Platelet aggregation but not activation and degranulation during the acute post-ischemic reperfusion phase in livers with no underlying disease

PubMed Central

van Golen, Rowan F.; Stevens, Katarzyna M.; Colarusso, Pina; Jaeschke, Hartmut; Heger, Michal

2016-01-01

Background Platelets and P-selectin (CD62P) play an unequivocal role in the pathology of hepatic ischemia/reperfusion (I/R) injury. Inhibition or knock-out of P-selectin or immunodepletion of platelets results in amelioration of post-ischemic inflammation, reduced hepatocellular damage, and improved survival. However, P-selectin expression on platelets and endothelial cells, which concurs with platelet activation, has never been clearly demonstrated in I/R-subjected livers. Aims To determine whether platelets become activated and degranulate in the acute phase of liver I/R and whether the platelets interact with neutrophils. Methods Hepatic I/R was induced in male C57BL/6J mice (N = 12) using 37.5-min ischemia time. Platelets, endothelial cells, and neutrophils were fluorescently labeled by systemic administration of non-blocking antibodies. Cell kinetics were monitored by intravital spinning disk confocal microscopy during 90 min of reperfusion. Image analysis and quantification was performed with dedicated software. Results Platelets adhered to sinusoids more extensively in post-ischemic livers compared to livers not subjected to I/R and formed aggregates, which occurred directly after ischemia. Platelets and endothelial cells did not express P-selectin in post-ischemic livers. There was no interaction between platelets and neutrophils. Conclusions Platelets aggregate but do not become activated and do not degranulate in post-ischemic livers. There is no platelet-neutrophil interplay during the early reperfusion phase in a moderate model of hepatic I/R injury. The mechanisms underlying the biological effects of platelets and P-selectin in this setting warrant further investigation. Relevance for patients I/R in surgical liver patients may compromise outcome due to post-ischemic oxidative stress and sterile inflammation. Both processes are mediated in part by platelets. Understanding platelet function during I/R is key to developing effective interventions for I

The role of microglia and myeloid immune cells in acute cerebral ischemia

PubMed Central

Benakis, Corinne; Garcia-Bonilla, Lidia; Iadecola, Costantino; Anrather, Josef

2015-01-01

The immune response to acute cerebral ischemia is a major contributor to stroke pathobiology. The inflammatory response is characterized by the participation of brain resident cells and peripheral leukocytes. Microglia in the brain and monocytes/neutrophils in the periphery have a prominent role in initiating, sustaining and resolving post-ischemic inflammation. In this review we aim to summarize recent literature concerning the origins, fate and role of microglia, monocytes and neutrophils in models of cerebral ischemia and to discuss their relevance for human stroke. PMID:25642168

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.

Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy: Advances in Diagnosis and Treatment.

PubMed

Novak, Iona; Morgan, Cathy; Adde, Lars; Blackman, James; Boyd, Roslyn N; Brunstrom-Hernandez, Janice; Cioni, Giovanni; Damiano, Diane; Darrah, Johanna; Eliasson, Ann-Christin; de Vries, Linda S; Einspieler, Christa; Fahey, Michael; Fehlings, Darcy; Ferriero, Donna M; Fetters, Linda; Fiori, Simona; Forssberg, Hans; Gordon, Andrew M; Greaves, Susan; Guzzetta, Andrea; Hadders-Algra, Mijna; Harbourne, Regina; Kakooza-Mwesige, Angelina; Karlsson, Petra; Krumlinde-Sundholm, Lena; Latal, Beatrice; Loughran-Fowlds, Alison; Maitre, Nathalie; McIntyre, Sarah; Noritz, Garey; Pennington, Lindsay; Romeo, Domenico M; Shepherd, Roberta; Spittle, Alicia J; Thornton, Marelle; Valentine, Jane; Walker, Karen; White, Robert; Badawi, Nadia

2017-09-01

Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months' corrected age. To systematically review best available evidence for early, accurate diagnosis of cerebral palsy and to summarize best available evidence about cerebral palsy-specific early intervention that should follow early diagnosis to optimize neuroplasticity and function. This study systematically searched the literature about early diagnosis of cerebral palsy in MEDLINE (1956-2016), EMBASE (1980-2016), CINAHL (1983-2016), and the Cochrane Library (1988-2016) and by hand searching. Search terms included cerebral palsy, diagnosis, detection, prediction, identification, predictive validity, accuracy, sensitivity, and specificity. The study included systematic reviews with or without meta-analyses, criteria of diagnostic accuracy, and evidence-based clinical guidelines. Findings are reported according to the PRISMA statement, and recommendations are reported according to the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument. Six systematic reviews and 2 evidence-based clinical guidelines met inclusion criteria. All included articles had high methodological Quality Assessment of Diagnostic Accuracy Studies (QUADAS) ratings. In infants, clinical signs and symptoms of cerebral palsy emerge and evolve before age 2 years; therefore, a combination of standardized tools should be used to predict risk in conjunction with clinical history. Before 5 months' corrected age, the most predictive tools for detecting risk are term-age magnetic resonance imaging (86%-89% sensitivity), the Prechtl Qualitative Assessment of General Movements (98% sensitivity), and the Hammersmith Infant Neurological Examination (90% sensitivity). After 5 months' corrected age, the most predictive tools for detecting risk are magnetic resonance imaging (86

Early optical detection of cerebral edema in vivo.

PubMed

Gill, Amandip S; Rajneesh, Kiran F; Owen, Christopher M; Yeh, James; Hsu, Mike; Binder, Devin K

2011-02-01

Cerebral edema is a significant cause of morbidity and mortality in diverse disease states. Currently, the means to detect progressive cerebral edema in vivo includes the use of intracranial pressure (ICP) monitors and/or serial radiological studies. However, ICP measurements exhibit a high degree of variability, and ICP monitors detect edema only after it becomes sufficient to significantly raise ICP. The authors report the development of 2 distinct minimally invasive fiberoptic near-infrared (NIR) techniques able to directly detect early cerebral edema. Cytotoxic brain edema was induced in adult CD1 mice via water intoxication by intraperitoneal water administration (30% body weight intraperitoneally). An implantable dual-fiberoptic probe was stereotactically placed into the cerebral cortex and connected to optical source and detector hardware. Optical sources consisted of either broadband halogen illumination or a single-wavelength NIR laser diode, and the detector was a sensitive NIR spectrometer or optical power meter. In one subset of animals, a left-sided craniectomy was performed to obtain cortical biopsies for water-content determination to verify cerebral edema. In another subset of animals, an ICP transducer was placed on the contralateral cortex, which was synchronized to a computer and time stamped. Using either broadband illumination with NIR spectroscopy or single-wavelength laser diode illumination with optical power meter detection, the authors detected a reduction in NIR optical reflectance during early cerebral edema. The time intervals between water injection (Time Point 0), optical trigger (defined as a 2-SD change in optical reflectance from baseline), and defined threshold ICP values of 10, 15 and 20 mm Hg were calculated. Reduction in NIR reflectance occurred significantly earlier than any of the ICP thresholds (p < 0.001). Saline-injected control mice exhibited a steady baseline optical signal. There was a significant correlation between

Delayed administration of parecoxib, a specific COX-2 inhibitor, attenuated postischemic neuronal apoptosis by phosphorylation Akt and GSK-3β.

PubMed

Ye, Zhi; Wang, Na; Xia, Pingping; Wang, E; Yuan, Yajing; Guo, Qulian

2012-02-01

Parecoxib is a recently described novel COX-2 inhibitor whose functional significance and neuroprotective mechanisms remain elusive. Therefore, in this study, we aimed to investigate whether delayed administration of parecoxib inhibited mitochondria-mediated neuronal apoptosis induced by ischemic reperfusion injury via phosphorylating Akt and its downstream target protein, glycogen synthase kinase 3β (GSK-3β). Adult male Sprague-Dawley rats were administered parecoxib (10 or 30 mg kg(-1), IP) or isotonic saline twice a day starting 24 h after middle cerebral artery occlusion (MCAO) for three consecutive days. Cerebral infarct volume, apoptotic neuron, caspase-3 immunoreactivity and the protein expression of p-Akt, p-GSK-3β and Cytochrome C in cerebral ischemic cortex were evaluated at 96 h after reperfusion. Parecoxib significantly diminished infarct volume and attenuated neuron apoptosis in a dose-independent manner, compared with MCAO group alone. Increased p-Akt and p-GSK-3β was observed in the ischemic penumbra of parecoxib group after stroke. Moreover, parecoxib also reduced the release of Cytochrome C from mitochondrial into cytosol and attenuated the caspase-3 immunoreactivity in the penumbra. Taken together, these results suggested that parecoxib ameliorated postischemic mitochondria-mediated neuronal apoptosis induced by focal cerebral ischemia in rats and this neuroprotective potential is involved in phosphorylation of Akt and GSK-3β.

Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure

PubMed Central

Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

2015-01-01

A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

Conditioned Medium Derived from Neural Progenitor Cells Induces Long-term Post-ischemic Neuroprotection, Sustained Neurological Recovery, Neurogenesis, and Angiogenesis.

PubMed

Doeppner, Thorsten R; Traut, Viktorija; Heidenreich, Alexander; Kaltwasser, Britta; Bosche, Bert; Bähr, Mathias; Hermann, Dirk M

2017-03-01

Adult neural progenitor cells (NPCs) induce post-ischemic long-term neuroprotection and brain remodeling by releasing of survival- and plasticity-promoting mediators. To evaluate whether secreted factors may mimic neuroprotective and restorative effects of NPCs, we exposed male C57BL6 mice to focal cerebral ischemia and intravenously applied conditioned medium (CM) derived from subventricular zone NPCs. CM dose-dependently reduced infarct volume and brain leukocyte infiltration after 48 h when delivered up to 12 h after focal cerebral ischemia. Neuroprotection persisted in the post-acute stroke phase yielding enhanced neurological recovery that lasted throughout the 28-day observation period. Increased Bcl-2, phosphorylated Akt and phosphorylated STAT-3 abundance, and reduced caspase-3 activity and Bax abundance were noted in ischemic brains of CM-treated mice at 48 h post-stroke, indicative of enhanced cell survival signaling. Long-term neuroprotection was associated with increased brain glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF) concentrations at 28 days resulting in increased neurogenesis and angiogenesis. The observation that NPC-derived CM induces sustained neuroprotection and neurological recovery suggests that cell transplantation may be dispensable when secreted factors are instead administered.

Depletion of NADP(H) due to CD38 activation triggers endothelial dysfunction in the postischemic heart.

PubMed

Reyes, Levy A; Boslett, James; Varadharaj, Saradhadevi; De Pascali, Francesco; Hemann, Craig; Druhan, Lawrence J; Ambrosio, Giuseppe; El-Mahdy, Mohamed; Zweier, Jay L

2015-09-15

In the postischemic heart, coronary vasodilation is impaired due to loss of endothelial nitric oxide synthase (eNOS) function. Although the eNOS cofactor tetrahydrobiopterin (BH4) is depleted, its repletion only partially restores eNOS-mediated coronary vasodilation, indicating that other critical factors trigger endothelial dysfunction. Therefore, studies were performed to characterize the unidentified factor(s) that trigger endothelial dysfunction in the postischemic heart. We observed that depletion of the eNOS substrate NADPH occurs in the postischemic heart with near total depletion from the endothelium, triggering impaired eNOS function and limiting BH4 rescue through NADPH-dependent salvage pathways. In isolated rat hearts subjected to 30 min of ischemia and reperfusion (I/R), depletion of the NADP(H) pool occurred and was most marked in the endothelium, with >85% depletion. Repletion of NADPH after I/R increased NOS-dependent coronary flow well above that with BH4 alone. With combined NADPH and BH4 repletion, full restoration of NOS-dependent coronary flow occurred. Profound endothelial NADPH depletion was identified to be due to marked activation of the NAD(P)ase-activity of CD38 and could be prevented by inhibition or specific knockdown of this protein. Depletion of the NADPH precursor, NADP(+), coincided with formation of 2'-phospho-ADP ribose, a CD38-derived signaling molecule. Inhibition of CD38 prevented NADP(H) depletion and preserved endothelium-dependent relaxation and NO generation with increased recovery of contractile function and decreased infarction in the postischemic heart. Thus, CD38 activation is an important cause of postischemic endothelial dysfunction and presents a novel therapeutic target for prevention of this dysfunction in unstable coronary syndromes.

Neuroprotective mechanism of BNG-1 against focal cerebral ischemia: a neuroimaging and neurotrophin study.

PubMed

Chi, Nai-Fang; Liu, Ho-Ling; Yang, Jen-Tsung; Lin, Jr-Rung; Liao, Shu-Li; Peng, Bo-Han; Lee, Yen-Tung; Lee, Tsong-Hai

2014-01-01

BNG-1 is a herb complex used in traditional Chinese medicine to treat stroke. In this study, we attempted to identify the neuroprotective mechanism of BNG-1 by using neuroimaging and neurotrophin analyses of a stroke animal model. Rats were treated with either saline or BNG-1 for 7 d after 60-min middle cerebral artery occlusion by filament model. The temporal change of magnetic resonance (MR) imaging of brain was studied using a 7 Tesla MR imaging (MRI) system and the temporal expressions of neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) in brain were analyzed before operation and at 4 h, 2 d, and 7 d after operation. Compared with the saline group, the BNG-1 group exhibited a smaller infarction volume in the cerebral cortex in T2 image from as early as 4 h to 7 d, less edema in the cortex in diffusion weighted image from 2 to 7 d, earlier reduction of postischemic hyperperfusion in both the cortex and striatum in perfusion image at 4 h, and earlier normalization of the ischemic pattern in the striatum in susceptibility weighted image at 2 d. NT-3 and BDNF levels were higher in the BNG-1 group than the saline group at 7 d. We concluded that the protective effect of BNG-1 against cerebral ischemic injury might act through improving cerebral hemodynamics and recovering neurotrophin generation.

The Early Needs of Children with Cerebral Palsy: A Comprehensive View.

ERIC Educational Resources Information Center

Blackman, James A.; Healy, Alfred

Intended for professionals and parents, this monograph focuses on the service needs of young children with cerebral palsy. Section I presents an overview of cerebral palsy, including etiology, incidence, and history of management. Section II describes service needs in the following areas: prevention; early identification; treatment; the…

Improved wound healing of postischemic cutaneous flaps with the use of bone marrow-derived stem cells.

PubMed

Hu, Melissa; Ludlow, David; Alexander, J Steven; McLarty, Jerry; Lian, Timothy

2014-03-01

To determine if the intravascular delivery of mesenchymal stem cells improves wound healing and blood perfusion to postischemic cutaneous flap tissues. Randomized controlled study. A murine model of a cutaneous flap was created based on the inferior epigastric vessels. Mice (n = 14) underwent 3.5 hours of ischemia followed by reperfusion. Bone marrow stromal cells (BMSCs) 1 × 10(6) were injected intravenously. Wound healing was then assessed measuring percent flap necrosis, flap perfusion, and tensile strength of the flap after a period of 14 days. Localization of BMSCs was determined with radiolabeled and fluorescent labeled BMSCs. Postischemic cutaneous flap tissues treated with BMSCs demonstrated significantly less necrosis than control flaps (P <0.01). Beginning on postoperative day 5, BMSC-treated flaps demonstrated greater blood perfusion than untreated flaps (P <0.01). Tensile strength of BMSC-treated cutaneous flaps was significantly higher (P <0.01), with a mean strength of 283.4 ± 28.4 N/m than control flaps with a mean of 122.4 ± 23.5 N/m. Radiolabeled BMSCs localized to postischemic flaps compared to untreated tissues (P = 0.001). Fluorescent microscopy revealed incorporation of BMSCs into endothelial and epithelial tissues of postischemic flaps. This study demonstrates that the intravascular delivery of BMSCs increases wound healing and promotes flap survival following ischemia-reperfusion injury of cutaneous tissue flaps. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Nicotine and estrogen synergistically exacerbate cerebral ischemic injury.

PubMed

Raval, A P; Hirsch, N; Dave, K R; Yavagal, D R; Bramlett, H; Saul, I

2011-05-05

The greater incidence of myocardial infarction, cardiac arrest, and ischemic stroke among women who smoke and use oral contraception (OC) compared to women who do not smoke and who do or do not use OC may be due in part to how nicotine influences endocrine function in women. For example, we recently demonstrated that chronic exposure to nicotine, the addictive agent in tobacco smoke responsible for the elevated risk of cardiac arrest, abolishes the endogenous or exogenous 17β-estradiol-conferred protection of the hippocampus against global cerebral ischemia (a potential outcome of cardiac arrest) in naive or ovariectomized female rats. In the current study we examined the hypotheses that (1) a synergistic deleterious effect of nicotine plus oral contraceptives exacerbates post-ischemic hippocampal damage in female rats, and (2) nicotine directly inhibits estrogen-mediated intracellular signaling in the hippocampus. To test first hypothesis and to simulate smoking behavior-induced nicotine levels in the human body, we implanted osmotic pumps containing nicotine in the female rats for 16 days. Furthermore, we mimicked the use of oral contraceptives in females by administering oral contraceptives orally to the rat. Rats exposed to either nicotine alone or in combination with oral contraceptives were subjected to an episode of cerebral ischemia and the resultant brain damage was quantified. These results showed for the first time that nicotine with oral contraceptives did indeed exacerbate post-ischemic CA1 damage as compared to nicotine alone in naive female rats. In ex vivo hippocampal slice cultures, we found that nicotine alone or with 17β-estradiol directly hinders estrogen receptors-mediated phosphorylation of cyclic-AMP element binding protein, a process required for neuronal survival and also exacerbates ischemic damage. Thus, nicotine can affect the outcome of cerebral ischemia by influencing brain endocrine function directly rather than through indirect

Sepiapterin reduces postischemic injury in the rat heart.

PubMed

Tiefenbacher, Christiane P; Lee, Ching-Hua; Kapitza, Jolanthe; Dietz, Volker; Niroomand, Feraydoon

2003-10-01

A reduced availability of tetrahydrobiopterin (BH4), an essential cofactor for NO-synthesis, is causally involved in the development of endothelial dysfunction associated with ischemia/reperfusion. We, therefore, investigated the effect of sepiapterin, a substrate for BH4 synthesis, on postischemic injury in myocardial infarction and myocardial stunning. In rats, myocardial stunning was induced by repetitive ischemia (5 x 10-min ligature of the left coronary artery, 5 x 20-min reperfusion) and myocardial infarction by 50-min ligature and 60-min reperfusion. Myocardial blood flow was determined by H2-clearance, regional myocardial function by pulsed Doppler and infarct size by tetrazolium staining. Myeloperoxidase (MPO) activity was measured as a marker of neutrophil extravasation. cGMP was determined in rat serum as an indicator of increased NO synthesis. In animals treated with sepiapterin, regional myocardial function was significantly improved in both myocardial stunning and infarction and infarct size was significantly reduced. MPO activity decreased with sepiapterin treatment in both models. The systemic level of cGMP was reduced both following myocardial stunning and myocardial infarction in the control group. Pretreatment with sepiapterin induced a significant increase of cGMP level at the end of the protocol in both models. Substitution of sepiapterin reduces postischemic injury both in myocardial stunning and infarction apparently by ameliorating the availability of NO, thereby attenuating the activation of neutrophils in ischemia/reperfusion.

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.

Early Diagnosis and Early Intervention in Cerebral Palsy

PubMed Central

Hadders-Algra, Mijna

2014-01-01

This paper reviews the opportunities and challenges for early diagnosis and early intervention in cerebral palsy (CP). CP describes a group of disorders of the development of movement and posture, causing activity limitation that is attributed to disturbances that occurred in the fetal or infant brain. Therefore, the paper starts with a summary of relevant information from developmental neuroscience. Most lesions underlying CP occur in the second half of gestation, when developmental activity in the brain reaches its summit. Variations in timing of the damage not only result in different lesions but also in different neuroplastic reactions and different associated neuropathologies. This turns CP into a heterogeneous entity. This may mean that the best early diagnostics and the best intervention methods may differ for various subgroups of children with CP. Next, the paper addresses possibilities for early diagnosis. It discusses the predictive value of neuromotor and neurological exams, neuroimaging techniques, and neurophysiological assessments. Prediction is best when complementary techniques are used in longitudinal series. Possibilities for early prediction of CP differ for infants admitted to neonatal intensive care and other infants. In the former group, best prediction is achieved with the combination of neuroimaging and the assessment of general movements, in the latter group, best prediction is based on carefully documented milestones and neurological assessment. The last part reviews early intervention in infants developing CP. Most knowledge on early intervention is based on studies in high-risk infants without CP. In these infants, early intervention programs promote cognitive development until preschool age; motor development profits less. The few studies on early intervention in infants developing CP suggest that programs that stimulate all aspects of infant development by means of family coaching are most promising. More research is urgently needed

NADPH oxidase-derived overproduction of reactive oxygen species impairs postischemic neovascularization in mice with type 1 diabetes.

PubMed

Ebrahimian, Téni G; Heymes, Christophe; You, Dong; Blanc-Brude, Olivier; Mees, Barend; Waeckel, Ludovic; Duriez, Micheline; Vilar, José; Brandes, Ralph P; Levy, Bernard I; Shah, Ajay M; Silvestre, Jean-Sébastien

2006-08-01

We hypothesized that diabetes-induced oxidative stress may affect postischemic neovascularization. The response to unilateral femoral artery ligation was studied in wild-type or gp91(phox)-deficient control or type 1 diabetic mice or in animals treated with the anti-oxidant N-acetyl-l-cysteine (NAC) or with in vivo electrotransfer of a plasmid encoding dominant-negative Rac1 (50 microg) for 21 days. Postischemic neovascularization was reduced in diabetic mice in association with down-regulated vascular endothelial growth factor-A protein levels. In diabetic animals vascular endothelial growth factor levels and postischemic neovascularization were restored to nondiabetic levels by the scavenging of reactive oxygen species (ROS) by NAC administration or the inhibition of ROS generation by gp91(phox) deficiency or by administration of dominant-negative Rac1. Finally, diabetes reduced the ability of adherent bone marrow-derived mononuclear cells (BM-MNCs) to differentiate into endothelial progenitor cells. Treatment with NAC (3 mmol/L), apocynin (200 micromol/L), or the p38MAPK inhibitor LY333351 (10 micromol/L) up-regulated the number of endothelial progenitor cell colonies derived from diabetic BM-MNCs by 1.5-, 1.6-, and 1.5-fold, respectively (P < 0.05). In the ischemic hindlimb model, injection of diabetic BM-MNCs isolated from NAC-treated or gp91(phox)-deficient diabetic mice increased neovascularization by approximately 1.5-fold greater than untreated diabetic BM-MNCs (P < 0.05). Thus, inhibition of NADPH oxidase-derived ROS overproduction improves the angiogenic and vasculogenic processes and restores postischemic neovascularization in type 1 diabetic mice.

Cerebral Palsy: A Lifelong Challenge Asks for Early Intervention

PubMed Central

Panteliadis, Christos P; Hagel, Christian; Karch, Dieter; Heinemann, Karl

2015-01-01

One of the oldest and probably well-known examples of cerebral palsy is the mummy of the Pharaoh Siptah about 1196–1190 B.C., and a letter from Hippocrates (460–390 B.C.). Cerebral palsy (CP) is one of the most common congenital or acquired neurological impairments in paediatric patients, and refers to a group of children with motor disability and related functional defects. The visible core of CP is characterized by abnormal coordination of movements and/or muscle tone which manifest very early in the development. Resulting from pre- or perinatal brain damage CP is not a progressive condition per se. However, without systematic medical and physiotherapeutic support the dystonia leads to muscle contractions and to deterioration of the handicap. Here we review the three general spastic manifestations of CP hemiplegia, diplegia and tetraplegia, describe the diagnostic procedures and delineate a time schedule for an early intervention. PMID:26191093

[Effect of a new derivative of glutamic and apovincaminic acids on brain metabolism in post-ischemic period].

PubMed

Makarova, L M; Prikhod'ko, M A; Pogorelyĭ, V E; Skachilova, S Ia; Mirzoian, R S

2014-01-01

Neuroprotective properties of the new derivative of glutamic and apovincaminic acids, ethyl -(3-alpha,16-alpha)-eburnamenin-14-carbopxylate of 2-aminopentadionic acid (LHT 1-02) were studied on a model of acute brain ischemia in cats. LHT 1-02 has proved to be more effective than the reference drugs vinpocetin and glycine in preventing the reperfusive damage, which was manifested by decreased postischemic hyperglycemia, activated utilization of oxygen in the brain, and suppressed postischemic metabolic lactate acidosis. Thus, the results of this comparative study show expediency of further investigations of LHT 1 - 02 as a potential neuroprotective drug.

