular intervals. Blood glucose levels rose from 51.3 ± 10.9 to 203.9 ± 38.9 mg/dL and declined to 133.4 ± 22.0 mg/dL, at the end of the experiment. Regional CBF changes consisted of four clusters: cerebral cortex, thalamus, hypothalamus, and mesencephalon. Increases in the hypothalamic blood flow occurred concurrently with the regulatory response to systemic glucose change, whereas CBF declined for other clusters. The return to baseline of hypothalamic blood flow was observed while CBF was still increasing in other brain regions. The spatial pattern of extra-hypothalamic CBF changes was correlated with the patterns of several cerebral networks including the default mode network. These findings suggest that hypothalamic blood flow response to systemic glucose levels can potentially be explained by regulatory activity. The response of extra-hypothalamic clusters followed a different time course and its spatial pattern resembled that of the default-mode network.

A broadband continuous-wave multichannel near-infrared system for measuring regional cerebral blood flow and oxygen consumption in newborn piglets.

PubMed

Diop, Mamadou; Elliott, Jonathan T; Tichauer, Kenneth M; Lee, Ting-Yim; St Lawrence, Keith

2009-05-01

Near-infrared spectroscopy (NIRS) is a promising technique for assessing brain function in newborns, particularly due to its portability and sensitivity to cerebral hemodynamics and oxygenation. Methods for measuring cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) have been developed based on broadband continuous-wave NIRS. However, broadband NIRS apparatus typically have only one detection channel, which limits their applicability to measuring regional CBF and CMRO(2). In this study, a relatively simple multiplexing approach based on electronically controlled mechanical shutters is proposed to expand the detection capabilities from one to eight channels. The tradeoff is an increase in the sampling interval; however, this has negligible effects on CBF measurements for intervals less than or equal to 1 s. The ability of the system to detect focal brain injury was demonstrated in piglets by injecting endothelin-1 (ET-1) into the cerebral cortex. For validation, CBF was independently measured by computed tomography (CT) perfusion. The average reduction in CBF from the source-detector pair that interrogated the injured region was 51%+/-9%, which was in good agreement with the CBF reduction measured by CT perfusion (55%+/-5%). No significant changes in regional CMRO(2) were observed. The average regional differential pathlength prior to ET-1 injection was 8.4+/-0.2 cm (range of 7.1-9.6 cm) and did not significantly change after the injury.

Production of a novel bioflocculant and its flocculation performance in aluminum removal.

PubMed

Li, Lixin; Ma, Fang; Zuo, Huimin

2016-04-02

A novel bioflocculant CBF with high flocculating activity, produced by mixed culture of Rhizobium radiobacter F2 and Bacillus sphaericus F6 from soil, was investigated with regard to its production and flocculation performance in Al(III) removal. The most preferred carbon source, nitrogen source and C/N ratio (w/w) for strains F2 and F6 to produce CBF were glucose, urea and 20, respectively. The optimal inoculum size for CBF production was 10 % (v/v). The optimal initial pH, culture temperature and shaking speed were 7-8, 30°C and 140 r/min for 24 h, respectively, under which the flocculating activity of the bioflocculant reached 98.52 %. According to literature review, flocculant dosage, coagulant aid dosage, pH, hydraulic condition of coagulation and sedimentation time are considered as influencing parameters for CBF flocculation performance in Al(III) removal by L16(4(5)) orthogonal design. The optimal conditions for Al(III) removal obtained through analysis and verification experiments were as follows: CBF, 28 mg/L; coagulant aid, 1.5 mL/L; initial pH, 8.0; and hydraulic conditions of coagulation: stir speed, 160 r/min; stir time, 40 s; and sedimentation time, 30 min. Under the optimal conditions, the removal efficiency of Al(III) was 92.95 %. Overall, these findings indicate that bioflocculant CBF offers an effective alternative method of decreasing Al(III) during drinking water treatment.

Role of CBFs as Integrators of Chloroplast Redox, Phytochrome and Plant Hormone Signaling during Cold Acclimation

PubMed Central

Kurepin, Leonid V.; Dahal, Keshav P.; Savitch, Leonid V.; Singh, Jas; Bode, Rainer; Ivanov, Alexander G.; Hurry, Vaughan; Hüner, Norman P. A.

2013-01-01

Cold acclimation of winter cereals and other winter hardy species is a prerequisite to increase subsequent freezing tolerance. Low temperatures upregulate the expression of C-repeat/dehydration-responsive element binding transcription factors (CBF/DREB1) which in turn induce the expression of COLD-REGULATED (COR) genes. We summarize evidence which indicates that the integration of these interactions is responsible for the dwarf phenotype and enhanced photosynthetic performance associated with cold-acclimated and CBF-overexpressing plants. Plants overexpressing CBFs but grown at warm temperatures mimic the cold-tolerant, dwarf, compact phenotype; increased photosynthetic performance; and biomass accumulation typically associated with cold-acclimated plants. In this review, we propose a model whereby the cold acclimation signal is perceived by plants through an integration of low temperature and changes in light intensity, as well as changes in light quality. Such integration leads to the activation of the CBF-regulon and subsequent upregulation of COR gene and GA 2-oxidase (GA2ox) expression which results in a dwarf phenotype coupled with increased freezing tolerance and enhanced photosynthetic performance. We conclude that, due to their photoautotrophic nature, plants do not rely on a single low temperature sensor, but integrate changes in light intensity, light quality, and membrane viscosity in order to establish the cold-acclimated state. CBFs appear to act as master regulators of these interconnecting sensing/signaling pathways. PMID:23778089

Retinoic acids and trichostatin A (TSA), a histone deacetylase inhibitor, induce human pyruvate dehydrogenase kinase 4 (PDK4) gene expression.

PubMed

Kwon, Hye-Sook; Huang, Boli; Ho Jeoung, Nam; Wu, Pengfei; Steussy, Calvin N; Harris, Robert A

2006-01-01

Induction of pyruvate dehydrogenase kinase 4 (PDK4) conserves glucose and substrates for gluconeogenesis and thereby helps regulate blood glucose levels during starvation. We report here that retinoic acids (RA) as well as Trichostatin A (TSA), an inhibitor of histone deacetylase (HDAC), regulate PDK4 gene expression. Two retinoic acid response elements (RAREs) to which retinoid X receptor alpha (RXRalpha) and retinoic acid receptor alpha (RARalpha) bind and activate transcription are present in the human PDK4 (hPDK4) proximal promoter. Sp1 and CCAAT box binding factor (CBF) bind to the region between two RAREs. Mutation of either the Sp1 or the CBF site significantly decreases basal expression, transactivation by RXRalpha/RARalpha/RA, and the ability of TSA to stimulate hPDK4 gene transcription. By the chromatin immunoprecipitation assay, RA and TSA increase acetylation of histones bound to the proximal promoter as well as occupancy of CBP and Sp1. Interaction of p300/CBP with E1A completely prevented hPDK4 gene activation by RXRalpha/RARalpha/RA and TSA. The p300/CBP may enhance acetylation of histones bound to the hPDK4 promoter and cooperate with Sp1 and CBF to stimulate transcription of the hPDK4 gene in response to RA and TSA.

In vivo cerebral blood flow autoregulation studies using rheoencephalography

NASA Astrophysics Data System (ADS)

Bodo, M.; Pearce, F.; Garcia, A.; Van Albert, S.; Settle, T.; Szebeni, J.; Baranyi, L.; Hartings, J.; Armonda, R.

2010-04-01

Acute management of patients with traumatic brain/blast injury is a challenge. To minimize secondary injury and improve outcome, it is critical to detect neurological deterioration early, when it is potentially reversible. One potential monitoring method is cerebral electrical impedance (rheoencephalography-REG) because of its non-invasiveness and good time resolution. Reported here are the results of cerebral blood flow (CBF) manipulations comparing electroencephalogram (EEG) with REG (both intra-cerebral) and measuring with surface and skull REG electrodes. Our hypothesis was that REG would reflect spreading depression and CBF autoregulation. Animal experiments were performed using one rat (four trials with intracerebral electrodes), monkeys (n=8, with surface electrodes) and pigs (n = 24 pigs with skull electrodes; 57 trials, 19 types of liposomes). Challenges included intracranial pressure (ICP) elevation, liposome infusion, and hemorrhage. Data were stored on a PC and evaluated off line. CBF autoregulation was evaluated both by visual inspection and by a Matlab script. These studies confirmed that REG reflects CBF autoregulation and that REG is useful for detecting spreading depression (SD), vasospasm and the lower limit of CBF autoregulation. These findings have clinical relevance for use in noninvasive neuro-monitoring in the neurosurgery intensive care and during transportation of patients with brain injury.

Induction and imaging of photothrombotic stroke in conscious and freely moving rats

NASA Astrophysics Data System (ADS)

Lu, Hongyang; Li, Yao; Yuan, Lu; Li, Hangdao; Lu, Xiaodan; Tong, Shanbao

2014-09-01

In experimental stroke research, anesthesia is common and serves as a major reason for translational failure. Real-time cerebral blood flow (CBF) monitoring during stroke onset can provide important information for the prediction of brain injury; however, this is difficult to achieve in clinical practice due to various technical problems. We created a photothrombotic focal ischemic stroke model utilizing our self-developed miniature headstage in conscious and freely moving rats. In this model, a high spatiotemporal resolution imager using laser speckle contrast imaging technology was integrated to acquire real-time two-dimensional CBF information during thrombosis. The feasibility, stability, and reliability of the system were tested in terms of CBF, behavior, and T2-weighted magnetic resonance imaging (MRI) findings. After completion of occlusion, the CBF in the targeted cortex of the stroke group was reduced to 16±9% of the baseline value. The mean infarct volume measured by MRI 24 h postmodeling was 77±11 mm3 and correlated well with CBF (R2=0.74). This rodent model of focal cerebral ischemia and real-time blood flow imaging opens the possibility of performing various fundamental and translational studies on stroke without the influence of anesthetics.

Base-line O sub 2 extraction influences cerebral blood flow response to hematocrit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hudak, M.L.; Tang, Yuilin; Massik, J.

1988-01-01

The authors have shown that the fall in cerebral blood flow (CBF) as hematocrit (Hct) rises is due to the independent effects of increasing red blood cell (RBC) concentration and arterial O{sub 2} content (Ca{sub O{sub 2}}). In the present study, they tested the hypothesis that the magnitude of the effect of RBC concentration depends on the base-line cerebral fractional oxygen extraction (E). Pentobarbital-anesthetized 1- to 7-day-old sheep were first exchange transfused with plasma to lower Hct to 20%. Base-line E was set to either high or low levels by induction of hypocarbia, or hypercarbia. A second isovolemic exchange transfusionmore » with pure methemoglobin-containing adult sheep red cells then raised Hct with no significant increase in Ca{sub O{sub 2}}. Pa{sub CO{sub 2}} was maintained and other variables with potential effect on CBF did not change. CBF corrected for any individual alteration in CMRo{sub 2}. This study supports the hypothesis that the magnitude of the decline in CBF secondary to an increase in RBC concentration depends on the initial E. The effect of RBC concentration on CBF is greatest when E is low.« less

Spatio-temporal dynamics of perfusion and oximetry during ictal discharges in the rat neocortex

PubMed Central

Zhao, Mingrui; Ma, Hongtao; Suh, Minah; Schwartz, Theodore H.

2009-01-01

Epileptic events elicit a large focal increase in cerebral blood flow (CBF) to perfuse metabolically active neurons in the focus. Conflicting data exists, however, on whether hemoglobin saturation increases or decreases in the focus and surrounding cortex, and whether CBF increases globally or is decreased in adjacent areas. How these hemodynamic events correlate with actual changes in tissue oxygenation is also not known. Using laser Doppler flowmetry, oxygen microsensors and intrinsic optical imaging spectroscopy, we demonstrate that the dip in hemoglobin in the focus correlates with a profound but temporary decrease in tissue oxygenation in spite of a large increase in cerebral blood flow (CBF). Furthermore, CBF simultaneously decreases in the cortex immediately adjacent to the focus. These events are then replaced with a longer duration, less focal increase in CBF, CBV and hyperoxygenation, the duration of which correlates with the duration of the seizure. These findings raise the question of whether transient focal hypoxia and vascular steal might contribute to progressive deleterious effects of chronic epilepsy on the adult and developing brain. Possible mechanisms based on recent astrocyte-based models of neurovascular coupling are discussed. Implications for functional magnetic resonance imaging of epileptic events are discussed. PMID:19261877

Role of cerebral blood flow in extreme breath holding

PubMed Central

Ainslie, Philip N.; Hoiland, Ryan L.; Willie, Chris K.; MacLeod, David B.; Madden, Dennis; Maslov, Petra Zubin; Drviš, Ivan; Dujić, Željko

2016-01-01

Abstract The role of cerebral blood flow (CBF) on a maximal breath-hold (BH) in ultra-elite divers was examined. Divers (n = 7) performed one control BH, and one BH following oral administration of the non-selective cyclooxygenase inhibitor indomethacin (1.2 mg/kg). Arterial blood gases and CBF were measured prior to (baseline), and at BH termination. Compared to control, indomethacin reduced baseline CBF and cerebral delivery of oxygen (CDO2) by about 26% (p < 0.01). Indomethacin reduced maximal BH time from 339 ± 51 to 319 ± 57 seconds (p = 0.04). In both conditions, the CDO2 remained unchanged from baseline to the termination of apnea. At BH termination, arterial oxygen tension was higher following oral administration of indomethacin compared to control (4.05 ± 0.45 vs. 3.44 ± 0.32 kPa). The absolute increase in CBF from baseline to the termination of apnea was lower with indomethacin (p = 0.01). These findings indicate that the impact of CBF on maximal BH time is likely attributable to its influence on cerebral H+ washout, and therefore central chemoreceptive drive to breathe, rather than to CDO2. PMID:28123816

Role of cerebral blood flow in extreme breath holding.

PubMed

Bain, Anthony R; Ainslie, Philip N; Hoiland, Ryan L; Willie, Chris K; MacLeod, David B; Madden, Dennis; Maslov, Petra Zubin; Drviš, Ivan; Dujić, Željko

2016-01-01

The role of cerebral blood flow (CBF) on a maximal breath-hold (BH) in ultra-elite divers was examined. Divers (n = 7) performed one control BH, and one BH following oral administration of the non-selective cyclooxygenase inhibitor indomethacin (1.2 mg/kg). Arterial blood gases and CBF were measured prior to (baseline), and at BH termination. Compared to control, indomethacin reduced baseline CBF and cerebral delivery of oxygen (CDO 2 ) by about 26% (p < 0.01). Indomethacin reduced maximal BH time from 339 ± 51 to 319 ± 57 seconds (p = 0.04). In both conditions, the CDO 2 remained unchanged from baseline to the termination of apnea. At BH termination, arterial oxygen tension was higher following oral administration of indomethacin compared to control (4.05 ± 0.45 vs. 3.44 ± 0.32 kPa). The absolute increase in CBF from baseline to the termination of apnea was lower with indomethacin (p = 0.01). These findings indicate that the impact of CBF on maximal BH time is likely attributable to its influence on cerebral H + washout, and therefore central chemoreceptive drive to breathe, rather than to CDO 2 .

Increased putamen hypercapnic vasoreactivity in levodopa-induced dyskinesia.

PubMed

Jourdain, Vincent A; Schindlbeck, Katharina A; Tang, Chris C; Niethammer, Martin; Choi, Yoon Young; Markowitz, Daniel; Nazem, Amir; Nardi, Dominic; Carras, Nicholas; Feigin, Andrew; Ma, Yilong; Peng, Shichun; Dhawan, Vijay; Eidelberg, David

2017-10-19

In a rodent model of Parkinson's disease (PD), levodopa-induced involuntary movements have been linked to striatal angiogenesis - a process that is difficult to document in living human subjects. Angiogenesis can be accompanied by localized increases in cerebral blood flow (CBF) responses to hypercapnia. We therefore explored the possibility that, in the absence of levodopa, local hypercapnic CBF responses are abnormally increased in PD patients with levodopa-induced dyskinesias (LID) but not in their nondyskinetic (NLID) counterparts. We used H215O PET to scan 24 unmedicated PD subjects (12 LID and 12 NLID) and 12 matched healthy subjects in the rest state under normocapnic and hypercapnic conditions. Hypercapnic CBF responses were compared to corresponding levodopa responses from the same subjects. Group differences in hypercapnic vasoreactivity were significant only in the posterior putamen, with greater CBF responses in LID subjects compared with the other subjects. Hypercapnic and levodopa-mediated CBF responses measured in this region exhibited distinct associations with disease severity: the former correlated with off-state motor disability ratings but not symptom duration, whereas the latter correlated with symptom duration but not motor disability. These are the first in vivo human findings linking LID to microvascular changes in the basal ganglia.

Investigating the physiology of brain activation with MRI

NASA Astrophysics Data System (ADS)

Buxton, Richard B.; Uludag, Kamil; Dubowitz, David J.

2004-04-01

Functional magnetic resonance imaging (fMRI) has become a powerful tool for investigating the working human brain based on the blood oxygenation level dependent (BOLD) effect on the MR signal. However, despite the widespread use of fMRI techniques for mapping brain activation, the basic physiological mechanisms underlying the observed signal changes are still poorly understood. Arterial spin labeling (ASL) techniques, which measure cerebral blood flow (CBF) and the BOLD effect simultaneously, provide a useful tool for investigating these physiological questions. In this paper, recent results of studies manipulating the baseline CBF both pharmacologically and physiologically will be discussed. These data are consistent with a feed-forward mechanism of neurovascular coupling, and suggest that the CBF change itself may be a more robust reflection of neural activity changes than the BOLD effect. Consistent with these data, a new thermodynamic hypothesis is proposed for the physiological function of CBF regulation: maintenance of the [O2]/[CO2] concentration ratio at the mitochondria in order to preserve the free energy available from oxidative metabolism. A kinetic model based on this hypothesis provides a reasonable quantitative description of the CBF changes associated with neural activity and altered blood gases (CO2 and O2).

Cerebral blood flow velocity and cranial fluid volume decrease during +Gz acceleration

NASA Technical Reports Server (NTRS)

Kawai, Y.; Puma, S. C.; Hargens, A. R.; Murthy, G.; Warkander, D.; Lundgren, C. E.

1997-01-01

Cerebral blood flow (CBF) velocity and cranial fluid volume, which is defined as the total volume of intra- and extracranial fluid, were measured using transcranial Doppler ultrasonography and rheoencephalography, respectively, in humans during graded increase of +Gz acceleration (onset rate: 0.1 G/s) without straining maneuvers. Gz acceleration was terminated when subjects' vision decreased to an angle of less than or equal to 60 degrees, which was defined as the physiological end point. In five subjects, mean CBF velocity decreased 48% from a baseline value of 59.4 +/- 11.2 cm/s to 31.0 +/- 5.6 cm/s (p<0.01) with initial loss of peripheral vision at 5.7 +/- 0.9 Gz. On the other hand, systolic CBF velocity did not change significantly during increasing +Gz acceleration. Cranial impedance, which is proportional to loss of cranial fluid volume, increased by 2.0 +/- 0.8% above the baseline value at the physiological end point (p<0.05). Both the decrease of CBF velocity and the increase of cranial impedance correlated significantly with Gz. These results suggest that +Gz acceleration without straining maneuvers decreases CBF velocity to half normal and probably causes a caudal fluid shift from both intra- and extracranial tissues.

Rice phytochrome-interacting factor protein OsPIFff14 represses OsDREB1B gene expression through an extended N-box and interacts preferentially with the active form of phytochrome B

USDA-ARS?s Scientific Manuscript database

DREB1/CBF genes, known as major regulators of plant stress responses, are rapidly and transiently induced by low temperatures. Using a Yeast one Hybrid screening, we identified a putative Phytochrome-Interacting bHLH Factor (OsPIF14), as binding to the OsDREB1B promoter. bHLH proteins are able to bi...

Optimization of Photosynthetic Productivity in Contrasting Environments by Regulons Controlling Plant Form and Function

PubMed Central

Demmig-Adams, Barbara; Baker, Christopher R.

2018-01-01

We review the role of a family of transcription factors and their regulons in maintaining high photosynthetic performance across a range of challenging environments with a focus on extreme temperatures and water availability. Specifically, these transcription factors include CBFs (C-repeat binding factors) and DREBs (dehydration-responsive element-binding), with CBF/DREB1 primarily orchestrating cold adaptation and other DREBs serving in heat, drought, and salinity adaptation. The central role of these modulators in plant performance under challenging environments is based on (i) interweaving of these regulators with other key signaling networks (plant hormones and redox signals) as well as (ii) their function in integrating responses across the whole plant, from light-harvesting and sugar-production in the leaf to foliar sugar export and water import and on to the plant’s sugar-consuming sinks (growth, storage, and reproduction). The example of Arabidopsis thaliana ecotypes from geographic origins with contrasting climates is used to describe the links between natural genetic variation in CBF transcription factors and the differential acclimation of plant anatomical and functional features needed to support superior photosynthetic performance in contrasting environments. Emphasis is placed on considering different temperature environments (hot versus cold) and light environments (limiting versus high light), on trade-offs between adaptations to contrasting environments, and on plant lines minimizing such trade-offs. PMID:29543762

Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis

PubMed Central

Zwolinska-Wcislo, Malgorzata; Brzozowski, Tomasz; Ptak-Belowska, Agata; Targosz, Aneta; Urbanczyk, Katarzyna; Kwiecien, Slawomir; Sliwowski, Zbigniew

2011-01-01

AIM: To determine the effect of non-selective cyclooxygenase (COX) inhibitors, selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis. METHODS: Rats with 2,4,6 trinitrobenzenesulfon-ic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle, aspirin (ASA) (a non-selective COX inhibitor), celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days. The area of colonic lesions, colonic blood flow (CBF), myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2, inducible form of nitric oxide synthase (iNOS), IL-1β and tumor necrosis factor (TNF)-α were assessed. The effects of glyceryl trinitrate (GTN), a NO donor, and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-​tetramethyl-1H-imidazolyl-1-oxy-3-oxide, onopotassium salt (carboxy-PTIO), a NO scavenger, administered without and with ASA or NO-ASA, and the involvement of capsaicin-sensitive afferent nerves in the mechanism of healing the experimental colitis was also determined. RESULTS: Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF, a significant rise in colonic weight, MPO activity and plasma IL-1β and TNF-α levels. These effects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560), but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E2 (PGE2) analog. Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NOx content and CBF, suppression of MPO and downregulation of COX-2, iNOS, IL-1β and TNF-α mRNAs. Treatment with GTN, the NO donor, significantly inhibited the ASA-induced colonic lesions and increased CBF, while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASA-induced improvement of colonic healing and the accompanying increase in the CBF. These effects were restored by co-treatment with calcitonin gene related peptide (CGRP) and NO-ASA in capsaicin-denervated animals. CONCLUSION: NO-releasing ASA, in contrast to ASA, COX-1 inhibitors, and SC-560, accelerated the healing of colitis via a mechanism involving NO mediated improvement of microcirculation and activation of sensory nerves releasing CGRP. PMID:22039321

Analysis of Stress-Responsive Gene Expression in Cultivated and Weedy Rice Differing in Cold Stress Tolerance

PubMed Central

Pereira, Andy; Tseng, Te-Ming; Zimmer, Paulo Dejalma; Burgos, Nilda Roma

2015-01-01

Rice (Oryza sativa L.) cultivars show impairment of growth in response to environmental stresses such as cold at the early seedling stage. Locally adapted weedy rice is able to survive under adverse environmental conditions, and can emerge in fields from greater soil depth. Cold-tolerant weedy rice can be a good genetic source for developing cold-tolerant, weed-competitive rice cultivars. An in-depth analysis is presented here of diverse indica and japonica rice genotypes, mostly weedy rice, for cold stress response to provide an understanding of different stress adaptive mechanisms towards improvement of the rice crop performance in the field. We have tested a collection of weedy rice genotypes to: 1) classify the subspecies (ssp.) grouping (japonica or indica) of 21 accessions; 2) evaluate their sensitivity to cold stress; and 3) analyze the expression of stress-responsive genes under cold stress and a combination of cold and depth stress. Seeds were germinated at 25°C at 1.5- and 10-cm sowing depth for 10d. Seedlings were then exposed to cold stress at 10°C for 6, 24 and 96h, and the expression of cold-, anoxia-, and submergence-inducible genes was analyzed. Control plants were seeded at 1.5cm depth and kept at 25°C. The analysis revealed that cold stress signaling in indica genotypes is more complex than that of japonica as it operates via both the CBF-dependent and CBF-independent pathways, implicated through induction of transcription factors including OsNAC2, OsMYB46 and OsF-BOX28. When plants were exposed to cold + sowing depth stress, a complex signaling network was induced that involved cross talk between stresses mediated by CBF-dependent and CBF-independent pathways to circumvent the detrimental effects of stresses. The experiments revealed the importance of the CBF regulon for tolerance to both stresses in japonica and indica ssp. The mechanisms for cold tolerance differed among weedy indica genotypes and also between weedy indica and cultivated japonica ssp. as indicated by the up/downregulation of various stress-responsive pathways identified from gene expression analysis. The cold-stress response is described in relation to the stress signaling pathways, showing complex adaptive mechanisms in different genotypes. PMID:26230579

Regional Cerebral Blood Flow during Wakeful Rest in Older Subjects with Mild to Severe Obstructive Sleep Apnea

PubMed Central

Baril, Andrée-Ann; Gagnon, Katia; Arbour, Caroline; Soucy, Jean-Paul; Montplaisir, Jacques; Gagnon, Jean-François; Gosselin, Nadia

2015-01-01

Objectives: To evaluate changes in regional cerebral blood flow (rCBF) during wakeful rest in older subjects with mild to severe obstructive sleep apnea (OSA) and healthy controls, and to identify markers of OSA severity that predict altered rCBF. Design: High-resolution 99mTc-HMPAO SPECT imaging during wakeful rest. Setting: Research sleep laboratory affiliated with a University hospital. Participants: Fifty untreated OSA patients aged between 55 and 85 years, divided into mild, moderate, and severe OSA, and 20 age-matched healthy controls. Interventions: N/A. Measurements: Using statistical parametric mapping, rCBF was compared between groups and correlated with clinical, respiratory, and sleep variables. Results: Whereas no rCBF change was observed in mild and moderate groups, participants with severe OSA had reduced rCBF compared to controls in the left parietal lobules, left precentral gyrus, bilateral postcentral gyri, and right precuneus. Reduced rCBF in these regions and in areas of the bilateral frontal and left temporal cortex was associated with more hypopneas, snoring, hypoxemia, and sleepiness. Higher apnea, microarousal, and body mass indexes were correlated to increased rCBF in the basal ganglia, insula, and limbic system. Conclusions: While older individuals with severe obstructive sleep apnea (OSA) had hypoperfusion in the sensorimotor and parietal areas, respiratory variables and subjective sleepiness were correlated with extended regions of hypoperfusion in the lateral cortex. Interestingly, OSA severity, sleep fragmentation, and obesity correlated with increased perfusion in subcortical and medial cortical regions. Anomalies with such a distribution could result in cognitive deficits and reflect impaired vascular regulation, altered neuronal integrity, and/or undergoing neurodegenerative processes. Citation: Baril AA, Gagnon K, Arbour C, Soucy JP, Montplaisir J, Gagnon JF, Gosselin N. Regional cerebral blood flow during wakeful rest in older subjects with mild to severe obstructive sleep apnea. SLEEP 2015;38(9):1439–1449. PMID:25761981

Voxel-level comparison of arterial spin-labeled perfusion magnetic resonance imaging in adolescents with internet gaming addiction

PubMed Central

2013-01-01

Background Although recent studies have clearly demonstrated functional and structural abnormalities in adolescents with internet gaming addiction (IGA), less is known about how IGA affects perfusion in the human brain. We used pseudocontinuous arterial spin-labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) to measure the effects of IGA on resting brain functions by comparing resting cerebral blood flow in adolescents with IGA and normal subjects. Methods Fifteen adolescents with IGA and 18 matched normal adolescents underwent structural and perfusion fMRI in the resting state. Direct subtraction, voxel-wise general linear modeling was performed to compare resting cerebral blood flow (CBF) between the 2 groups. Correlations were calculated between the mean CBF value in all clusters that survived AlphaSim correction and the Chen Internet Addiction Scale (CIAS) scores, Barratt Impulsiveness Scale-11 (BIS-11) scores, or hours of Internet use per week (hours) in the 15 subjects with IGA. Results Compared with control subjects, adolescents with IGA showed significantly higher global CBF in the left inferior temporal lobe/fusiform gyrus, left parahippocampal gyrus/amygdala, right medial frontal lobe/anterior cingulate cortex, left insula, right insula, right middle temporal gyrus, right precentral gyrus, left supplementary motor area, left cingulate gyrus, and right inferior parietal lobe. Lower CBF was found in the left middle temporal gyrus, left middle occipital gyrus, and right cingulate gyrus. There were no significant correlations between mean CBF values in all clusters that survived AlphaSim correction and CIAS or BIS-11 scores or hours of Internet use per week. Conclusions In this study, we used ASL perfusion fMRI and noninvasively quantified resting CBF to demonstrate that IGA alters the CBF distribution in the adolescent brain. The results support the hypothesis that IGA is a behavioral addiction that may share similar neurobiological abnormalities with other addictive disorders. PMID:23937918

Cerebral blood flow laterality derived from arterial spin labeling as a biomarker for assessing the disease severity of parkinson's disease.

PubMed

Yamashita, Koji; Hiwatashi, Akio; Togao, Osamu; Kikuchi, Kazufumi; Yamaguchi, Hiroo; Suzuki, Yuriko; Kamei, Ryotaro; Yamasaki, Ryo; Kira, Jun-Ichi; Honda, Hiroshi

2017-06-01

To evaluate cerebral blood flow (CBF) laterality derived from arterial spin labeling (ASL) in early-stage Parkinson's disease (PD) patients compared with those with advanced stages. Thirty-eight patients with PD (21 patients in early stages, 17 patients in advanced stages) were retrospectively studied. The CBF maps derived from 3T ASL data were co-registered to the corresponding 3DT1WI using SPM 12 software. Caudate nucleus (CN), putamen (PT), globus pallidus (GP), and thalamus (TH) were manually traced on the representative axial slices of 3DT1WI. CBF of the CN, PT, GP, and TH was measured using corresponding pixels on the co-registered CBF maps. A laterality index (LI) was calculated as the ratio of the contralateral CBF to primary affected side CBF. Each LI was compared between early and advanced stages of PD using the Mann-Whitney U-test. The LIs were also compared between each stage of PD. In the CN, the LIs were significantly higher in early stages (mean LI ± SD, 95% confidence interval = 1.06 ± 0.14, 1.00-1.13) than in advanced stages (0.94 ± 0.14, 0.87-1.01; P < 0.05). We also observed a tendency toward decreased LIs with disease severity (1.10 ± 0.14, 0.99-1.21 for Hoehn and Yahr stage I; 1.04 ± 0.14, 0.92-1.12 for stage II; 0.96 ± 0.11, 0.89-1.10 for stage III; 0.93 ± 0.17, 0.81-1.05 for stage IV). The evaluation of CBF laterality pattern in the CN using ASL may be useful for assessing the disease severity of PD patients. 3 J. MAGN. RESON. IMAGING 2017;45:1821-1826. © 2016 International Society for Magnetic Resonance in Medicine.

Usefulness of rCBF analysis in diagnosing Parkinson's disease: supplemental role with MIBG myocardial scintigraphy.

PubMed

Nagamachi, Shigeki; Wakamatsu, Hideyuki; Kiyohara, Shogo; Fujita, Seigo; Futami, Shigemi; Tamura, Shozo; Nakazato, Masamitsu; Yamashita, Syuichi; Arita, Hideo; Nishii, Ryuichi; Kawai, Keiichi

2008-08-01

(123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is a useful tool for differentiating idiopathic Parkinson's disease (PD) from parkinsonism (PS) caused by other disorders. However, cardiac MIBG uptake is affected by various causes. Alternatively, hypoperfusion in the occipital lobe of PD is reported recently. The objective is to clarify the correlation between regional cerebral blood flow (rCBF) alteration and cardiac MIBG uptake in PD. In addition, we examined whether additional brain perfusion analysis improved the differential diagnostic ability for PD from PS when compared with MIBG scintigraphy alone. Forty-nine patients with PD (27 mild groups: Hoehn and Yahr stages I, II; 22 severe groups: Hoehn and Yahr stages III, IV) and 28 patients with PS participated. We compared absolute rCBF values between PD and PS. In addition, we determined correlation between MIBG parameters and each rCBF value. Finally, we compared the diagnostic ability for the differentiation of PD from PS between two diagnostic criteria, each MIBG index abnormality alone [heart-to-mediastinum ratio, H/M (E) < 1.9, H/E (D) < 1.7, washout rate > 40%] and each MIBG index abnormality or occipital lobe hypoperfusion (<36 ml/100 g per min). Absolute rCBF value of occipital lobe was significantly lower in severe PD as compared with PS or mild PD. In the correlation analysis, rCBF of occipital lobe correlated positively with MIBG parameters (H/M). Regarding the diagnostic ability, sensitivity improved by accounting for occipital hypoperfusion as compared with MIBG indices alone. In contrast, neither specificity nor accuracy improved by adding occipital lobe analysis. MIBG parameters (H/M) correlated positively with occipital hypoperfusion in PD. In the differential diagnosis between PD and PS, although its usefulness might be limited, analysis of rCBF in the occipital lobe added to (123)I-MIBG myocardial imaging can be recommended.

Are there adaptive changes in the human brain of patients with Parkinson's disease treated with long-term deep brain stimulation of the subthalamic nucleus? A 4-year follow-up study with regional cerebral blood flow SPECT.

PubMed

Sestini, Stelvio; Pupi, Alberto; Ammannati, Franco; Silvia, Ramat; Sorbi, Sandro; Castagnoli, Antonio

2007-10-01

The aim of this follow-up study was to assess persistent motor and regional cerebral blood flow (rCBF) changes in patients with Parkinson's disease (PD) treated with high-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN). Ten PD patients with STN-DBS underwent three rCBF SPECT studies at rest, once preoperatively in the off-drug condition (T(0)), and twice postoperatively in the off-drug/off-stimulation conditions at 5 +/- 2 (T(1)) and 42 +/- 7 months (T(2)). Patients were assessed using the UPDRS, H&Y and S&E scales. SPM was used to investigate baseline rCBF changes from the preoperative condition to the postoperative conditions and the relationship between rCBF and UPDRS scores used as covariate of interest. Parkinsonian patients showed a clinical improvement which was significant only on follow-up at 42 months. The main effect of treatment from T(0) to T(1) was to produce baseline rCBF increases in the pre-supplementary motor area (pre-SMA), premotor cortex and somatosensory association cortex. From T(1) to T(2) a further baseline rCBF increase was detected in the pre-SMA (p < 0.0001). A correlation was detected between the slight improvement in motor scores and the rCBF increase in the pre-SMA (p < 0.0001), which is known to play a crucial role in clinical progression. Our study suggests the presence of adaptive functional changes in the human brain of PD patients treated with long-term STN-DBS. Such adaptive processes seem to occur in the pre-SMA and to play only a slightly beneficial role in terms of functional compensation of motor impairment.

Limited reliability of computed tomographic perfusion acute infarct volume measurements compared with diffusion-weighted imaging in anterior circulation stroke.