Key Role of CD36 in Toll-Like Receptor 2 Signaling in Cerebral Ischemia

PubMed Central

Abe, Takato; Shimamura, Munehisa; Jackman, Katherine; Kurinami, Hitomi; Anrather, Josef; Zhou, Ping; Iadecola, Costantino

2010-01-01

Background and Purpose Toll-like receptors (TLRs) and the scavenger receptor CD36 are key molecular sensors for the innate immune response to invading pathogens. However, these receptors may also recognize endogenous “danger signals” generated during brain injury, such as cerebral ischemia, and trigger a maladaptive inflammatory reaction. Indeed, CD36 and TLR2 and 4 are involved in the inflammation and related tissue damage caused by brain ischemia. Because CD36 may act as a coreceptor for TLR2 heterodimers (TLR2/1 or TLR2/6), we tested whether such interaction plays a role in ischemic brain injury. Methods The TLR activators FSL-1 (TLR2/6), Pam3 (TLR2/1), or lipopolysaccharide (TLR4) were injected intracerebroventricularly into wild-type or CD36-null mice, and inflammatory gene expression was assessed in the brain. The effect of TLR activators on the infarct produced by transient middle cerebral artery occlusion was also studied. Results The inflammatory response induced by TLR2/1 activation, but not TLR2/6 or TLR4 activation, was suppressed in CD36-null mice. Similarly, TLR2/1 activation failed to increase infarct volume in CD36-null mice, whereas TLR2/6 or TLR4 activation exacerbated postischemic inflammation and increased infarct volume. In contrast, the systemic inflammatory response evoked by TLR2/6 activation, but not by TLR2/1 activation, was suppressed in CD36-null mice. Conclusions In the brain, TLR2/1 signaling requires CD36. The cooperative signaling of TLR2/1 and CD36 is a critical factor in the inflammatory response and tissue damage evoked by cerebral ischemia. Thus, suppression of CD36-TLR2/1 signaling could be a valuable approach to minimize postischemic inflammation and the attendant brain injury. PMID:20360550

[Cerebral protection].

PubMed

Cattaneo, A D

1993-09-01

metabolic standpoint, exposure to isoflurane at concentration of 2 MAC is credited with providing the same potential for protection as high dose barbiturate (isoelectric EEG). A possible major difference between barbiturates and isoflurane is the modest cerebral vasodilation induced by the latter while barbiturates are associated with decreased CBF. This suggests that in focal ischemia isoflurane may elicit an intracerebral steal. 3) Calcium entry blockers. Some calcium entry blockers with the distinctive feature of acting preferably on cerebral as opposed to systemic vascular smooth muscles may exert beneficial effects during or after brain ischemia. Two such drugs which have shown promise are nimodipine and lidoflazine. In animal and human studies nimodipine has been reported to improve the neurologic outcome of both the cerebral vasospasm and the postischemic hypoperfusion state.(ABSTRACT TRUNCATED AT 400 WORDS)

Equilibrative nucleoside transporter 1 (ENT1) regulates postischemic blood flow during acute kidney injury in mice

PubMed Central

Grenz, Almut; Bauerle, Jessica D.; Dalton, Julee H.; Ridyard, Douglas; Badulak, Alexander; Tak, Eunyoung; McNamee, Eóin N.; Clambey, Eric; Moldovan, Radu; Reyes, German; Klawitter, Jost; Ambler, Kelly; Magee, Kristann; Christians, Uwe; Brodsky, Kelley S.; Ravid, Katya; Choi, Doo-Sup; Wen, Jiaming; Lukashev, Dmitriy; Blackburn, Michael R.; Osswald, Hartmut; Coe, Imogen R.; Nürnberg, Bernd; Haase, Volker H.; Xia, Yang; Sitkovsky, Michail; Eltzschig, Holger K.

2012-01-01

A complex biologic network regulates kidney perfusion under physiologic conditions. This system is profoundly perturbed following renal ischemia, a leading cause of acute kidney injury (AKI) — a life-threatening condition that frequently complicates the care of hospitalized patients. Therapeutic approaches to prevent and treat AKI are extremely limited. Better understanding of the molecular pathways promoting postischemic reflow could provide new candidate targets for AKI therapeutics. Due to its role in adapting tissues to hypoxia, we hypothesized that extracellular adenosine has a regulatory function in the postischemic control of renal perfusion. Consistent with the notion that equilibrative nucleoside transporters (ENTs) terminate adenosine signaling, we observed that pharmacologic ENT inhibition in mice elevated renal adenosine levels and dampened AKI. Deletion of the ENTs resulted in selective protection in Ent1–/– mice. Comprehensive examination of adenosine receptor–knockout mice exposed to AKI demonstrated that renal protection by ENT inhibitors involves the A2B adenosine receptor. Indeed, crosstalk between renal Ent1 and Adora2b expressed on vascular endothelia effectively prevented a postischemic no-reflow phenomenon. These studies identify ENT1 and adenosine receptors as key to the process of reestablishing renal perfusion following ischemic AKI. If translatable from mice to humans, these data have important therapeutic implications. PMID:22269324

Methylene Blue Ameliorates Ischemia/Reperfusion-Induced Cerebral Edema: An MRI and Transmission Electron Microscope Study.

PubMed

Fang, Qing; Yan, Xu; Li, Shaowu; Sun, Yilin; Xu, Lixin; Shi, Zhongfang; Wu, Min; Lu, Yi; Dong, Liping; Liu, Ran; Yuan, Fang; Yang, Shao-Hua

2016-01-01

The neuroprotective effect of methylene blue (MB) has been identified against various brain disorders, including ischemic stroke. In the present study, we evaluated the effects of MB on postischemic brain edema using magnetic resonance imaging (MRI) and transmission electron microscopy (TEM). Adult male rats were subjected to transient focal cerebral ischemia induced by 1 h middle cerebral artery occlusion (MCAO), followed by reperfusion. MB was infused intravenously immediately after reperfusion (3 mg/kg) and again at 3 h post-occlusion (1.5 mg/kg). Normal saline was administered as vehicle control. Sequential MRIs, including apparent diffusion coefficient (ADC) and T2-weighted imaging (T2WI), were obtained at 0.5, 2.5, and 48 h after the onset of stroke. Separated groups of animals were sacrificed at 2.5 and 48 h after stroke for ultrastructural analysis by TEM. In addition, final lesion volumes were analyzed by triphenyltetrazolium chloride (TTC) staining at 48 h after stroke. Ischemic stroke induced ADC lesion volume at 0.5 h during MCAOs that were temporally recovered at 1.5 h after reperfusion. No significant difference in ADC-defined lesion was observed between vehicle and MB treatment groups. At 48 h after stroke, MB significantly reduced ADC lesion and T2WI lesion volume and attenuated cerebral swelling. Consistently, MB treatment significantly decreased TTC-defined lesion volume at 48 h after stroke. TEM revealed remarkable swollen astrocytes, astrocytic perivascular end-feet, and concurrent shrunken neurons in the penumbra at 2.5 and 48 h after MCAO. MB treatment attenuated astrocyte swelling, the perivascular astrocytic foot process, and endothelium and also alleviated neuron degeneration. This study demonstrated that MB could decrease postischemic brain edema and provided additional evidence that future clinical investigation of MB for the treatment of ischemic stroke is warrented.

Reparative neurogenesis after cerebral ischemia: Clinical application prospects

NASA Astrophysics Data System (ADS)

Khodanovich, M. Yu.

2015-11-01

At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.

L-NAME reduces infarction, neurological deficit and blood-brain barrier disruption following cerebral ischemia in mice.

PubMed

Ding-Zhou, Li; Marchand-Verrecchia, Catherine; Croci, Nicole; Plotkine, Michel; Margaill, Isabelle

2002-12-20

The role of nitric oxide (NO) in the development of post-ischemic cerebral infarction has been extensively examined, but fewer studies have investigated its role in other outcomes. In the present study, we first determined the temporal evolution of infarct volume, NO production, neurological deficit and blood-brain barrier disruption in a model of transient focal cerebral ischemia in mice. We then examined the effect of the nonselective NO-synthase inhibitor N(omega)-nitro-L-arginine-methylester (L-NAME). L-NAME given at 3 mg/kg 3 h after ischemia reduced by 20% the infarct volume and abolished the increase in brain NO production evaluated by its metabolites (nitrites/nitrates) 48 h after ischemia. L-NAME with this protocol also reduced the neurological deficit evaluated by the grip test and decreased by 65% the extravasation of Evans blue, an index of blood-brain barrier breakdown. These protective activities of L-NAME suggest that NO has multiple deleterious effects in cerebral ischemia.

Cerebral activation of mitogen-activated protein kinases after circulatory arrest and low flow cardiopulmonary bypass.

PubMed

Aharon, Alon S; Mulloy, Matthew R; Drinkwater, Davis C; Lao, Oliver B; Johnson, Mahlon D; Thunder, Megan; Yu, Chang; Chang, Paul

2004-11-01

Mitogen-activated protein kinases (MAPK) are important intermediates in the signal transduction pathways involved in neuronal dysfunction following cerebral ischemia-reperfusion injury. One subfamily, extracellular regulated kinase 1/2, has been heavily implicated in the pathogenesis of post-ischemic neuronal damage. However, the contribution of extracellular regulated kinase 1/2 to neuronal damage following deep hypothermic circulatory arrest and low flow cardiopulmonary bypass is unknown. We attempted to correlate the extent of neuronal damage present following deep hypothermic circulatory arrest and low flow cardiopulmonary bypass with phosphorylated extracellular regulated kinase 1/2 expression in the cerebral vascular endothelium. Piglets underwent normal flow cardiopulmonary bypass (n=4) deep hypothermic circulatory arrest (n=6) and low flow cardiopulmonary bypass (n=5). Brains were harvested following 24 h of post-cardiopulmonary bypass recovery. Cerebral cortical watershed zones, hippocampus, basal ganglia, thalamus, cerebellum, mesencephalon, pons and medulla were evaluated using hematoxylin and eosin staining. A section of ischemic cortex was evaluated by immunohistochemistry with rabbit polyclonal antibodies against phosphorylated extracellular regulated kinase 1/2. Compared to cardiopulmonary bypass controls, the deep hypothermic circulatory arrest and low flow cardiopulmonary bypass piglets exhibited diffuse ischemic changes with overlapping severity and distribution. Significant neuronal damage occurred in the frontal watershed zones and basal ganglia of the deep hypothermic circulatory arrest group (P<0.05). No detectable phosphorylated extracellular regulated kinase 1/2 immunoreactivity was found in the cardiopulmonary bypass controls; however, ERK 1/2 immunoreactivity was present in the cerebral vascular endothelium of the deep hypothermic circulatory arrest and low flow cardiopulmonary bypass groups. Our results indicate that phosphorylated

Effect of desipramine on spontaneous activity of hippocampal CA1 neuron after transient cerebral ischemia in rats.

PubMed

Zhu, Z T; Zhang, X X; Liu, J; Jin, G Z

1996-01-01

To study the spontaneous firing of CA1 neurons in rat hippocampus after transient cerebral ischemia and the effect of desipramine (Des) on the post-ischemic electric activity of CA1 neurons. Single-unit extracellular recordings were performed in rats on d 3 after 10 min of cerebral ischemia by occlusion of 4 arteries. Des and saline were injected into a tail vein. The histological changes of CA1 neurons was assessed by the neuronal density of the CA1 sector. The spontaneous firing rate of CA1 neurons on d 3 after ischemia was enhanced in comparison with the control value. Des (0.2 and 0.4 mg.kg-1, i.v., n = 5 & 6, respectively) reduced dose-dependently the increase of firing rate with maximal inhibition by 6 min (58% & 85%) to 9 min (69% & 94%) (vs vehicle group, P < 0.01). About 50% cells in CA1 region showed necrotic changes. Des antagonized the hyperexcitability of CA1 neurons after cerebral ischemia.

In situ targeting of dendritic cells sets tolerogenic environment and ameliorates CD4+ T-cell response in the postischemic liver.

PubMed

Funken, Dominik; Ishikawa-Ankerhold, Hellen; Uhl, Bernd; Lerchenberger, Maximilian; Rentsch, Markus; Mayr, Doris; Massberg, Steffen; Werner, Jens; Khandoga, Andrej

2017-11-01

CD4 + T cells recruited to the liver play a key role in the pathogenesis of ischemia/reperfusion (I/R) injury. The mechanism of their activation during alloantigen-independent I/R is not completely understood. We hypothesized that liver-resident dendritic cells (DCs) interact with CD4 + T cells in the postischemic liver and that modulation of DCs or T-cell-DC interactions attenuates liver inflammation. In mice, warm hepatic I/R (90/120-240 min) was induced. Tolerogenic DCs were generated in situ by pretreatment of animals with the vitamin D analog paricalcitol. A mAb-CD44 was used for blockade of CD4 + T-cell-DC interactions. As shown by 2-photon in vivo microscopy as well as confocal microscopy, CD4 + T cells were closely colocalized with DCs in the postischemic liver. Pretreatment with paricalcitol attenuated I/R-induced maturation of DCs (flow cytometry), CD4 + T-cell recruitment into the liver (intravital microscopy), and hepatocellular/microvascular damage (intravital microscopy, alanine aminotransferase/aspartate aminotransferase, histology). However, interruption of T-cell-DC interaction increased proinflammatory DC maturation and even enhanced tissue damage. Simultaneous treatment with an anti-CD44mAb completely abolished the beneficial effect of paricalcitol on T-cell migration and tissue injury. Our study demonstrates for the first time that hepatic DCs interact with CD4 + T cells in the postischemic liver in vivo ; modulation of DCs and/or generation of tolerogenic DCs attenuates intrahepatic CD4 + T-cell recruitment and reduces I/R injury; and interruption of CD44-dependent CD4 + T-cell-DC interactions enhances tissue injury by preventing the modulatory effect of hepatic DCs on T cells, especially type 1 T helper effector cells. Thus, hepatic DCs are strongly involved in the promotion of CD4 + T-cell-dependent postischemic liver inflammation.-Funken, D., Ishikawa-Ankerhold, H., Uhl, B., Lerchenberger, M., Rentsch, M., Mayr, D., Massberg, S., Werner, J

Chronic hyperperfusion and angiogenesis follow subacute hypoperfusion in the thalamus of rats with focal cerebral ischemia

PubMed Central

Hayward, Nick MEA; Yanev, Pavel; Haapasalo, Annakaisa; Miettinen, Riitta; Hiltunen, Mikko; Gröhn, Olli; Jolkkonen, Jukka

2011-01-01

Cerebral blood flow (CBF) is disrupted after focal ischemia in rats. We examined long-term hemodynamic and cerebrovascular changes in the rat thalamus after focal cerebral ischemia. Cerebral blood flow quantified by arterial spin labeling magnetic resonance imaging was decreased in the ipsilateral and contralateral thalamus 2 days after cerebral ischemia. Partial thalamic CBF recovery occurred by day 7, then the ipsilateral thalamus was chronically hyperperfused at 30 days and 3 months compared with its contralateral side. This contrasted with permanent hypoperfusion in the ipsilateral cortex. Angiogenesis was indicated by endothelial cell (RECA-1) immunohistochemistry that showed increased blood vessel branching in the ipsilateral thalamus at the end of the 3-month follow-up. Only transient thalamic IgG extravasation was observed, indicating that the blood–brain barrier was intact after day 2. Angiogenesis was preceded by transiently altered expression levels of cadherin family adhesion molecules, cadherin-7, protocadherin-1, and protocadherin-17. In conclusion, thalamic pathology after focal cerebral ischemia involved long-term hemodynamic changes and angiogenesis preceded by altered expression of vascular adhesion factors. Postischemic angiogenesis in the thalamus represents a novel type of remote plasticity, which may support removal of necrotic brain tissue and aid functional recovery. PMID:21081957

Reparative neurogenesis after cerebral ischemia: Clinical application prospects

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

Khodanovich, M. Yu., E-mail: khodanovich@mail.tsu.ru

At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die beforemore » reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.« less

Postischemic revascularization: from cellular and molecular mechanisms to clinical applications.

PubMed

Silvestre, Jean-Sébastien; Smadja, David M; Lévy, Bernard I

2013-10-01

After the onset of ischemia, cardiac or skeletal muscle undergoes a continuum of molecular, cellular, and extracellular responses that determine the function and the remodeling of the ischemic tissue. Hypoxia-related pathways, immunoinflammatory balance, circulating or local vascular progenitor cells, as well as changes in hemodynamical forces within vascular wall trigger all the processes regulating vascular homeostasis, including vasculogenesis, angiogenesis, arteriogenesis, and collateral growth, which act in concert to establish a functional vascular network in ischemic zones. In patients with ischemic diseases, most of the cellular (mainly those involving bone marrow-derived cells and local stem/progenitor cells) and molecular mechanisms involved in the activation of vessel growth and vascular remodeling are markedly impaired by the deleterious microenvironment characterized by fibrosis, inflammation, hypoperfusion, and inhibition of endogenous angiogenic and regenerative programs. Furthermore, cardiovascular risk factors, including diabetes, hypercholesterolemia, hypertension, diabetes, and aging, constitute a deleterious macroenvironment that participates to the abrogation of postischemic revascularization and tissue regeneration observed in these patient populations. Thus stimulation of vessel growth and/or remodeling has emerged as a new therapeutic option in patients with ischemic diseases. Many strategies of therapeutic revascularization, based on the administration of growth factors or stem/progenitor cells from diverse sources, have been proposed and are currently tested in patients with peripheral arterial disease or cardiac diseases. This review provides an overview from our current knowledge regarding molecular and cellular mechanisms involved in postischemic revascularization, as well as advances in the clinical application of such strategies of therapeutic revascularization.

Heme Oxygenase-1 Gene Therapy Provides Cardioprotection Via Control of Post-Ischemic Inflammation: An Experimental Study in a Pre-Clinical Pig Model.

PubMed

Hinkel, Rabea; Lange, Philipp; Petersen, Björn; Gottlieb, Elena; Ng, Judy King Man; Finger, Stefanie; Horstkotte, Jan; Lee, Seungmin; Thormann, Michael; Knorr, Maike; El-Aouni, Chiraz; Boekstegers, Peter; Reichart, Bruno; Wenzel, Philip; Niemann, Heiner; Kupatt, Christian

2015-07-14

Heme oxygenase-1 (HO-1) is an inducible stress-responsive enzyme converting heme to bilirubin, carbon monoxide, and free iron, which exerts anti-inflammatory and antiapoptotic effects. Although efficient cardioprotection after HO-1 overexpression has been reported in rodents, its role in attenuating post-ischemic inflammation is unclear. This study assessed the efficacy of recombinant adenoassociated virus (rAAV)-encoding human heme oxygenase-1 (hHO-1) in attenuating post-ischemic inflammation in a murine and a porcine ischemia/reperfusion model. Murine ischemia was induced by 45 min of left anterior descending occlusion, followed by 24 h of reperfusion and functional as well as fluorescent-activated cell sorting analysis. Porcine hearts were subjected to 60 min of ischemia and 24h of reperfusion before hemodynamic and histologic analyses were performed. Human microvascular endothelial cells transfected with hHO-1 displayed an attenuated interleukin-6 and intercellular adhesion molecule 1 expression, resulting in reduced monocytic THP-1 cell recruitment in vitro. In murine left anterior descending occlusion and reperfusion, the post-ischemic influx of CD45(+) leukocytes, Ly-6G(+) neutrophils, and Ly-6C(high) monocytes was further exacerbated in HO-1-deficient hearts and reversed by rAAV.hHO-1 treatment. Conversely, in our porcine model of ischemia, the post-ischemic influx of myeloperoxidase-positive neutrophils and CD14(+) monocytes was reduced by 49% and 87% after rAAV.hHO-1 transduction, similar to hHO-1 transgenic pigs. Functionally, rAAV.hHO-1 and hHO-1 transgenic left ventricles displayed a smaller loss of ejection fraction than control animals. Whereas HO-1 deficiency exacerbates post-ischemic cardiac inflammation in mice, hHO-1 gene therapy attenuates inflammation after ischemia and reperfusion in murine and porcine hearts. Regional hHO-1 gene therapy provides cardioprotection in a pre-clinical porcine ischemia/reperfusion model. Copyright © 2015 American

Plasmin Inhibitors Prevent Leukocyte Accumulation and Remodeling Events in the Postischemic Microvasculature

PubMed Central

Reichel, Christoph A.; Lerchenberger, Max; Uhl, Bernd; Rehberg, Markus; Berberich, Nina; Zahler, Stefan; Wymann, Matthias P.; Krombach, Fritz

2011-01-01

Clinical trials revealed beneficial effects of the broad-spectrum serine protease inhibitor aprotinin on the prevention of ischemia-reperfusion (I/R) injury. The underlying mechanisms remained largely unclear. Using in vivo microscopy on the cremaster muscle of male C57BL/6 mice, aprotinin as well as inhibitors of the serine protease plasmin including tranexamic acid and ε-aminocaproic acid were found to significantly diminish I/R-elicited intravascular firm adherence and (subsequent) transmigration of neutrophils. Remodeling of collagen IV within the postischemic perivenular basement membrane was almost completely abrogated in animals treated with plasmin inhibitors or aprotinin. In separate experiments, incubation with plasmin did not directly activate neutrophils. Extravascular, but not intravascular administration of plasmin caused a dose-dependent increase in numbers of firmly adherent and transmigrated neutrophils. Blockade of mast cell activation as well as inhibition of leukotriene synthesis or antagonism of the platelet-activating-factor receptor significantly reduced plasmin-dependent neutrophil responses. In conclusion, our data suggest that extravasated plasmin(ogen) mediates neutrophil recruitment in vivo via activation of perivascular mast cells and secondary generation of lipid mediators. Aprotinin as well as the plasmin inhibitors tranexamic acid and ε-aminocaproic acid interfere with this inflammatory cascade and effectively prevent postischemic neutrophil responses as well as remodeling events within the vessel wall. PMID:21364954

Hippocampal arterial cerebral blood volume in early psychosis

PubMed Central

Talati, Pratik; Rane, Swati; Donahue, Manus J.; Heckers, Stephan

2016-01-01

Recent studies of patients in the early stage of psychosis have revealed increased cerebral blood volume (CBV) in specific subfields of the anterior hippocampus. These studies required injection of a contrast agent to measure steady state CBV. Here we used a novel, non-invasive method, inflow-based-vascular-space-occupancy with dynamic subtraction (iVASO-DS), to measure the arterial component of CBV (aCBV) in a single slice of the hippocampus. Based on evidence from contrast-enhanced CBV studies, we hypothesized increased aCBV in the anterior hippocampus in early psychosis. We used 3T MRI to generate iVASO-derived aCBV maps in 17 medicated patients (average duration of illness = 7.6 months) and 25 matched controls. We did not find hemispheric or regional group differences in hippocampal aCBV. The limited spatial resolution of the iVASO-DS method did not allow us to test for aCBV differences in specific subfields of the hippocampus. Future studies should investigate venous and arterial CBV changes in the hippocampus of early psychosis patients. PMID:27644028

Role of calcium in the constriction of isolated cerebral arteries

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

Wendling, W.W.

1987-01-01

Calcium entry blockers (CEB) have been used in the experimental treatment or prevention of many cerebrovascular disorders including stroke, post-ischemic hypoperfusion after cardiac arrest, cerebral vasospasm after subarachnoid hemorrhage, and migraine headache. However, the mechanism of action of these drugs on the cerebral circulation is poorly understood. This study examined the effects of calcium antagonists, Ca/sup 2 +/-deficient solutions, and vasocostrictors on cerebrovascular tone and /sup 45/Ca fluxes, to determine the role of calcium in cerebral arterial constriction. A Scatchard plot of /sup 45/Ca binding to BMCA showed that Ca/sup 2 +/ was bound at either low or high affinitymore » binding sties. The four vasoconstrictors (potassium, serotonin, PGF/sub 2 ..cap alpha../, or SQ-26,655) each increased low affinity /sup 45/Ca uptake into BMCA. The results demonstrate that: (1) Potassium and serotonin constrict BMCA mainly by promoting Ca/sup 2 +/ influx through CEB-sensitive channels; (2) PGF/sub 2 ..cap alpha../ and SQ-26,655 constrict BMCA in part by promoting Ca/sup 2 +/ influx through CEB-sensitive channels, and in part by releasing Ca/sup 2 +/ from depletable internal stores; (3) The major action of CEB on BMCA is to block vasoconstrictor-induced Ca/sup 2 +/ uptake through both potential-operated (K/sup +/-stimulated) and receptor-operated channels.« less

Role of nitric oxide synthases in early blood-brain barrier disruption following transient focal cerebral ischemia.

PubMed

Jiang, Zheng; Li, Chun; Arrick, Denise M; Yang, Shu; Baluna, Alexandra E; Sun, Hong

2014-01-01

The role of nitric oxide synthases (NOSs) in early blood-brain barrier (BBB) disruption was determined using a new mouse model of transient focal cerebral ischemia. Ischemia was induced by ligating the middle cerebral artery (MCA) at its M2 segment and reperfusion was induced by releasing the ligation. The diameter alteration of the MCA, arterial anastomoses and collateral arteries were imaged and measured in real time. BBB disruption was assessed by Evans Blue (EB) and sodium fluorescein (Na-F) extravasation at 3 hours of reperfusion. The reperfusion produced an extensive vasodilation and a sustained hyperemia. Although expression of NOSs was not altered at 3 hours of reperfusion, L-NAME (a non-specific NOS inhibitor) abolished reperfusion-induced vasodilation/hyperemia and significantly reduced EB and Na-F extravasation. L-NIO (an endothelial NOS (eNOS) inhibitor) significantly attenuated cerebral vasodilation but not BBB disruption, whereas L-NPA and 7-NI (neuronal NOS (nNOS) inhibitors) significantly reduced BBB disruption but not cerebral vasodilation. In contrast, aminoguanidine (AG) (an inducible NOS (iNOS) inhibitor) had less effect on either cerebral vasodilation or BBB disruption. On the other hand, papaverine (PV) not only increased the vasodilation/hyperemia but also significantly reduced BBB disruption. Combined treatment with L-NAME and PV preserved the vasodilation/hyperemia and significantly reduced BBB disruption. Our findings suggest that nNOS may play a major role in early BBB disruption following transient focal cerebral ischemia via a hyperemia-independent mechanism.