PubMed

Schaefer, Pamela W; Souza, Leticia; Kamalian, Shervin; Hirsch, Joshua A; Yoo, Albert J; Kamalian, Shahmir; Gonzalez, R Gilberto; Lev, Michael H

2015-02-01

Diffusion-weighted imaging (DWI) can reliably identify critically ischemic tissue shortly after stroke onset. We tested whether thresholded computed tomographic cerebral blood flow (CT-CBF) and CT-cerebral blood volume (CT-CBV) maps are sufficiently accurate to substitute for DWI for estimating the critically ischemic tissue volume. Ischemic volumes of 55 patients with acute anterior circulation stroke were assessed on DWI by visual segmentation and on CT-CBF and CT-CBV with segmentation using 15% and 30% thresholds, respectively. The contrast:noise ratios of ischemic regions on the DWI and CT perfusion (CTP) images were measured. Correlation and Bland-Altman analyses were used to assess the reliability of CTP. Mean contrast:noise ratios for DWI, CT-CBF, and CT-CBV were 4.3, 0.9, and 0.4, respectively. CTP and DWI lesion volumes were highly correlated (R(2)=0.87 for CT-CBF; R(2)=0.83 for CT-CBV; P<0.001). Bland-Altman analyses revealed little systemic bias (-2.6 mL) but high measurement variability (95% confidence interval, ±56.7 mL) between mean CT-CBF and DWI lesion volumes, and systemic bias (-26 mL) and high measurement variability (95% confidence interval, ±64.0 mL) between mean CT-CBV and DWI lesion volumes. A simulated treatment study demonstrated that using CTP-CBF instead of DWI for detecting a statistically significant effect would require at least twice as many patients. The poor contrast:noise ratios of CT-CBV and CT-CBF compared with those of DWI result in large measurement error, making it problematic to substitute CTP for DWI in selecting individual acute stroke patients for treatment. CTP could be used for treatment studies of patient groups, but the number of patients needed to identify a significant effect is much higher than the number needed if DWI is used. © 2014 American Heart Association, Inc.

Relationship between cardiac function and resting cerebral blood flow: MRI measurements in healthy elderly subjects.

PubMed

Henriksen, Otto M; Jensen, Lars T; Krabbe, Katja; Larsson, Henrik B W; Rostrup, Egill

2014-11-01

Although both impaired cardiac function and reduced cerebral blood flow are associated with ageing, current knowledge of the influence of cardiac function on resting cerebral blood flow (CBF) is limited. The aim of this study was to investigate the potential effects of cardiac function on CBF. CBF and cardiac output were measured in 31 healthy subjects 50-75 years old using magnetic resonance imaging techniques. Mean values of CBF, cardiac output and cardiac index were 43.6 ml per 100 g min(-1), 5.5 l min(-1) and 2.7 l min(-1) m(-2), respectively, in males, and 53.4 ml per 100 g min(-1), 4.3 l min(-1) and 2.4 l min(-1) m(-2), respectively, in females. No effects of cardiac output or cardiac index on CBF or structural signs of brain ageing were observed. However, fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac index (r(2) = 0.22, P = 0.008) and furthermore lower in males than in females (8.6% versus 12.5%, P = 0.003). Fractional brain flow was also inversely correlated with cerebral white matter lesion grade, although this effect was not significant when adjusted for age. Frequency analysis of heart rate variability showed a gender-related inverse association of increased low-to-high-frequency power ratio with CBF and fractional brain flow. The findings do not support a direct effect of cardiac function on CBF, but demonstrates gender-related differences in cardiac output distribution. We propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Development of a cerebral circulation model for the automatic control of brain physiology.

PubMed

Utsuki, T

2015-01-01

In various clinical guidelines of brain injury, intracranial pressure (ICP), cerebral blood flow (CBF) and brain temperature (BT) are essential targets for precise management for brain resuscitation. In addition, the integrated automatic control of BT, ICP, and CBF is required for improving therapeutic effects and reducing medical costs and staff burden. Thus, a new model of cerebral circulation was developed in this study for integrative automatic control. With this model, the CBF and cerebral perfusion pressure of a normal adult male were regionally calculated according to cerebrovascular structure, blood viscosity, blood distribution, CBF autoregulation, and ICP. The analysis results were consistent with physiological knowledge already obtained with conventional studies. Therefore, the developed model is potentially available for the integrative control of the physiological state of the brain as a reference model of an automatic control system, or as a controlled object in various control simulations.

Control of the cerebral circulation and metabolism by the rostral ventrolateral medulla: Possible role in the cerebrovascular response to hypoxia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Underwood, M.D.

1988-01-01

Neurons within the rostral ventrolateral medulla (RVL) corresponding to the location of adrenaline neurons of the C1 group (C1 area) maintain resting levels of arterial pressure (AP) and mediate the reflex cardiovascular responses to baro- and chemoreceptor activation and cerebral ischemia. The author therefore sought to determine whether neurons in the C1 area: (a) modulate regional cerebral blood flow (rCBF) and/or cerebral glucose utilization (rCGU), (b) participate in the maintenance of resting levels of CBF and CGU, and (c) mediate the CBF response to hypoxia. Rats were anesthetized, paralyzed and ventilated. The RVL was stimulated electrically or chemically, with kainicmore » acid; lesions were placed electrolytically. rCBF was measured using 14-C-iodoantipyrine and rCGU with {sup 14}C-2-deoxyglucose in 11 dissected brain regions.« less

Cerebral blood flow changes in very-late-onset schizophrenia-like psychosis with catatonia before and after successful treatment.

PubMed

Tsujino, Naohisa; Nemoto, Takahiro; Yamaguchi, Taiju; Katagiri, Naoyuki; Tohgi, Nao; Ikeda, Ryu; Shiraga, Nobuyuki; Mizumura, Sunao; Mizuno, Masafumi

2011-10-01

The purpose of the present study was to investigate regional cerebral blood flow (rCBF) changes in a patient with very-late-onset schizophrenia-like psychosis (VLOS) with catatonia. A 64-year-old woman developed catatonia after experiencing persecutory delusions. The patient's rCBF was examined using single photon emission computed tomography (SPECT) with easy Z-score imaging system. Before treatment, hypoperfusion was observed in the striatum and the thalamus, whereas hyperperfusion was observed in the left lateral frontal cortex and the left temporal cortex. After treatment, the disproportions in rCBF disappeared, and hyperperfusion was observed in the motor cortex. Sequential SPECT findings suggest that rCBF abnormalities may be correlated with the symptomatology of catatonia in patients with VLOS. © 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.

Complementary acupuncture in Parkinson's disease: a spect study.

PubMed

Huang, Yong; Jiang, Xuemei; Zhuo, Ying; Wik, Gustav

2010-02-01

We studied cerebral effects of complementary acupuncture in Parkinson's disease using single photon emission computed tomography (SPECT) measures of 99mTc-ECD and 99mTc-TRODAT-4, before and after five weeks of treatment. Ten patients were randomly assigned to receive levodopa alone (controls) or levodopa and complementary scalp electro-acupuncture. Before treatment, no hemispheric regional cerebral blood flow (rCBF) differences were found, whereas striatal dopamine transporter (DAT) activity was lower in the most affected hemisphere. Treatment with levodopa alone did not change rCBF, whereas it increased basal ganglion DAT activity in the most affected hemisphere. Patients who received levodopa and complementary acupuncture had increased rCBF in the frontal lobe, the occipital lobe, the basal ganglion, and the cerebellum in the most affected hemisphere as compared to baseline, but there were no changes in basal ganglia DAT levels. Thus, complementary acupuncture treatment in Parkinson's disease may affect rCBF but not basal ganglion DAT.

[The effect of nimodipine on cochlear blood flow in the guinea pig].

PubMed

Meyer, P; Werner, E; Schmidt, R; Grützmacher, W; Gehrig, W; Seuter, F

1994-10-01

The influence of nimodipine (Nimotop, CAS 66085-59-4), a selectively cerebrovascularly acting 1,4-dihydropyridine calcium antagonist, on the cochlear blood flow (CBF) was studied in 19 guinea pigs (6 controls). The hydrogen clearance measurements were carried out under alpha-chloralose-ethylurethane anaesthesia, artificial respiration with simultaneous control of electrocardiogram, blood pressure, body temperature and arterial pH (hourly). The indirect measurement of CBF was carried out by means of hydrogen clearance in the perilymphatic space (basal turn) before and after intravenous application of 1 microgram nimodipine/kg/min. The mean arterial blood pressure remained within the +/- 5% range of the initial value during the experiment. Under treatment with nimodipine the CBF showed a non-significant average increase of 4.69% and under placebo (20% ethanol, 17% polyethylenglycol 400, citrate buffer), a non-significant average decrease of 6.16%. The influence of nimodipine on CBF was underlined by the overcompensation of the placebo effect.

Cerebral cortical neurons with activity linked to central neurogenic spontaneous and evoked elevations in cerebral blood flow

NASA Technical Reports Server (NTRS)

Golanov, E. V.; Reis, D. J.

1996-01-01

We recorded neurons in rat cerebral cortex with activity relating to the neurogenic elevations in regional cerebral blood flow (rCBF) coupled to stereotyped bursts of EEG activity, burst-cerebrovascular wave complexes, appearing spontaneously or evoked by electrical stimulation of rostral ventrolateral medulla (RVL) or fastigial nucleus (FN). Of 333 spontaneously active neurons only 15 (5%), in layers 5-6, consistently (P < 0.05, chi-square) increased their activity during the earliest potential of the complex, approximately 1.3 s before the rise of rCBF, and during the minutes-long elevation of rCBF elicited by 10 s of stimulation of RVL or FN. The results indicate the presence of a small population of neurons in deep cortical laminae whose activity correlates with neurogenic elevations of rCBF. These neurons may function to transduce afferent neuronal signals into vasodilation.

Hypothyroidism Is Associated With Coronary Endothelial Dysfunction in Women.

PubMed

Sara, Jaskanwal D; Zhang, Ming; Gharib, Hossein; Lerman, Lilach O; Lerman, Amir

2015-07-29

Hypothyroidism is associated with an increased risk of coronary artery disease, beyond that which can be explained by its association with conventional cardiovascular risk factors. Coronary endothelial dysfunction precedes atherosclerosis, has been linked to adverse cardiovascular events, and may account for some of the increased risk in patients with hypothyroidism. The aim of this study was to determine whether there is an association between epicardial and microvascular coronary endothelial dysfunction and hypothyroidism. In 1388 patients (mean age 50.5 [12.3] years, 34% male) presenting with stable chest pain to Mayo Clinic, Rochester, MN for diagnostic coronary angiography, and who were found to have nonobstructive coronary artery disease (<40% stenosis), we invasively assessed coronary artery endothelial-dependent microvascular and epicardial function by evaluating changes in coronary blood flow (% Δ CBF Ach) and diameter (% Δ CAD Ach), respectively, in response to intracoronary infusions of acetylcholine. Patients were divided into 2 groups: hypothyroidism, defined as a documented history of hypothyroidism or a thyroid-stimulating hormone (TSH) >10.0 mU/mL, n=188, and euthyroidism, defined as an absence of a history of hypothyroidism in the clinical record and/or 0.3

A nitric oxide donor reduces brain injury and enhances recovery of cerebral blood flow after hypoxia-ischemia in the newborn rat.

PubMed

Wainwright, Mark S; Grundhoefer, Dava; Sharma, Shruti; Black, Stephen M

2007-03-26

Nitric oxide (NO) released in response to hypoxia-ischemia (HI) in the newborn brain may mediate both protective and pathologic responses. We sought to determine whether pharmacologic increase of NO using an NO donor would reduce neurologic injury resulting from HI in the postnatal day 7 rat. We measured NO levels and CBF in the presence of either a NOS inhibitor, N-nitro-l-arginine methyl ester (L-NAME) or an NO donor (Z)-1-[N-(2-amino-ethyl)-N-(2-ammonio-ethyl)amino]diazen-1-ium-1,2-diolate (DETANONOate). Both inhibition of NOS and administration of an NO donor reduced neuropathologic injury after 7-day recovery. NO levels decreased in both ischemic and contralateral hemispheres during HI. This response was prevented by treatment with DETANONOate. Despite the decrease in NO, CBF increased during ischemia in the contralateral hemisphere but decreased when combined with brief hypoxia. Treatment with L-NAME abolished these increases, which were not altered by DETANONOate. Reduction of cellular metabolism by mild hypothermia also reduced both NO and CBF. Following prolonged HI, CBF remained decreased in the ischemic hemisphere up to 24-h recovery. This decrease was prevented by treatment with DETANONOate. These data show that administration of an NO donor reduces neurologic injury following HI in the newborn rat. This mechanism of this protection, in part, is due to an increase in the rate of recovery of CBF compared to vehicle-treated animals. Augmentation of NO-dependent increases in CBF may serve to improve neurologic outcome after perinatal asphyxia.

A NITRIC OXIDE DONOR REDUCES BRAIN INJURY AND ENHANCES RECOVERY OF CEREBRAL BLOOD FLOW AFTER HYPOXIA-ISCHEMIA IN THE NEWBORN RAT

PubMed Central

Wainwright, Mark S.; Grundhoefer, Dava; Sharma, Shruti; Black, Stephen M.

2007-01-01

Nitric oxide (NO) released in response to hypoxia-ischemia (HI) in the newborn brain may mediate both protective and pathologic responses. We sought to determine whether pharmacologic increase of NO using an NO donor would reduce neurologic injury resulting from HI in the postnatal day 7 rat. We measured NO levels and CBF in the presence of either a NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME) or an NO donor (Z)-1-[N-(2aminoethyl)-N-(2-ammonio-ethyl)amino]diazen-1-ium-1,2-diolate (DETANONOate). Both inhibition of NOS and administration of an NO donor reduced neuropathologic injury after 7-day recovery. NO levels decreased in both ischemic and contralateral hemispheres during HI. This response was prevented by treatment with DETANONOate. Despite the decrease in NO, CBF increased during ischemia in the contralateral hemisphere but decreased when combined with brief hypoxia. Treatment with L-NAME abolished these increases, which were not altered by DETANONOate. Reduction of cellular metabolism by mild hypothermia also reduced both NO and CBF. Following prolonged HI, CBF remained decreased in the ischemic hemisphere up to 24-hour recovery. This decrease was prevented by treatment with DETANONOate. These data show that administration of an NO donor reduces neurologic injury following HI in the newborn rat. This mechanism of this protection, in part, is due to an increase in the rate of recovery of CBF compared to vehicle-treated animals. Augmentation of NO-dependent increases in CBF may serve to improve neurologic outcome after perinatal asphyxia. PMID:17270345

Evolutionary appearance of genes encoding proteins associated with box H/ACA snoRNAs: Cbf5p in Euglena gracilis, an early diverging eukaryote, and candidate Gar1p and Nop10p homologs in archaebacteria

PubMed Central

Watanabe, Yoh-ichi; Gray, Michael W.

2000-01-01

A reverse transcription–polymerase chain reaction (RT–PCR) approach was used to clone a cDNA encoding the Euglena gracilis homolog of yeast Cbf5p, a protein component of the box H/ACA class of snoRNPs that mediate pseudouridine formation in eukaryotic rRNA. Cbf5p is a putative pseudouridine synthase, and the Euglena homolog is the first full-length Cbf5p sequence to be reported for an early diverging unicellular eukaryote (protist). Phylogenetic analysis of putative pseudouridine synthase sequences confirms that archaebacterial and eukaryotic (including Euglena) Cbf5p proteins are specifically related and are distinct from the TruB/Pus4p clade that is responsible for formation of pseudouridine at position 55 in eubacterial (TruB) and eukaryotic (Pus4p) tRNAs. Using a bioinformatics approach, we also identified archaebacterial genes encoding candidate homologs of yeast Gar1p and Nop10p, two additional proteins known to be associated with eukaryotic box H/ACA snoRNPs. These observations raise the possibility that pseudouridine formation in archaebacterial rRNA may be dependent on analogs of the eukaryotic box H/ACA snoRNPs, whose evolutionary origin may therefore predate the split between Archaea (archaebacteria) and Eucarya (eukaryotes). Database searches further revealed, in archaebacterial and some eukaryotic genomes, two previously unrecognized groups of genes (here designated ‘PsuX’ and ‘PsuY’) distantly related to the Cbf5p/TruB gene family. PMID:10871366

Increase in coronary blood flow by intra-aortic balloon counterpulsation in a porcine model of myocardial reperfusion.

PubMed

Bonios, Michael J; Pierrakos, Charalampos N; Argiriou, Michael; Dalianis, Argirios; Terrovitis, John V; Dolou, Paraskevi; Drakos, Stavros G; Koudoumas, Dimitrios; Charitos, Christos E; Anastasiou-Nana, Maria I

2010-02-04

Studies of the IABP have reported variable effects on coronary blood flow (CBF). The purpose of the present study was to measure the changes in coronary blood flow induced by intra-aortic balloon pump (IABP) counterpulsation in normal and reperfused porcine myocardium. A 30-ml IABP was placed in the descending aorta of 6 open-chest pigs. Each pig underwent occlusion of the mid-left anterior descending (LAD) coronary artery for 1 h, followed by reperfusion for 2 h. The effects of IABP support on systolic aortic pressure (SAP) and aortic end-diastolic pressure were recorded. The mean CBF, distal to the LAD occlusion site was measured at baseline and during reperfusion, with and without IABP counterpulsation. The IABP decreased SAP and aortic end-diastolic pressure in normal and reperfused myocardium, and maintained a peak aortic diastolic augmentation at the level of SAP. In normal myocardium, the IABP decreased mean CBF by 8.4+/-2.2% (p<0.001). At 2, 15, 30, 60, 90 and 120 min of reperfusion, the IABP increased mean CBF by 11.5+/-6.8%, 8.0+/-7.0%, 11.2+/-6.9%, 12.4+/-12.9%, 23.5+/-9.9% and 8.9+/-6.9%, of the corresponding value without the assistance of the IABP (all p<0.05). In the normal heart, IABP counterpulsation decreased CBF, probably because of a decrease in myocardial oxygen demand from a decreased afterload. During reperfusion the IABP increased CBF, suggesting that it might effectively mitigate the no-reflow phenomenon. Copyright 2008 Elsevier Ireland Ltd. All rights reserved.

Transcranial Doppler of the middle cerebral artery indicates regional gray matter cerebral perfusion.

PubMed

Pasha, Evan P; Tarumi, Takashi; Haley, Andreana P; Tanaka, Hirofumi

2017-11-30

We determined if transcranial color-coded Doppler derived hemodynamics are associated with MRI-based cerebral blood flow (CBF) in regions clinically important to dementia in healthy middle-aged adults. In 30 subjects (18m/12f; age  =  52  ±  1 years), blood flow velocity (BFV) and cerebrovascular conductance (CVC) were measured with transcranial color-coded Doppler (TCCD) at the middle cerebral artery (MCA) and cerebral blood flow (CBF) was assessed with arterial spin labeled perfusion MRI. BFV and CVC were associated with hippocampus (r  =  0.58 and r  =  0.61, both p  <  0.01) and occipitoparietal (r  =  0.50 and r  =  0.58, both p  <  0.01) CBF. CVC was further associated with posterior cingulate CBF (r  =  0.58 p  <  0.01). Independent of age and sex, BFV and CVC were associated with hippocampus (r  =  0.59 and r  =  0.55, both p  <  0.003) and occipitoparietal (r  =  0.50 and r  =  0.57, both p  <  0.01) CBF. CVC was independently associated with posterior cingulate CBF (r  =  0.38, p  =  0.049). TCCD-measured BFV and CVC of the MCA are indicators of cerebral perfusion to clinically valuable brain regions in healthy middle-aged adults. TCCD may not be a good indicator of blood flow to cerebral white matter.

Cerebral Blood Flow and BOLD Responses to a Memory Encoding Task: A Comparison Between Healthy Young and Elderly Adults

PubMed Central

Restom, Khaled; Bangen, Katherine J.; Bondi, Mark W.; Perthen, Joanna E.; Liu, Thomas T.

2007-01-01

Functional magnetic resonance imaging (fMRI) studies of the medial temporal lobe have primarily made use of the blood oxygenation level dependent (BOLD) response to neural activity. The interpretation of the BOLD signal as a measure of medial temporal lobe function can be complicated, however, by changes in the cerebrovascular system that can occur with both normal aging and age-related diseases, such as Alzheimer's disease. Quantitative measures of the functional cerebral blood flow (CBF) response offer a useful complement to BOLD measures, and have been shown to aid in the interpretation of fMRI studies. Despite these potential advantages, the application of ASL to fMRI studies of cognitive tasks and at-risk populations has been limited. In this study, we demonstrate the application of ASL fMRI to obtain measures of the CBF and BOLD responses to the encoding of natural scenes in healthy young (mean 25 years) and elderly (mean 74 years) adults. The percent CBF increase in the medial temporal lobe was significantly higher in the older adults, whereas the CBF levels during baseline and task conditions and during a separate resting-state scan were significantly lower in the older group. The older adults also showed slightly higher values for the BOLD response amplitude and the absolute change in CBF, but the age group differences were not significant. The percent CBF and BOLD responses are consistent with an age-related increase in the cerebral metabolic rate of oxygen metabolism (CMRO2) response to memory encoding. PMID:17590353

Quantification of Load Dependent Brain Activity in Parametric N-Back Working Memory Tasks using Pseudo-continuous Arterial Spin Labeling (pCASL) Perfusion Imaging.

PubMed

Zou, Qihong; Gu, Hong; Wang, Danny J J; Gao, Jia-Hong; Yang, Yihong

2011-04-01

Brain activation and deactivation induced by N-back working memory tasks and their load effects have been extensively investigated using positron emission tomography (PET) and blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI). However, the underlying mechanisms of BOLD fMRI are still not completely understood and PET imaging requires injection of radioactive tracers. In this study, a pseudo-continuous arterial spin labeling (pCASL) perfusion imaging technique was used to quantify cerebral blood flow (CBF), a well understood physiological index reflective of cerebral metabolism, in N-back working memory tasks. Using pCASL, we systematically investigated brain activation and deactivation induced by the N-back working memory tasks and further studied the load effects on brain activity based on quantitative CBF. Our data show increased CBF in the fronto-parietal cortices, thalamus, caudate, and cerebellar regions, and decreased CBF in the posterior cingulate cortex and medial prefrontal cortex, during the working memory tasks. Most of the activated/deactivated brain regions show an approximately linear relationship between CBF and task loads (0, 1, 2 and 3 back), although several regions show non-linear relationships (quadratic and cubic). The CBF-based spatial patterns of brain activation/deactivation and load effects from this study agree well with those obtained from BOLD fMRI and PET techniques. These results demonstrate the feasibility of ASL techniques to quantify human brain activity during high cognitive tasks, suggesting its potential application to assessing the mechanisms of cognitive deficits in neuropsychiatric and neurological disorders.

A new graphic method for estimation of distribution volume in chronic ischemic brain lesions on I-123 IMP SPECT; in prediction of regional CBF increase by bypass surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Odano, I.; Ohkubo, M.; Takahashi, N.

1994-05-01

The estimate the distribution volume (Vd) of Iodine-123 IMP brain SPECT, we developed a new graphic plot, the rate constant square method, which was useful to predict an increase of rCBF in the ischemic lesions caused by bypass surgery. The tracer kinetics of IMP was assumed to be a 2-compartment model as follows: dCb(t)/dt=K1Ca(t)-k2Cb(t), where K1 is rCBF(ml/g/min), k2 is the washout constant(/min), and K1/k2 is defined as distribution volume (Vd:ml/g). When input function Ca(t) is prepared, we can determine the relationship between K1, Delayed/Early ratio and Vd on the graph. The method was applied to 13 patients with chronicmore » cerebral infarction. Regional CBF was measured by the microsphere model and early and delayed scans were performed. In the normal area, K1 and Delayed/Early ratio were 0.5 ml/g/min and 1.0, respectively, then Vd (=31.5 ml/g) was obtained on the graph. 30.0 ml/g, the value in the infarct area was reduced. After bypass surgery undertaken on five patients, we observed a significant relationship between % increase of rCBF in the lesions and values of Vd. Since Vd reflects the extent of IMP retention in the brain tissue, we can predict an increase of rCBF by the bypass operation using this method.« less

Parasympathetic reflex vasodilation in the cerebral hemodynamics of rats.

PubMed

Ishii, Hisayoshi; Sato, Toshiya; Izumi, Hiroshi

2014-04-01

We investigated the role of parasympathetic reflex vasodilation in the regulation of the cerebral hemodynamics, and whether GABAA receptors modulate the response. We examined the effects of activation of the parasympathetic fibers through trigeminal afferent inputs on blood flow in the internal carotid artery (ICABF) and the cerebral blood vessels (rCBF) in parietal cortex in urethane-anesthetized rats. Electrical stimulation of the central cut end of the lingual nerve (LN) elicited intensity- and frequency-dependent increases in ICABF that were independent of changes in external carotid artery blood flow. Increases in ICABF were elicited by LN stimulation regardless of the presence or absence of sympathetic innervation. The ICABF increases evoked by LN stimulation were almost abolished by the intravenous administration of hexamethonium (10 mg kg(-1)) and were reduced significantly by atropine administration (0.1 mg kg(-1)). Although the LN stimulation alone had no significant effect on rCBF, LN stimulation in combination with a blocker of the GABAA receptor pentylenetetrazole increased the rCBF markedly. This increase in rCBF was reduced significantly by the administration of hexamethonium and atropine. These observations indicate that the increases in both ICABF and rCBF are evoked by parasympathetic activation via the trigeminal-mediated reflex. The rCBF increase evoked by LN stimulation is thought to be limited by the GABAA receptors in the central nervous system. These results suggest that the parasympathetic reflex vasodilation and its modulation mediated by GABA receptors within synaptic transmission in the brainstem are involved in the regulation of the cerebral hemodynamics during trigeminal afferent inputs.

Therapy-related longitudinal brain perfusion changes in patients with chronic pelvic pain syndrome.

PubMed

Weisstanner, Christian; Mordasini, Livio; Thalmann, George N; Verma, Rajeev K; Rummel, Christian; Federspiel, Andrea; Kessler, Thomas M; Wiest, Roland

2017-08-03

The imaging method most frequently employed to identify brain areas involved in neuronal processing of nociception and brain pain perception is blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). Arterial spin labelling (ASL), in contrast, offers advantages when slow varying changes in brain function are investigated. Chronic pelvic pain syndrome (CPPS) is a disorder of, mostly, young males that leads to altered pain perceptions in structures related to the pelvis. We aimed to investigate the potential of ASL to monitor longitudinal cranial blood flow (CBF) changes in patients with CPPS. In a randomised, placebo-controlled, double-blind single centre trial, we investigated treatment effects in CPPS after 12 weeks in patients that underwent sono-electro-magnetic therapy vs placebo. We investigated changes of CBF related to treatment outcome using pseudo-continuous arterial spin labelling (pCASL)-MRI. We observed CBF downregulation in the prefrontal cortex and anterior cingulate cortex and upregulation in the dorsolateral prefrontal cortex in responders. Nonresponders presented with CBF upregulation in the hippocampus. In patients with a history of CPPS of less than 12 months, there were significant correlations between longitudinal CBF changes and the Chronic Prostatitis Symptom Index pain subscore within the joint clusters anterior cingulate cortex and left anterior prefrontal cortex in responders, and the right hippocampus in nonresponders. We demonstrated therapy-related and stimulus-free longitudinal CBF changes in core areas of the pain matrix using ASL. ASL may act as a complementary noninvasive method to functional MRI and single-photon emission computed tomography / positron emission tomography, especially in the longitudinal assessment of pain response in clinical trials.

Assessment of cerebral blood perfusion reserve with acetazolamide using 3D spiral ASL MRI: Preliminary experience in pediatric patients.

PubMed

Hu, Houchun H; Li, Zhiqiang; Pokorney, Amber L; Chia, Jonathan M; Stefani, Niccolo; Pipe, James G; Miller, Jeffrey H

2017-01-01

To demonstrate the clinical feasibility of a new non-Cartesian cylindrically-distributed spiral 3D pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging (MRI) pulse sequence in pediatric patients in quantifying cerebral blood flow (CBF) response to an acetazolamide (ACZ) vasodilator challenge. MRI exams were performed on two 3 Tesla Philips Ingenia systems using 32 channel head coil arrays. After local institutional review board approval, the 3D spiral-based pCASL technique was added to a standard brain MRI exam and evaluated in 13 pediatric patients (average age: 11.7±6.4years, range: 1.4-22.2years). All patients were administered ACZ for clinically indicated reasons. Quantitative whole-brain CBF measurements were computed pre- and post-ACZ to assess cerebrovascular reserve. 3D spiral pCASL data were successfully reconstructed in all 13 cases. In 11 patients, CBF increased 2.8% to 93.2% after administration of ACZ. In the two remaining patients, CBF decreased by 2.4 to 6.0% after ACZ. The group average change in CBF due to ACZ was approximately 25.0% and individual changes were statistically significant (p<0.01) in all patients using a paired t-test analysis. CBF perfusion data were diagnostically useful in supporting conventional MR angiography and clinical findings. 3D cylindrically-distributed spiral pCASL MRI provides a robust approach to assess cerebral blood flow and reserve in pediatric patients. Copyright © 2016 Elsevier Inc. All rights reserved.

76. (Credit CBF) Inside of laboratory at McNeil Street Station, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

76. (Credit CBF) Inside of laboratory at McNeil Street Station, c1912. Laboratory located over clear water well at this time. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

Fatigue and Cognitive Fatigability in Mild Traumatic Brain Injury are Correlated with Altered Neural Activity during Vigilance Test Performance.

PubMed

Möller, Marika C; Nordin, Love Engström; Bartfai, Aniko; Julin, Per; Li, Tie-Qiang

2017-01-01

Fatigue is the most frequently reported persistent symptom following a mild traumatic brain injury (mTBI), but the explanations for the persisting fatigue symptoms in mTBI remain controversial. In this study, we investigated the change of cerebral blood flow during the performance of a psychomotor vigilance task (PVT) by using pseudo-continuous arterial spin labeling (PCASL) MRI technique to better understand the relationship between fatigability and brain activity in mTBI. Ten patients (mean age: 37.5 ± 11.2 years) with persistent complaints of fatigue after mTBI and 10 healthy controls (mean age 36.9 ± 11.0 years) were studied. Both groups completed a 20-min long PVT inside a clinical MRI scanner during simultaneous measurements of reaction time and regional cerebral blood flow (rCBF) with PCASL technique. Cognitive fatigability and neural activity during PVT were analyzed by dividing the performance and rCBF data into quintiles in addition to the assessment of self-rated fatigue before and after the PVT. The patients showed significant fatigability during the PVT while the controls had a stable performance. The variability in performance was also significantly higher among the patients, indicating monitoring difficulty. A three-way ANOVA, modeling of the rCBF data demonstrated that there was a significant interaction effect between the subject group and performance time during PVT in a mainly frontal/thalamic network, indicating that the pattern of rCBF change for the mTBI patients differed significantly from that of healthy controls. In the mTBI patients, fatigability at the end of the PVT was related to increased rCBF in the right middle frontal gyrus, while self-rated fatigue was related to increased rCBF in left medial frontal and anterior cingulate gyri and decreases of rCBF in a frontal/thalamic network during this period. This study demonstrates that PCASL is a useful technique to investigate neural correlates of fatigability and fatigue in mTBI patients. Patients suffering from fatigue after mTBI used different brain networks compared to healthy controls during a vigilance task and in mTBI, there was a distinction between rCBF changes related to fatigability vs. perceived fatigue. Whether networks for fatigability and self-rated fatigue are different, needs to be investigated in future studies.

Discriminative Power of Arterial Spin Labeling Magnetic Resonance Imaging and 18F-Fluorodeoxyglucose Positron Emission Tomography Changes for Amyloid-β-Positive Subjects in the Alzheimer's Disease Continuum.

PubMed

Tosun, Duygu; Schuff, Norbert; Jagust, William; Weiner, Michael W

2016-01-01

Recent studies have demonstrated that arterial spin labeling magnetic resonance imaging (ASL-MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) identify similar regional abnormalities and have comparable diagnostic accuracy in Alzheimer's disease (AD). The agreement between these modalities in the AD continuum, which is an important concept for early detection and disease monitoring, is yet unclear. We aimed to assess the ability of the cerebral blood flow (CBF) measures from ASL-MRI and cerebral metabolic rate for glucose (CMRgl) measures from FDG-PET to distinguish amyloid-β-positive (Aβ+) subjects in the AD continuum from healthy controls. The study included asymptomatic, cognitively normal (CN) controls and patients with early mild cognitive impairment (MCI), late MCI, and AD, all with significant levels of cortical Aβ based on their florbetapir PET scans to restrict the study to patients truly in the AD continuum. The discrimination power of each modality was based on the whole-brain patterns of CBF and CMRgl changes identified by partial least squares logistic regression, a multivariate analysis technique. While CBF changes in the posterior inferior aspects of the brain and a pattern of CMRgl changes in the superior aspects of the brain including frontal and parietal regions best discriminated the Aβ+ subjects in the early disease stages from the Aβ- CN subjects, there was a greater agreement in the whole-brain patterns of CBF and CMRgl changes that best discriminated the Aβ+ subjects from the Aβ- CN subjects in the later disease stages. Despite the differences in the whole-brain patterns of CBF and CMRgl changes, the discriminative powers of both modalities were similar with statistically nonsignificant performance differences in sensitivity and specificity. The results comparing measurements of CBF to CMRgl add to previous reports that MRI-measured CBF has a similar diagnostic ability to detect AD as has FDG-PET. Our findings that CBF and CMRgl changes occur in different brain regions in Aβ+ subjects across the AD continuum compared with Aβ- CN subjects may be the result of methodological differences. Alternatively, these findings may signal alterations in neurovascular coupling which alter relationships between brain perfusion and glucose metabolism in the AD continuum. © 2015 S. Karger AG, Basel.

Perfusion deficits detected by arterial spin-labeling in patients with TIA with negative diffusion and vascular imaging.

PubMed

Qiao, X J; Salamon, N; Wang, D J J; He, R; Linetsky, M; Ellingson, B M; Pope, W B

2013-01-01

A substantial portion of clinically diagnosed TIA cases is imaging-negative. The purpose of the current study is to determine if arterial spin-labeling is helpful in detecting perfusion abnormalities in patients presenting clinically with TIA. Pseudocontinuous arterial spin-labeling with 3D background-suppressed gradient and spin-echo was acquired on 49 patients suspected of TIA within 24 hours of symptom onset. All patients were free of stroke history and had no lesion-specific findings on general MR, DWI, and MRA sequences. The calculated arterial spin-labeling CBF maps were scored from 1-3 on the basis of presence and severity of perfusion disturbance by 3 independent observers blinded to patient history. An age-matched cohort of 36 patients diagnosed with no cerebrovascular events was evaluated as a control. Interobserver agreement was assessed by use of the Kendall concordance test. Scoring of perfusion abnormalities on arterial spin-labeling scans of the TIA cohort was highly concordant among the 3 observers (W = 0.812). The sensitivity and specificity of arterial spin-labeling in the diagnosis of perfusion abnormalities in TIA was 55.8% and 90.7%, respectively. In 93.3% (70/75) of the arterial spin-labeling CBF map readings with positive scores (≥2), the brain regions where perfusion abnormalities were identified by 3 observers matched with the neurologic deficits at TIA onset. In this preliminary study, arterial spin-labeling showed promise in the detection of perfusion abnormalities that correlated with clinically diagnosed TIA in patients with otherwise normal neuroimaging results.