Kynurenine 3-mono-oxygenase inhibitors attenuate post-ischemic neuronal death in organotypic hippocampal slice cultures.

PubMed

Carpenedo, Raffaella; Meli, Elena; Peruginelli, Fiamma; Pellegrini-Giampietro, Domenico E; Moroni, Flavio

2002-09-01

Kynurenine 3-mono-oxygenase (KMO) inhibitors reduce 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN) neosynthesis and facilitate kynurenine metabolism towards kynurenic acid (KYNA) formation. They also reduce tissue damage in models of focal or transient global cerebral ischemia in vivo. We used organotypic hippocampal slice cultures exposed to oxygen and glucose deprivation (OGD) to investigate KMO mechanism(s) of neuroprotective activity. Exposure of the slices to 30 min of OGD caused CA1 pyramidal cell death and significantly decreased the amount of KYNA released in the incubation medium. The KMO inhibitors (m-nitrobenzoyl)-alanine (30-100 micro m) or 3,4-dimethoxy-[-N-4-(nitrophenyl)thiazol-2yl]-benzenesulfonamide (1-10 micro m) reduced post-ischemic neuronal death and increased KYNA concentrations in slice incubation media. The maximal concentration of KYNA detected in the incubation media of slices treated with KMO inhibitors was approximately 50 nm and was too low to efficiently interact with alpha7 nicotinic acetylcholine receptors or with the glycineb site of N-methyl-d-aspartate (NMDA) receptors. On the other hand, the addition of either 3-HK or QUIN (1-10 micro m) to OGD-exposed hippocampal slices prevented the neuroprotective activity of KMO inhibitors. Our results suggest that KMO inhibitors reduce the neuronal death found in the CA1 region of organotypic hippocampal slices exposed to 30 min of OGD by decreasing the local synthesis of 3-HK and QUIN.

Immunohistochemical Markers of Neural Progenitor Cells in the Early Embryonic Human Cerebral Cortex

PubMed Central

Vinci, L.; Ravarino, A.; Fanos, V.; Naccarato, A.G.; Senes, G.; Gerosa, C.; Bevilacqua, G.; Faa, G.; Ambu, R.

2016-01-01

The development of the human central nervous system represents a delicate moment of embryogenesis. The purpose of this study was to analyze the expression of multiple immunohistochemical markers in the stem/progenitor cells in the human cerebral cortex during the early phases of development. To this end, samples from cerebral cortex were obtained from 4 human embryos of 11 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained with several markers including GFAP, WT1, Nestin, Vimentin, CD117, S100B, Sox2, PAX2, PAX5, Tβ4, Neurofilament, CD44, CD133, Synaptophysin and Cyclin D1. Our study shows the ability of the different immunohistochemical markers to evidence different zones of the developing human cerebral cortex, allowing the identification of the multiple stages of differentiation of neuronal and glial precursors. Three important markers of radial glial cells are evidenced in this early gestational age: Vimentin, Nestin and WT1. Sox2 was expressed by the stem/progenitor cells of the ventricular zone, whereas the postmitotic neurons of the cortical plate were immunostained by PAX2 and NSE. Future studies are needed to test other important stem/progenitor cells markers and to better analyze differences in the immunohistochemical expression of these markers during gestation. PMID:26972711

Advanced fiber tracking in early acquired brain injury causing cerebral palsy.

PubMed

Lennartsson, F; Holmström, L; Eliasson, A-C; Flodmark, O; Forssberg, H; Tournier, J-D; Vollmer, B

2015-01-01

Diffusion-weighted MR imaging and fiber tractography can be used to investigate alterations in white matter tracts in patients with early acquired brain lesions and cerebral palsy. Most existing studies have used diffusion tensor tractography, which is limited in areas of complex fiber structures or pathologic processes. We explored a combined normalization and probabilistic fiber-tracking method for more realistic fiber tractography in this patient group. This cross-sectional study included 17 children with unilateral cerebral palsy and 24 typically developing controls. DWI data were collected at 1.5T (45 directions, b=1000 s/mm(2)). Regions of interest were defined on a study-specific fractional anisotropy template and mapped onto subjects for fiber tracking. Probabilistic fiber tracking of the corticospinal tract and thalamic projections to the somatosensory cortex was performed by using constrained spherical deconvolution. Tracts were qualitatively assessed, and DTI parameters were extracted close to and distant from lesions and compared between groups. The corticospinal tract and thalamic projections to the somatosensory cortex were realistically reconstructed in both groups. Structural changes to tracts were seen in the cerebral palsy group and included splits, dislocations, compaction of the tracts, or failure to delineate the tract and were associated with underlying pathology seen on conventional MR imaging. Comparisons of DTI parameters indicated primary and secondary neurodegeneration along the corticospinal tract. Corticospinal tract and thalamic projections to the somatosensory cortex showed dissimilarities in both structural changes and DTI parameters. Our proposed method offers a sensitive means to explore alterations in WM tracts to further understand pathophysiologic changes following early acquired brain injury. © 2015 by American Journal of Neuroradiology.

Posttranslational modulation of FoxO1 contributes to cardiac remodeling in post-ischemic heart failure.

PubMed

Kappel, Ben Arpad; Stöhr, Robert; De Angelis, Lorenzo; Mavilio, Maria; Menghini, Rossella; Federici, Massimo

2016-06-01

Forkhead box protein O1 (FoxO1) plays a key role in energy homeostasis, stress response and autophagy and is dysregulated in diabetes and ischemia. We investigated cardiac FoxO1 expression and posttranstranslational modifications after myocardial infarction (MI) and further tested if active posttranstranslational modulation of FoxO1 can alter cardiac remodeling in postischemic heart failure. Non-diabetic and diabetic C57BL/6 mice were subjected to MI by ligation of left anterior descending artery. In selected experiments we combined this model with intramyocardial injection of adenovirus expressing different isoforms of FoxO1. We used Millar catheter, histology, Western blot and metabolomics for further analyses. We show that after MI total cardiac FoxO1 is downregulated and partly recovers after 7 days. This downregulation is accompanied by fundamental posttranslational modifications of FoxO1, particularly acetylation. Adenovirus experiments revealed smaller infarction size and improved heart function in mice expressing a constitutively deacetylated variant of FoxO1 compared to a wild type variant of FoxO1 in both non-diabetic (MI size: -13.4 ± 3.5%; LVDP: +29.1 ± 9.4  mmHg; p < 0.05) and diabetic mice (MI size: -17.6 ± 3.7%; LVDP: +10.9 ± 3.6  mmHg; p < 0.05). Metabolomics analyses showed alterations in metabolites connected to muscle breakdown, collagen/elastin and energy metabolism between the two groups. First, our results demonstrate that myocardial ischemia is associated with downregulation and posttranslational modification of cardiac FoxO1. Second, we show in a mouse model of postischemic heart failure that posttranslational modulation of FoxO1 alters heart function involving collagen and protein metabolism. Therefore, posttranslational modifications of FoxO1 could be an option to target remodeling processes in postischemic heart failure. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Post-acute delivery of memantine promotes post-ischemic neurological recovery, peri-infarct tissue remodeling, and contralesional brain plasticity.

PubMed

Wang, Ya-Chao; Sanchez-Mendoza, Eduardo H; Doeppner, Thorsten R; Hermann, Dirk M

2017-03-01

The NMDA antagonist memantine preferentially inhibits extrasynaptic NMDA receptors, which are overactivated upon stroke and thought to disturb neuroplasticity. We hypothesized that memantine enhances post-ischemic neurological recovery, brain remodeling, and plasticity. C57BL6/j mice were exposed to intraluminal middle cerebral artery occlusion. Starting 72 hours post-stroke, vehicle or memantine (4 or 20 mg/kg/day) were subcutaneously delivered over 28 days. Neurological recovery, perilesional tissue remodeling and contralesional pyramidal tract plasticity were evaluated over 49 days. Memantine, delivered at 20 but not 4 mg/kg/day, persistently improved motor-coordination and spatial memory. Secondary striatal atrophy was reduced by memantine. This delayed neuroprotection was associated with reduced astrogliosis and increased capillary formation around the infarct rim. Concentrations of BDNF, GDNF, and VEGF were bilaterally elevated by memantine in striatum and cortex. Anterograde tract tracing studies revealed that memantine increased contralesional corticorubral sprouting across the midline in direction to the ipsilesional red nucleus. In the contralesional motor cortex, the NMDA receptor subunit GluN2B, which is predominantly expressed in extrasynaptic NMDA receptors, was transiently reduced by memantine after 14 days, whereas GluN2A and PSD-95, which preferentially co-localize with synaptic NMDA receptors, were increased after 28 days. Our data suggest the utility of memantine for enhancing post-acute stroke recovery.

Post-acute delivery of memantine promotes post-ischemic neurological recovery, peri-infarct tissue remodeling, and contralesional brain plasticity

PubMed Central

Wang, Ya-chao; Sanchez-Mendoza, Eduardo H; Doeppner, Thorsten R

2016-01-01

The NMDA antagonist memantine preferentially inhibits extrasynaptic NMDA receptors, which are overactivated upon stroke and thought to disturb neuroplasticity. We hypothesized that memantine enhances post-ischemic neurological recovery, brain remodeling, and plasticity. C57BL6/j mice were exposed to intraluminal middle cerebral artery occlusion. Starting 72 hours post-stroke, vehicle or memantine (4 or 20 mg/kg/day) were subcutaneously delivered over 28 days. Neurological recovery, perilesional tissue remodeling and contralesional pyramidal tract plasticity were evaluated over 49 days. Memantine, delivered at 20 but not 4 mg/kg/day, persistently improved motor-coordination and spatial memory. Secondary striatal atrophy was reduced by memantine. This delayed neuroprotection was associated with reduced astrogliosis and increased capillary formation around the infarct rim. Concentrations of BDNF, GDNF, and VEGF were bilaterally elevated by memantine in striatum and cortex. Anterograde tract tracing studies revealed that memantine increased contralesional corticorubral sprouting across the midline in direction to the ipsilesional red nucleus. In the contralesional motor cortex, the NMDA receptor subunit GluN2B, which is predominantly expressed in extrasynaptic NMDA receptors, was transiently reduced by memantine after 14 days, whereas GluN2A and PSD-95, which preferentially co-localize with synaptic NMDA receptors, were increased after 28 days. Our data suggest the utility of memantine for enhancing post-acute stroke recovery. PMID:27170698

Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion

PubMed Central

Ma, Jing; Zhang, Jing; Hou, Wei Wei; Wu, Xiao Hua; Liao, Ru Jia; Chen, Ying; Wang, Zhe; Zhang, Xiang Nan; Zhang, Li San; Zhou, Yu Dong; Chen, Zhong; Hu, Wei Wei

2015-01-01

Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion develops with progressive white matter and cognitive impairments, yet no effective therapy is available. We investigated the temporal effects of minocycline on an experimental SIVD exerted by right unilateral common carotid arteries occlusion (rUCCAO). Minocycline treated at the early stage (day 0–3), but not the late stage after rUCCAO (day 4–32) alleviated the white matter and cognitive impairments, and promoted remyelination. The actions of minocycline may not involve the inhibition of microglia activation, based on the effects after the application of a microglial activation inhibitor, macrophage migration inhibitory factor, and co-treatment with lipopolysaccharides. Furthermore, minocycline treatment at the early stage promoted the proliferation of oligodendrocyte progenitor cells (OPCs) in subventricular zone, increased OPC number and alleviated apoptosis of mature oligodendrocytes in white matter. In vitro, minocycline promoted OPC proliferation and increased the percentage of OPCs in S and G2/M phases. We provided direct evidence that early treatment is critical for minocycline to alleviate white matter and cognitive impairments after chronic cerebral hypoperfusion, which may be due to its robust effects on OPC proliferation and mature oligodendrocyte loss. So, early therapeutic time window may be crucial for its application in SIVD. PMID:26174710

Protective Mechanism of STAT3-siRNA on Cerebral Ischemia Injury

NASA Astrophysics Data System (ADS)

He, Jinting; Yang, Le; Liang, Wenzhao

2018-01-01

Nerve cells in ischemic brain injury will occur a series of complex signal transduction pathway changes and produce the corresponding biological function, thus affecting the central nervous system functionally different cells in the ischemic brain injury metabolism, division, Differentiation and death process, while changes in signal pathways also play an important role in the repair process of the post-ischemic nervous system. JAK/STAT pathway and vascular lesions have some relevance, but its exact mechanism after cerebral ischemia is not yet fully understood. This study is intended to further explore the JAK / STAT pathway in the functional site of STAT3 in neuronal ischemia Hypoxic injury and related molecular mechanisms, targeting these targets design intervention strategies to block the signal pathway, in order to provide a theoretical basis for the treatment of ischemic brain damage in this pathway.

Interleukin-6 mediates enhanced thrombus development in cerebral arterioles following a brief period of focal brain ischemia

PubMed Central

Tang, Ya Hui; Vital, Shantel; Russell, Janice; Seifert, Hilary; Granger, D. Neil

2015-01-01

Objective The cerebral microvasculature is rendered more vulnerable to thrombus formation following a brief (5.0 min) period of focal ischemia. This study examined the contribution of interleukin-6 (IL-6), a neuroprotective and prothrombotic cytokine produced by the brain, to transient ischemia-induced thrombosis in cerebral arterioles. Approach & results The middle cerebral artery of C57BL/6J mice was occluded for 5 minutes, followed by 24 hrs of reperfusion (MCAo/R). Intravital fluorescence microscopy was used to monitor thrombus development in cerebral arterioles induced by light/dye photoactivation. Thrombosis was quantified as the time of onset of platelet aggregation on the vessel wall and the time for complete blood flow cessation. MCAo/R in wild type (WT) mice yielded an acceleration of thrombus formation that was accompanied by increased IL-6 levels in plasma and in post-ischemic brain tissue. The exaggerated thrombosis response to MCAo/R was blunted in WT mice receiving an IL-6 receptor-blocking antibody and in IL-6 deficient (IL-6−/−) mice. Bone marrow chimeras, produced by transplanting IL-6−/− marrow into WT recipients, did not exhibit protection against MCAo/R-induced thrombosis. Conclusions The increased vulnerability of the cerebral vasculature to thrombus development after MCAo/R is mediated by IL-6, which is likely derived from brain cells rather than circulating blood cells. These findings suggest that anti-IL-6 therapy may reduce the likelihood of cerebral thrombus development after a transient ischemic attack. PMID:26054883

[The Battelle developmental inventory screening test for early detection of developmental disorders in cerebral palsy].

PubMed

Moraleda-Barreno, E; Romero-López, M; Cayetano-Menéndez, M J

2011-12-01

Cerebral palsy is usually associated with motor, cognitive, and language deficits, and with other disorders that cause disability in daily living skills, personal independence, social interaction and academic activities. Early detection of these deficits in the clinical setting is essential to anticipate and provide the child with the necessary support for adapting to the environment in all possible areas. The main objective of this study is to demonstrate that these deficits can be detected at an early age and comprehensively through the use of a brief development scale. We studied 100 children between 4 and 70 months old, half of them with cerebral palsy and the other half without any disorder. All subjects were evaluated using the Battelle Developmental Inventory screening test. We compared the developmental quotients in both groups and between the subjects with different motor impairments, using a simple prospective ex post facto design. The test detected statistically significant differences between the clinical group and the control group at all age levels. Statistically significant differences were also found between tetraplegia and other motor disorders. There were no differences by gender. The deficit in development associated with cerebral palsy can be quantified at early ages through the use of a brief development scale, thus we propose that the systematic implementation of protocols with this screening tool would be helpful for treatment and early intervention. This would also help in anticipating and establishing the means for the multidisciplinary actions required, and could provide guidance to other health professionals, to provide adequate school, social, and family support,. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Cerebral oximetry during infant cardiac surgery: evaluation and relationship to early postoperative outcome.

PubMed

Kussman, Barry D; Wypij, David; DiNardo, James A; Newburger, Jane W; Mayer, John E; del Nido, Pedro J; Bacha, Emile A; Pigula, Frank; McGrath, Ellen; Laussen, Peter C

2009-04-01

We examined changes in cerebral oxygen saturation during infant heart surgery and its relationship to anatomic diagnosis and early outcome. Regional cerebral oxygen saturation (rSO(2)) was measured by near-infrared spectroscopy in 104 infants undergoing biventricular repair without aortic arch obstruction as part of a randomized trial of hemodilution to a hematocrit of 25% vs 35%. Before cardiopulmonary bypass (CPB), infants with tetralogy of Fallot had higher rSO(2) values compared to those with D-transposition of the great arteries (D-TGA) or ventricular septal defect (P < 0.001). During CPB cooling, low flow, and at the termination of CPB, D-TGA subjects had the highest rSO(2) values (P < 0.001). There were no significant associations between intraoperative rSO(2) and early postoperative outcomes after adjustment for diagnosis. In 39 D-TGA subjects with > or =5 min of deep hypothermic circulatory arrest (DHCA), there was no correlation between the rSO(2) (91% +/- 6%) or hematocrit (29.2% +/- 5.5%) at the onset of arrest and the rate of decline in rSO(2) during arrest. Intraoperative rSO(2) varies according to anatomic diagnosis but accounts for very little of the variance in early outcome. As measured by frontal near-infrared spectroscopy, higher levels of hematocrit and current perfusion techniques appear to provide an adequate oxygen reservoir prior to relatively short periods of DHCA.

γδ T cells as early sensors of tissue damage and mediators of secondary neurodegeneration

PubMed Central

Gelderblom, Mathias; Arunachalam, Priyadharshini; Magnus, Tim

2014-01-01

Spontaneous or medically induced reperfusion occurs in up to 70% of patients within 24 h after cerebral ischemia. Reperfusion of ischemic brain tissue can augment the inflammatory response that causes additional injury. Recently, T cells have been shown to be an essential part of the post-ischemic tissue damage, and especially IL-17 secreting T cells have been implicated in the pathogenesis of a variety of inflammatory reactions in the brain. After stroke, it seems that the innate γδ T cells are the main IL-17 producing cells and that the γδ T cell activation constitutes an early and mainly damaging immune response in stroke. Effector mechanism of γδ T cell derived IL-17 in the ischemic brain include the induction of metalloproteinases, proinflammatory cytokines and neutrophil attracting chemokines, leading to a further amplification of the detrimental inflammatory response. In this review, we will give an overview on the concepts of γδ T cells and IL-17 in stroke pathophysiology and on their potential importance for human disease conditions. PMID:25414640

Severe subarachnoid hemorrhage associated with cerebral venous thrombosis in early pregnancy: a case report.

PubMed

Yamamoto, Junkoh; Kakeda, Shingo; Takahashi, Mayu; Idei, Masaru; Nakano, Yoshiteru; Soejima, Yoshiteru; Saito, Takeshi; Akiba, Daisuke; Shibata, Eiji; Korogi, Yukunori; Nishizawa, Shigeru

2013-12-01

Cerebral venous thrombosis (CVT) rarely induces subarachnoid hemorrhage (SAH). During late pregnancy and puerperium, CVT is an uncommon but important cause of stroke. However, severe SAH resulting from CVT is extremely rare during early pregnancy. We report on a rare case of severe SAH due to CVT, and discuss the potential pitfalls of CVT diagnosis in early pregnancy. A 32-year-old pregnant woman (9th week of pregnancy) presented with slight head dullness. Initial magnetic resonance imaging (MRI) revealed focal, abnormal signal intensity in the left thalamus. Nine days later, the patient developed a generalized seizure and severe SAH was detected with computed tomography (CT) scan. MRI and cerebral angiography revealed a completely thrombosed superior sagittal sinus, vein of Galen, straight sinus, and right transverse sinus. Transvaginal sonography indicated a missed abortion. The day after admission, the patient presented again with a progressive loss of consciousness and signs of herniation. The patient underwent emergency decompressive craniotomy, followed by intrauterine curettage. Two months later, she made an excellent recovery except for a slight visual field defect. A rare case of severe SAH due to CVT is reported, with emphasis on the potential pitfalls of CVT diagnosis in early pregnancy. Copyright © 2013 Elsevier Inc. All rights reserved.

Studies on the neuroprotective action of kynurenine mono-oxygenase inhibitors in post-ischemic brain damage.

PubMed

Moroni, Flavio; Carpenedo, Raffaella; Cozzi, Andrea; Meli, Elena; Chiarugi, Alberto; Pellegrini-Giampietro, Domenico E

2003-01-01

Kynurenine 3-mono-oxygenase (KMO) inhibitors facilitate kynurenic acid (KYNA) neosynthesis and reduce the formation of 3OH-kynurenine (3-HK) and quinolinic acid (QUIN). They also attenuate post-ischemic brain damage and decrease glutamate (Glu) content in brain extracellular spaces. To investigate KMO mechanism(s) of neuroprotection, we performed experiments in gerbils subjected to bilateral carotid occlusion and in organotypic rat hippocampal slice cultures exposed to oxygen and glucose deprivation (OGD). In gerbils, direct application of KYNA (100 nM, through reverse microdialysis in the hippocampus) completely prevented the increase in Glu output induced by transient (5 min) occlusion of the carotids. In rat hippocampal slices exposed for 30 min to OGD, KMO inhibitors (m-nitrobenzoyl)-alanine (mNBA, 30-100 microM) or 3,4-dimethoxy-[-N-4-(nitrophenyl)thiazol-2yl]-benzenesulfonamide (Ro 61-8048, 1-10 microM) reduced post-ischemic neuronal death and increased KYNA concentrations in the incubation medium. KYNA may antagonize glycineb or alpha7 nicotinic acetylcholine receptors but the concentrations in the incubation medium never reached values that could efficiently antagonize receptor function. On the contrary, 3-HK (1-10 microM) added to slices exposed to OGD in the presence of KMO inhibitors completely prevented the neuroprotective effects of the inhibitors. Our findings suggest that KMO inhibitors reduce OGD-induced pyramidal cell death by decreasing 3-HK (and possibly QUIN) synthesis.

Protective Effect of Ad-VEGF-Bone Mesenchymal Stem Cells on Cerebral Infarction.

PubMed

Chen, Bo; Zhang, Feng; Li, Qiao-Yu; Gong, Aihua; Lan, Qing

2016-01-01

To understand the mechanism of intracerebroventricular transplantation of vascular endothelial growth factor (VEGF) genemodified bone mesenchymal stem cells (BMSCs) in rats after cerebral infarction. The middle cerebral artery occlusion ischemia/reperfusion (MCAO I/R) model was established in rats using the Zea-Longa suture method. A recombinant adenovirus (Ad-VEGF) was engineered to express VEGF. The rats were divided into 3 groups. Control BMSC infected with control adenovirus (BMSC-Ad), BMSC infected by Ad-VEGF (BMSC-Ad-VEGF), and phosphate buffered saline (PBS) suspension were injected into the intracerebroventricular system of the rats in groups 1, 2 and 3 respectively, 24 hours after middle cerebral artery occlusion (MCAO). The neurological function of rats was evaluated with the modified Neurological Severity Scores (mNSS). The infarct volume of brain in rats was determined using 2,3,5-triphenyltetrazolium chloride (TTC) stain at 14 days. GFAP and pGSK3β expression of ischemic penumbra was determined using immunohistochemical method. GFAP, pAKT, AKT, and pGSK3β expressions were determined with Western blot. Functional improvement was accelerated in animals receiving BMSC-Ad, while improvement at all times between 7 days and 28 days post MCAO was significantly greater in animals transplanted with BMSC-Ad-VEGF than for other treated animals. The number of GFAP-labeled cells was prevented by post-ischemic BMSC-Ad-VEGF treatment; pMCAO activate the PI3K/AKT/GSK3β pathway to reduce reactive gliosis. Our findings demonstrate that PI3K/AKT/GSK3β pathway could reduce reactive gliosis, ameliorate neurological deficit, diminish the percentage of cerebral infarction volume in rats, and facilitate angiogenesis.

Hypoglycemia Prevents Increase in Lactic Acidosis During Reperfusion After Temporary Cerebral Ischemia in Rats

PubMed Central

Sappey-Marinier, Dominique; Chileuitt, Laureano; Weiner, Michael W.; Faden, Alan I.; Weinstein, Philip R.

2009-01-01

Sequential 31P and 1H MRS was used to measure cerebral phosphate metabolites, intracellular pH, and lactate in normoglycemic and hypoglycemic rats during 30 min of complete cerebral ischemia and 5.5 h of reperfusion. These results were correlated with brain levels of free fatty acids (FFAs), excitatory amino acids, cations, and water content at death. The lactate/N-acetyl aspartate ratio was not significantly different between groups before or during occlusion. During reperfusion, the ratio was higher in normoglycemic rats from 3 to 85 min (p≤ 0.05), and recovery time was faster in hypoglycemic rats (29 vs 45 min; p = 0.04), suggesting reduced lactate production and faster recovery of aerobic metabolism. During occlusion, significant but comparable decrease of intracellular pH occurred in each group. Intracellular pH was higher in hypoglycemic rats at 140 min and 260 min of reperfusion. Water content, Na and K+ concentrations, and FFA and excitatory amino acid levels were not significantly different between groups, but hypoglycemic rats had less depletion of levels of Mg2+ (p=0.011). These results show that hypoglycemia has a limited but potentially beneficial effect on postischemic lactic acidosis. PMID:8771092

Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling.

PubMed

Liu, Xiaobai; Wang, Zhenhua; Wang, Ping; Yu, Bo; Liu, Yunhui; Xue, Yixue

2013-07-21

It has been supposed that green tea polyphenols (GTPs) have neuroprotective effects on brain damage after brain ischemia in animal experiments. Little is known regarding GTPs' protective effects against the blood-brain barrier (BBB) disruption after ischemic stroke. We investigated the effects of GTPs on the expression of claudin-5, occludin, and ZO-1, and the corresponding cellular mechanisms involved in the early stage of cerebral ischemia. Male Wistar rats were subjected to a middle cerebral artery occlusion (MCAO) for 0, 30, 60, and 120 min. GTPs (400 mg/kg/day) or vehicle was administered by intragastric gavage twice a day for 30 days prior to MCAO. At different time points, the expression of claudin-5, occludin, ZO-1, and PKCα signaling pathway in microvessel fragments of cerebral ischemic tissue were evaluated. GTPs reduced BBB permeability at 60 min and 120 min after ischemia as compared with the vehicle group. Transmission electron microscopy also revealed that GTPs could reverse the opening of tight junction (TJ) barrier at 60 min and 120 min after MACO. The decreased mRNA and protein expression levels of claudin-5, occludin, and ZO-1 in microvessel fragments of cerebral ischemic tissue were significantly prevented by treatment with GTPs at the same time points after ischemia in rats. Furthermore, GTPs could attenuate the increase in the expression levels of PKCα mRNA and protein caused by cerebral ischemia. These results demonstrate that GTPs may act as a potential neuroprotective agent against BBB damage at the early stage of focal cerebral ischemia through the regulation of TJ and PKCα signaling.

Acute lipophilicity-dependent effect of intravascular simvastatin in the early phase of focal cerebral ischemia.

PubMed

Beretta, S; Pastori, C; Sala, G; Piazza, F; Ferrarese, C; Cattalini, A; de Curtis, M; Librizzi, L

2011-05-01

The acute effects of simvastatin lactone (lipophilic) and simvastatin acid (hydrophilic) on transient focal ischemia were assessed using the isolated guinea pig brain maintained in vitro by arterial perfusion. This new model of cerebral ischemia allows the assessment of the very early phase of the ischemic process, with the functional preservation of the vascular and neuronal compartments and the blood-brain barrier (bbb). The middle cerebral artery was transiently tied for 30 min followed by reperfusion for 60 min. Statins (nanomolar doses) were administered by intravascular continuous infusion starting 60 min before ischemia induction. Brain cortical activity and arterial vascular tone were continuously recorded. At the end of the experiment immunoreactivity for microtubule-associated protein 2 (MAP-2), expression of survival kinases (ERK and Akt) and total anti-oxidant capacity were assayed. Brains treated with simvastatin lactone showed i) reduced amplitude and delayed onset of ischemic depressions, ii) preservation of MAP-2 immunoreactivity, iii) activation of ERK signaling in the ischemic hemisphere and iv) increase in whole-brain anti-oxidant capacity. Treatment with the bbb-impermeable simvastatin acid was ineffective on the above-mentioned parameters. Vascular resistance recordings and Akt signaling were unchanged by any statin treatment. Our findings suggest that intravascular-delivered simvastatin exerts an acute lipophilicity-dependent protective effect in the early phase of cerebral ischemia. Copyright © 2011 Elsevier Ltd. All rights reserved.

Improving reconstituted HDL composition for efficient post-ischemic reduction of ischemia reperfusion injury.

PubMed

Brulhart-Meynet, Marie-Claude; Braunersreuther, Vincent; Brinck, Jonas; Montecucco, Fabrizio; Prost, Jean-Christophe; Thomas, Aurelien; Galan, Katia; Pelli, Graziano; Pedretti, Sarah; Vuilleumier, Nicolas; Mach, François; Lecour, Sandrine; James, Richard W; Frias, Miguel A

2015-01-01

New evidence shows that high density lipoproteins (HDL) have protective effects beyond their role in reverse cholesterol transport. Reconstituted HDL (rHDL) offer an attractive means of clinically exploiting these novel effects including cardioprotection against ischemia reperfusion injury (IRI). However, basic rHDL composition is limited to apolipoprotein AI (apoAI) and phospholipids; addition of bioactive compound may enhance its beneficial effects. The aim of this study was to investigate the role of rHDL in post-ischemic model, and to analyze the potential impact of sphingosine-1-phosphate (S1P) in rHDL formulations. The impact of HDL on IRI was investigated using complementary in vivo, ex vivo and in vitro IRI models. Acute post-ischemic treatment with native HDL significantly reduced infarct size and cell death in the ex vivo, isolated heart (Langendorff) model and the in vivo model (-48%, p<0.01). Treatment with rHDL of basic formulation (apoAI + phospholipids) had a non-significant impact on cell death in vitro and on the infarct size ex vivo and in vivo. In contrast, rHDL containing S1P had a highly significant, protective influence ex vivo, and in vivo (-50%, p<0.01). This impact was comparable with the effects observed with native HDL. Pro-survival signaling proteins, Akt, STAT3 and ERK1/2 were similarly activated by HDL and rHDL containing S1P both in vitro (isolated cardiomyocytes) and in vivo. HDL afford protection against IRI in a clinically relevant model (post-ischemia). rHDL is significantly protective if supplemented with S1P. The protective impact of HDL appears to target directly the cardiomyocyte.

Early superficial temporal artery to middle cerebral artery bypass in acute ischemic stroke.

PubMed

Lee, Sang-Bok; Huh, Pil-Woo; Kim, Dal-Soo; Yoo, Do-Sung; Lee, Tae-Gyu; Cho, Kyoung-Suok

2013-08-01

To evaluate the effects and safety of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis in the early stage after an acute ischemic event and the improvement of present symptoms in patients with intracranial atherosclerotic occlusive disease with stroke/stroke in progress. From 2006 to 2010, 20 patients (15 males and five females) with atherosclerotic cerebrovascular disease were treated with an STA-MCA bypass. All of the patients presented with an acute ischemic stroke or stroke in progress despite maximal medical treatment. The patients underwent an STA-MCA bypass within 7 days from symptom onset. The clinical outcome and hemodynamic study of the 20 patients were preoperatively and postoperatively investigated. A pooled analysis was performed, and the results were compared with those obtained from other delayed STA-MCA bypass studies. Among the 20 patients who underwent an early STA-MCA bypass, fourteen (70%) patients achieved a good functional outcome (mRS 0, n=3; mRS 1, n=9; mRS 2, n=2). Prior to surgery, the mean basal regional cerebral blood flow (rCBF) and cerebrovascular reserve capacity (CVR) in the symptomatic hemisphere were 37.3±4.3 ml/100 g/min and -1.68±2.9%. The mean basal rCBF and CVR had significantly increased postoperatively, and no reperfusion-induced hemorrhage had occurred. In the pooled analysis, no significant differences were observed in the clinical outcome (P=0.328) or in the incidence of postoperative complications (P=0.516) between patients who underwent an early STA-MCA bypass and in patients who underwent a delayed STA-MCA bypass in previous studies. In this study, which consisted of 20 carefully selected patients with acute ischemic stroke, an early STA-MCA bypass was safely and effectively performed, and in some cases, an early STA-MCA bypass resulted in rapid neurological improvement. An early STA-MCA bypass was beneficial in select patients who had acute ischemic stroke with imaging evidence of a small

Early Surgery for Endocarditis Complicated by Preoperative Cerebral Emboli Is Not Associated With Worsened Outcomes

PubMed Central

Sorabella, Robert A.; Han, Sang Myung; Grbic, Mark; Wu, Yeu Sanz; Takyama, Hiroo; Kurlansky, Paul; Borger, Michal A.; Argenziano, Michael; Gordon, Rachel; George, Isaac

2015-01-01

Background Valve surgery for patients presenting with infective endocarditis (IE) complicated by stroke is thought to carry elevated risk of postoperative complications. Our aim is to compare outcomes of IE patients who undergo surgery early after diagnosis of septic cerebral emboli with patients without preoperative emboli. Methods All patients undergoing surgery for left-sided IE between 1996–2013 at our institution were reviewed. Patients undergoing surgery > 14 days after embolic stroke diagnosis (n=11) and those with purely hemorrhagic lesions were excluded from analysis (n=7). In total, 308 were included in the study and stratified according to the presence (STR, n=54) or absence of a preoperative septic cerebral embolus (NoSTR, n=254). Primary outcomes of interest were development of new postoperative stroke and 30-day mortality. Results Mean time to surgical intervention from stroke onset was 6.0 ± 4.1 days. S. aureus (39% STR vs. 21% NoSTR, p = 0.004) and annular abscess at surgery (52% STR vs. 27% NoSTR, p < 0.001) were more prevalent in STR patients. There was no significant difference in 30-day mortality (9.3% STR vs. 7.1% NoSTR, p = 0.57) or rate of new postoperative stroke [5 (9.4%) STR vs. 12 (4.7%) NoSTR, p = 0.19] between groups. Additionally, there was no difference in 10-year survival between groups (log rank p = 0.74). Conclusions Early surgical intervention in patients with IE complicated by preoperative septic cerebral emboli does not lead to significantly worse postoperative outcomes. Early surgery for IE following embolic stroke warrants consideration, particularly in patients with high-risk features such as S. aureus and/or annular abscess. PMID:26116483

Progressive impairment of regional myocardial perfusion after initial restoration of postischemic blood flow.

PubMed

Ambrosio, G; Weisman, H F; Mannisi, J A; Becker, L C

1989-12-01

The "no-reflow" phenomenon, the occurrence of areas with very low flow in hearts reperfused after ischemia, is thought to be largely established at the time of reperfusion as a result of microvascular damage induced by ischemia. In the present study we sought to determine whether additional impairment of tissue perfusion might also occur during the course of reperfusion. Open-chest dogs were subjected to 90 minutes of left circumflex coronary artery occlusion and reperfused for 2 minutes (n = 7) or 3.5 hours (n = 8). Myocardial perfusion was visualized in left ventricular slices following in vivo injection of the fluorescent dye thioflavin-S just before killing. The area of impaired perfusion (absent thioflavin) averaged 9.5 +/- 3.0% of the risk region in dogs reperfused for 2 minutes, whereas it was nearly three times as large in dogs reperfused for 3.5 hours (25.9 +/- 8.2% of the risk region, p less than 0.05). Serial measurements of flow by microspheres during reperfusion demonstrated zones within the postischemic myocardium that were hyperemic 2 minutes after reperfusion, with adequate flow still present at 30 minutes, but with a subsequent marked fall in perfusion. After 3.5 hours these areas showed negligible flow (0.13 +/- 0.3 ml/min/g) and no thioflavin uptake. Tissue samples showing postischemic impairment in perfusion has received virtually no collateral flow during ischemia (less than 0.01 ml/min/g), whereas collateral flow was significantly higher in adjacent thioflavin-positive zones (0.04 +/- 0.01 ml/min/g in endocardial samples and 0.07 +/- 0.02 ml/min/g in samples from the midmyocardium, p less than 0.001 vs. thioflavin-negative areas). Areas that showed late impairment of flow invariably demonstrated contraction band necrosis, which contrasted with the pattern of coagulation necrosis observed in areas of "true" (i.e., immediate) no-reflow. Intracapillary erythrocyte stasis and marked intravascular neutrophil accumulation (to levels greater than 20

Cerebral Oximetry During Infant Cardiac Surgery: Evaluation of and Relationship to Early Postoperative Outcome

PubMed Central

Kussman, Barry D.; Wypij, David; DiNardo, James A.; Newburger, Jane W.; Mayer, John E.; del Nido, Pedro J.; Bacha, Emile A.; Pigula, Frank; McGrath, Ellen; Laussen, Peter C.

2009-01-01

Background We examined changes in cerebral oxygen saturation during infant heart surgery and its relationship to anatomic diagnosis and early outcome Methods Regional cerebral oxygen saturation (rSO2) was measured by near-infrared spectroscopy in 104 infants undergoing biventricular repair without aortic arch obstruction as part of a randomized trial of hemodilution to a hematocrit of 25% versus 35%. Results Prior to cardiopulmonary bypass (CPB), infants with tetralogy of Fallot had higher rSO2 values compared to those with D-transposition of the great arteries (D-TGA) or ventricular septal defect (P < 0.001). During CPB cooling, low flow and at the termination of CPB, D-TGA subjects had the highest rSO2 values (P < 0.001). There were no significant associations between intraoperative rSO2 and early postoperative outcomes after adjustment for diagnosis. In 39 D-TGA subjects with ≥5 minutes of deep hypothermic circulatory arrest, there was no correlation between the rSO2 (91 ± 6%) or hematocrit (29.2 ± 5.5%) at the onset of arrest and the rate of decline in rSO2 during arrest. Conclusions Intraoperative rSO2 varies according to anatomic diagnosis but accounts for very little of the variance in early outcome. As measured by frontal near-infrared spectroscopy, higher levels of hematocrit and current perfusion techniques appear to provide an adequate oxygen reservoir prior to relatively short periods of deep hypothermic circulatory arrest. PMID:19299774

[Identification of early irreversible damage area in a rat model of cerebral ischemia and reperfusion].

PubMed

Liu, S; Guo, Y

2000-02-01

To observe the early neuron ischemic damage in focal cerebral ischemia/reperfusion with histostaining methods of argyrophil III (AG III), Toludine blue(TB), and H&E, and to make out the 'separating line' between the areas of reversible and irreversible early ischemic damage. Forty-two male Wistar rats were randomly divided into the following groups: pseudo-surgical, blank-control, O2R0(occluded for 2 hours and reperfused for 0 hour), O2R0.5, O2R2, O2R4, O2R24. There were 6 rats in each group. Rats in experimental groups were suffered focal cerebral ischemia/reperfusion through a nylon suture method. After a special processor for tissue manage, the brain were coronal sectioned and stained with H&E, TB, and AG III. The area where dark neurons dwell in (ischemic core) were calculated with image analysis system. The success rate of ischemic model for this experiment is 90%. After being stained with argyrophil III method, normal neurons appear yellow or pale brown, which is hardly distinguished from the pale brown background. The ischemic neuron stained black, and has collapsed body and "corkscrew-like" axon or dentries, which were broken to some extent. The neuropil in the dark neurons dwelt area appears gray or pale black, which is apparently different from the pale brown neighborhood area. The distribution of dark neurons in cortex varies according to different layers, and has a character of columnar form. The dark neurons present as early as 2 hours ischemia without reperfusion with AG III method. AG III stain could selectively display early ischemic neurons, the area dwelt by dark neurons represent early ischemic core. Dark neuron is possibly the irreversibly damaged neuron. Identification of dark neurons could be helpful in the discrimination between early ischemic center and penumbra.

Rapamycin decreased blood-brain barrier permeability in control but not in diabetic rats in early cerebral ischemia.

PubMed

Chi, Oak Z; Kiss, Geza K; Mellender, Scott J; Liu, Xia; Weiss, Harvey R

2017-07-27

Diabetes causes functional and structural changes in blood-brain barrier (BBB). The mammalian target of rapamycin (mTOR) has been associated with glucose metabolism, diabetes, and altering BBB permeability. Since there is only a narrow therapeutic window (3h) for stroke victims, it is important to investigate BBB disruption in the early stage of cerebral ischemia. We compared the degree of BBB disruption in diabetic and in control rats at two hours of reperfusion after one hour of middle cerebral artery (MCA) occlusion with or without inhibition of mTOR. Two weeks after streptozotocin ip to induce diabetes, MCA occlusion was performed. In half of the rats, an mTOR inhibitor, rapamycin was given for 2days before MCA occlusion. After one hour of MCA occlusion and two hours of the reperfusion, the transfer coefficient (K i ) of 14 C-α-aminoisobutyric acid was determined to quantify degree of BBB disruption. Ischemia-reperfusion increased the K i in the control animals. Streptozotocin increased the K i in the ischemic-reperfused (IR-C, +22%) as well as in the contralateral cortex (CC, +40%). Rapamycin decreased the K i in the IR-C (-32%) as well as in the CC (-26%) in the control rats. However, rapamycin did not affect K i in the IR-C or in the CC in the diabetic rats. Our data demonstrated a greater BBB disruption in diabetes in the ischemic as well as non-ischemic cortex even in the early stage of cerebral ischemia-reperfusion and that acute administration of rapamycin did not significantly affect BBB permeability in diabetes. From our quantitative analysis of BBB disruption, the vulnerability of BBB in diabetes has been emphasized in the early stage of cerebral ischemia-reperfusion and a less important role of the mTOR pathway is suggested in altering BBB permeability in diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Does early communication mediate the relationship between motor ability and social function in children with cerebral palsy?

PubMed

Lipscombe, Belinda; Boyd, Roslyn N; Coleman, Andrea; Fahey, Michael; Rawicki, Barry; Whittingham, Koa

2016-01-01

Children diagnosed with neurodevelopmental conditions such as cerebral palsy (CP) are at risk of experiencing restrictions in social activities negatively impacting their subsequent social functioning. Research has identified motor and communication ability as being unique determinants of social function capabilities in children with CP, to date, no research has investigated whether communication is a mediator of the relationship between motor ability and social functioning. To investigate whether early communication ability at 24 months corrected age (ca.) mediates the relationship between early motor ability at 24 months ca. and later social development at 60 months ca. in a cohort of children diagnosed with cerebral palsy (CP). A cohort of 71 children (43 male) diagnosed with CP (GMFCS I=24, 33.8%, II=9, 12.7%, III=12, 16.9%, IV=10, 14.1%, V=16, 22.5%) were assessed at 24 and 60 months ca. Assessments included the Gross Motor Function Measure (GMFM), the Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS-DP) Infant-Toddler Checklist and the Paediatric Evaluation of Disability Inventory (PEDI). A mediation model was examined using bootstrapping. Early communication skills mediated the relationship between early motor abilities and later social functioning, b=0.24 (95% CI=0.08-0.43 and the mediation model was significant, F (2, 68)=32.77, p<0.001, R(2)=0.49. Early communication ability partially mediates the relationship between early motor ability and later social function in children with CP. This demonstrates the important role of early communication in ongoing social development. Early identification of communication delay and enriched language exposure is crucial in this population. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oxygen therapy reduces secondary hemorrhage after thrombolysis in thromboembolic cerebral ischemia.

PubMed

Sun, Li; Zhou, Wei; Mueller, Christian; Sommer, Clemens; Heiland, Sabine; Bauer, Alexander T; Marti, Hugo H; Veltkamp, Roland

2010-09-01

Hyperbaric oxygen (HBO) and normobaric hyperoxia (NBO) protect the brain parenchyma and the cerebral microcirculation against ischemia. We studied their effect on secondary hemorrhage after thrombolysis in two thromboembolic middle cerebral artery occlusion (MCAO) (tMCAO) models. Beginning 60 minutes after tMCAO with either thrombin-induced thromboemboli (TT) or calcium-induced thromboemboli (CT), spontaneously hypertensive rats (n=96) breathed either air, 100% O(2) (NBO), or 100% O(2) at 3 bar (HBO) for 1 hour. Immediately thereafter, recombinant tissue plasminogen activator (rt-PA, 9 mg/kg) was injected. Although significant reperfusion was observed after thrombolysis in TT-tMCAO, vascular occlusion persisted in CT-tMCAO. In TT-tMCAO, NBO and HBO significantly reduced diffusion-weighted imaging-magnetic resonance imaging (MRI) lesion volume and postischemic blood-brain barrier (BBB) permeability on postcontrast T1-weighted images. NBO and, significantly more potently, HBO reduced macroscopic hemorrhage on T2* MRI and on corresponding postmortem cryosections. Oxygen therapy lowered hemoglobin content and attenuated activation of matrix metalloproteinases in the ischemic hemisphere. In contrast, NBO and HBO failed to reduce infarct size in CT but both decreased BBB damage and microscopic hemorrhagic transformation. Only HBO reduced hemoglobin extravasation in the ischemic hemisphere. In conclusion, NBO and HBO decrease infarct size after thromboembolic ischemia only if recanalization is successful. As NBO and HBO also reduce postthrombolytic intracerebral hemorrhage, combining the two with thrombolysis seems promising.

Neuroprotective Effect of Antioxidants and Moderate Hypoxia as Combined Preconditioning in Cerebral Ischemia.

PubMed

Levchenkova, O S; Novikov, V E; Parfenov, E A; Kulagin, K N

2016-12-01

We studied combined effect of moderate hypoxia and compounds pQ-4, pQ-915, pQ-1032, and pQ-1104 on neurological deficit and survival of rats after bilateral ligation of common carotid arteries. Preconditioning including moderate hypoxia and treatment with compound pQ-4 produced a neuroprotective effect and increased animal survival during the early (by 51%) and late (by 33.5%) periods of modeled ischemia and reduced neurological deficit (by 50% and 41%, respectively). Moreover, this combination of preconditioning factors prevented postischemic excessive activation of free radical oxidation in brain hemispheres and blood serum.

Hyperventilation, cerebral perfusion, and syncope.

PubMed

Immink, R V; Pott, F C; Secher, N H; van Lieshout, J J

2014-04-01

This review summarizes evidence in humans for an association between hyperventilation (HV)-induced hypocapnia and a reduction in cerebral perfusion leading to syncope defined as transient loss of consciousness (TLOC). The cerebral vasculature is sensitive to changes in both the arterial carbon dioxide (PaCO2) and oxygen (PaO2) partial pressures so that hypercapnia/hypoxia increases and hypocapnia/hyperoxia reduces global cerebral blood flow. Cerebral hypoperfusion and TLOC have been associated with hypocapnia related to HV. Notwithstanding pronounced cerebrovascular effects of PaCO2 the contribution of a low PaCO2 to the early postural reduction in middle cerebral artery blood velocity is transient. HV together with postural stress does not reduce cerebral perfusion to such an extent that TLOC develops. However when HV is combined with cardiovascular stressors like cold immersion or reduced cardiac output brain perfusion becomes jeopardized. Whether, in patients with cardiovascular disease and/or defect, cerebral blood flow cerebral control HV-induced hypocapnia elicits cerebral hypoperfusion, leading to TLOC, remains to be established.

Testing the Language of German Cerebral Palsy Patients with Right Hemispheric Language Organization after Early Left Hemispheric Damage

ERIC Educational Resources Information Center

Schwilling, Eleonore; Krageloh-Mann, Ingeborg; Konietzko, Andreas; Winkler, Susanne; Lidzba, Karen

2012-01-01

Language functions are generally represented in the left cerebral hemisphere. After early (prenatally acquired or perinatally acquired) left hemispheric brain damage language functions may be salvaged by reorganization into the right hemisphere. This is different from brain lesions acquired in adulthood which normally lead to aphasia. Right…

Early control of distal internal carotid artery during carotid endarterectomy: does it reduce cerebral microemboli?

PubMed

Mommertz, G; Das, M; Langer, S; Koeppel, T A; Krings, T; Mess, W H; Schiefer, J; Jacobs, M J

2010-06-01

According to the results of the large trials on carotid endarterectomy (CEA), this type of surgery is only warranted if perioperative mortality and morbidity are kept considerably low. Less attention has been paid to methods of cerebral protection during CEA, although intraoperative transcranial Doppler (TCD) can visualise intracerebral microemboli (MES) during routine carotid dissection, although MES occur throughout the CEA, only those during dissection are related to neurological outcome. Prevention of MES by means of early control of the distal internal carotid artery dislodging from the carotid artery plaque during dissection is very likely the mechanism behind an eventual benefit from this approach. Hence, the amount of MES might serve as a surrogate parameter for the risk of periprocedural neurological events. So, the aim of the present study was to evaluate whether early control of the distal carotid artery during CEA is capable of reducing the number of MES by means of a prospective randomised trial. Twenty-eight patients (29 procedures) could be prospectively included in our study. Before surgery we randomly assigned the patients to two groups: group A (N.=12): CEA by means of early control of the distal internal carotid artery; group B (N.=17): CEA with dissection of the total carotid bifurcation before clamping the arteries. Periprocedurally, we continuously monitored the cerebral blood flow in the ipsilateral middle cerebral artery by means of TCD. Pre- and postoperative morbidity were independently verified by a neurologist <2 days before and not later than five days after the procedure. Values of microembolic signs during dissection were summarised with arithmetic means and standard deviations. For further analysis non parametric Wilcoxon test was performed between both methods. P-values <0.05 were considered as statistically significant. Wilcoxon test was performed to compare both methods concerning clamp- and procedure times. We performed EEA 26

Automation of Classical QEEG Trending Methods for Early Detection of Delayed Cerebral Ischemia: More Work to Do.