Cloning of an ets-Related Transcription Factor Involved in a Novel Epigenetic Mechanism of Mammary Carcinogenesis

DTIC Science & Technology

2001-05-01

dystrophin gene promoter is regulated by YY1 and DPBF (33). Other studies showed that serum response factor (SRF) is required for muscle-specific...transcriptional activation through CArG boxes (68) and that SRF competes with YY1 for binding to wild-type CArG elements (51). CBF-A has significant...between SRF and YY1 proteins at CArG elements has been described in chicken skeletal muscle cells(36). Our previous study in a rat mammary carcinoma cell

88. (Credit CBF) Twelve Mile Bayou Pumping Station and force ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

88. (Credit CBF) Twelve Mile Bayou Pumping Station and force main for pumping water over levee and into the canal (Blind Bayou), March 1913. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

Transcranial Doppler ultrasound study of the effects of nitrous oxide on cerebral autoregulation during neurosurgical anesthesia: a randomized controlled trial.

PubMed

Iacopino, Domenico G; Conti, Alfredo; Battaglia, Calogero; Siliotti, Clotilde; Lucanto, Tullio; Santamaria, Letterio B; Tomasello, Francesco

2003-07-01

Nitrous oxide has an adverse effect on cerebrovascular hemodynamics. Increased intracranial pressure, cerebral blood flow (CBF), cerebral metabolic rate of O2 (CMRO2), and reduced autoregulation indices have been reported, but their magnitudes are still being debated. This study was designed to evaluate the effect of N2O on CBF and autoregulatory indexes during N2O-sevoflurane anesthesia in a prospective randomized controlled series of patients. Two groups of 20 patients were studied on the basis of the use of N2O in the anesthetic gas mixture. The transient hyperemic response test, which relies on transcranial Doppler ultrasound techniques, was used to assess cerebral hemodynamics. The time-averaged mean flow velocity, considered to be an index of actual CBF, increased significantly (p < 0.001) after introduction of N2O. The hyperemic response, considered as the index of autoregulatory potential, decreased significantly after introduction of N2O into the gas mixture (p < 0.001). The increase in CBF and the reduction in autoregulatory indices suggest caution in using N2O during sevoflurane anesthesia, especially in patients with reduced autoregulatory reserve and during neurosurgical interventions. Transcranial Doppler ultrasonography is an efficacious method to evaluate the effects of anesthetic agents on CBF.

Correcting for the echo-time effect after measuring the cerebral blood flow by arterial spin labeling.

PubMed

Foucher, Jack R; Roquet, Daniel; Marrer, Corinne; Pham, Bich-Thuy; Gounot, Daniel

2011-10-01

To take into account the echo time (TE) influence on arterial spin labeling (ASL) signal when converting it in regional cerebral blood flow (rCBF). Gray matter ASL signal decrease with increasing TE as a consequence of the difference in the apparent transverse relaxation rates between labeled water in capillaries and nonlabeled water in the tissue (δR 2*). We aimed to measure ASL/rCBF changes in different parts of the brain and correct them. Fifteen participants underwent ASL measurements at TEs of 9.7-30 ms. Decreases in ASL values were localized by statistical parametric mapping. The corrections assessed were a subject-per-subject adjustment, an average δR 2* value adjustment, and a two-compartment model adjustment. rCBF decreases associated with increasing TEs were found for gray matter and were corrected using an average δR 2* value of 20 s(-1) . Conversely, for white matter, rCBF values increased with increasing TEs (δR 2* = -23 s(-1)). Our correction was as good as using a two-compartment model. However, it must be done separately for the gray and white matter rCBF values because the capillary R 2* values are, respectively, larger and smaller than those of surrounding tissues. Copyright © 2011 Wiley-Liss, Inc.

Quantification of regional cerebral blood flow and volume with dynamic susceptibility contrast-enhanced MR imaging.

PubMed

Rempp, K A; Brix, G; Wenz, F; Becker, C R; Gückel, F; Lorenz, W J

1994-12-01

Quantification of regional cerebral blood flow (rCBF) and volume (rCBV) with dynamic magnetic resonance (MR) imaging. After bolus administration of a paramagnetic contrast medium, rapid T2*-weighted gradient-echo images of two sections were acquired for the simultaneous creation of concentration-time curves in the brain-feeding arteries and in brain tissue. Absolute rCBF and rCBV values were determined for gray and white brain matter in 12 subjects with use of principles of the indicator dilution theory. The mean rCBF value in gray matter was 69.7 mL/min +/- 29.7 per 100 g tissue and in white matter, 33.6 mL/min +/- 11.5 per 100 g tissue; the average rCBV was 8.0 mL +/- 3.1 per 100 g tissue and 4.2 mL +/- 1.0 per 100 g tissue, respectively. An age-related decrease in rCBF and rCBV for gray and white matter was observed. Preliminary data demonstrate that the proposed technique allows the quantification of rCBF and rCBV. Although the results are in good agreement with data from positron emission tomography studies, further evaluation is needed to establish the validity of method.

Sidelobe reduction and capacity improvement of open-loop collaborative beamforming in wireless sensor networks

PubMed Central

2017-01-01

Collaborative beamforming (CBF) with a finite number of collaborating nodes (CNs) produces sidelobes that are highly dependent on the collaborating nodes’ locations. The sidelobes cause interference and affect the communication rate of unintended receivers located within the transmission range. Nulling is not possible in an open-loop CBF since the collaborating nodes are unable to receive feedback from the receivers. Hence, the overall sidelobe reduction is required to avoid interference in the directions of the unintended receivers. However, the impact of sidelobe reduction on the capacity improvement at the unintended receiver has never been reported in previous works. In this paper, the effect of peak sidelobe (PSL) reduction in CBF on the capacity of an unintended receiver is analyzed. Three meta-heuristic optimization methods are applied to perform PSL minimization, namely genetic algorithm (GA), particle swarm algorithm (PSO) and a simplified version of the PSO called the weightless swarm algorithm (WSA). An average reduction of 20 dB in PSL alongside 162% capacity improvement is achieved in the worst case scenario with the WSA optimization. It is discovered that the PSL minimization in the CBF provides capacity improvement at an unintended receiver only if the CBF cluster is small and dense. PMID:28464000

Modeling magnetization transfer effects of Q2TIPS bolus saturation in multi-TI pulsed arterial spin labeling.

PubMed

Petr, Jan; Schramm, Georg; Hofheinz, Frank; Langner, Jens; van den Hoff, Jörg

2014-10-01

To estimate the relaxation time changes during Q2TIPS bolus saturation caused by magnetization transfer effects and to propose and evaluate an extended model for perfusion quantification which takes this into account. Three multi inversion-time pulsed arterial spin labeling sequences with different bolus saturation duration were acquired for five healthy volunteers. Magnetization transfer exchange rates in tissue and blood were obtained from control image saturation recovery. Cerebral blood flow (CBF) obtained using the extended model and the standard model was compared. A decrease of obtained CBF of 6% (10%) was observed in grey matter when the duration of bolus saturation increased from 600 to 900 ms (1200 ms). This decrease was reduced to 1.6% (2.8%) when the extended quantification model was used. Compared with the extended model, the standard model underestimated CBF in grey matter by 9.7, 15.0, and 18.7% for saturation durations 600, 900, and 1200 ms, respectively. Results for simulated single inversion-time data showed 5-16% CBF underestimation depending on blood arrival time and bolus saturation duration. Magnetization transfer effects caused by bolus saturation pulses should not be ignored when performing quantification as they can cause appreciable underestimation of the CBF. Copyright © 2013 Wiley Periodicals, Inc.

Levonorgestrel decreases cilia beat frequency of human fallopian tubes and rat oviducts without changing morphological structure.

PubMed

Zhao, Weihong; Zhu, Qian; Yan, Mingxing; Li, Cheng; Yuan, Jiangjing; Qin, Guojuan; Zhang, Jian

2015-02-01

Levonorgestrel, a derivative of progesterone, effectively protects women against unwanted pregnancy as an emergency contraceptive. Previous studies have not been successful in determining the mechanism by which levonorgestrel acts. In the present study we analysed cilia beat action and cilia morphology following levonorgestrel exposure in vitro and in vivo using both light and electron microscopy. There was a significant decrease in the ciliary beat frequency (CBF) of human fallopian tubes between mucosal explants bathed in 5 μmol/L levonorgestrel and those bathed in medium alone (P < 0.05). There was a tendency for CBF to decrease more in the ampulla than in isthmus, but there were no differences between the proliferative and secretory phases. In rat oviducts, levonorgestrel produced a similar reduction in CBF (~ 10%) compared with the saline control group (P < 0.05). Histological and ultrastructural analysis demonstrated no changes in the percentage of ciliated cells or in the classic '9 + 2' structure of cilia following levonorgestrel treatment in either system. Thus, levonorgestrel reduces CBF without damaging cilia morphology. Decreases in CBF may indicate a pathological role for levonorgestrel in the transportation of the ovum and zygote in the fallopian tube. © 2014 Wiley Publishing Asia Pty Ltd.

Within-session effect of repeated stress exposure on extinction circuitry function in social anxiety disorder.

PubMed

Åhs, Fredrik; Gingnell, Malin; Furmark, Tomas; Fredrikson, Mats

2017-03-30

Anxiety reduction following repeated exposure to stressful experiences is generally held to depend on neural processes involved in extinction of conditioned fear. We predicted that repeated exposure to stressful experiences would change activity throughout the circuitry serving extinction, including ventromedial prefrontal cortex (vmPFC), the hippocampus and the amygdala. To test this prediction, 36 participants diagnosed with SAD performed two successive speeches in front of an observing audience while regional cerebral blood flow (rCBF) was recorded using positron emission tomography. To control for non-anxiolytic effects of repeated exposure, rCBF was also measured during repeated presentations of neutral and angry facial expressions. Results showed that anxiety ratings and heart rate decreased from the first to the second speech, indicating an anxiolytic effect of repeated exposure. Exposure attenuated rCBF in the amygdala whereas no change in rCBF was observed in the vmPFC or hippocampus. The rCBF-reductions in the amygdala were greater following repetition of the speech task than repetition of face exposure indicating that they were specific to anxiety attenuation and not due to a reduced novelty. Our findings suggest that amygdala-related attenuation processes are key to understanding the working mechanisms of exposure therapy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of blockade of cerebral lymphatic drainage on regional cerebral blood flow and brain edema after subarachnoid hemorrhage.

PubMed

Sun, Bao-Liang; Xia, Zuo-Li; Wang, Jing-Ru; Yuan, Hui; Li, Wen-Xia; Chen, Yu-She; Yang, Ming-Feng; Zhang, Su-Ming

2006-01-01

The study was designed to observe the influence of blockade of cerebral lymphatic drainage on the regional cerebral blood flow (rCBF) and brain edema after experimental subarachnoid hemorrhage (SAH). Wistar rats were divided into non-SAH, SAH, and SAH plus cervical lymphatic blockade (SAH + CLB) groups. Autologous arterial hemolysate was injected into rat's cisterna magna to induce SAH. The rCBF was recorded continuously by a laser Doppler flowmeter. Intracranial pressure (ICP) was also monitored. After 24 hours and 72 hours of SAH, the rats were sacrificed and the brain was harvested for water content detection. It was found that there was no obvious change of rCBF and brain water content during the experiment in non-SAH group. An immediate and persistent drop in rCBF was found in SAH group. The drop in rCBF was more obvious in SAH + CLB group. CLB also worsened the SAH-induced increase in ICP. The brain water content 24 hours and 72 hours after induction of SAH in SAH group increased significantly. CLB led to a further increase of brain water content. In conclusion, blockade of cerebral lymphatic drainage pathway deteriorates the secondary cerebral ischemia and brain edema after SAH.

86. (Credit CBF) Canal between Twelve Mile Bayou and Cross ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

86. (Credit CBF) Canal between Twelve Mile Bayou and Cross Bayou in the bed of Blind Bayou (constructed 1901-1903). Photo taken in November of 1911. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA

Hippocampal Dysfunction in Gulf War Veterans: Investigation with ASL Perfusion MR Imaging and Physostigmine Challenge

PubMed Central

Li, Xiufeng; Spence, Jeffrey S.; Buhner, David M.; Hart, John; Cullum, C. Munro; Biggs, Melanie M.; Hester, Andrea L.; Odegard, Timothy N.; Carmack, Patrick S.; Haley, Robert W.

2011-01-01

Purpose: To determine, with arterial spin labeling (ASL) perfusion magnetic resonance (MR) imaging and physostigmine challenge, if abnormal hippocampal blood flow in ill Gulf War veterans persists 11 years after initial testing with single photon emission computed tomography and nearly 20 years after the 1991 Gulf War. Materials and Methods: The local institutional review board approved this HIPAA-compliant study. Veterans were screened for contraindications and gave written informed consent before the study. In a semiblinded retrospective protocol, veterans in three Gulf War illness groups—syndrome 1 (impaired cognition), syndrome 2 (confusion-ataxia), and syndrome 3 (central neuropathic pain)—and a control group received intravenous infusions of saline in an initial session and physostigmine in a second session, 48 hours later. Each infusion was followed by measurement of hippocampal regional cerebral blood flow (rCBF) with pulsed ASL. A mixed-effects linear model adjusted for age was used to test for differences in rCBF after the cholinergic challenge across the four groups. Results: Physostigmine significantly decreased hippocampal rCBF in control subjects (P < .0005) and veterans with syndrome 1 (P < .05) but significantly increased hippocampal rCBF in veterans with syndrome 2 (P < .005) and veterans with syndrome 3 (P < .002). The abnormal increase in rCBF was found to have progressed to the left hippocampus of the veterans with syndrome 2 and to both hippocampi of the veterans with syndrome 3. Conclusion: Chronic hippocampal perfusion dysfunction persists or worsens in veterans with certain Gulf War syndromes. ASL MR imaging examination of hippocampal rCBF in a cholinergic challenge experiment may be useful as a diagnostic test for this condition. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101715/-/DC1 PMID:21914840

External carotid compression: a novel technique to improve cerebral perfusion during selective antegrade cerebral perfusion for aortic arch surgery.

PubMed

Grocott, Hilary P; Ambrose, Emma; Moon, Mike

2016-10-01

Selective antegrade cerebral perfusion (SACP) involving cannulation of either the axillary or innominate artery is a commonly used technique for maintaining cerebral blood flow (CBF) during the use of hypothermic cardiac arrest (HCA) for operations on the aortic arch. Nevertheless, asymmetrical CBF with hypoperfusion of the left cerebral hemisphere is a common occurrence during SACP. The purpose of this report is to describe an adjunctive maneuver to improve left hemispheric CBF during SACP by applying extrinsic compression to the left carotid artery. A 77-yr-old male patient with a history of aortic valve replacement presented for emergent surgical repair of an acute type A aortic dissection of a previously known ascending aortic aneurysm. His intraoperative course included cannulation of the right axillary artery, which was used as the aortic inflow during cardiopulmonary bypass and also allowed for subsequent SACP during HCA. After the onset of HCA, the innominate artery was clamped at its origin to allow for SACP. Shortly thereafter, however, the left-sided cerebral oxygen saturation (SrO2) began to decrease. Augmenting the PaO2, PaCO2 and both SACP pressure and flow failed to increase left hemispheric SrO2. Following the use of ultrasound guidance to confirm the absence of atherosclerotic disease in the carotid artery, external pressure was applied partially compressing the artery. With the carotid compression, the left cerebral saturation abruptly increased, suggesting pressurization of the left cerebral hemispheric circulation and augmentation of CBF. Direct ultrasound visualization and cautious partial compression of the left carotid artery may address asymmetrical CBF that occurs with SACP during HCA for aortic arch surgery. This strategy may lead to improved symmetry of CBF and corresponding cerebral oximetry measurements during aortic arch surgery.

Near-infrared spectroscopy versus magnetic resonance imaging to study brain perfusion in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

PubMed

Wintermark, P; Hansen, A; Warfield, S K; Dukhovny, D; Soul, J S

2014-01-15

The measurement of brain perfusion may provide valuable information for assessment and treatment of newborns with hypoxic-ischemic encephalopathy (HIE). While arterial spin labeled perfusion (ASL) magnetic resonance imaging (MRI) provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values, it is logistically challenging to obtain. Near-infrared spectroscopy (NIRS) might be an alternative, as it permits noninvasive and continuous monitoring of cerebral hemodynamics and oxygenation at the bedside. The purpose of this study is to determine the correlation between measurements of brain perfusion by NIRS and by MRI in term newborns with HIE treated with hypothermia. In this prospective cohort study, ASL-MRI and NIRS performed during hypothermia were used to assess brain perfusion in these newborns. Regional cerebral blood flow (CBF) values, measured from 1-2 MRI scans for each patient, were compared to mixed venous saturation values (SctO2) recorded by NIRS just before and after each MRI. Analysis included groupings into moderate versus severe HIE based on their initial background pattern of amplitude-integrated electroencephalogram. Twelve concomitant recordings were obtained of seven neonates. Strong correlation was found between SctO2 and CBF in asphyxiated newborns with severe HIE (r=0.88; p value=0.0085). Moreover, newborns with severe HIE had lower CBF (likely lower oxygen supply) and extracted less oxygen (likely lower oxygen demand or utilization) when comparing SctO2 and CBF to those with moderate HIE. NIRS is an effective bedside tool to monitor and understand brain perfusion changes in term asphyxiated newborns, which in conjunction with precise measurements of CBF obtained by MRI at particular times, may help tailor neuroprotective strategies in term newborns with HIE. Copyright © 2013 Elsevier Inc. All rights reserved.

Near-Infrared Spectroscopy versus Magnetic Resonance Imaging To Study Brain Perfusion in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia

PubMed Central

Wintermark, P.; Hansen, A.; Warfield, SK.; Dukhovny, D.; Soul, JS.

2014-01-01

Background The measurement of brain perfusion may provide valuable information for assessment and treatment of newborns with hypoxic-ischemic encephalopathy (HIE). While arterial spin labeled perfusion (ASL) magnetic resonance imaging (MRI) provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values, it is logistically challenging to obtain. Near-infrared spectroscopy (NIRS) might be an alternative, as it permits noninvasive and continuous monitoring of cerebral hemodynamics and oxygenation at the bedside. Objective The purpose of this study is to determine the correlation between measurements of brain perfusion by NIRS and by MRI in term newborns with HIE treated with hypothermia. Design/Methods In this prospective cohort study, ASL-MRI and NIRS performed during hypothermia were used to assess brain perfusion in these newborns. Regional cerebral blood flow values (CBF), measured from 1–2 MRI scans for each patient, were compared to mixed venous saturation values (SctO2) recorded by NIRS just before and after each MRI. Analysis included groupings into moderate versus severe HIE based on their initial background pattern of amplitude-integrated electroencephalogram. Results Twelve concomitant recordings were obtained of seven neonates. Strong correlation was found between SctO2 and CBF in asphyxiated newborns with severe HIE (r = 0.88; p value = 0.0085). Moreover, newborns with severe HIE had lower CBF (likely lower oxygen supply) and extracted less oxygen (likely lower oxygen demand or utilization) when comparing SctO2 and CBF to those with moderate HIE. Conclusions NIRS is an effective bedside tool to monitor and understand brain perfusion changes in term asphyxiated newborns, which in conjunction with precise measurements of CBF obtained by MRI at particular times, may help tailor neuroprotective strategies in term newborns with HIE. PMID:23631990

Safety assessment of thiolated polymers: effect on ciliary beat frequency in human nasal epithelial cells.

PubMed

Palmberger, Thomas F; Augustijns, Patrick; Vetter, Anja; Bernkop-Schnürch, Andreas

2011-12-01

The aim of this study was to investigate the nasal safety of gel formulations of thiolated polymers (thiomers) by assessing their effect on ciliary beat frequency (CBF) in human nasal epithelial cells. Poly(acrylic acid) 450 kDa-cysteine (PAA-cys) and alginate-cysteine (alg-cys) were synthesized by covalent attachment of L-cysteine to the polymeric backbone. The cationic polymer chitosan-thiobutylamidine (chito-TBA) was synthesized by attaching iminothiolane to chitosan. CBF using was measured by a photometric system. CBF was measured before incubating the cells with test gels, during incubation and after washing out the polymeric test gels to evaluate reversibility of cilio-inhibition. The influence of viscosity on CBF was determined by using hydroxyethylcellulose (HEC)-gels of various concentrations. Ciliary beating was observed to be affected by viscosity, but cilia were still beating in the presence of a HEC-gel displaying an apparent viscosity of 25 Pa.s. In case of thiolated polymers and their unmodified control, a concentration-dependent decrease in CBF could be observed. PAA-cys, alg-cys, chito-TBA and their corresponding unmodified controls exhibited a moderate cilio-inhibitory effect, followed by a partial recovery of CBF when used at a concentration of 1%. Alg-cys 2% and chito-TBA 2% (m/v) gels exhibited severe cilio-inhibition, which was partially reversible. L-cysteine and reduced glutathione led to mild cilio-inhibition at concentrations of 3% (m/v). Taking into account that dilution after application and cilio-modifying effects is usually more pronounced under in vitro conditions, thiomers can be considered as suitable excipients for nasal drug delivery systems.

Clinical comparison of 99mTc exametazime and 123I Ioflupane SPECT in patients with chronic mild traumatic brain injury.

PubMed

Newberg, Andrew B; Serruya, Mijail; Gepty, Andrew; Intenzo, Charles; Lewis, Todd; Amen, Daniel; Russell, David S; Wintering, Nancy

2014-01-01

This study evaluated the clinical interpretations of single photon emission computed tomography (SPECT) using a cerebral blood flow and a dopamine transporter tracer in patients with chronic mild traumatic brain injury (TBI). The goal was to determine how these two different scan might be used and compared to each other in this patient population. Twenty-five patients with persistent symptoms after a mild TBI underwent SPECT with both (99m)Tc exametazime to measure cerebral blood flow (CBF) and (123)I ioflupane to measure dopamine transporter (DAT) binding. The scans were interpreted by two expert readers blinded to any case information and were assessed for abnormal findings in comparison to 10 controls for each type of scan. Qualitative CBF scores for each cortical and subcortical region along with DAT binding scores for the striatum were compared to each other across subjects and to controls. In addition, symptoms were compared to brain scan findings. TBI patients had an average of 6 brain regions with abnormal perfusion compared to controls who had an average of 2 abnormal regions (p<0.001). Patient with headaches had lower CBF in the right frontal lobe, and higher CBF in the left parietal lobe compared to patients without headaches. Lower CBF in the right temporal lobe correlated with poorer reported physical health. Higher DAT binding was associated with more depressive symptoms and overall poorer reported mental health. There was no clear association between CBF and DAT binding in these patients. Overall, both scans detected abnormalities in brain function, but appear to reflect different types of physiological processes associated with chronic mild TBI symptoms. Both types of scans might have distinct uses in the evaluation of chronic TBI patients depending on the clinical scenario.

Decreased steady-state cerebral blood flow velocity and altered dynamic cerebral autoregulation during 5-h sustained 15% O2 hypoxia.

PubMed

Nishimura, Naoko; Iwasaki, Ken-ichi; Ogawa, Yojiro; Aoki, Ken

2010-05-01

Effects of hypoxia on cerebral circulation are important for occupational, high-altitude, and aviation medicine. Increased risk of fainting might be attributable to altered cerebral circulation by hypoxia. Dynamic cerebral autoregulation is reportedly impaired immediately by mild hypoxia. However, continuous exposure to hypoxia causes hyperventilation, resulting in hypocapnia. This hypocapnia is hypothesized to restore impaired dynamic cerebral autoregulation with reduced steady-state cerebral blood flow (CBF). However, no studies have examined hourly changes in alterations of dynamic cerebral autoregulation and steady-state CBF during sustained hypoxia. We therefore examined cerebral circulation during 5-h exposure to 15% O2 hypoxia and 21% O2 in 13 healthy volunteers in a sitting position. Waveforms of blood pressure and CBF velocity in the middle cerebral artery were measured using finger plethysmography and transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis. As expected, steady-state CBF velocity decreased significantly from 2 to 5 h of hypoxia, accompanying 2- to 3-Torr decreases in end-tidal CO2 (ETCO2). Furthermore, transfer function gain and coherence in the very-low-frequency range increased significantly at the beginning of hypoxia, indicating impaired dynamic cerebral autoregulation. However, contrary to the proposed hypothesis, indexes of dynamic cerebral autoregulation showed no significant restoration despite ETCO2 reductions, resulting in persistent higher values of very-low-frequency power of CBF velocity variability during hypoxia (214+/-40% at 5 h of hypoxia vs. control) without significant increases in blood pressure variability. These results suggest that sustained mild hypoxia reduces steady-state CBF and continuously impairs dynamic cerebral autoregulation, implying an increased risk of shortage of oxygen supply to the brain.

Brain regions associated with cognitive impairment in patients with Parkinson disease: quantitative analysis of cerebral blood flow using 123I iodoamphetamine SPECT.

PubMed

Hattori, Naoya; Yabe, Ichiro; Hirata, Kenji; Shiga, Tohru; Sakushima, Ken; Tsuji-Akimoto, Sachiko; Sasaki, Hidenao; Tamaki, Nagara

2013-05-01

Cognitive impairment is a representative neuropsychiatric presentation that accompanies Parkinson disease (PD). The purpose of this study was to localize the cerebral regions associated with cognitive impairment in patients with PD using quantitative SPECT. Thirty-two patients with PD (mean [SD] age, 75 [8] years; 25 women; Hoehn-Yahr scores from 2 to 5) underwent quantitative brain SPECT using 123I iodoamphetamine. Parametric images of regional cerebral blood flow (rCBF) were spatially normalized to the standard brain atlas. First, voxel-by-voxel comparison between patients with PD with versus without cognitive impairment was performed to visualize overall trend of regional differences. Next, the individual quantitative rCBF values were extracted in representative cortical regions using a standard region-of-interest template to compare the quantitative rCBF values. Patients with cognitive impairment showed trends of lower rCBF in the left frontal and temporal cortices as well as in the bilateral medial frontal and anterior cingulate cortices in the voxel-by-voxel analyses. Region-of-interest-based analysis demonstrated significantly lower rCBF in the bilateral anterior cingulate cortices (right, 25.8 [5.5] vs 28.9 [5.7] mL per 100 g/min, P < 0.05; left, 25.8 [5.8] vs 29.1 [5.7] mL per 100 g/min, P < 0.05) associated with cognitive impairment. Patients with cognitive impairment showed lower rCBF in the left frontal and temporal cortices as well as in the bilateral medial frontal and anterior cingulate cortices. The results suggested dysexecutive function as an underlining mechanism of cognitive impairment in patients with PD.

Role of CO2 in the cerebral hyperemic response to incremental normoxic and hyperoxic exercise

PubMed Central

Wildfong, K. W.; Hoiland, R. L.; Harper, M.; Lewis, N. C.; Pool, A.; Smith, S. L.; Kuca, T.; Ainslie, P. N.

2016-01-01

Cerebral blood flow (CBF) is temporally related to exercise-induced changes in partial pressure of end-tidal carbon dioxide (PetCO2); hyperoxia is known to enhance this relationship. We examined the hypothesis that preventing PetCO2 from rising (isocapnia) during submaximal exercise with and without hyperoxia [end-tidal Po2 (PetO2) = 300 mmHg] would attenuate the increases in CBF. Additionally, we aimed to identify the magnitude that breathing, per se, influences the CBF response to normoxic and hyperoxic exercise. In 14 participants, CBF (intra- and extracranial) measurements were measured during exercise [20, 40, 60, and 80% of maximum workload (Wmax)] and during rest while ventilation (V̇e) was volitionally increased to mimic volumes achieved during exercise (isocapnic hyperpnea). While V̇e was uncontrolled during poikilocapnic exercise, during isocapnic exercise and isocapnic hyperpnea, V̇e was increased to prevent PetCO2 from rising above resting values (∼40 mmHg). Although PetCO2 differed by 2 ± 3 mmHg during normoxic poikilocapnic and isocapnic exercise, except for a greater poikilocapnic compared with isocapnic increase in blood velocity in the posterior cerebral artery at 60% Wmax, the between condition increases in intracranial (∼12-15%) and extracranial (15–20%) blood flow were similar at each workload. The poikilocapnic hyperoxic increases in both intra- and extracranial blood-flow (∼17–29%) were greater compared with poikilocapnic normoxia (∼8–20%) at intensities >40% Wmax (P < 0.01). During both normoxic and hyperoxic conditions, isocapnia normalized both the intracranial and extracranial blood-flow differences. Isocapnic hyperpnea did not alter CBF. Our findings demonstrate a differential effect of PetCO2 on CBF during exercise influenced by the prevailing PetO2. PMID:26769951

Cerebral blood flow is reduced in patients with sepsis syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowton, D.L.; Bertels, N.H.; Prough, D.S.

The relationship between sepsis-induced CNS dysfunction and changes in brain blood flow remains unknown, and animal studies examining the influence of sepsis on cerebral blood flow (CBF) do not satisfactorily address that relationship. We measured CBF and cerebrovascular reactivity to CO/sub 2/ in nine patients with sepsis syndrome using the /sup 133/Xe clearance technique. Mean CBF was 29.6 +/- 15.8 (SD) ml/100 g.min, significantly lower than the normal age-matched value in this laboratory of 44.9 +/- 6.2 ml/100 g.min (p less than .02). This depression did not correlate with changes in mean arterial pressure. Despite the reduction in CBF, themore » specific reactivity of the cerebral vasculature to changes in CO/sub 2/ was normal, 1.3 +/- 0.9 ml/100 g.min/mm Hg. Brain blood flow is reduced in septic humans; the contribution of this reduction to the metabolic and functional changes observed in sepsis requires further study.« less

Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olesen, J.; Larsen, B.; Lauritzen, M.

1981-04-01

Regional cerebral blood flow (rCBF) was measured in 254 areas of a hemisphere with the xenon 133 intraarterial injection method. Six cases of classic migraine were followed from the normal state into the prodromal phase, and in 3 cases further into the headache phase. One patient with common migraine was similarly followed during his only classic attack. The attacks were initiated by focal hyperemia in 3 patients. During prodromes all patients displayed occipitoparietal rCBF reduction (oligemia), but in only 1 case did the reduction approach critical values. Oligemia gradually spread anteriorly in the course of 15 to 45 minutes. Inmore » 4 patients a global oligemia was observed. In 4 patients severe headache was present concomitantly with oligemia and with no sign of hyperemia or nonhomogeneous brain perfusion. The normal rCBF increase during cortical activity (hand movement, speech, and similar activities) was impaired in 6 patients. The results indicate that the vasospastic model of the migraine attack is too simplistic.« less

Database of normal human cerebral blood flow measured by SPECT: II. Quantification of I-123-IMP studies with ARG method and effects of partial volume correction.

PubMed

Inoue, Kentaro; Ito, Hiroshi; Shidahara, Miho; Goto, Ryoi; Kinomura, Shigeo; Sato, Kazunori; Taki, Yasuyuki; Okada, Ken; Kaneta, Tomohiro; Fukuda, Hiroshi

2006-02-01

The limited spatial resolution of SPECT causes a partial volume effect (PVE) and can lead to the significant underestimation of regional tracer concentration in the small structures surrounded by a low tracer concentration, such as the cortical gray matter of an atrophied brain. The aim of the present study was to determine, using 123I-IMP and SPECT, normal CBF of elderly subjects with and without PVE correction (PVC), and to determine regional differences in the effect of PVC and their association with the regional tissue fraction of the brain. Quantitative CBF SPECT using 123I-IMP was performed in 33 healthy elderly subjects (18 males, 15 females, 54-74 years old) using the autoradiographic method. We corrected CBF for PVE using segmented MR images, and analyzed quantitative CBF and regional differences in the effect of PVC using tissue fractions of gray matter (GM) and white matter (WM) in regions of interest (ROIs) placed on the cortical and subcortical GM regions and deep WM regions. The mean CBF in GM-ROIs were 31.7 +/- 6.6 and 41.0 +/- 8.1 ml/100 g/min for males and females, and in WM-ROIs, 18.2 +/- 0.7 and 22.9 +/- 0.8 ml/100 g/min for males and females, respectively. The mean CBF in GM-ROIs after PVC were 50.9 +/- 12.8 and 65.8 +/- 16.1 ml/100 g/min for males and females, respectively. There were statistically significant differences in the effect of PVC among ROIs, but not between genders. The effect of PVC was small in the cerebellum and parahippocampal gyrus, and it was large in the superior frontal gyrus, superior parietal lobule and precentral gyrus. Quantitative CBF in GM recovered significantly, but did not reach values as high as those obtained by invasive methods or in the H2(15)O PET study that used PVC. There were significant regional differences in the effect of PVC, which were considered to result from regional differences in GM tissue fraction, which is more reduced in the frontoparietal regions in the atrophied brain of the elderly.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoff, M; Rane-Levandovsky, S; Andre, J

Purpose: Traditional arterial spin labeling (ASL) acquisitions with echo planar imaging (EPI) readouts suffer from image distortion due to susceptibility effects, compromising ASL’s ability to accurately quantify cerebral blood flow (CBF) and assess disease-specific patterns associated with CBF abnormalities. Phase labeling for additional coordinate encoding (PLACE) can remove image distortion; our goal is to apply PLACE to improve the quantitative accuracy of ASL CBF in humans. Methods: Four subjects were imaged on a 3T Philips Ingenia scanner using a 16-channel receive coil with a 21/21/10cm (frequency/phase/slice direction) field-of-view. An ASL sequence with a pseudo-continuous ASL (pCASL) labeling scheme was employedmore » to acquire thirty dynamics of single-shot EPI data, with control and label datasets for all dynamics, and PLACE gradients applied on odd dynamics. Parameters included a post-labeling delay = 2s, label duration = 1.8s, flip angle = 90°, TR/TE = 5000/23.5ms, and 2.9/2.9/5.0mm (frequency/phase/slice direction) voxel size. “M0” EPI-reference images and T1-weighted spin-echo images with 0.8/1.0/3.3mm (frequency/phase/slice directions) voxel size were also acquired. Complex conjugate image products of pCASL odd and even dynamics were formed, a linear phase ramp applied, and data expanded and smoothed. Data phase was extracted to map control, label, and M0 magnitude image pixels to their undistorted locations, and images were rebinned to original size. All images were corrected for motion artifacts in FSL 5.0. pCASL images were registered to M0 images, and control and label images were subtracted to compute quantitative CBF maps. Results: pCASL image and CBF map distortions were removed by PLACE in all subjects. Corrected images conformed well to the anatomical T1-weighted reference image, and deviations in corrected CBF maps were evident. Conclusion: Eliminating pCASL distortion with PLACE can improve CBF quantification accuracy using minimal pulse sequence modifications and no additional scan time, improving ASL’s clinical applicability.« less

SU-D-18C-02: Feasibility of Using a Short ASL Scan for Calibrating Cerebral Blood Flow Obtained From DSC-MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, P; Chang, T; Huang, K

2014-06-01

Purpose: This study aimed to evaluate the feasibility of using a short arterial spin labeling (ASL) scan for calibrating the dynamic susceptibility contrast- (DSC-) MRI in a group of patients with internal carotid artery stenosis. Methods: Six patients with unilateral ICA stenosis enrolled in the study on a 3T clinical MRI scanner. The ASL-cerebral blood flow (-CBF) maps were calculated by averaging different number of dynamic points (N=1-45) acquired by using a Q2TIPS sequence. For DSC perfusion analysis, arterial input function was selected to derive the relative cerebral blood flow (rCBF) map and the delay (Tmax) map. Patient-specific CF wasmore » calculated from the mean ASL- and DSC-CBF obtained from three different masks: (1)Tmax< 3s, (2)combined gray matter mask with mask 1, (3)mask 2 with large vessels removed. One CF value was created for each number of averages by using each of the three masks for calibrating the DSC-CBF map. The CF value of the largest number of averages (NL=45) was used to determine the acceptable range(< 10%, <15%, and <20%) of CF values corresponding to the minimally acceptable number of average (NS) for each patient. Results: Comparing DSC CBF maps corrected by CF values of NL (CBFL) in ACA, MCA and PCA territories, all masks resulted in smaller CBF on the ipsilateral side than the contralateral side of the MCA territory(p<.05). The values obtained from mask 1 were significantly different than the mask 3(p<.05). Using mask 3, the medium values of Ns were 4(<10%), 2(<15%) and 2(<20%), with the worst case scenario (maximum Ns) of 25, 4, and 4, respectively. Conclusion: This study found that reliable calibration of DSC-CBF can be achieved from a short pulsed ASL scan. We suggested use a mask based on the Tmax threshold, the inclusion of gray matter only and the exclusion of large vessels for performing the calibration.« less

Quantifying the test-retest reliability of cerebral blood flow measurements in a clinical model of on-going post-surgical pain: A study using pseudo-continuous arterial spin labelling.