PubMed

Wickering, Ellis; Gaspard, Nicolas; Zafar, Sahar; Moura, Valdery J; Biswal, Siddharth; Bechek, Sophia; OʼConnor, Kathryn; Rosenthal, Eric S; Westover, M Brandon

2016-06-01

The purpose of this study is to evaluate automated implementations of continuous EEG monitoring-based detection of delayed cerebral ischemia based on methods used in classical retrospective studies. We studied 95 patients with either Fisher 3 or Hunt Hess 4 to 5 aneurysmal subarachnoid hemorrhage who were admitted to the Neurosciences ICU and underwent continuous EEG monitoring. We implemented several variations of two classical algorithms for automated detection of delayed cerebral ischemia based on decreases in alpha-delta ratio and relative alpha variability. Of 95 patients, 43 (45%) developed delayed cerebral ischemia. Our automated implementation of the classical alpha-delta ratio-based trending method resulted in a sensitivity and specificity (Se,Sp) of (80,27)%, compared with the values of (100,76)% reported in the classic study using similar methods in a nonautomated fashion. Our automated implementation of the classical relative alpha variability-based trending method yielded (Se,Sp) values of (65,43)%, compared with (100,46)% reported in the classic study using nonautomated analysis. Our findings suggest that improved methods to detect decreases in alpha-delta ratio and relative alpha variability are needed before an automated EEG-based early delayed cerebral ischemia detection system is ready for clinical use.

Global ischemia in dogs: cerebrovascular CO2 reactivity and autoregulation.

PubMed

Nemoto, E M; Snyder, J V; Carroll, R G; Morita, H

1975-01-01

One hypothesis on the pathogenesis of post-ischemic-anoxic encephalopathy is impaired cerebral perfusion or the no-reflow phenomenon. Therapies aimed at preventing the development of this phenomenon are increased cerebral perfusion pressure (CPP) and hyperventilation or hypercapnia. Using a dog model in which we have described the progressive development of post-ischemic (PI) cerebral hypoperfusion after 15 minutes of global ischemia induced by aortic and vena cavae clamping, our aims in this study were to determine during the PI cerebral hypoperfusion period: (1) cerebrovascular reactivity to CO2, and (2) cerebral blood (CBF) autoregulation. Post-ischemic cerebral hypoperfusion to about 50% of normal was not accompanied by raised intracranial pressure (ICP) but cerebrovascular CO2 reactivity was markedly attenuated while maintaining some kind of autoregulatory phenomenon. Cerebral uptake of oxygen was not significantly affected by changing PACO2 from 20 to 60 torr at constant CPP or by changing CPP from 64 to 104 torr at constant PaCO2. These results suggest that increasing both CPP and hypocapnia/hypercapnia would not significantly attenuate PI neurological deficit after global cerebral ischemia. However, in two dogs inadvertently hemodiluted in the PI period, increasing CPP from 50 to 200 torr increased CBF by 200%, suggesting that hemodilution plus increased CPP may be effective therapy for amelioration of post-ischemic-anoxic encephalopathy. The significance of our findings on cerebrovascular CO2 reactivity and autoregulation with respect to the mechanism of the no-reflow phenomenon is discussed.

AAC and Early Intervention for Children with Cerebral Palsy: Parent Perceptions and Child Risk Factors

PubMed Central

Smith, Ashlyn L.; Hustad, Katherine C.

2015-01-01

The current study examined parent perceptions of communication, the focus of early intervention goals and strategies, and factors predicting the implementation of augmentative and alternative communication (AAC) for 26, 2-year-old children with cerebral palsy. Parents completed a communication questionnaire and provided early intervention plans detailing child speech and language goals. Results indicated that receptive language had the strongest association with parent perceptions of communication. Children who were not talking received a greater number of intervention goals, had a greater variety of goals, and had more AAC goals than children who were emerging and established talkers. Finally, expressive language had the strongest influence on AAC decisions. Results are discussed in terms of the relationship between parent perceptions and language skills, communication as an emphasis in early intervention, AAC intervention decisions, and the importance of receptive language. PMID:26401966

The Relationship between Motor Abilities and Early Social Development in a Preschool Cohort of Children with Cerebral Palsy

ERIC Educational Resources Information Center

Whittingham, Koa; Fahey, Michael; Rawicki, Barry; Boyd, Roslyn

2010-01-01

Aim: To investigate the relationship between motor ability and early social development in a cohort of preschool children with cerebral palsy (CP). Design: Population-based cohort study. Methods: Participants were 122 children with CP assessed at 18, 24 and 30 months, corrected age (ca). Motor ability was measured by the Gross Motor Function…

Improvement in Cerebral and Ocular Hemodynamics Early after Carotid Endarterectomy in Patients of Severe Carotid Artery Stenosis with or without Contralateral Carotid Occlusion.

PubMed

Wang, Jian; Wang, Weici; Jin, Bi; Zhang, Yanrong; Xu, Ping; Xiang, Feixiang; Zheng, Yi; Chen, Juan; Sheng, Shi; Ouyang, Chenxi; Li, Yiqing

2016-01-01

Purpose. To investigate the alternation in cerebral and ocular blood flow velocity (BFV) in patients of carotid stenosis (CS) with or without contralateral carotid occlusion (CO) early after carotid endarterectomy (CEA). Patients and Methods. Nineteen patients underwent CEA for ≥50% CS. Fourteen patients had the unilateral CS, and five patients had the ipsilateral CS and the contralateral CO. Transcranial Doppler (TCD) and Color Doppler Imaging (CDI) were performed before and early after CEA. Results. In patients with unilateral CS, significant improvements in BFV were observed in anterior cerebral artery (ACA) and middle cerebral artery (MCA) on the ipsilateral side after CEA. In patients of ipsilateral CS and contralateral CO, significant improvements in BFV were observed in the ACA and MCA not only on the ipsilateral side but also on the contralateral side postoperatively. The ipsilateral ophthalmic artery (OA) retrograde flows in two patients were recovered to anterograde direction following CEA. The BFV in short posterior ciliary artery (SPCA) of the ipsilateral side significantly increased postoperatively irrespective of the presence of contralateral CO. Conclusions. CEA improved cerebral anterior circulation hemodynamics especially in patients of unilateral CS and contralateral CO, normalized the OA reverse flow, and increased the blood perfusion of SPCA.

The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle artery occlusion in mice

PubMed Central

Gelderblom, Mathias; Leypoldt, Frank; Lewerenz, Jan; Birkenmayer, Gabriel; Orozco, Denise; Ludewig, Peter; Thundyil, John; Arumugam, Thiruma V; Gerloff, Christian; Tolosa, Eva; Maher, Pamela; Magnus, Tim

2012-01-01

The development of the brain tissue damage in ischemic stroke is composed of an immediate component followed by an inflammatory response with secondary tissue damage after reperfusion. Fisetin, a flavonoid, has multiple biological effects, including neuroprotective and antiinflammatory properties. We analyzed the effects of fisetin on infarct size and the inflammatory response in a mouse model of stroke, temporary middle cerebral artery occlusion, and on the activation of immune cells, murine primary and N9 microglial and Raw264.7 macrophage cells and human macrophages, in an in vitro model of inflammatory immune cell activation by lipopolysaccharide (LPS). Fisetin not only protected brain tissue against ischemic reperfusion injury when given before ischemia but also when applied 3 hours after ischemia. Fisetin also prominently inhibited the infiltration of macrophages and dendritic cells into the ischemic hemisphere and suppressed the intracerebral immune cell activation as measured by intracellular tumor necrosis factor α (TNFα) production. Fisetin also inhibited LPS-induced TNFα production and neurotoxicity of macrophages and microglia in vitro by suppressing nuclear factor κB activation and JNK/Jun phosphorylation. Our findings strongly suggest that the fisetin-mediated inhibition of the inflammatory response after stroke is part of the mechanism through which fisetin is neuroprotective in cerebral ischemia. PMID:22234339

Protective effect of green tea polyphenol EGCG against neuronal damage and brain edema after unilateral cerebral ischemia in gerbils.

PubMed

Lee, Hyung; Bae, Jae Hoon; Lee, Seong-Ryong

2004-09-15

Previous studies have demonstrated that a green tea polyphenol, (-)-epigallocatechine gallate (EGCG), has a potent free radical scavenging and antioxidant effect. Glutamate leads to excitotoxicity and oxidative stress, which are important pathophysiologic responses to cerebral ischemia resulting in brain edema and neuronal damage. We investigated the effect of EGCG on excitotoxic neuronal damage in a culture system and the effect on brain edema formation and lesion after unilateral cerebral ischemia in gerbils. In vitro, excitotoxicity was induced by 24-hr incubation with N-methyl-D-aspartate (NMDA; 10 microM), AMPA (10 microM), or kainate (20 microM). EGCG (5 microM) was added to the culture media alone or with excitotoxins. We examined malondialdehyde (MDA) level and neuronal viability to evaluate the effect of EGCG. In vivo, unilateral cerebral ischemia was induced by occlusion of the right common carotid artery for 30, 60, or 90 min and followed by reperfusion of 24 hr. Brain edema, MDA, and infarction were examined to evaluate the protective effect of EGCG. EGCG (25 or 50 mg/kg, intraperitoneally) was administered twice, at 30 min before and immediately after ischemia. EGCG reduced excitotoxin-induced MDA production and neuronal damage in the culture system. In the in vivo study, treatment of gerbils with the lower EGCG dose failed to show neuroprotective effects; however, the higher EGCG dose attenuated the increase in MDA level caused by cerebral ischemia. EGCG also reduced the formation of postischemic brain edema and infarct volume. These results demonstrate EGCG may have future possibilities as a neuroprotective agent against excitotoxicity-related neurologic disorders such as brain ischemia.

Expression of S100 protein and protective effect of arundic acid on the rat brain in chronic cerebral hypoperfusion.

PubMed

Ohtani, Ryo; Tomimoto, Hidekazu; Wakita, Hideaki; Kitaguchi, Hiroshi; Nakaji, Kayoko; Takahashi, Ryosuke

2007-03-02

S100 protein is expressed primarily by astroglia in the brain, and accumulates in and around the ischemic lesions. Arundic acid, a novel astroglia-modulating agent, is neuroprotective in acute cerebral infarction, whereas the protective effects remain unknown during chronic cerebral hypoperfusion. Rats undergoing chronic cerebral hypoperfusion were subjected to a bilateral ligation of the common carotid arteries, and were allowed to survive for 3, 7 and 14 days. The animals received a daily intraperitoneal injection of 5.0, 10.0 or 20.0 mg/kg of arundic acid, or vehicle, for 14 days. Alternatively, other groups of rats received a delayed intraperitoneal injection of 20.0 mg/kg of arundic acid or vehicle, which started from 1, 3 or 7 days after ligation and continued to 14 days. The degree of white matter (WM) lesions and the numerical density of S100 protein-immunoreactive astroglia were estimated. In the WM of rats with vehicle injections, the number of S100 protein-immunoreactive astroglia increased significantly after chronic cerebral hypoperfusion as compared to the sham-operation. A dosage of 10.0 and 20.0 mg/kg of arundic acid suppressed the numerical increase in S100 protein-immunoreactive astroglia and the WM lesions. These pathological changes were suppressed with delayed treatment up to 7 days in terms of astroglial activation, and up to 3 days in terms of the WM lesions. The protective effects of arundic acid against WM lesions were demonstrated in a dose-dependent manner, and even after postischemic treatments. These results suggest the potential usefulness of arundic acid in the treatment of cerebrovascular WM lesions.

Intrauterine inflammation, cerebral oxygen consumption and susceptibility to early brain injury in very preterm newborns.

PubMed

Stark, Michael J; Hodyl, Nicolette A; Belegar V, Kiran Kumar; Andersen, Chad C

2016-03-01

In utero exposure to inflammation results in elevated cerebral oxygen consumption. This increased metabolic demand may contribute to the association between chorioamnionitis and intraventricular haemorrhage (P/IVH). We hypothesised that intrauterine inflammation imposes an elevated cerebral metabolic load and increased fractional oxygen extraction (cFTOE) with cFTOE further increased in the presence of early P/IVH. Eighty-three infants ≤30 weeks gestation were recruited. Exposure to intrauterine inflammation was determined by placental histology. Total internal carotid blood flow (Doppler ultrasound) and near infrared spectroscopy were measured and cerebral oxygen delivery (mcerbDO2), consumption (mcerbVO2) and cFTOE were calculated on days 1 and 3 of life. Primary outcome was defined as death or P/IVH >grade II (cranial sonograph) by day 3. Infants exposed to intrauterine inflammation had higher total internal carotid blood flow (92 vs 63 mL/kg/min) and mcerbDO2 (13.7 vs 10.1 mL/kg/min) than those not exposed to inflammation. Newborns with P/IVH had both higher oxygen consumption and extraction compared with those without sonographic injury regardless of exposure to intrauterine inflammation. Further, in preterms exposed to inflammation, those with P/IVH had higher consumption (6.1 vs 4.8 mL/kg/min) and extraction than those without injury. These differences were observed only on day 1 of life. Although P/IVH is multifactorial in preterm newborns, it is likely that cerebral hypoxic-ischaemia plays a central pathophysiological role. These data provide a mechanistic insight into this process and suggests that the increased cerebral metabolic load imposed by the presence of inflammation results in a higher risk of critical hypoxic ischaemia in the preterm with increased susceptibility to significant P/IVH. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Quantitative analysis of computed tomography images and early detection of cerebral edema for pediatric traumatic brain injury patients: retrospective study.

PubMed

Kim, Hakseung; Kim, Gwang-dong; Yoon, Byung C; Kim, Keewon; Kim, Byung-Jo; Choi, Young Hun; Czosnyka, Marek; Oh, Byung-Mo; Kim, Dong-Joo

2014-10-22

The purpose of this study was to identify whether the distribution of Hounsfield Unit (HU) values across the intracranial area in computed tomography (CT) images can be used as an effective diagnostic tool for determining the severity of cerebral edema in pediatric traumatic brain injury (TBI) patients. CT images, medical records and radiology reports on 70 pediatric patients were collected. Based on radiology reports and the Marshall classification, the patients were grouped as mild edema patients (n=37) or severe edema patients (n=33). Automated quantitative analysis using unenhanced CT images was applied to eliminate artifacts and identify the difference in HU value distribution across the intracranial area between these groups. The proportion of pixels with HU=17 to 24 was highly correlated with the existence of severe cerebral edema (P<0.01). This proportion was also able to differentiate patients who developed delayed cerebral edema from mild TBI patients. A significant difference between deceased patients and surviving patients in terms of the HU distribution came from the proportion of pixels with HU=19 to HU=23 (P<0.01). The proportion of pixels with an HU value of 17 to 24 in the entire cerebral area of a non-enhanced CT image can be an effective basis for evaluating the severity of cerebral edema. Based on this result, we propose a novel approach for the early detection of severe cerebral edema.

[Analysis of 58 neonatal cases with cerebral infarction].

PubMed

Li, Zhi-hua; Chen, Chao

2013-01-01

Cerebral infarction (CI) is one of severe diseases of central nervous system in neonates, and some infants with CI could have poor prognosis in the long term. This study aimed to analyze the clinical data and prognosis of all neonatal cases with cerebral infarction in recent years and to help future clinical work. Totally 58 neonatal cases with CI admitted to NICU of the hospital from January 1999 to December 2010 were included in this study. We analyzed all clinical data and prognosis by retrospective analysis. Fifty-two term babies and six preterm babies were included. There were altogether 51 cases with asphyxia and 7 with hemorrhagic cerebral infarction. Perinatal hypoxia-ischemia was the most common high-risk factor and it accounted for 46.6%. Seizure was the most frequent initial symptom and the most common clinical manifestation (accounted for 77.6%), and it was followed by intermittent cyanosis, apnea and lethargy. Cerebral CT scan and magnetic resonance imaging were major methods to help to make the diagnosis and they also had close relation with prognosis. Diffusion weighted imaging was very helpful to diagnose infarction in early stage. Left middle cerebral artery was the most common artery to be involved. Supportive therapy and symptomatic treatment were the main methods in the acute stage of neonatal cerebral infarction. Those babies with poor prognosis mostly had large infarction involving cerebral hemisphere, thalamus and basal ganglia. Neonatal cerebral infarction was a severe brain injury affecting long tern nervous system prognosis. Perinatal hypoxia was the most common high-risk factor and seizure was the most frequent initial symptom. Diffusion weighted imaging was valuable to diagnose infarction in early stage. Most of infants with poor prognosis had large infarction involving hemisphere, thalamus and basal ganglia. Early diagnosis with brain imaging would be helpful for rehabilitation therapy and improving prognosis.

Dyslipidemia links obesity to early cerebral neurochemical alterations

PubMed Central

Haley, Andreana P.; Gonzales, Mitzi M.; Tarumi, Takashi; Tanaka, Hirofumi

2013-01-01

Objective To examine the role of hypertension, hyperglycemia and dyslipidemia in potentially accounting for obesity-related brain vulnerability in the form of altered cerebral neurochemistry. Design and Methods Sixty-four adults, ages 40 to 60 years, underwent a health screen and proton magnetic resonance spectroscopy (1H MRS) of occipitoparietal grey matter to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI) and glutamate (Glu) relative to creatine (Cr). The causal steps approach and non-parametric bootstrapping were utilized to assess if fasting glucose, mean arterial pressure or peripheral lipid/lipoprotein levels mediate the relationship between body mass index (BMI) and cerebral neurochemistry. Results Higher BMI was significantly related to higher mI/Cr, independent of age and sex. BMI was also significantly related to two of the proposed mediators, triglyceride and HDL-cholesterol, which were also independently related to increased mI/Cr. Finally, the relationship between BMI and mI/Cr, was significantly attenuated after inclusion of triglyceride and HDL-cholesterol into the model, one at a time, indicating statistical mediation. Conclusions Higher triglyceride and lower HDL levels statistically account for the association between BMI and myo-inositol, pointing towards a potentially critical role for dyslipidemia in the development of cerebral neurochemical alterations in obesity. PMID:23512296

Dyslipidemia links obesity to early cerebral neurochemical alterations.

PubMed

Haley, Andreana P; Gonzales, Mitzi M; Tarumi, Takashi; Tanaka, Hirofumi

2013-10-01

To examine the role of hypertension, hyperglycemia, and dyslipidemia in potentially accounting for obesity-related brain vulnerability in the form of altered cerebral neurochemistry. Sixty-four adults, ages 40-60 years, underwent a health screen and proton magnetic resonance spectroscopy ((1) H MRS) of occipitoparietal gray matter to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI), and glutamate (Glu) relative to creatine (Cr). The causal steps approach and nonparametric bootstrapping were utilized to assess if fasting glucose, mean arterial pressure or peripheral lipid/lipoprotein levels mediate the relationship between body mass index (BMI) and cerebral neurochemistry. Higher BMI was significantly related to higher mI/Cr, independent of age and sex. BMI was also significantly related to two of the proposed mediators, triglyceride, and HDL-cholesterol, which were also independently related to increased mI/Cr. Finally, the relationship between BMI and mI/Cr was significantly attenuated after inclusion of triglyceride and HDL-cholesterol into the model, one at a time, indicating statistical mediation. Higher triglyceride and lower HDL levels statistically account for the association between BMI and myo-inositol, pointing toward a potentially critical role for dyslipidemia in the development of cerebral neurochemical alterations in obesity. Copyright © 2013 The Obesity Society.

Is impaired cerebral vasoreactivity an early marker of cognitive decline in multiple sclerosis patients?

PubMed

Metzger, Aude; Le Bars, Emmanuelle; Deverdun, Jeremy; Molino, François; Maréchal, Bénédicte; Picot, Marie-Christine; Ayrignac, Xavier; Carra, Clarisse; Bauchet, Luc; Krainik, Alexandre; Labauge, Pierre; Menjot de Champfleur, Nicolas

2018-03-01

The link between cerebral vasoreactivity and cognitive status in multiple sclerosis remains unclear. The aim of the present study was to investigate a potential decrease of cerebral vasoreactivity in multiple sclerosis patients and correlate it with cognitive status. Thirty-three patients with multiple sclerosis (nine progressive and 24 remitting forms, median age: 39 years, 12 males) and 22 controls underwent MRI with a hypercapnic challenge to assess cerebral vasoreactivity and a neuropsychological assessment. Cerebral vasoreactivity, measured as the cerebral blood flow percent increase normalised by end-tidal carbon dioxide variation, was assessed globally and by regions of interest using the blood oxygen level-dependent technique. Non-parametric statistics tests were used to assess differences between groups, and associations were estimated using linear models. Cerebral vasoreactivity was lower in patients with cognitive impairment than in cognitively normal patients (p=0.004) and was associated with education level in patients (R 2 = 0.35; p = 0.047). There was no decrease in cerebral vasoreactivity between patients and controls. Cognitive impairment in multiple sclerosis may be mediated through decreased cerebral vasoreactivity. Cerebral vasoreactivity could therefore be considered as a marker of cognitive decline in multiple sclerosis. • Cerebral vasoreactivity does not differ between multiple sclerosis patients and controls. • Cerebral vasoreactivity measure is linked to cognitive impairment in multiple sclerosis. • Cerebral vasoreactivity is linked to level of education in multiple sclerosis.

Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder

PubMed Central

Moises, H W; Wollschläger, D; Binder, H

2015-01-01

In search for the elusive schizophrenia pathway, candidate genes for the disorder from a discovery sample were localized within the energy-delivering and ischemia protection pathway. To test the adult vascular-ischemic (AVIH) and the competing neurodevelopmental hypothesis (NDH), functional genomic analyses of practically all available schizophrenia-associated genes from candidate gene, genome-wide association and postmortem expression studies were performed. Our results indicate a significant overrepresentation of genes involved in vascular function (P<0.001), vasoregulation (that is, perivascular (P<0.001) and shear stress (P<0.01), cerebral ischemia (P<0.001), neurodevelopment (P<0.001) and postischemic repair (P<0.001) among schizophrenia-associated genes from genetic association studies. These findings support both the NDH and the AVIH. The genes from postmortem studies showed an upregulation of vascular-ischemic genes (P=0.020) combined with downregulated synaptic (P=0.005) genes, and ND/repair (P=0.003) genes. Evidence for the AVIH and the NDH is critically discussed. We conclude that schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder. Adult postischemic repair involves ND genes for adult neurogenesis, synaptic plasticity, glutamate and increased long-term potentiation of excitatory neurotransmission (i-LTP). Schizophrenia might be caused by the cerebral analog of microvascular angina. PMID:26261884

Functional genomics indicate that schizophrenia may be an adult vascular-ischemic disorder.

PubMed

Moises, H W; Wollschläger, D; Binder, H

2015-08-11

In search for the elusive schizophrenia pathway, candidate genes for the disorder from a discovery sample were localized within the energy-delivering and ischemia protection pathway. To test the adult vascular-ischemic (AVIH) and the competing neurodevelopmental hypothesis (NDH), functional genomic analyses of practically all available schizophrenia-associated genes from candidate gene, genome-wide association and postmortem expression studies were performed. Our results indicate a significant overrepresentation of genes involved in vascular function (P < 0.001), vasoregulation (that is, perivascular (P < 0.001) and shear stress (P < 0.01), cerebral ischemia (P < 0.001), neurodevelopment (P < 0.001) and postischemic repair (P < 0.001) among schizophrenia-associated genes from genetic association studies. These findings support both the NDH and the AVIH. The genes from postmortem studies showed an upregulation of vascular-ischemic genes (P = 0.020) combined with downregulated synaptic (P = 0.005) genes, and ND/repair (P = 0.003) genes. Evidence for the AVIH and the NDH is critically discussed. We conclude that schizophrenia is probably a mild adult vascular-ischemic and postischemic repair disorder. Adult postischemic repair involves ND genes for adult neurogenesis, synaptic plasticity, glutamate and increased long-term potentiation of excitatory neurotransmission (i-LTP). Schizophrenia might be caused by the cerebral analog of microvascular angina.

Reaction Time is a Marker of Early Cognitive and Behavioral Alterations in Pure Cerebral Small Vessel Disease.

PubMed

Jouvent, Eric; Reyes, Sonia; De Guio, François; Chabriat, Hugues

2015-01-01

The assessment of early and subtle cognitive and behavioral effects of cerebral small vessel disease (SVD) requires specific and long-lasting evaluations performed by experienced neuropsychologists. Simpler tools would be helpful for daily clinical practice. To determine whether a simple reaction time task that lasts 5 minutes and can be performed without external supervision on any tablet or laptop can be used as a proxy of early cognitive and behavioral alterations in CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic form of pure SVD related to NOTCH3 mutations. Twenty-two genetically confirmed patients with CADASIL having preserved global cognitive abilities and without disability (MMSE >24 and modified Rankin's scale ≤1) were compared to 29 age-and-gender matched controls to determine group differences according to: 1) conventional neuropsychological and behavioral testing; 2) a computerized battery evaluating reaction time, processing speed, and executive functions. In a second step, correlations between reaction time and cognitive and behavioral alterations detected using both conventional and computerized testing were tested in patients. Reaction time was significantly higher in patients than in controls (mean in patients: 283 ms - in controls: 254 ms, p = 0.03). In patients, reaction time was significantly associated with conventional and chronometric tests of executive functions, working memory, and apathy. Reaction time obtained using a very simple task may serve as a proxy of early cognitive and behavioral alterations in SVD and could be easily used in daily clinical practice.