PubMed

Hodkinson, Duncan J; Krause, Kristina; Khawaja, Nadine; Renton, Tara F; Huggins, John P; Vennart, William; Thacker, Michael A; Mehta, Mitul A; Zelaya, Fernando O; Williams, Steven C R; Howard, Matthew A

2013-01-01

Arterial spin labelling (ASL) is increasingly being applied to study the cerebral response to pain in both experimental human models and patients with persistent pain. Despite its advantages, scanning time and reliability remain important issues in the clinical applicability of ASL. Here we present the test-retest analysis of concurrent pseudo-continuous ASL (pCASL) and visual analogue scale (VAS), in a clinical model of on-going pain following third molar extraction (TME). Using ICC performance measures, we were able to quantify the reliability of the post-surgical pain state and ΔCBF (change in CBF), both at the group and individual case level. Within-subject, the inter- and intra-session reliability of the post-surgical pain state was ranked good-to-excellent (ICC > 0.6) across both pCASL and VAS modalities. The parameter ΔCBF (change in CBF between pre- and post-surgical states) performed reliably (ICC > 0.4), provided that a single baseline condition (or the mean of more than one baseline) was used for subtraction. Between-subjects, the pCASL measurements in the post-surgical pain state and ΔCBF were both characterised as reliable (ICC > 0.4). However, the subjective VAS pain ratings demonstrated a significant contribution of pain state variability, which suggests diminished utility for interindividual comparisons. These analyses indicate that the pCASL imaging technique has considerable potential for the comparison of within- and between-subjects differences associated with pain-induced state changes and baseline differences in regional CBF. They also suggest that differences in baseline perfusion and functional lateralisation characteristics may play an important role in the overall reliability of the estimated changes in CBF. Repeated measures designs have the important advantage that they provide good reliability for comparing condition effects because all sources of variability between subjects are excluded from the experimental error. The ability to elicit reliable neural correlates of on-going pain using quantitative perfusion imaging may help support the conclusions derived from subjective self-report.

Reduced perfusion in normal-appearing white matter in mild to moderate hypertension as revealed by 3D pseudocontinuous arterial spin labeling.

PubMed

Wang, Ting; Li, Yanhua; Guo, Xinhong; Huang, Diandian; Ma, Lin; Wang, Danny J J; Lou, Xin

2016-03-01

To investigate the hemodynamic changes of normal-appearing white matter (NAWM) in hypertension using the 3D pseudocontinuous arterial spin labeling (pCASL) technique. Seventy-three subjects, including a patient group (n = 41; 30 males; age = 47.7 ± 8.3 years; test-time blood pressure [BP] = 155 ± 23/98 ± 11 mmHg) and an age-matched control group (n = 32; 14 males; age = 46 ± 8.3 years; test-time BP = 117 ± 8/76 ± 10 mmHg), were recruited and scanned on a 3.0T magnetic resonance imaging (MRI) system using routine MRI sequences and 3D pCASL sequence. The routine MRI sequences were used to further define the NAWM. The cerebral blood flow (CBF) values in various regions of interest (ROIs) were extracted. One-way analysis of variance (ANOVA) and unpaired t-test were performed to evaluate the significance of the intergroup difference in CBF modifications. Compared to healthy volunteers, CBF values in global gray matter (GM) and various NAWM regions were found to be lower (P < 0.05) in hypertensive patients, except for genu of corpus callosum (CC), cingulate gyrus, amygdala, pallidum, putamen, and thalamus (P > 0.05). Furthermore, compared to the control group, mild hypertension showed significantly reduced CBF in various ROIs (P < 0.05), but no intergroup differences in GM, R anterior horn of periventricular WM, and genu of CC (P > 0.05), while moderate hypertension showed reduced CBF in all ROIs (P < 0.05). However, it was observed that, between mild and moderate hypertensive patients, there were no statistically significant difference in CBF values except for genu of CC (P < 0.05). 3D pCASL has the ability to detect subtle hemodynamic abnormalities in NAWM regions at relatively early stages of hypertension. The observed decreases in CBF in these regions may suggest an increased risk of cerebral small vessel diseases. © 2015 Wiley Periodicals, Inc.

Impact of Competing Risk of Mortality on Association of Weight Loss With Risk of Central Body Fractures in Older Men: A Prospective Cohort Study.

PubMed

Ensrud, Kristine E; Harrison, Stephanie L; Cauley, Jane A; Langsetmo, Lisa; Schousboe, John T; Kado, Deborah M; Gourlay, Margaret L; Lyons, Jennifer G; Fredman, Lisa; Napoli, Nicolas; Crandall, Carolyn J; Lewis, Cora E; Orwoll, Eric S; Stefanick, Marcia L; Cawthon, Peggy M

2017-03-01

To determine the association of weight loss with risk of clinical fractures at the hip, spine, and pelvis (central body fractures [CBFs]) in older men with and without accounting for the competing risk of mortality, we used data from 4523 men (mean age 77.5 years). Weight change between baseline and follow-up (mean 4.5 years between examinations) was categorized as moderate loss (loss ≥10%), mild loss (loss 5% to <10%), stable (<5% change) or gain (gain ≥5%). Participants were contacted every 4 months after the follow-up examination to ascertain vital status (deaths verified by death certificates) and ask about fractures (confirmed by radiographic reports). Absolute probability of CBF by weight change category was estimated using traditional Kaplan-Meier method and cumulative incidence function accounting for competing mortality risk. Risk of CBF by weight change category was determined using conventional Cox proportional hazards regression and subdistribution hazards models with death as a competing risk. During an average of 8 years, 337 men (7.5%) experienced CBF and 1569 (34.7%) died before experiencing this outcome. Among men with moderate weight loss, CBF probability was 6.8% at 5 years and 16.9% at 10 years using Kaplan-Meier versus 5.7% at 5 years and 10.2% at 10 years using a competing risk approach. Men with moderate weight loss compared with those with stable weight had a 1.6-fold higher adjusted risk of CBF (HR 1.59; 95% CI, 1.06 to 2.38) using Cox models that was substantially attenuated in models accounting for competing mortality risk and no longer significant (subdistribution HR 1.16; 95% CI, 0.77 to 1.75). Results were similar in analyses substituting hip fracture for CBF. Older men with weight loss who survive are at increased risk of CBF, including hip fracture. However, ignoring the competing mortality risk among men with weight loss substantially overestimates their long-term fracture probability and relative fracture risk. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

The anesthetic effects on vasopressor modulation of cerebral blood flow in an immature swine model.

PubMed

Bruins, Benjamin; Kilbaugh, Todd J; Margulies, Susan S; Friess, Stuart H

2013-04-01

The effect of various sedatives and anesthetics on vasopressor modulation of cerebral blood flow (CBF) in children is unclear. In adults, isoflurane has been described to decrease CBF to a lesser extent than fentanyl and midazolam. Most large-animal models of neurocritical care use inhaled anesthetics for anesthesia. Investigations involving modulations of CBF would have improved translatability within a model that more closely approximates the current practice in the pediatric intensive care unit. Fifteen 4-week-old piglets were given 1 of 2 anesthetic protocols: total IV anesthesia (TIVA) (midazolam 1 mg/kg/h and fentanyl 100 μg/kg/h, n = 8) or ISO (isoflurane 1.5%-2% and fentanyl 100 μg/kg/h, n = 7). Mean arterial blood pressure, intracranial pressure (ICP), CBF, and brain tissue oxygen tension were measured continuously as piglets were exposed to escalating doses of arginine vasopressin, norepinephrine (NE), and phenylephrine (PE). Baseline CBF was similar in the 2 groups (ISO 38 ± 10 vs TIVA 35 ± 26 mL/100 g/min) despite lower baseline cerebral perfusion pressure in the ISO group (45 ± 11 vs 71 ± 11 mm Hg; P < 0.0005). Piglets in the ISO group displayed increases in ICP with PE and NE (11 ± 4 vs 16 ± 4 mm Hg and 11 ± 8 vs 18 ± 5 mm Hg; P < 0.05), but in the TIVA group, only exposure to PE resulted in increases in ICP when comparing maximal dose values with baseline data (11 ± 4 vs 15 ± 5 mm Hg; P < 0.05). Normalized CBF displayed statistically significant increases regarding anesthetic group and vasopressor dose when piglets were exposed to NE and PE (P < 0.05), suggesting an impairment of autoregulation within ISO, but not TIVA. The vasopressor effect on CBF was limited when using a narcotic-benzodiazepine-based anesthetic protocol compared with volatile anesthetics, consistent with a preservation of autoregulation. Selection of anesthetic drugs is critical to investigate mechanisms of cerebrovascular hemodynamics, and in translating critical care investigations between the laboratory and bedside.

Separation of input function for rapid measurement of quantitative CMRO2 and CBF in a single PET scan with a dual tracer administration method

NASA Astrophysics Data System (ADS)

Kudomi, Nobuyuki; Watabe, Hiroshi; Hayashi, Takuya; Iida, Hidehiro

2007-04-01

Cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF) and cerebral blood flow (CBF) images can be quantified using positron emission tomography (PET) by administrating 15O-labelled water (H152O) and oxygen (15O2). Conventionally, those images are measured with separate scans for three tracers C15O for CBV, H152O for CBF and 15O2 for CMRO2, and there are additional waiting times between the scans in order to minimize the influence of the radioactivity from the previous tracers, which results in a relatively long study period. We have proposed a dual tracer autoradiographic (DARG) approach (Kudomi et al 2005), which enabled us to measure CBF, OEF and CMRO2 rapidly by sequentially administrating H152O and 15O2 within a short time. Because quantitative CBF and CMRO2 values are sensitive to arterial input function, it is necessary to obtain accurate input function and a drawback of this approach is to require separation of the measured arterial blood time-activity curve (TAC) into pure water and oxygen input functions under the existence of residual radioactivity from the first injected tracer. For this separation, frequent manual sampling was required. The present paper describes two calculation methods: namely a linear and a model-based method, to separate the measured arterial TAC into its water and oxygen components. In order to validate these methods, we first generated a blood TAC for the DARG approach by combining the water and oxygen input functions obtained in a series of PET studies on normal human subjects. The combined data were then separated into water and oxygen components by the present methods. CBF and CMRO2 were calculated using those separated input functions and tissue TAC. The quantitative accuracy in the CBF and CMRO2 values by the DARG approach did not exceed the acceptable range, i.e., errors in those values were within 5%, when the area under the curve in the input function of the second tracer was larger than half of the first one. Bias and deviation in those values were also compatible to that of the conventional method, when noise was imposed on the arterial TAC. We concluded that the present calculation based methods could be of use for quantitatively calculating CBF and CMRO2 with the DARG approach.

Kinetic analysis of IMP split dose method for two consecutive measurement of cerebral blood flow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishizawa, S.; Yonekura, Y.; Tanaka, F.

1994-05-01

The split dose method for two consecutive measurements of cerebral blood flow (CBF) with I-123 IMP seems to offer a great merit to the SPECT study of the brain. However, because of complexity of the dynamics of IMP, it is not clear if microsphere (MS) model permits a estimation of CBF for the 2nd dose. We applied kinetic (KN) analysis based on 2 compartment model to the dynamic SPECT scan data, and compared the results with those obtained by MS model. Dynamic SPECT (1-min scans for 50 min) was performed using 3-head SPECT camera in 5 patients to test themore » reproducibility of measured CBF and in 9 patients to test the vascular response to acetazolamide (ACZ). Two doses of IMP (111 MBq each) were injected at the time of, and 25 min after, the scan initiation. ACZ (1g) was administered at 13 min. Arterial blood samples were drawn manually during the scan and an octanol extracted input function was obtained. Dynamic scan data for 22 min was used for CBF by KN analysis (K1), and 4-min scan data at 5 min for CBF by MS model (Km), for each dose. For 2nd CBF by MS model, simple subtraction of brain activity due to the I st dose was done using 4-min scan data just prior to the 2nd dose. Reproducibility of measured CBF by KN analysis was excellent (r=0.949, 1st K1=39.2{plus_minus}5.6 and 2nd K1=38.5{plus_minus}6.6 ml/l00g/min: mean{plus_minus}SD). Vascular response to ACZ was good (1st K1=42.4{plus_minus}7.8 to 2nd K1=67.9{plus_minus}10.0) in areas without ischemia, but poor (1st K1=41.1{plus_minus}8.5 to 2nd K1=46.1{plus_minus}11.1) in ischemic areas. Compared to KN analysis, MS model underestimated 3.5% for the 1st CBF measurement and 12.8% for the 2nd. However, excellent correlation was observed not only between 1st K1 and Km (r=0.993, slope=0.920) but between 2nd K1 and Km (r=0.994, slope=0.814), and the results permitted a reasonable correction for Km.« less

Absolute cerebral blood flow quantification with pulsed arterial spin labeling during hyperoxia corrected with the simultaneous measurement of the longitudinal relaxation time of arterial blood.

PubMed

Pilkinton, David T; Hiraki, Teruyuki; Detre, John A; Greenberg, Joel H; Reddy, Ravinder

2012-06-01

Quantitative arterial spin labeling (ASL) estimates of cerebral blood flow (CBF) during oxygen inhalation are important in several contexts, including functional experiments calibrated with hyperoxia and studies investigating the effect of hyperoxia on regional CBF. However, ASL measurements of CBF during hyperoxia are confounded by the reduction in the longitudinal relaxation time of arterial blood (T(1a) ) from paramagnetic molecular oxygen dissolved in blood plasma. The aim of this study is to accurately quantify the effect of arbitrary levels of hyperoxia on T(1a) and correct ASL measurements of CBF during hyperoxia on a per-subject basis. To mitigate artifacts, including the inflow of fresh spins, partial voluming, pulsatility, and motion, a pulsed ASL approach was implemented for in vivo measurements of T(1a) in the rat brain at 3 Tesla. After accounting for the effect of deoxyhemoglobin dilution, the relaxivity of oxygen on blood was found to closely match phantom measurements. The results of this study suggest that the measured ASL signal changes are dominated by reductions in T(1a) for brief hyperoxic inhalation epochs, while the physiologic effects of oxygen on the vasculature account for most of the measured reduction in CBF for longer hyperoxic exposures. Copyright © 2011 Wiley-Liss, Inc.

Effects of flow changes on radiotracer binding: Simultaneous measurement of neuroreceptor binding and cerebral blood flow modulation.

PubMed

Sander, Christin Y; Mandeville, Joseph B; Wey, Hsiao-Ying; Catana, Ciprian; Hooker, Jacob M; Rosen, Bruce R

2017-01-01

The potential effects of changes in blood flow on the delivery and washout of radiotracers has been an ongoing question in PET bolus injection studies. This study provides practical insight into this topic by experimentally measuring cerebral blood flow (CBF) and neuroreceptor binding using simultaneous PET/MRI. Hypercapnic challenges (7% CO 2 ) were administered to non-human primates in order to induce controlled increases in CBF, measured with pseudo-continuous arterial spin labeling. Simultaneously, dopamine D 2 /D 3 receptor binding of [ 11 C]raclopride or [ 18 F]fallypride was monitored with dynamic PET. Experiments showed that neither time activity curves nor quantification of binding through binding potentials ( BP ND ) were measurably affected by CBF increases, which were larger than two-fold. Simulations of experimental procedures showed that even large changes in CBF should have little effect on the time activity curves of radiotracers, given a set of realistic assumptions. The proposed method can be applied to experimentally assess the flow sensitivity of other radiotracers. Results demonstrate that CBF changes, which often occur due to behavioral tasks or pharmacological challenges, do not affect PET [ 11 C]raclopride or [ 18 F]fallypride binding studies and their quantification. The results from this study suggest flow effects may have limited impact on many PET neuroreceptor tracers with similar properties.

Near-infrared diffuse optical monitoring of cerebral blood flow and oxygenation for the prediction of vasovagal syncope

NASA Astrophysics Data System (ADS)

Cheng, Ran; Shang, Yu; Wang, Siqi; Evans, Joyce M.; Rayapati, Abner; Randall, David C.; Yu, Guoqiang

2014-01-01

Significant drops in arterial blood pressure and cerebral hemodynamics have been previously observed during vasovagal syncope (VVS). Continuous and simultaneous monitoring of these physiological variables during VVS is rare, but critical for determining which variable is the most sensitive parameter to predict VVS. The present study used a novel custom-designed diffuse correlation spectroscopy flow-oximeter and a finger plethysmograph to simultaneously monitor relative changes of cerebral blood flow (rCBF), cerebral oxygenation (i.e., oxygenated/deoxygenated/total hemoglobin concentration: r[HbO2]/r[Hb]/rTHC), and mean arterial pressure (rMAP) during 70 deg head-up tilt (HUT) in 14 healthy adults. Six subjects developed presyncope during HUT. Two-stage physiological responses during HUT were observed in the presyncopal group: slow and small changes in measured variables (i.e., Stage I), followed by rapid and dramatic decreases in rMAP, rCBF, r[HbO2], and rTHC (i.e., Stage II). Compared to other physiological variables, rCBF reached its breakpoint between the two stages earliest and had the largest decrease (76±8%) during presyncope. Our results suggest that rCBF has the best sensitivity for the assessment of VVS. Most importantly, a threshold of ˜50% rCBF decline completely separated the subjects from those without presyncope, suggesting its potential for predicting VVS.

Inter-Vendor Reproducibility of Pseudo-Continuous Arterial Spin Labeling at 3 Tesla

PubMed Central

Mutsaerts, Henri J. M. M.; Steketee, Rebecca M. E.; Heijtel, Dennis F. R.; Kuijer, Joost P. A.; van Osch, Matthias J. P.; Majoie, Charles B. L. M.; Smits, Marion; Nederveen, Aart J.

2014-01-01

Purpose Prior to the implementation of arterial spin labeling (ASL) in clinical multi-center studies, it is important to establish its status quo inter-vendor reproducibility. This study evaluates and compares the intra- and inter-vendor reproducibility of pseudo-continuous ASL (pCASL) as clinically implemented by GE and Philips. Material and Methods 22 healthy volunteers were scanned twice on both a 3T GE and a 3T Philips scanner. The main difference in implementation between the vendors was the readout module: spiral 3D fast spin echo vs. 2D gradient-echo echo-planar imaging respectively. Mean and variation of cerebral blood flow (CBF) were compared for the total gray matter (GM) and white matter (WM), and on a voxel-level. Results Whereas the mean GM CBF of both vendors was almost equal (p = 1.0), the mean WM CBF was significantly different (p<0.01). The inter-vendor GM variation did not differ from the intra-vendor GM variation (p = 0.3 and p = 0.5 for GE and Philips respectively). Spatial inter-vendor CBF and variation differences were observed in several GM regions and in the WM. Conclusion These results show that total GM CBF-values can be exchanged between vendors. For the inter-vendor comparison of GM regions or WM, these results encourage further standardization of ASL implementation among vendors. PMID:25090654

Inter-vendor reproducibility of pseudo-continuous arterial spin labeling at 3 Tesla.

PubMed

Mutsaerts, Henri J M M; Steketee, Rebecca M E; Heijtel, Dennis F R; Kuijer, Joost P A; van Osch, Matthias J P; Majoie, Charles B L M; Smits, Marion; Nederveen, Aart J

2014-01-01

Prior to the implementation of arterial spin labeling (ASL) in clinical multi-center studies, it is important to establish its status quo inter-vendor reproducibility. This study evaluates and compares the intra- and inter-vendor reproducibility of pseudo-continuous ASL (pCASL) as clinically implemented by GE and Philips. 22 healthy volunteers were scanned twice on both a 3T GE and a 3T Philips scanner. The main difference in implementation between the vendors was the readout module: spiral 3D fast spin echo vs. 2D gradient-echo echo-planar imaging respectively. Mean and variation of cerebral blood flow (CBF) were compared for the total gray matter (GM) and white matter (WM), and on a voxel-level. Whereas the mean GM CBF of both vendors was almost equal (p = 1.0), the mean WM CBF was significantly different (p<0.01). The inter-vendor GM variation did not differ from the intra-vendor GM variation (p = 0.3 and p = 0.5 for GE and Philips respectively). Spatial inter-vendor CBF and variation differences were observed in several GM regions and in the WM. These results show that total GM CBF-values can be exchanged between vendors. For the inter-vendor comparison of GM regions or WM, these results encourage further standardization of ASL implementation among vendors.

Polynitroxyl albumin and albumin therapy after pediatric asphyxial cardiac arrest: effects on cerebral blood flow and neurologic outcome

PubMed Central

Manole, Mioara D; Kochanek, Patrick M; Foley, Lesley M; Hitchens, T Kevin; Bayır, Hülya; Alexander, Henry; Garman, Robert; Ma, Li; Hsia, Carleton J C; Ho, Chien; Clark, Robert S B

2012-01-01

Postresuscitation cerebral blood flow (CBF) disturbances and generation of reactive oxygen species likely contribute to impaired neurologic outcome after pediatric cardiac arrest (CA). Hence, we determined the effects of the antioxidant colloid polynitroxyl albumin (PNA) versus albumin or normal saline (NS) on CBF and neurologic outcome after asphyxial CA in immature rats. We induced asphyxia for 9 minutes in male and female postnatal day 16 to 18 rats randomized to receive PNA, albumin, or NS at resuscitation from CA or sham surgery. Regional CBF was measured serially from 5 to 150 minutes after resuscitation by arterial spin-labeled magnetic resonance imaging. We assessed motor function (beam balance and inclined plane), spatial memory retention (water maze), and hippocampal neuronal survival. Polynitroxyl albumin reduced early hyperemia seen 5 minutes after CA. In contrast, albumin markedly increased and prolonged hyperemia. In the delayed period after resuscitation (90 to 150 minutes), CBF was comparable among groups. Both PNA- and albumin-treated rats performed better in the water maze versus NS after CA. This benefit was observed only in males. Hippocampal neuron survival was similar between injury groups. Treatment of immature rats with PNA or albumin resulted in divergent acute changes in CBF, but both improved spatial memory retention in males after asphyxial CA. PMID:22126915

Cutaneous blood flow in psoriasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klemp, P.; Staberg, B.

1983-12-01

The disappearance rate of /sup 133/Xe was studied in 20 patients with psoriasis vulgaris, using an epicutaneous labeling technique in involved skin lesions or normal-appearing skin of the proximal extensor site of the forearm. Control experiments were performed in 10 normal subjects. Calculations of the cutaneous blood flow (CBF) in psoriatic skin lesions were performed using a tissue-to-blood partition coefficient for /sup 133/Xe, lambda c,pso, of 1.2 ml/100 g/min. lambda c,pso was estimated after the relative content of water, lipids, and proteins had been analyzed in psoriatic skin biopsies of 6 patients with untreated psoriasis. The mean relative content ofmore » water was markedly reduced to 23.5 +/- 1.5% (SEM), and lipids and proteins were markedly increased to 2.5 +/- 0.7% and 74.0 +/- 2.2, respectively, compared to previously published data for normal skin (water 72.5%, lipids 1%, proteins 26.5%). Mean CBF in untreated psoriatic skin was 63.5 +/- 9.0 ml/100 g/min. This was significantly higher than the mean CBF in 10 normal subjects, 6.3 +/- 0.5 ml/100 g/min (p much less than 0.0001). Mean CBF in normal-appearing skin in patients with psoriasis was 11.0 +/- 1.3 ml/100 g/min. This was significantly higher than CBF in normal subjects (p less than 0.0002).« less

Imaging of cerebral blood flow in patients with severe traumatic brain injury in the neurointensive care.

PubMed

Rostami, Elham; Engquist, Henrik; Enblad, Per

2014-01-01

Ischemia is a common and deleterious secondary injury following traumatic brain injury (TBI). A great challenge for the treatment of TBI patients in the neurointensive care unit (NICU) is to detect early signs of ischemia in order to prevent further advancement and deterioration of the brain tissue. Today, several imaging techniques are available to monitor cerebral blood flow (CBF) in the injured brain such as positron emission tomography (PET), single-photon emission computed tomography, xenon computed tomography (Xenon-CT), perfusion-weighted magnetic resonance imaging (MRI), and CT perfusion scan. An ideal imaging technique would enable continuous non-invasive measurement of blood flow and metabolism across the whole brain. Unfortunately, no current imaging method meets all these criteria. These techniques offer snapshots of the CBF. MRI may also provide some information about the metabolic state of the brain. PET provides images with high resolution and quantitative measurements of CBF and metabolism; however, it is a complex and costly method limited to few TBI centers. All of these methods except mobile Xenon-CT require transfer of TBI patients to the radiological department. Mobile Xenon-CT emerges as a feasible technique to monitor CBF in the NICU, with lower risk of adverse effects. Promising results have been demonstrated with Xenon-CT in predicting outcome in TBI patients. This review covers available imaging methods used to monitor CBF in patients with severe TBI.

99mTc-HMPAO SPECT of the brain in mild to moderate traumatic brain injury patients: compared with CT--a prospective study.

PubMed

Nedd, K; Sfakianakis, G; Ganz, W; Uricchio, B; Vernberg, D; Villanueva, P; Jabir, A M; Bartlett, J; Keena, J

1993-01-01

Single photon emission computed tomography (SPECT) with Technetium-99m hexamethyl propylenamine oxime (Tc-99m-HMPAO) was used in 20 patients with mild to moderate traumatic brain injury (TBI) to evaluate the effects of brain trauma on regional cerebral blood flow (rCBF). SPECT scan was compared with CT scan in 16 patients. SPECT showed intraparenchymal differences in rCBF more often than lesions diagnosed with CT scans (87.5% vs. 37.5%). In five of six patients with lesions in both modalities, the area of involvement was relatively larger on SPECT scans than on CT scans. Contrecoup changes were seen in five patients on SPECT alone, two patients with CT alone and one patient had contrecoup lesions on CT and SPECT. Of the eight patients (50%) with skull fractures, seven (43.7%) had rCBF findings on SPECT scan and five (31.3%) demonstrated decrease in rCBF in brain underlying the fracture. All these patients with fractures had normal brain on CT scans. Conversely, extra-axial lesions and fractures evident on CT did not visualize on SPECT, but SPECT demonstrated associated changes in rCBF. Although there is still lack of clinical and pathological correlation, SPECT appears to be a promising method for a more sensitive evaluation of axial lesions in patients with mild to moderate TBI.

Imaging of Cerebral Blood Flow in Patients with Severe Traumatic Brain Injury in the Neurointensive Care

PubMed Central

Rostami, Elham; Engquist, Henrik; Enblad, Per

2014-01-01

Ischemia is a common and deleterious secondary injury following traumatic brain injury (TBI). A great challenge for the treatment of TBI patients in the neurointensive care unit (NICU) is to detect early signs of ischemia in order to prevent further advancement and deterioration of the brain tissue. Today, several imaging techniques are available to monitor cerebral blood flow (CBF) in the injured brain such as positron emission tomography (PET), single-photon emission computed tomography, xenon computed tomography (Xenon-CT), perfusion-weighted magnetic resonance imaging (MRI), and CT perfusion scan. An ideal imaging technique would enable continuous non-invasive measurement of blood flow and metabolism across the whole brain. Unfortunately, no current imaging method meets all these criteria. These techniques offer snapshots of the CBF. MRI may also provide some information about the metabolic state of the brain. PET provides images with high resolution and quantitative measurements of CBF and metabolism; however, it is a complex and costly method limited to few TBI centers. All of these methods except mobile Xenon-CT require transfer of TBI patients to the radiological department. Mobile Xenon-CT emerges as a feasible technique to monitor CBF in the NICU, with lower risk of adverse effects. Promising results have been demonstrated with Xenon-CT in predicting outcome in TBI patients. This review covers available imaging methods used to monitor CBF in patients with severe TBI. PMID:25071702

New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain

PubMed Central

Venkat, Poornima; Chopp, Michael; Chen, Jieli

2016-01-01

The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases. PMID:27374823

New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain.

PubMed

Venkat, Poornima; Chopp, Michael; Chen, Jieli

2016-06-30

The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases.

Quantitative agreement between [(15)O]H2O PET and model free QUASAR MRI-derived cerebral blood flow and arterial blood volume.

PubMed

Heijtel, D F R; Petersen, E T; Mutsaerts, H J M M; Bakker, E; Schober, P; Stevens, M F; van Berckel, B N M; Majoie, C B L M; Booij, J; van Osch, M J P; van Bavel, E T; Boellaard, R; Lammertsma, A A; Nederveen, A J

2016-04-01

The purpose of this study was to assess whether there was an agreement between quantitative cerebral blood flow (CBF) and arterial cerebral blood volume (CBVA) measurements by [(15)O]H2O positron emission tomography (PET) and model-free QUASAR MRI. Twelve healthy subjects were scanned within a week in separate MRI and PET imaging sessions, after which quantitative and qualitative agreement between both modalities was assessed for gray matter, white matter and whole brain region of interests (ROI). The correlation between CBF measurements obtained with both modalities was moderate to high (r(2): 0.28-0.60, P < 0.05), although QUASAR significantly underestimated CBF by 30% (P < 0.001). CBVA was moderately correlated (r(2): 0.28-0.43, P < 0.05), with QUASAR yielding values that were only 27% of the [(15)O]H2O-derived values (P < 0.001). Group-wise voxel statistics identified minor areas with significant contrast differences between [(15)O]H2O PET and QUASAR MRI, indicating similar qualitative CBVA and CBF information by both modalities. In conclusion, the results of this study demonstrate that QUASAR MRI and [(15)O]H2O PET provide similar CBF and CBVA information, but with systematic quantitative discrepancies. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluation of MRI Models in the Measurement of CMRO2 and Its Relationship With CBF

PubMed Central

Lin, Ai-Ling; Fox, Peter T.; Yang, Yihong; Lu, Hanzhang; Tan, Li-Hai; Gao, Jia-Hong

2008-01-01

The aim of this study was to investigate the various MRI biophysical models in the measurements of local cerebral metabolic rate of oxygen (CMRO2) and the corresponding relationship with cerebral blood flow (CBF) during brain activation. This aim was addressed by simultaneously measuring the relative changes in CBF, cerebral blood volume (CBV), and blood oxygen level dependent (BOLD) MRI signals in the human visual cortex during visual stimulation. A radial checkerboard delivered flash stimulation at five different frequencies. Two MRI models, the single-compartment model (SCM) and the multi-compartment model (MCM), were used to determine the relative changes in CMRO2 using three methods: [1] SCM with parameters identical to those used in a prior MRI study (M = 0.22; α = 0.38); [2] SCM with directly measured parameters (M from hypercapnia and α from measured δCBV and δCBF); and [3] MCM. The magnitude of relative changes in CMRO2 and the nonlinear relationship between CBF and CMRO2 obtained with Methods [2] and [3] were not in agreement with those obtained using Method [1]. However, the results of Methods [2] and [3] were aligned with positron emission tomography findings from the literature. Our results indicate that if appropriate parameters are used, the SCM and MCM models are equivalent for quantifying the values of CMRO2 and determining the flow-metabolism relationship. PMID:18666102

Choroidal hemodynamic changes during isometric exercise in patients with inactive central serous chorioretinopathy.

PubMed

Tittl, Michael; Maar, Noemi; Polska, Elzbieta; Weigert, Günther; Stur, Michael; Schmetterer, Leopold

2005-12-01

Imaging studies suggest that the choroidal vasculature may be altered in central serous chorioretinopathy. Little is known, however, about the regulation of ocular blood flow in patients with central serous chorioretinopathy (CSC). The hypothesis for the present study was that choroidal blood flow changes during an increase in ocular perfusion pressure induced by isometric exercise may be altered in CSC. An observer-masked, two-cohort study was performed in 14 nonsmoking patients with chronic-relapsing but inactive CSC and in 14 healthy nonsmoking volunteers. Both groups were matched for age and sex. Subfoveal choroidal blood flow (CBF) was assessed with laser Doppler flowmetry, and ocular perfusion pressure (OPP) was calculated from mean arterial pressure (MAP) and intraocular pressure (IOP). Changes of CBF during isometric exercise over a period of 6 minutes were measured. Whereas the increase of MAP, the pulse rate, and the OPP were comparable between the two study groups, subfoveal CBF increased significantly more in the group of patients with CSC (P < 0.001). IOP remained unchanged in both groups during isometric exercise. At an 85% increase in OPP, subfoveal CBF was approximately twice as high in the patients with CSC compared with the healthy control group. The data indicate an abnormal subfoveal CBF regulation in patients with relapsing CSC compared with age-matched, nonsmoking, healthy volunteers during isometric exercise.

Cerebral blood flow with [15O]water PET studies using an image-derived input function and MR-defined carotid centerlines

NASA Astrophysics Data System (ADS)

Fung, Edward K.; Carson, Richard E.

2013-03-01

Full quantitative analysis of brain PET data requires knowledge of the arterial input function into the brain. Such data are normally acquired by arterial sampling with corrections for delay and dispersion to account for the distant sampling site. Several attempts have been made to extract an image-derived input function (IDIF) directly from the internal carotid arteries that supply the brain and are often visible in brain PET images. We have devised a method of delineating the internal carotids in co-registered magnetic resonance (MR) images using the level-set method and applying the segmentations to PET images using a novel centerline approach. Centerlines of the segmented carotids were modeled as cubic splines and re-registered in PET images summed over the early portion of the scan. Using information from the anatomical center of the vessel should minimize partial volume and spillover effects. Centerline time-activity curves were taken as the mean of the values for points along the centerline interpolated from neighboring voxels. A scale factor correction was derived from calculation of cerebral blood flow (CBF) using gold standard arterial blood measurements. We have applied the method to human subject data from multiple injections of [15O]water on the HRRT. The method was assessed by calculating the area under the curve (AUC) of the IDIF and the CBF, and comparing these to values computed using the gold standard arterial input curve. The average ratio of IDIF to arterial AUC (apparent recovery coefficient: aRC) across 9 subjects with multiple (n = 69) injections was 0.49 ± 0.09 at 0-30 s post tracer arrival, 0.45 ± 0.09 at 30-60 s, and 0.46 ± 0.09 at 60-90 s. Gray and white matter CBF values were 61.4 ± 11.0 and 15.6 ± 3.0 mL/min/100 g tissue using sampled blood data. Using IDIF centerlines scaled by the average aRC over each subjects’ injections, gray and white matter CBF values were 61.3 ± 13.5 and 15.5 ± 3.4 mL/min/100 g tissue. Using global average aRC values, the means were unchanged, and intersubject variability was noticeably reduced. This MR-based centerline method with local re-registration to [15O]water PET yields a consistent IDIF over multiple injections in the same subject, thus permitting the absolute quantification of CBF without arterial input function measurements.

62. (Credit CBF) Operating floor of filter room, c1912. The ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

62. (Credit CBF) Operating floor of filter room, c1912. The remodeled New York horizontal pressure filters (now gravity filters) are in the foreground; the remodelled Hyatt tub filters are in the background. - McNeil Street Pumping Station, McNeil Street & Cross Bayou, Shreveport, Caddo Parish, LA