Relationship of Early Spontaneous Type V Blood Pressure Fluctuation after Thrombolysis in Acute Cerebral Infarction Patients and the Prognosis

PubMed Central

Zuo, Lian; Wan, Ting; Xu, Xiahong; Liu, Feifeng; Li, Changsong; Li, Ying; Zhang, Yue; Zhang, Jing; Bao, Huan; Li, Gang

2016-01-01

We examined the relationship between an early spontaneous type V blood pressure fluctuation and the post-thrombolysis prognosis of patients with acute cerebral infarction. Patients were admitted consecutively. All patients were categorized into the type V blood pressure fluctuation group or non-type V blood pressure group. Their blood pressure was monitored before thrombolysis and until 6 h after thrombolysis. Baseline data and clinical outcomes were compared. Of 170 patients, 43 (25.2%) had an early type V blood pressure fluctuation. The National Institute of Health Stroke Scale (NIHSS) score before thrombolysis and 24 h after thrombolysis, and the modified Rankin scale score at 90 days differed significantly between the two groups (P < 0.05). Multiple logistic regression analysis showed that an unfavorable prognosis at 3 months was associated with the NIHSS score before thrombolysis (P = 0.000) but probably not with this blood pressure fluctuation (P = 0.058). An early spontaneous type V blood pressure fluctuation is common in patients with acute cerebral infarction who received venous thrombolysis, especially if they have a higher NIHSS score before thrombolysis. The type V blood pressure fluctuation may not influence patients’ prognosis; however, this needs to be confirmed in future trials. PMID:27278121

Dyke-Davidoff-Masson syndrome: case report of fetal unilateral ventriculomegaly and hypoplastic left middle cerebral artery.

PubMed

Piro, Ettore; Piccione, Maria; Marrone, Gianluca; Giuffrè, Mario; Corsello, Giovanni

2013-05-14

Prenatal ultrasonographic detection of unilateral cerebral ventriculomegaly arises suspicion of pathological condition related to cerebrospinal fluid flow obstruction or cerebral parenchimal pathology. Dyke-Davidoff-Masson syndrome is a rare condition characterized by cerebral hemiatrophy, calvarial thickening, skull and facial asymmetry, contralateral hemiparesis, cognitive impairment and seizures. Congenital and acquired types are recognized and have been described, mainly in late childhood, adolescence and adult ages. We describe a female infant with prenatal diagnosis of unilateral left ventriculomegaly in which early brain MRI and contrast enhanced-MRI angiography, showed cerebral left hemiatrophy associated with reduced caliber of the left middle cerebral artery revealing the characteristic findings of the Dyke-Davidoff-Masson syndrome. Prenatal imaging, cerebral vascular anomaly responsible for the cerebral hemiatrophy and the early clinical evolution have never been described before in such a young child and complete the acquired clinical descriptions in older children. Differential diagnosis, genetic investigations, neurophysiologic assessments, short term clinical and developmental follow up are described. Dyke-Davidoff-Masson syndrome must be ruled out in differential diagnosis of fetal unilateral ventriculomegaly. Early clinical assessment, differential diagnosis and cerebral imaging including cerebral MRI angiography allow the clinicians to diagnose also in early infancy this rare condition.

Blood -brain barrier disruption was less under isoflurane than pentobarbital anesthesia via a PI3K/Akt pathway in early cerebral ischemia.

PubMed

Chi, Oak Z; Mellender, Scott J; Kiss, Geza K; Liu, Xia; Weiss, Harvey R

2017-05-01

One of the important factors altering the degree of blood-brain barrier (BBB) disruption in cerebral ischemia is the anesthetic used. The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway has been reported to be involved in modulating BBB permeability and in isoflurane induced neuroprotection. This study was performed to compare the degree of BBB disruption in focal cerebral ischemia under isoflurane vs pentobarbital anesthesia and to determine whether inhibition of PI3K/Akt would affect the disruption in the early stage of focal cerebral ischemia. Permanent middle cerebral artery (MCA) occlusion was performed in rats under 1.4% isoflurane or pentobarbital (50mg/kg i.p.) anesthesia with controlled ventilation. In half of each group LY294002, which is a PI3K/Akt inhibitor, was applied on the ischemic cortex immediately after MCA occlusion. After one hour of MCA occlusion, the transfer coefficient (K i ) of 14 C-α-aminoisobutyric acid ( 14 C-AIB) was determined to quantify the degree of BBB disruption. MCA occlusion increased the K i both in the isoflurane and pentobarbital anesthetized rats. However, the value of K i was lower under isoflurane (11.5±6.0μL/g/min) than under pentobarbital (18.3±7.1μL/g/min) anesthesia. The K i of the contralateral cortex of the pentobarbital group was higher (+74%) than that of the isoflurane group. Application of LY294002 on the ischemic cortex increased the K i (+99%) only in the isoflurane group. The degree of BBB disruption by MCA occlusion was significantly lower under isoflurane than pentobarbital anesthesia in the early stage of cerebral ischemia. Our data demonstrated the importance of choice of anesthetics and suggest that PI3K/Akt signaling pathway plays a significant role in altering BBB disruption in cerebral ischemia during isoflurane but not during pentobarbital anesthesia. Copyright © 2017 Elsevier Inc. All rights reserved.

[Post-ischemic innate immunity and its application for novel therapeutic strategy targeting brain inflammation].

PubMed

Ito, Minako; Kondo, Taisuke; Shichita, Takashi; Yoshimura, Akihiko

2013-07-01

Stroke or brain ischemia is one of the major causes of death and disability worldwide. Post-ischemic inflammation is an essential step in the progression of brain ischemia-reperfusion injury. In a mouse stroke model, we have reported that IL-23 produced from infiltrating macrophages induces IL-17 producing T cells. IL-17 is mainly produced from gammadeltaT cells and promotes delayed (day 3-4) ischemic brain damage. We also demonstrated that peroxiredoxin (Prx) family proteins released extracellularly from necrotic brain cells induce expression of inflammatory cytokines including IL-23 in macrophages through activation of Toll-like receptor 2(TLR2) and TLR4, thereby promoting neural cell death. We thus propose that regulation of the IL-23-IL-17 axis including gammadeltaT cells, macrophages, and extracellular Prxs could be a potent neuroprotective tool.

Early diagnosis of Alzheimer's disease and Parkinson's disease associated with dementia using cerebral perfusion SPECT.

PubMed

Song, In-Uk; Chung, Yong-An; Chung, Sung-Woo; Jeong, Jaeseung

2014-01-01

Since patterns of cognitive dysfunction in mild Parkinson's disease associated with dementia (PDD) are similar to those in mild Alzheimer's disease (AD), it is difficult to accurately differentiate between these two types of dementia in their early phases using neuropsychological tests. The purpose of the current study was to investigate differences in cerebral perfusion patterns of patients with AD and PDD at the earliest stages using single photon emission computed tomography (SPECT). We consecutively recruited 31 patients with mild PDD, 32 patients with mild probable AD and 33 age-matched healthy subjects. All subjects underwent (99m)Tc-hexamethylpropyleneamine oxime perfusion SPECT and completed general neuropsychological tests. We found that both mild PDD and AD patients showed distinct hypoperfusion in frontal, parietal and temporal regions, compared with healthy subjects. More importantly, hypoperfusion in occipital and cerebellar regions was observed only in mild PDD. The observation of a significant decrease in cerebral perfusion in occipital and cerebellar regions in patients with mild PDD is likely useful to differentiate between PDD and AD at the earliest stages. © 2013 S. Karger AG, Basel.

Cerebral monitoring during cardiopulmonary bypass in children.

PubMed

Kern, F H; Schell, R M; Greeley, W J

1993-07-01

Although cerebral monitoring during CPB remains primarily investigational, recent data support its clinical utility. In particular, it is cerebral metabolic monitoring that provides meaningful information in terms of preparing the brain for dhCPB and dhCA. Cerebral blood flow or cerebral blood flow velocity monitoring is less beneficial due to the presence of luxuriant cerebral blood flow at deep hypothermic temperatures. Conventional temperature monitoring can be improved upon by adding jugular venous oxygen saturation monitoring to satisfy the primary goal of cerebral protection--uniform cerebral cooling and metabolic suppression. Although online measures of cerebral cellular metabolism are not widely available, early experience with near infrared technology suggests that it is a feasible and reliable monitor of cerebral metabolic activity and is likely to represent an important noninvasive continuous monitor in the near future. CMRO2 recovery data have suggested that cerebral metabolic suppression is more severe the longer the period of dhCA. Cerebral protection strategies, such as intermittent cerebral perfusion have demonstrated less metabolic suppression of dhCA in animal models and are currently undergoing clinical evaluation in our institution. Finally, the postoperative period remains a high-risk period for neurologic injury because temperatures are normothermic, cardiac output is reduced, cerebral autoregulation is impaired, and management strategies, such as hyperventilation, are commonly used to increase pulmonary blood flow with little knowledge on its effects on cerebral perfusion.

Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia.

PubMed

Liu, Yu-Cheng; Lee, Yu-Da; Wang, Hwai-Lee; Liao, Kate Hsiurong; Chen, Kuen-Bao; Poon, Kin-Shing; Pan, Yu-Ling; Lai, Ted Weita

2017-01-01

Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8-24 h, whereas the late phase of BBB disruption begins 48-58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in comparison

Novel therapeutic strategies targeting innate immune responses and early inflammation after stroke.

PubMed

Shichita, Takashi; Ago, Tetsuro; Kamouchi, Masahiro; Kitazono, Takanari; Yoshimura, Akihiko; Ooboshi, Hiroaki

2012-11-01

Post-ischemic inflammation is an essential step in the progression of ischemic stroke. This review focuses on the function of infiltrating immune cells, macrophages, and T cells, in ischemic brain injury. The brain is a sterile organ; however, the activation of Toll-like receptor (TLR) 2 and TLR4 is pivotal in the beginning of post-ischemic inflammation. Some endogenous TLR ligands are released from injured brain cells, including high mobility group box 1 and peroxiredoxin family proteins, and activate the infiltrating macrophages and induce the expression of inflammatory cytokines. Following this step, T cells also infiltrate into the ischemic brain and mediate post-ischemic inflammation in the delayed phase. Various cytokines from helper T cells and γδT cells function as neurotoxic (IL-23/IL-17, IFN-γ) or neuroprotective (IL-10, IL-4) mediators. Novel neuroprotective strategies should therefore be developed through more detailed understanding of this process and the regulation of post-ischemic inflammation. © 2012 The Authors Journal of Neurochemistry © International Society for Neurochemistry.

Neuronal precursor cell proliferation in the hippocampus after transient cerebral ischemia: a comparative study of two rat strains using stereological tools.

PubMed

Kelsen, Jesper; Larsen, Marianne H; Sørensen, Jens Christian; Møller, Arne; Frøkiaer, Jørgen; Nielsen, Søren; Nyengaard, Jens R; Mikkelsen, Jens D; Rønn, Lars Christian B

2010-04-06

We are currently investigating microglial activation and neuronal precursor cell (NPC) proliferation after transient middle cerebral artery occlusion (tMCAo) in rats. This study aimed: (1) to investigate differences in hippocampal NPC proliferation in outbred male spontaneously hypertensive rats (SHRs) and Sprague-Dawley rats (SDs) one week after tMCAo; (2) to present the practical use of the optical fractionator and 2D nucleator in stereological brain tissue analyses; and (3) to report our experiences with an intraluminal tMCAo model where the occluding filament is advanced 22 mm beyond the carotid bifurcation and the common carotid artery is clamped during tMCAo. Twenty-three SDs and twenty SHRs were randomized into four groups subjected to 90 minutes tMCAo or sham. BrdU (50 mg/kg) was administered intraperitoneally twice daily on Day 4 to 7 after surgery. On Day 8 all animals were euthanized. NeuN-stained tissue sections were used for brain and infarct volume estimation with the 2D nucleator and Cavalieri principle. Brains were studied for the presence of activated microglia (ED-1) and hippocampal BrdU incorporation using the optical fractionator. We found no significant difference or increase in post-ischemic NPC proliferation between the two strains. However, the response to remote ischemia may differ between SDs and SHRs. In three animals increased post-stroke NPC proliferation was associated with hippocampal ischemic injury. The mean infarct volume was 89.2 +/- 76.1 mm3 in SHRs and 16.9 +/- 22.7 mm3 in SDs (p < 0.005). Eight out of eleven SHRs had ischemic neocortical damage in contrast to only one out of 12 SDs. We observed involvement of the anterior choroidal and hypothalamic arteries in several animals from both strains and the anterior cerebral artery in two SHRs. We found no evidence of an early hippocampal NPC proliferation one week after tMCAo in both strains. Infarction within the anterior choroidal artery could induce hippocampal ischemia and

Relationship of neonatal cerebral blood flow velocity asymmetry with early motor, cognitive and language development in term infants.

PubMed

Wu, Ying-Chin; Hsieh, Wu-Shiun; Hsu, Chyong-Hsin; Chiu, Nan-Chang; Chou, Hung-Chieh; Chen, Chien-Yi; Peng, Shinn-Forng; Hung, Han-Yang; Chang, Jui-Hsing; Chen, Wei J; Jeng, Suh-Fang

2013-05-01

The objective of this study was to examine the relationships of Doppler cerebral blood flow velocity (CBFV) asymmetry measures with developmental outcomes in term infants. Doppler CBFV parameters (peak systolic velocity [PSV] and mean velocity [MV]) of the bilateral middle cerebral arteries of 52 healthy term infants were prospectively examined on postnatal days 1-5, and then their motor, cognitive and language development was evaluated with the Bayley Scales of Infant and Toddler Development, Third Edition, at 6, 12, 18 and 24 months of age. The left CBFV asymmetry measure (PSV or MV) was calculated by subtracting the right-side value from the left-side value. Left CBFV asymmetry measures were significantly positively related to motor scores at 6 (r = 0.3-0.32, p < 0.05) and 12 (r = 0.35, p < 0.05) months of age, but were not related to cognitive or language outcome. Thus, the leftward hemodynamic status of the middle cerebral arteries, as measured by cranial Doppler ultrasound in the neonatal period, predicts early motor outcome in term infants. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Fulminant cerebral infarction of anterior and posterior cerebral circulation after ascending type of facial necrotizing fasciitis.

PubMed

Lee, Jun Ho; Choi, Hui-Chul; Kim, Chulho; Sohn, Jong Hee; Kim, Heung Cheol

2014-01-01

Necrotizing fasciitis is a soft tissue infection that is characterized by extensive necrosis of the subcutaneous fat, neurovascular structures, and fascia. Cerebral infarction after facial necrotizing fasciitis has been rarely reported. A 61-year-old woman with diabetes was admitted with painful swelling of her right cheek. One day later, she was stuporous and quadriplegic. A computed tomographic scan of her face revealed right facial infection in the periorbital soft tissue, parotid, buccal muscle, and maxillary sinusitis. A computed tomographic scan of the brain revealed cerebral infarction in the right hemisphere, left frontal area, and both cerebellum. Four days later, she died from cerebral edema and septic shock. Involvement of the cerebral vasculature, such as the carotid or vertebral artery by necrotizing fasciitis, can cause cerebral infarction. Facial necrotizing fasciitis should be treated early with surgical treatment and the appropriate antibiotic therapy. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Design of the NL-ENIGMA study: Exploring the effect of Souvenaid on cerebral glucose metabolism in early Alzheimer's disease.

PubMed

Scheltens, Nienke M E; Kuyper, Ingrid S; Boellaard, Ronald; Barkhof, Frederik; Teunissen, Charlotte E; Broersen, Laus M; Lansbergen, Marieke M; van der Flier, Wiesje M; van Berckel, Bart N M; Scheltens, Philip

2016-11-01

Alzheimer's disease is associated with early synaptic loss. Specific nutrients are known to be rate limiting for synapse formation. Studies have shown that administering specific nutrients may improve memory function, possibly by increasing synapse formation. This Dutch study explores the Effect of a specific Nutritional Intervention on cerebral Glucose Metabolism in early Alzheimer's disease (NL-ENIGMA, Dutch Trial Register NTR4718, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4718). The NL-ENIGMA study is designed to test whether the specific multinutrient combination Fortasyn Connect present in the medical food Souvenaid influences cerebral glucose metabolism as a marker for improved synapse function. This study is a double-blind, randomized controlled parallel-group single-center trial. Forty drug-naive patients with mild cognitive impairment or mild dementia with evidence of amyloid deposition are 1:1 randomized to receive either the multinutrient combination or placebo once daily. Main exploratory outcome parameters include absolute quantitative positron emission tomography with 18 F-fluorodeoxyglucose (including arterial sampling) and standard uptake value ratios normalized for the cerebellum or pons after 24 weeks. We expect the NL-ENIGMA study to provide further insight in the potential of this multinutrient combination to improve synapse function.

Neuropeptide Y - an early biomarker for cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

PubMed

Schebesch, Karl-Michael; Brawanski, Alexander; Bele, Sylvia; Schödel, Petra; Herbst, Andreas; Bründl, Elisabeth; Kagerbauer, Simone Maria; Martin, Jan; Lohmeier, Anette; Stoerr, Eva-Maria; Proescholdt, Martin

2013-12-01

In the human brain, the potent vasoconstrictive neuropeptide Y (NPY) is abundantly expressed. Neuropeptide Y, which is stored in perivascular nerve fibers of the cerebral arteries, regulates the cerebral vascular diameter as well as cerebral blood flow. However, the role of NPY in the pathogenesis of cerebral vasospasm (CV) related to subarachnoid hemorrhage (SAH) is unclear. We prospectively analyzed and compared the release of endogenous NPY in the cerebrospinal fluid (CSF) of 66 patients with SAH to NPY release in a control group. Additionally, we correlated the levels of NPY with CV and consecutive ischemic stroke. Sixty-six consecutive patients (40 women, 26 men; mean age 53·1 years) with aneurysmal SAH were included. In the SAH group, CSF was drawn daily from day 1 to day 10 after the onset of SAH. The CSF of 29 patients undergoing spinal anesthesia for orthopedic surgery served as control samples. The NPY levels were determined in duplicate CSF samples by means of a competitive enzyme immunoassay (EIA). The levels of NPY in CSF were correlated with the development of CV over the 10-day period after the onset of SAH and to the occurrence of consecutive ischemic stroke. To evaluate CSF NPY levels as a predictive biomarker for vasospasm, we calculated the sensitivity and specificity as well as the positive and negative predictive values. The NPY levels were significantly higher in the SAH group than in the control group (p < 0·001). The treatment modality (clip versus coil) did not influence the level of NPY in CSF (p > 0·05). Patients with CV showed significantly higher NPY levels than patients without CV during the entire observation period. The NPY levels of the non-CV group dissipated over time, whereas the CV group showed continuously increasing values. The NPY levels from day 4 to 10 were significantly higher in patients with CV-related stroke than in non-stroke patients. Using 0·3 ng/ml as a cut-off value, NPY levels on day 3 predicted the occurrence

Cholangiocarcinoma associated with limbic encephalitis and early cerebral abnormalities detected by 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography-positron emission tomography: a case report.

PubMed

Schmidt, Sergio L; Schmidt, Juliana J; Tolentino, Julio C; Ferreira, Carlos G; de Almeida, Sergio A; Alvarenga, Regina P; Simoes, Eunice N; Schmidt, Guilherme J; Canedo, Nathalie H S; Chimelli, Leila

2016-07-20

Limbic encephalitis was originally described as a rare clinical neuropathological entity involving seizures and neuropsychological disturbances. In this report, we describe cerebral patterns visualized by positron emission tomography in a patient with limbic encephalitis and cholangiocarcinoma. To our knowledge, there is no other description in the literature of cerebral positron emission tomography findings in the setting of limbic encephalitis and subsequent diagnosis of cholangiocarcinoma. We describe a case of a 77-year-old Caucasian man who exhibited persistent cognitive changes 2 years before his death. A cerebral scan obtained at that time by 2-deoxy-2-[fluorine-18]fluoro- D -glucose integrated with computed tomography-positron emission tomography showed low radiotracer uptake in the frontal and temporal lobes. Cerebrospinal fluid analysis indicated the presence of voltage-gated potassium channel antibodies. Three months before the patient's death, a lymph node biopsy indicated a cholangiocarcinoma, and a new cerebral scan obtained by 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography-positron emission tomography showed an increment in the severity of metabolic deficit in the frontal and parietal lobes, as well as hypometabolism involving the temporal lobes. Two months before the patient's death, cerebral metastases were detected on a contrast-enhanced computed tomographic scan. Postmortem examination revealed a cholangiocarcinoma with multiple metastases including the lungs and lymph nodes. The patient's brain weighed 1300 g, and mild cortical atrophy, ex vacuo dilation of the ventricles, and mild focal thickening of the cerebellar leptomeninges, which were infiltrated by neoplastic epithelial cells, were observed. These findings support the need for continued vigilance in malignancy surveillance in patients with limbic encephalitis and early cerebral positron emission tomographic scan abnormalities. The difficulty in early

The ultrasound brain helmet: early human feasibility study of multiple simultaneous 3D scans of cerebral vasculature

NASA Astrophysics Data System (ADS)

Lindsey, Brooks D.; Ivancevich, Nikolas M.; Whitman, John; Light, Edward; Fronheiser, Matthew; Nicoletto, Heather A.; Laskowitz, Daniel T.; Smith, Stephen W.

2009-02-01

We describe early stage experiments to test the feasibility of an ultrasound brain helmet to produce multiple simultaneous real-time 3D scans of the cerebral vasculature from temporal and suboccipital acoustic windows of the skull. The transducer hardware and software of the Volumetrics Medical Imaging real-time 3D scanner were modified to support dual 2.5 MHz matrix arrays of 256 transmit elements and 128 receive elements which produce two simultaneous 64° pyramidal scans. The real-time display format consists of two coronal B-mode images merged into a 128° sector, two simultaneous parasagittal images merged into a 128° × 64° C-mode plane, and a simultaneous 64° axial image. Real-time 3D color Doppler images acquired in initial clinical studies after contrast injection demonstrate flow in several representative blood vessels. An offline Doppler rendering of data from two transducers simultaneously scanning via the temporal windows provides an early visualization of the flow in vessels on both sides of the brain. The long-term goal is to produce real-time 3D ultrasound images of the cerebral vasculature from a portable unit capable of internet transmission, thus enabling interactive 3D imaging, remote diagnosis and earlier therapeutic intervention. We are motivated by the urgency for rapid diagnosis of stroke due to the short time window of effective therapeutic intervention.

Increased postischemic brain injury in mice deficient in uracil-DNA glycosylase

PubMed Central

Endres, Matthias; Biniszkiewicz, Detlev; Sobol, Robert W.; Harms, Christoph; Ahmadi, Michael; Lipski, Andreas; Katchanov, Juri; Mergenthaler, Philipp; Dirnagl, Ulrich; Wilson, Samuel H.; Meisel, Andreas; Jaenisch, Rudolf

2004-01-01

Uracil-DNA glycosylase (UNG) is involved in base excision repair of aberrant uracil residues in nuclear and mitochondrial DNA. Ung knockout mice generated by gene targeting are viable, fertile, and phenotypically normal and have regular mutation rates. However, when exposed to a nitric oxide donor, Ung–/– fibroblasts show an increase in the uracil/cytosine ratio in the genome and augmented cell death. After combined oxygen-glucose deprivation, Ung–/– primary cortical neurons have increased vulnerability to cell death, which is associated with early mitochondrial dysfunction. In vivo, UNG expression and activity are low in brains of naive WT mice but increase significantly after reversible middle cerebral artery occlusion and reperfusion. Moreover, major increases in infarct size are observed in Ung–/– mice compared with littermate control mice. In conclusion, our results provide compelling evidence that UNG is of major importance for tissue repair after brain ischemia. PMID:15199406

Effects of Combined Milrinone and Levosimendan Treatment on Systolic and Diastolic Function During Postischemic Myocardial Dysfunction in a Porcine Model.

PubMed

Axelsson, Birger; Häggmark, Sören; Svenmarker, Staffan; Johansson, Göran; Gupta, Anil; Tydén, Hans; Wouters, Patrick; Haney, Michael

2016-09-01

It is not known whether there are positive or negative interactions on ventricular function when a calcium-sensitizing inotrope is added to a phosphodiesterase inhibitor in the clinical setting of acute left ventricular (LV) dysfunction. We hypothesized that when levosimendan is added to milrinone treatment, there will be synergetic inotropic and lusitropic effects. This was tested in an anesthetized porcine postischemic global LV injury model, where ventricular pressures and volumes (conductance volumetry) were measured. A global ischemic injury was induced by repetitive left main stem coronary artery occlusions. Load-independent indices of LV function were assessed before and after ventricular injury, after milrinone treatment, and finally after addition of levosimendan to the milrinone treatment. Nonparametric, within-group comparisons were made. The protocol was completed in 12 pigs, 7 of which received the inotrope treatment and 5 of which served as controls. Milrinone led to positive lusitropic effects seen by improvement in tau after myocardial stunning. The addition of levosimendan to milrinone further increased lusitropic state. The latter effect could however not be attributed solely to levosimendan, since lusitropic state also improved spontaneously in time-matched controls at the same rate during the corresponding period. When levosimendan was added to milrinone infusion, there was no increase in systolic function (preload recruitable stroke work) compared to milrinone treatment alone. We conclude that in this model of postischemic LV dysfunction, there appears to be no clear improvement in systolic or diastolic function after addition of levosimendan to established milrinone treatment but also no negative effects of levosimendan in this context. © The Author(s) 2016.

Enhanced peripheral dopamine impairs post-ischemic healing by suppressing angiotensin receptor type 1 expression in endothelial cells and inhibiting angiogenesis.

PubMed

Sarkar, Chandrani; Ganju, Ramesh K; Pompili, Vincent J; Chakroborty, Debanjan

2017-02-01

Increased circulating catecholamines have been linked with cardiovascular anomalies as well as with peripheral vascular diseases. Although the roles of epinephrine and norepinephrine have received considerable attention, the role of the other catecholamine, dopamine, has been less studied. Since dopamine is a potent endogenous inhibitor of angiogenesis and as angiogenesis is essential for ischemic healing, we therefore studied the role played by dopamine during ischemic healing using dopamine D 2 receptor knockout (KOD2) mice. Although concentration of dopamine and its rate-limiting enzyme, tyrosine hydroxylase, was considerably high in the muscle tissues of wild-type and KOD2 mice with unilateral hind limb ischemia (HLI), recovery was significantly faster in the KOD2 mice compared to the wild-type controls, thereby indicating that peripheral dopamine might have a role in this healing process. In addition, we observed significant differences in post-ischemic angiogenesis between these two groups. Our study further revealed that elevated dopamine independently suppressed activation of local tissue-based renin-angiotensin system (RAS), a critical growth factor system stimulating angiogenesis in ischemia. Angiotensin II (ATII) and its receptor, angiotensin receptor type 1 (AT1R), are the key players in RAS-mediated angiogenesis. Dopamine acting through its D 2 receptors in endothelial cells inhibited ATII-mediated angiogenesis by suppressing the expression of AT1R in these cells. This study thus for the first time demonstrates the role played by dopamine in prolonging post-ischemic recovery. Therefore, pharmacological intervention inhibiting the action of dopamine holds promise as future therapeutic strategy for the treatment of HLI and other peripheral arterial diseases.

Mechanisms of filtration failure during postischemic injury of the human kidney. A study of the reperfused renal allograft.

PubMed

Alejandro, V; Scandling, J D; Sibley, R K; Dafoe, D; Alfrey, E; Deen, W; Myers, B D

1995-02-01

Postischemic filtration failure in experimental animals results primarily from depression of the transcapillary hydraulic pressure difference (delta P), a quantity that cannot be determined in humans. To circumvent this limitation we determined the GFR and each of its remaining determinants in transplanted kidneys. Findings in 12 allografts that exhibited subsequent normofiltration (group 1) were compared with those in 11 allografts that exhibited persistent hypofiltration (group 2). Determinations were made intraoperatively in the exposed graft after 1-3 h of reperfusion. GFR (6 +/- 2 vs 29 +/- 5 ml/min) and renal plasma flow by Doppler flow meter (140 +/- 30 vs 315 +/- 49 ml/min) were significantly lower in group 2 than group 1. Morphometric analysis of glomeruli obtained by biopsy and a structural hydrodynamic model of viscous flow revealed the glomerular ultrafiltration coefficient to be similar, averaging 3.5 +/- 0.6 and 3.1 +/- 0.2 ml/(min.mmHg) in group 2 vs 1, respectively. Corresponding values for plasma oncotic pressure were also similar, averaging 19 +/- 1 vs 21 +/- 1 mmHg. We next used a mathematical model of glomerular ultrafiltration and a sensitivity analysis to calculate the prevailing range for delta P from the foregoing measured quantities. This revealed delta P to vary from only 20-21 mmHg in group 2 vs 34-45 mmHg in group 1 (P < 0.001). Further morphometric analysis revealed the diameters of Bowman's space and tubular lumens, as well as the percentage of tubular cells that were necrotic or devoid of brush border, to be similar in the two groups. We thus conclude (a) that delta P depression is the predominant cause of hypofiltration in this form of postischemic injury; and (b) that afferent vasoconstriction rather than tubular obstruction is the proximate cause of the delta P depression.

Proinflammatory cytokines correlate with early exercise attenuating anxiety-like behavior after cerebral ischemia.

PubMed

Zhang, Qi; Zhang, Jingjun; Yan, Yuzhong; Zhang, Pengyue; Zhang, Wei; Xia, Rong

2017-11-01

Stroke may cause neuropsychiatric problems, which have negative effects on cognitive functions and behavior. Exercise plays an important role in reducing the occurrence and development of stroke, the concrete mechanism is not fully clarified. In this study, we attempted to determine whether early treadmill exercise attenuates anxiety-like behavior by regulation of inflammation after brain ischemia. We subjected adult male rats to middle cerebral artery occlusion (MCAO) for 90 min and trained rats started to run on a treadmill from postoperative day 1 to day 14. The effects of treadmill on cognitive functions, anxiety-like behavior, and immune activation were analyzed by Morris water maze test, open field test, elevated plus maze test, and enzyme-linked immunosorbent assay. Early treadmill exercise significantly improved cognitive function, alleviated anxiety-like behavior in ischemic rats model; this improvement was associated with significantly decreased activation of astrocytes and microglia cells and proinflammatory markers (platelet-activating factor [PAF], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], intercellular adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1 [VCAM-1]). Our results indicated that early treadmill exercise attenuated anxiety-like behavior by decreasing inflammation response, exercise conferred a great benefit of attenuating anxiety-like behavior via anti-inflammatory treatment may prove to be a novel neuroprotective strategy for stroke.

Postischemic changes in the immunophilin FKBP12 in the rat brain.

PubMed

Kato, H; Oikawa, T; Otsuka, K; Takahashi, A; Itoyama, Y

2000-12-08

An immunosuppressant tacrolimus (FK506) protects against neuronal damage following cerebral ischemia. On the other hand, the major physiological role of the immunophilin FK506-binding protein-12 (FKBP12) is a modulation of intracellular calcium flux. Since an increase in intracellular calcium concentration is a major mediator of ischemic neuronal death, we investigated the changes in FKBP12 following cerebral ischemia in the rat. We induced focal cerebral ischemia by intraluminal occlusion of the middle cerebral artery for 1 h, and global cerebral ischemia for 10 min by bilateral carotid artery occlusion combined with hypotension. The animals were killed at 4 h to 7 days after reperfusion. Immunohistochemistry was performed on paraffin sections using a monoclonal antibody raised against recombinant FKBP12. Immunoreactivity to FKBP12 in control brains was most pronounced in the CA1 subfield of the hippocampus and the striatum, the localization being primarily neuronal. Following focal ischemia, FKBP12 immunoreactivity decreased rapidly in the ischemic core by 4 h, but increased in surviving neurons in penumbra areas (4 h-7 days). Within an area of infarction, invading leukocytes and macrophages exhibited immunoreactivity to FKBP12 (3-7 days). Following global ischemia, FKBP12 immunoreactivity in CA1 neurons decreased after 1 day, and then it was lost between 2 and 7 days, although many CA1 neurons showed a transient increase in FKBP12 at 2 days. No FKBP12 immunoreactivity was observed in reactive glial cells. Thus, FKBP12 declined in dying neurons, whereas FKBP12 was upregulated in less severely injured neurons. The findings suggest that (1) FKBP12 plays an important role in the process of neuronal survival and death following cerebral ischemia, and (2) FKBP12 is involved in inflammatory reactions that occur within an area of infarction.

Early fibrinogen degradation coagulopathy: a predictive factor of parenchymal hematomas in cerebral rt-PA thrombolysis.

PubMed

Sun, Xuhong; Berthiller, Julien; Trouillas, Paul; Derex, Laurent; Diallo, Laho; Hanss, Michel

2015-04-15

The purpose of this study was to systematically determine the correlations between the post-thrombolytic changes of hemostasis parameters and the occurrence of early intracerebral hemorrhage (ICH). In 72 consecutive patients with cerebral infarcts treated with rt-PA, plasma levels of fibrinogen, plasminogen, alpha2-antiplasmin, factor XIII, fibrin(ogen) degradation products (FDPs) and d-Dimers were measured at baseline, 2 and 24h after thrombolysis. Correlations were studied between the hemostasis events and early (less than 24h) hemorrhagic infarcts (HIs) or parenchymatous hematomas (PH). Of 72 patients, 6 patients (8.3%) had early PHs, 11 (15.3%) had early HIs, and 55 (76.4%) had no bleeding. Early HIs were not linked to any hemostasis parameter at any time. Univariate comparison of patients having early PHs with non-bleeding patients showed hemostasis abnormalities at 2h: high FDP (p=0.01), high Log FDP (p=0.01), low fibrinogen (p=0.01), and low Log fibrinogen (p=0.01). Logistic regression adjusted for age, NIHSS and diabetes confirmed these 2hour predictors: Log FDP (OR: 7.50; CI: 1.26 to 44.61, p=0.03), and Log fibrinogen (OR: 19.32; CI: 1.81 to 205.98, p=0.01). The decrease in fibrinogen less than 2g/L multiplies the odds of early PH by a factor 12.82. An early fibrinogen degradation coagulopathy involving an increase of FDP and a massive consumption of circulating fibrinogen is predictive of early parenchymal hematomas, indicating the occurrence of a particularly intense lysis of circulating fibrinogen. These results, if confirmed by future studies, suggest that early assays of fibrinogen and FDP may be useful in predicting the risk of post-thrombolytic intracerebral hematoma. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of an ion-pair HPLC method for investigation of energy charge changes in cerebral ischemia of mice and hypoxia of Neuro-2a cell line.

PubMed

Chen, Yunyun; Xing, Dongming; Wang, Wei; Ding, Yi; Du, Lijun

2007-06-01

The determination of adenine nucleotides and energy charge (EC) has great importance in the characterization of cerebral ischemic injury and post-ischemic recovery. An IP-HPLC method was developed for the quantification of AMP, ADP, ATP and EC in cerebral ischemia and hypoxia of the Neuro-2a cell line. The chromatographic conditions were: a Zorbax SB-C18 reversed-phase column; mobile phase 100 mM KH(2)PO(4), 1 mM tetrabutylammonium hydroxide, and 2.5% acetonitrile, brought to pH 7.0 with potassium hydroxide (4 M), filtered through a 0.45 microm Millipore filter and degassed prior to use. The flow-rate was 1.0 mL/min. The injection volume was 20 microL. Detection was performed at a wavelength of 254 nm under a constant temperature (27 +/- 1 degrees C). The method was validated by means of linearity, using calibration curves constructed with five concentration levels of each compound. The limit of detection was also determined. The system precision was calculated as the coefficient of variation for five injections for each compound tested. Cerebral tissue was homogenized (4 degrees C) in 1 mL of an ice-cold 6% trichloroacetic acid that contained ATPase inhibitor and obtained good recovery (>90%). The results show that the described method for the determination of adenine nucleotides by HPLC has good linearity, limit of detection, precision and specificity, and is simple and rapid to perform. Copyright 2007 John Wiley & Sons, Ltd.

Early primary biliary cholangitis is characterised by brain abnormalities on cerebral magnetic resonance imaging.

PubMed

Grover, V P B; Southern, L; Dyson, J K; Kim, J U; Crossey, M M E; Wylezinska-Arridge, M; Patel, N; Fitzpatrick, J A; Bak-Bol, A; Waldman, A D; Alexander, G J; Mells, G F; Chapman, R W; Jones, D E J; Taylor-Robinson, S D

2016-11-01

Brain change can occur in primary biliary cholangitis (PBC), potentially as a result of cholestatic and/or inflammatory processes. This change is linked to systemic symptoms of fatigue and cognitive impairment. To identify whether brain change occurs early in PBC. If the change develops early and is progressive, it may explain the difficulty in treating these symptoms. Early disease brain change was explored in 13 patients with newly diagnosed biopsy-proven precirrhotic PBC using magnetisation transfer, diffusion-weighted imaging and 1 H magnetic resonance spectroscopy. Results were compared to 17 healthy volunteers. Cerebral magnetisation transfer ratios were reduced in early PBC, compared to healthy volunteers, in the thalamus, putamen and head of caudate with no greater reduction in patients with greater symptom severity. Mean apparent diffusion coefficients were increased in the thalamus only. No 1 H magnetic resonance spectroscopy abnormalities were seen. Serum manganese levels were elevated in all PBC patients, but no relationship was seen with imaging or symptom parameters. There were no correlations between neuroimaging data, laboratory data, symptom severity scores or age. This is the first study to be performed in this precirrhotic patient population, and we have highlighted that neuroimaging changes are present at a much earlier stage than previously demonstrated. The neuroimaging abnormalities suggest that the brain changes seen in PBC occur early in the pathological process, even before significant liver damage has occurred. If such changes are linked to symptom pathogenesis, this could have important implications for the timing of second-line-therapy use. © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Acute posterior multifocal placoid pigment epitheliopathy associated with cerebral vasculitis.

PubMed

Weinstein, J M; Bresnick, G H; Bell, C L; Roschmann, R A; Brooks, B R; Strother, C M

1988-09-01

Acute multifocal posterior placoid pigment epitheliopathy (APMPPE) is an unusual self-limited retinal disorder that has been associated with various systemic complications. To our knowledge, three prior cases associated with cerebral vasculitis have been described. This article describes a patient with APMPPE and angiographically documented cerebral vasculitis who was notable because of (a) the presence of two different cerebral ischemic events, occurring 1 month apart, and (b) the long latency (3 months) between the onset of ocular symptoms and the second cerebral ischemic event. Recognition of the association between APMPPE and cerebral vasculitis may permit early treatment of CNS involvement and prevention of morbidity.

Edaravone, a free radical scavenger, attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

PubMed

Okamura, Koichi; Tsubokawa, Tamiji; Johshita, Hiroo; Miyazaki, Hiroshi; Shiokawa, Yoshiaki

2014-01-01

Thrombolysis due to acute ischemic stroke is associated with the risk of hemorrhagic infarction, especially after reperfusion. Recent experimental studies suggest that the main mechanism contributing to hemorrhagic infarction is oxidative stress caused by disruption of the blood-brain barrier. Edaravone, a free radical scavenger, decreases oxidative stress, thereby preventing hemorrhagic infarction during ischemia and reperfusion. In this study, we investigated the effects of edaravone on hemorrhagic infarction in a rat model of hemorrhagic transformation. We used a previously established hemorrhagic transformation model of rats with hyperglycemia. Hyperglycemia was induced by intraperitoneal injection of glucose to all rats (n  =  20). The rats with hyperglycemia showed a high incidence of hemorrhagic infarction. Middle cerebral artery occlusion (MCAO) for 1.5 hours followed by reperfusion for 24 hours was performed in edaravone-treated rats (n  =  10) and control rats (n  =  10). Upon completion of reperfusion, both groups were evaluated for infarct size and hemorrhage volume and the results obtained were compared. Edaravone significantly decreased infarct volume, with the average infarct volume in the edaravone-treated rats (227.6 mm(3)) being significantly lower than that in the control rats (264.0 mm(3)). Edaravone treatment also decreased the postischemic hemorrhage volumes (53.4 mm(3) in edaravone-treated rats vs 176.4 mm(3) in controls). In addition, the ratio of hemorrhage volume to infarct volume was lower in the edaravone-treated rats (23.5%) than in the untreated rats (63.2%). Edaravone attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia.

Low molecular weight fibroblast growth factor-2 signals via protein kinase C and myofibrillar proteins to protect against postischemic cardiac dysfunction.

PubMed

Manning, Janet R; Perkins, Sarah O; Sinclair, Elizabeth A; Gao, Xiaoqian; Zhang, Yu; Newman, Gilbert; Pyle, W Glen; Schultz, Jo El J

2013-05-15

Among its many biological roles, fibroblast growth factor-2 (FGF2) acutely protects the heart from dysfunction associated with ischemia/reperfusion (I/R) injury. Our laboratory has demonstrated that this is due to the activity of the low molecular weight (LMW) isoform of FGF2 and that FGF2-mediated cardioprotection relies on the activity of protein kinase C (PKC); however, which PKC isoforms are responsible for LMW FGF2-mediated cardioprotection, and their downstream targets, remain to be elucidated. To identify the PKC pathway(s) that contributes to postischemic cardiac recovery by LMW FGF2, mouse hearts expressing only LMW FGF2 (HMWKO) were bred to mouse hearts not expressing PKCα (PKCαKO) or subjected to a selective PKCε inhibitor (εV(1-2)) before and during I/R. Hearts only expressing LMW FGF2 showed significantly improved postischemic recovery of cardiac function following I/R (P < 0.05), which was significantly abrogated in the absence of PKCα (P < 0.05) or presence of PKCε inhibition (P < 0.05). Hearts only expressing LMW FGF2 demonstrated differences in actomyosin ATPase activity as well as increases in the phosphorylation of troponin I and T during I/R compared with wild-type hearts; several of these effects were dependent on PKCα activity. This evidence indicates that both PKCα and PKCε play a role in LMW FGF2-mediated protection from cardiac dysfunction and that PKCα signaling to the contractile apparatus is a key step in the mechanism of LMW FGF2-mediated protection against myocardial dysfunction.

Postischemic dementia with Alzheimer phenotype: selectively vulnerable versus resistant areas of the brain and neurodegeneration versus β-amyloid peptide.

PubMed

Pluta, Ryszard; Jabłoński, Mirosław; Czuczwar, Stanisław J

2012-01-01

The road to clarity for postischemic dementia mechanisms has been one fraught with a wide range of complications and numerous revisions with a lack of a final solution. Importantly, brain ischemia is a leading cause of death and cognitive impairment worldwide. However, the mechanisms of progressive cognitive decline following brain ischemia are not yet certain. Data from animal models and clinical pioneering studies of brain ischemia have demonstrated an increase in expression and processing of amyloid precursor protein to a neurotoxin oligomeric β-amyloid peptide. Functional and memory brain restoration after ischemic brain injury is delayed and incomplete due to a lesion related increase in the amount of the neurotoxin amyloid protein. Moreover, ischemic injury is strongly accelerated by aging, too. In this review, we will present our current thinking about biogenesis of amyloid from the amyloid precursor protein in ischemic brain injury, and how this factor presents etiological, therapeutic and diagnostic targets that are now under consideration. Progressive injury of the ischemic brain parenchyma may be caused not only by degeneration of selectively vulnerable neurons destroyed during ischemia but also by acute and chronic damage of resistant areas of the brain and progressive damage in the blood-brain barrier. We propose that in postischemic dementia an initial ischemic injury precedes the cerebrovascular and brain parenchyma accumulation of Alzheimer disease related neurotoxin β-amyloid peptide, which in turn amplifies the neurovascular dysfunction triggering focal ischemic episodes as a vicious cycle preceding final neurodegenerative pathology. Persistent ischemic blood-brain barrier insufficiency with accumulation of neurotoxin β-amyloid protein in the brain tissue, especially in extracellular perivascular space and blood-brain barrier microvessels, may gradually, over a lifetime, progress to brain atrophy and to full-blown ischemic dementia with

Cerebral infarction caused by traumatic carotid artery dissection.

PubMed

Bayır, Ayşegül; Aydoğdu Kıreşi, Demet; Söylemez, Ali; Demirci, Osman

2012-07-01

Traumatic carotid artery dissection, if not diagnosed and treated early, is a serious problem with permanent neurological deficit and a high mortality rate of up to 40%. We present a case with delayed diagnosis of traumatic carotid artery dissection in a 21-year-old female. While there were no ischemic infarct findings on the admission cerebral computerized tomography (CT), such findings were observed on two cerebral CTs taken because of the left hemiplegia noticed seven days later when the patient regained consciousness. The patient was referred to our emergency service, and definitive diagnosis was achieved with arterial Doppler ultrasonography, cerebral magnetic resonance imaging (MRI), diffusion MRI, and MR angiography. We did not consider invasive treatment since the neurological damage was permanent and dissection grade was IV according to angiography findings. The case was discharged within a week and physiotherapy was advised. Despite the advances in diagnostic methods, diagnosis of traumatic carotid artery dissection is still missed or delayed, as in the case presented here. Early diagnosis can ameliorate permanent neurological damage or even prevent it. However, the vital factors for early diagnosis are the obtained anamnesis leading to appropriate radiological examinations, detailed physical examination and high clinical suspicion.

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

Effects of edaravone, the free radical scavenger, on outcomes in acute cerebral infarction patients treated with ultra-early thrombolysis of recombinant tissue plasminogen activator.

PubMed

Lee, Xian-Ru; Xiang, Gui-Ling

2018-04-01

Edaravone, a free radical scavenger, alleviates blood-brain barrier disruption in conjunction with suppression of the inflammatory reaction in acute cerebral infarction. Thrombolysis with recombinant tissue plasminogen activator (rtPA) is an established therapy for acute cerebral infarction patients. The purpose of this study was to assess the effects of edaravone on outcomes in acute cerebral infarction patients treated with ultra-early thrombolysis of iv-rt-PA. We conducted a retrospective cohort study using the database of Ningbo First Hospital. We identified patients who were admitted with a primary diagnosis of acute cerebral infarction and treated with intravenous rtPA(iv-rtPA) within 3 h of symptom onset from March 1st in 2014 to October 31st in 2016.Thenceforth,the patients were divided into 2 groups by treatment with(edaravone group) or without edaravone(non-edaravone group). Glasgow Coma Scale (GCS) scores and mRS score at admission were used. Clinical background, risk factors for acute cerebral infarction hemorrhagic transformation, 7-day mortality, recanalization rate, bleeding complications and blood rheology indexes were collected. We also collected the following factors: National Institutes of Health Stroke Scale scores, barthel index. 136 patients treated without edaravone during hospitalization were selected in non-edaravone group while edaravone group included 132 patients treated with edaravone during hospitalization. The patient baseline distributions were well balanced between non-edaravone group and edaravone group. The rate of hemorrhagic transformation in non-edaravone group was higher than that in edaravone group (P ＜ 0.05). The NIHSS scores 7 days and 14 days after symptom onset were higher in non-edaravone group than in edaravone group (both P ＜ 0.05). Edaravone group showed a higher recanalization rate and a lower bleeding complications rate at discharge than the non-edaravone group (both P ＜ 0.05). The differences of

Post-ischemic conditioning in the rat retina is dependent upon ischemia duration and is not additive with ischemic pre-conditioning.

PubMed

Dreixler, John C; Shaikh, Afzhal R; Alexander, Michael; Savoie, Brian; Roth, Steven

2010-12-01

Ischemic pre-conditioning (IPC) provides neuroprotection in the rat retina from the damaging effects of severe ischemia. Recently, neuroprotection by retinal ischemic post-conditioning (Post-C), i.e., transient ischemia after more lengthy, damaging ischemia, was described, but its mechanisms are not yet known. One possible explanation of the effectiveness of Post-C is that it augments intrinsic neuroprotective mechanisms initiated during ischemia. Increasing duration of the damaging ischemic insult may therefore impact the effectiveness of Post-C. IPC, in contrast, sets in motion a series of neuroprotective events prior to the onset of ischemia. Thus, IPC and Post-C may operate by differing mechanisms. Accordingly, we examined the effect of retinal ischemic duration on post-ischemic outcome in vivo in rats after adding Post-C, and the impact of combining pre- and post-conditioning. Recovery after ischemia performed 24 h after IPC, or after Post-C performed 5 min after ischemia ended, was assessed functionally (electroretinography) and histologically at 7 days after ischemia. Durations of ischemia of 45 and 55 min were studied. Since recovery with IPC or Post-C alone, with 55 min of ischemia, did not achieve the same degree of effect (i.e., not complete recovery) exhibited in our previous studies of IPC using a different ischemia model, we also combined IPC and Post-C to test the hypothesis of the possible additive effects of the IPC and Post-C. We found that the recovery after Post-C was enhanced to a greater degree when ischemia was of longer duration. Post-C led to greater post-ischemic recovery compared to IPC. Both IPC and Post-C also attenuated structural damage to the retina. Contrary to our hypothesis, IPC and Post-C did not combine to enhance recovery after ischemia. In earlier studies, IPC attenuated post-ischemic apoptosis. To begin to examine the mechanism of Post-C, we studied its impact on apoptosis following ischemia. We examined apoptosis by

Working memory and fine motor skills predict early numeracy performance of children with cerebral palsy.

PubMed

Van Rooijen, Maaike; Verhoeven, Ludo; Steenbergen, Bert

2016-01-01

Early numeracy is an important precursor for arithmetic performance, academic proficiency, and work success. Besides their apparent motor difficulties, children with cerebral palsy (CP) often show additional cognitive disturbances. In this study, we examine whether working memory, non-verbal intelligence, linguistic skills, counting and fine motor skills are positively related to the early numeracy performance of 6-year-old children with CP. A total of 56 children (M = 6.0, SD = 0.61, 37 boys) from Dutch special education schools participated in this cross-sectional study. Of the total group, 81% of the children have the spastic type of CP (33% unilateral and 66% bilateral), 9% have been diagnosed as having diskinetic CP, 8% have been diagnosed as having spastic and diskinetic CP and 2% have been diagnosed as having a combination of diskinetic and atactic CP. The children completed standardized tests assessing early numeracy performance, working memory, non-verbal intelligence, sentence understanding and fine motor skills. In addition, an experimental task was administered to examine their basic counting performance. Structural equation modeling showed that working memory and fine motor skills were significantly related to the early numeracy performance of the children (β = .79 and p < .001, β = .41 and p < .001, respectively). Furthermore, counting was a mediating variable between working memory and early numeracy (β = .57, p < .001). Together, these findings highlight the importance of working memory for early numeracy performance in children with CP and they warrant further research into the efficacy of intervention programs aimed at working memory training.

A new strategy of CyberKnife treatment system based radiosurgery followed by early use of adjuvant bevacizumab treatment for brain metastasis with extensive cerebral edema.

PubMed

Wang, Yang; Wang, Enmin; Pan, Li; Dai, Jiazhong; Zhang, Nan; Wang, Xin; Liu, Xiaoxia; Mei, Guanghai; Sheng, Xiaofang

2014-09-01

Bevacizumab blocks the effects of vascular endothelial growth factor in leakage-prone capillaries and has been suggested as a new treatment for cerebral radiation edema and necrosis. CyberKnife is a new, frameless stereotactic radiosurgery system. This work investigated the safety and efficacy of CyberKnife followed by early bevacizumab treatment for brain metastasis with extensive cerebral edema. The eligibility criteria of the patients selected for radiosurgery followed by early use of adjuvant bevacizumab treatment were: (1) brain tumors from metastasis with one solitary brain lesion and symptomatic extensive cerebral edema; (2) >18 years of age; (3) the patient refused surgery due to the physical conditions and the risk of surgery; (4) no contraindications for bevacizumab. (5) bevacizumab was applied for a minimum of 2 injections and a maximum of 6 injections with a 2-week interval between treatments, beginning within 2 weeks of the CyberKnife therapy; (6) Karnofsky performance status (KPS) ≥30. Tumor size and edema were monitored by magnetic resonance imaging (MRI). Dexamethasone dosage, KPS, adverse event occurrence and associated clinical outcomes were also recorded. Eight patients were accrued for this new treatment. Radiation dose ranged from 20 to 33 Gy in one to five sessions, prescribed to the 61-71 % isodose line. Bevacizumab therapy was administered 3-10 days after completion of CyberKnife treatment for a minimum of two cycles (5 mg/kg, at 2-week intervals). MRI revealed average reductions of 55.8 % (post-gadolinium) and 63.4 % (T2/FLAIR). Seven patients showed significant clinical neurological improvements. Dexamethasone was reduced in all patients, with five successfully discontinuing dexamethasone treatment 4 weeks after bevacizumab initiation. Hypertension, a bevacizumab-related adverse event, occurred in one patient. After 3-8 months, all patients studied were alive and primary brain metastases were under control, 2 developed new brain

Early Numeracy in Cerebral Palsy: Review and Future Research

ERIC Educational Resources Information Center

van Rooijen, Maaike; Verhoeven, Ludo; Steenbergen, Bert

2011-01-01

Children with cerebral palsy (CP) often have problems with arithmetic, but the development of numerical abilities in these children has received only minor attention. In comparison, detailed accounts have been written on the arithmetic abilities of typically developing children, but a theoretical framework is still lacking. A promising perspective…

Resistance to Reperfusion Injury Following Short Term Postischemic Administration of Natural Honey in Globally Ischemic Isolated Rat Heart

PubMed Central

Vaez, Haleh; Samadzadeh, Mehrban; Zahednezhad, Fahimeh; Najafi, Moslem

2012-01-01

Purpose: Results of our previous study revealed that preischemic perfusion of honey before zero flow global ischemia had cardioprotective effects in rat. The present study investigated potential resistance to reperfusion injury following short term postischemic administration of natural honey in globally ischemic isolated rat heart. Methods: Male Wistar rats were divided into five groups (n=10-13). The rat hearts were isolated, mounted on a Langendorff apparatus, allowed to equilibrate for 30 min then subjected to 30 min global ischemia. In the control group, the hearts were reperfused with drug free normal Krebs-Henseleit (K/H) solution before ischemia and during 120 min reperfusion. In the treatment groups, reperfusion was initiated with K/H solution containing different concentration of honey (0.25, 0.5, 1 and 2%) for 15 min and was resumed until the end of 120 min with normal K/H solution. Results: In the control group, VEBs number was 784±199, while in honey concentration of 0.25, 0.5, 1 and 2%, it decreased to 83±23 (P<0.001), 138±48 (P<0.01), 142±37 (P<0.001) and 157±40 (P<0.01), respectively. Number and duration of VT and time spent in reversible VF were also reduced by honey. In the control group, the infarct size was 54.1±7.8%, however; honey (0.25, 0.5, 1 and 2%) markedly lowered the value to 12.4±2.4, 12.7±3.3, 11.3±2.6 and 7.9±1.7 (P<0.001), respectively. Conclusion: Postischemic administration of natural honey in global ischemia showed protective effects against ischemia/reperfusion (I/R) injuries in isolated rat heart. Antioxidant and radical scavenging activity, lipoperoxidation inhibition, reduction of necrotized tissue, presence of rich energy sources, various type of vitamins, minerals and enzymes and formation of NO-contain metabolites may probably involve in those cardioprotective effects. PMID:24312792

Type 2 diabetes impairs the ability of skeletal muscle pericytes to augment postischemic neovascularization in db/db mice.

PubMed

Hayes, Katherine L; Messina, Louis M; Schwartz, Lawrence M; Yan, Jinglian; Burnside, Amy S; Witkowski, Sarah

2018-05-01

Peripheral artery disease is an atherosclerotic occlusive disease that causes limb ischemia and has few effective noninterventional treatments. Stem cell therapy is promising, but concomitant diabetes may limit its effectiveness. We evaluated the therapeutic potential of skeletal muscle pericytes to augment postischemic neovascularization in wild-type and type 2 diabetic (T2DM) mice. Wild-type C57BL/6J and leptin receptor spontaneous mutation db/db T2DM mice underwent unilateral femoral artery excision to induce limb ischemia. Twenty-four hours after ischemia induction, CD45 - CD34 - CD146 + skeletal muscle pericytes or vehicle controls were transplanted into ischemic hindlimb muscles. At postoperative day 28, pericyte transplantation augmented blood flow recovery in wild-type mice (79.3 ± 5% vs. 61.9 ± 5%; P = 0.04), but not in T2DM mice (48.6% vs. 46.3 ± 5%; P = 0.51). Pericyte transplantation augmented collateral artery enlargement in wild-type (26.7 ± 2 μm vs. 22.3 ± 1 μm, P = 0.03), but not T2DM mice (20.4 ± 1.4 μm vs. 18.5 ± 1.2 μm, P = 0.14). Pericyte incorporation into collateral arteries was higher in wild-type than in T2DM mice ( P = 0.002). Unexpectedly, pericytes differentiated into Schwann cells in vivo. In vitro, Insulin increased Nox2 expression and decreased tubular formation capacity in human pericytes. These insulin-induced effects were reversed by N-acetylcysteine antioxidant treatment. In conclusion, T2DM impairs the ability of pericytes to augment neovascularization via decreased collateral artery enlargement and impaired engraftment into collateral arteries, potentially via hyperinsulinemia-induced oxidant stress. While pericytes show promise as a unique form of stem cell therapy to increase postischemic neovascularization, characterizing the molecular mechanisms by which T2DM impairs their function is essential to achieve their therapeutic potential.

Implied functional crossed cerebello-cerebral diaschisis and interhemispheric compensation during hand grasping more than 20 years after unilateral cerebellar injury in early childhood.

PubMed

Nakahachi, Takayuki; Ishii, Ryouhei; Canuet, Leonides; Iwase, Masao

2015-01-01

Crossed cerebello-cerebral diaschisis (CCCD) conventionally refers to decreased resting cerebral activity caused by injury to the contralateral cerebellum. We investigated whether functional activation of a contralesional cerebral cortical region controlling a specific task is reduced during task performance in a patient with a unilateral cerebellar lesion. We also examined functional compensation by the corresponding ipsilesional cerebral cortex. It was hypothesized that dysfunction of the primary sensorimotor cortex (SM1) contralateral to the cerebellar lesion would be detected together with a compensatory increase in neural activity of the ipsilesional SM1. To test these possibilities, we conducted non-invasive functional neuroimaging techniques for bilateral SM1 during hand grasping, a task known to activate predominantly the SM1 contralateral to the grasping hand. Activity in SM1 during hand grasping was measured electrophysiologically by magnetoencephalography and hemodynamically by near-infrared spectroscopy in an adult with mild right hemiataxia associated with a large injury of the right cerebellum due to resection of a tumor in early childhood. During left hand grasping, increased neural activity was detected predominantly in the right SM1, the typical developmental pattern. In contrast, neural activity increased in the bilateral SM1 with slight right-side dominance during right (ataxic) hand grasping. This study reported a case that implied functional CCCD and compensatory neural activity in the SM1 during performance of a simple hand motor task in an adult with unilateral cerebellar injury and mild hemiataxia 24 years prior to the study without rehabilitative interventions. This suggests that unilateral cerebellar injuries in early childhood may result in persistent functional abnormalities in the cerebrum into adulthood. Therapeutic treatments that target functional CCCD and interhemispheric compensation might be effective for treating ataxia due to

Does peripartum infection increase the incidence of cerebral palsy in extremely low birthweight infants?

PubMed

Costantine, Maged M; How, Helen Y; Coppage, Kristin; Maxwell, Rose A; Sibai, Baha M

2007-05-01

This study was undertaken to determine the perinatal predictors of cerebral palsy in extremely low birthweight infants (<1000 g). A case control study of infants with birthweight of less than 1000 g (19 with cerebral palsy and 38 controls) who survived beyond 18-22 months of corrected age was performed. Outcome variables included maternal demographics, obstetric complications, and neonatal outcome (gestational age at delivery, birthweight, Apgar scores, intrauterine growth restriction, respiratory distress syndrome, intraventricular hemorrhage, and neonatal sepsis). Data analysis consisted of t tests, chi2, and analysis of variance when appropriate. There were no significant differences between cerebral palsy and control groups with regard to mode of delivery, Apgar scores, preeclampsia, antenatal vaginal bleeding, or the use of magnesium sulfate. However, male gender (odds ratio 3.70; 95% CI 1.05-12.5), primigravid status (odds ratio 5.52; 95% CI 1.67-18.3), early neonatal sepsis (odds ratio 12.9; 95% CI 2.94-57.2) and chorioamnionitis, both clinical and histologic (odds ratio 3.71; 95% CI 1.16-11.9) were significantly associated with the development of cerebral palsy. The strong association between cerebral palsy and chorioamnionitis, as well as early neonatal sepsis, remain significant after adjustment for primigravid status and male gender. In extremely low birthweight infants, cerebral palsy was strongly associated with chorioamnionitis, early neonatal sepsis, male gender, and primigravid status.

Protective effect of cilazapril on the cerebral circulation.

PubMed

Véniant, M; Clozel, J P; Kuhn, H; Clozel, M

1992-01-01

The goal of an antihypertensive treatment is to prevent "end-organ" damage. Cerebral vascular complications are among the most important because they are life threatening and can occur even at an early stage of the disease. Recently, it has been shown that cilazapril can decrease the mortality of stroke-prone rats, suggesting a decrease in the incidence of strokes, which occur spontaneously in these animals. The present article reviews the different functional and morphological changes that may explain the cerebral protective effects of cilazapril, such as the normalization of cerebral vascular reserve, decrease in the media, increase in the external diameter, and normalization of the mechanics and endothelial function of cerebral arterioles. In addition, the inhibition by cilazapril of injury-induced proliferation of smooth muscle cells and the infiltration of the endothelium by macrophages could prevent the development of atherosclerosis.

Management of Spasticity in Children with Cerebral Palsy

PubMed Central

Shamsoddini, Alireza; Amirsalari, Susan; Hollisaz, Mohammad-Taghi; Rahimnia, Alireza; Khatibi-Aghda, Amideddin

2014-01-01

Cerebral palsy is the most common cause of spasticity and physical disability in children and spasticity is one of the commonest problems in those with neurological disease. The management of spasticity in children with cerebral palsy requires a multidisciplinary effort and should be started as early as possible. There are a number of treatments available for the management of spasticity. This article reviews the variety of options available for the clinical management of spasticity. PMID:25755853

The tonic response to the infant knee jerk as an early sign of cerebral palsy.

PubMed

Hamer, Elisa G; La Bastide-Van Gemert, Sacha; Boxum, Anke G; Dijkstra, Linze J; Hielkema, Tjitske; Jeroen Vermeulen, R; Hadders-Algra, Mijna

2018-04-01

Early identification of infants at risk of cerebral palsy (CP) is desirable in order to provide early intervention. We previously demonstrated differences in knee jerk responses between 3-month-old high risk and typically developing infants. To improve early identification by investigating whether the presence of tonic responses (continuous muscle activity occurring after the typical phasic response), clonus or contralateral responses to the knee jerk during infancy is associated with CP. Longitudinal EMG-study. We included 34 high-risk infants (median gestational age 31.9 weeks) who participated in the LEARN2MOVE 0-2 years trial. Video-recorded knee jerk EMG-assessments were performed during infancy (1-4 times). Developmental outcome was assessed at 21 months corrected age (CA). Binomial generalized estimating equations models with repeated measurements were fitted using predictor variables. Infants who later were diagnosed with CP (n = 18) showed more often than infants who were not diagnosed with CP i) tonic responses - from 4 months CA onwards, ii) clonus - from 13 months CA onwards, and iii) contralateral responses - from 15 months CA onwards. The main limitation is the relatively small sample size. The assessment of tonic responses to the knee jerk using EMG may be a valuable add-on tool to appraise a high risk of CP. Copyright © 2018 Elsevier B.V. All rights reserved.

11 Things to Know about Cerebral Palsy

MedlinePlus

... Button Past Emails 11 Things to Know about Cerebral Palsy Language: English (US) Español (Spanish) Recommend on Facebook ... and families living with CP. Early Signs of CP From birth to 5 years of age, a ...

The effect of cerebral palsy on arithmetic accuracy is mediated by working memory, intelligence, early numeracy, and instruction time.

PubMed

Jenks, Kathleen M; de Moor, Jan; van Lieshout, Ernest C D M; Maathuis, Karel G B; Keus, Inge; Gorter, Jan Willem

2007-01-01

The development of addition and subtraction accuracy was assessed in first graders with cerebral palsy (CP) in both mainstream (16) and special education (41) and a control group of first graders in mainstream education (16). The control group out-performed the CP groups in addition and subtraction accuracy and this difference could not be fully explained by differences in intelligence. Both CP groups showed evidence of working memory deficits. The three groups exhibited different developmental patterns in the area of early numeracy skills. Children with CP in special education were found to receive less arithmetic instruction and instruction time was positively related to arithmetic accuracy. Structural equation modeling revealed that the effect of CP on arithmetic accuracy is mediated by intelligence, working memory, early numeracy, and instruction time.

[Trismus, pseudobulbar syndrome and cerebral deep venous thrombosis].

PubMed

Alecu, C; De Bray, J M; Penisson-Besnier, I; Pasco-Papon, A; Dubas, F

2001-03-01

We report a case of cerebral deep venous thrombosis that manifested clinically by a pseudobulbar syndrome with major trismus, abnormal movements and static cerebellar syndrome. To our knowledge, only three other cases of deep cerebral venous thrombosis associated with cerebellar or pseudobulbar syndrome have been published since 1985. The relatively good prognosis in our patient could be explained by the partially intact internal cerebral veins as well as use of early anticoagulant therapy. There was a spontaneous hyperdensity of the falx cerebri and the tentorium cerebelli on the brain CT scan, an aspect highly contributive to diagnosis. This hyperdensity of the falx cerebri was found in 19 out of 22 cases of deep venous thrombosis detailed in the literature.

Pathogenesis, diagnosis and treatment of cerebral fat embolism.

PubMed

Zhou, Yihua; Yuan, Ying; Huang, Chahua; Hu, Lihua; Cheng, Xiaoshu

2015-01-01

In this study, we analyzed two cases of pure cerebral fat embolism and reviewed related literatures to explore the pathogenesis, clinical manifestations, diagnosis and treatment of cerebral fat embolism, improve the treatment efficiency and reduce the misdiagnosis rate. In our cases, patients fully returned to consciousness at the different times with good prognosis, normal vital signs and without obvious sequelae. For patients with the limb fractures, who developed coma without chest distress, dyspnea or other pulmonary symptoms 12 or 24 h post injury, cerebral fat embolism should be highly suspected, except for those with intracranial lesions, such as delayed traumatic intracerebral hemorrhage, etc. The early diagnosis and comprehensive treatment can improve prognosis.

Deep Hypothermic Circulatory Arrest vs. Antegrade Cerebral Perfusion in Cerebral Protection during the Surgical Treatment of Chronic Dissection of the Ascending and Arch Aorta

PubMed Central

Kamenskaya, Oksana Vasilyevna; Klinkova, Asya Stanislavovna; Chernyavsky, Alexander Mikhailovich; Lomivorotov, Vladimir Vladimirovich; Meshkov, Ivan Olegovich; Karaskov, Alexander Mikhailovich

2017-01-01

Abstract: Circulatory arrest during aortic surgery presents a risk of neurological complications. The present study aimed to investigate the effectiveness of deep hypothermic circulatory arrest (DHCA) vs. antegrade cerebral perfusion (ACP) in cerebral protection during the surgical treatment of chronic dissection of the ascending and arch aorta and to assess the quality-of-life (QoL) in the long-term postoperative period with respect to the used cerebral protection method. In a prospective, randomized study, 58 patients with chronic type I aortic dissection who underwent ascending aorta and aortic arch replacement surgery were included. Patients were allocated in two groups: 29 patients who underwent surgery under moderate hypothermia (24°C) combined with ACP and 29 patients who underwent surgery under DHCA (18°C) with craniocerebral hypothermia. The regional hemoglobin oxygen saturation (rSO2, %) were compared during surgery, neurological complications were analyzed during the early postoperative period, QoL was compared in the long-term postoperative period (1-year follow-up). During the early postoperative period, 37.9% of patients in the DHCA group exhibited neurological complications, compared with 13.8% of those in the ACP group (p < .05). The risk of neurological complications in the early postoperative period was dependent on the extent of rSO2 decrease during circulatory arrest. In the ACP group, rSO2 decreased by ≤17% from baseline during circulatory arrest. In the DHCA group, a more profound decrease in rSO2 (>30%) was recorded (p < .05). QoL in the long-term period after surgery improved, but it was not dependent on the cerebral protection method used during surgery. ACP during aortic replacement demonstrated the most advanced properties of cerebral protection that can be evidenced by a lesser degree of neurological complications, compared with patients who underwent surgery under conditions of DHCA. QoL after surgery was not dependent on the

The importance of regulation of blood glucose levels through activation of peripheral 5'-AMP-activated protein kinase on ischemic neuronal damage.

PubMed

Harada, Shinichi; Fujita-Hamabe, Wakako; Tokuyama, Shogo

2010-09-10

5'-AMP-activated protein kinase (AMPK) is a serine/threonine kinase that plays a key role in energy homeostasis. Recently, it was reported that centrally activated AMPK is involved in the development of ischemic neuronal damage, while the effect of peripherally activated AMPK on ischemic neuronal damage is not known. In addition, we have previously reported that the development of post-ischemic glucose intolerance could be one of the triggers for the aggravation of neuronal damage. In this study, we focused on effect of activation of peripheral or central AMPK on the development of ischemic neuronal damage. Male ddY mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Neuronal damage was estimated by histological and behavioral analysis after MCAO. In the liver and skeletal muscle, AMPK activity was not affected by MCAO. But, application of intraperitoneal metformin (250 mg/kg), an AMPK activator, significantly suppressed the development of post-ischemic glucose intolerance and ischemic neuronal damage without alteration of central AMPK activity. On the other hand, application of intracerebroventricular metformin (25, 100 microg/mouse) significantly exacerbated the development of neuronal damage observed on day 1 after MCAO, in a dose-dependent manner. These effects were significantly blocked by compound C, a specific AMPK inhibitor. These results suggest that central AMPK was activated by ischemic stress per se, however, peripheral AMPK was not altered. Furthermore, the regulation of post-ischemic glucose intolerance by activation of peripheral AMPK is of assistance for the suppression of cerebral ischemic neuronal damage. 2010 Elsevier B.V. All rights reserved.

Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?

PubMed Central

Aigbirhio, Franklin I.; Fryer, Tim D.; Menon, David K.; Warburton, Elizabeth A.; Baron, Jean-Claude

2015-01-01

Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1–6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD. PMID:26439113

Similar cerebral protective effectiveness of antegrade and retrograde cerebral perfusion during deep hypothermic circulatory arrest in aortic surgery: a meta-analysis of 7023 patients.

PubMed

Guo, Shasha; Sun, Yanhua; Ji, Bingyang; Liu, Jinping; Wang, Guyan; Zheng, Zhe

2015-04-01

In aortic arch surgery, deep hypothermic circulatory arrest (DHCA) combined with cerebral perfusion is employed worldwide as a routine practice. Even though antegrade cerebral perfusion (ACP) is more widely used than retrograde cerebral perfusion (RCP), the difference in benefit and risk between ACP and RCP during DHCA is uncertain. The purpose of this meta-analysis is to compare neurologic outcomes and early mortality between ACP and RCP in patients who underwent aortic surgery during DHCA. PubMed, EMBASE, and the Cochrane Library were searched using the key words "antegrade," "retrograde," "cerebral perfusion," "cardiopulmonary bypass," "extracorporeal circulation," and "cardiac surgery" for studies reporting on clinical endpoints including early mortality, stroke, temporary neurologic dysfunction (TND), and permanent neurologic dysfunction (PND) in aortic surgery requiring DHCA with ACP or RCP. Heterogeneity was analyzed with the Cochrane Q statistic and I(2) statistic. Publication bias was tested with Begg's funnel plot and Egger's test. Thirty-four studies were included in this meta-analysis, with 4262 patients undergoing DHCA + ACP and 2761 undergoing DHCA + RCP. The overall pooled relative risk for TND was 0.722 (95% CI = [0.579, 0.900]), and the z-score for overall effect was 2.9 (P = 0.004). There was low heterogeneity (I(2) = 18.7%). The analysis showed that patients undergoing DHCA + ACP had better outcomes than those undergoing DHCA + RCP in terms of TND, while there were no significant differences between groups in terms of PND, stroke, and early mortality. This meta-analysis indicates that DHCA + ACP has an advantage over DHCA + RCP in terms of TND, while the two methods show similar results in terms of PND, early mortality, and stroke. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Effect of pyrrolidone-pyroglutamic acid composition on blood flow in rat middle cerebral artery.

PubMed

Semkina, G A; Matsievskii, D D; Mirzoyan, N R

2006-01-01

We compared the effects of a pyrrolidone-pyroglutamic acid composition and nimodipine on blood circulation in the middle cerebral artery in rats. The composition produced a strong effect on blood supply to the brain, stimulated blood flow in the middle cerebral artery (by 60 +/- 9%) and decreased blood pressure (by 25.0 +/- 2.7%). The cerebrovascular effects of this composition differed from those of nimodipine. Nimodipine not only increased middle cerebral artery blood flow, but also decreased cerebral blood flow in the early period after treatment.

Early magnetic resonance detection of cortical necrosis and acute network injury associated with neonatal and infantile cerebral infarction.

PubMed

Okabe, Tetsuhiko; Aida, Noriko; Niwa, Tetsu; Nozawa, Kumiko; Shibasaki, Jun; Osaka, Hitoshi

2014-05-01

Knowledge of MRI findings in pediatric cerebral infarction is limited. To determine whether cortical necrosis and network injury appear in the acute phase in post-stroke children and to identify anatomical location of acute network injury and the ages at which these phenomena are seen. Images from 12 children (age range: 0-9 years; neonates [<1 month], n=5; infants [1 month-12 months], n=3; others [≥1 year], n=4) with acute middle cerebral artery (MCA) cortical infarction were retrospectively analyzed. Cortical necrosis was defined as hyperintense cortical lesions on T1-weighted imaging that lacked evidence of hemorrhage. Acute network injury was defined as hyperintense lesions on diffusion-weighted imaging that were not in the MCA territory and had fiber connections with the affected cerebral cortex. MRI was performed within the first week after disease onset. Cortical necrosis was only found in three neonates. Acute network injury was seen in the corticospinal tract (CST), thalamus and corpus callosum. Acute network injury along the CST was found in five neonates and one 7-month-old infant. Acute network injury was evident in the thalamus of four neonates and two infants (ages 4 and 7 months) and in the corpus callosum of five neonates and two infants (ages 4 and 7 months). The entire thalamus was involved in three children when infarction of MCA was complete. In acute MCA cortical infarction, MRI findings indicating cortical necrosis or acute network injury was frequently found in neonates and early infants. Response to injury in a developing brain may be faster than that in a mature one.

Effect of motor imagery in children with unilateral cerebral palsy: fMRI study.

PubMed

Chinier, Eva; N'Guyen, Sylvie; Lignon, Grégoire; Ter Minassian, Aram; Richard, Isabelle; Dinomais, Mickaël

2014-01-01

Motor imagery is considered as a promising therapeutic tool for rehabilitation of motor planning problems in patients with cerebral palsy. However motor planning problems may lead to poor motor imagery ability. The aim of this functional magnetic resonance imaging study was to examine and compare brain activation following motor imagery tasks in patients with hemiplegic cerebral palsy with left or right early brain lesions. We tested also the influence of the side of imagined hand movement. Twenty patients with clinical hemiplegic cerebral palsy (sixteen males, mean age 12 years and 10 months, aged 6 years 10 months to 20 years 10 months) participated in this study. Using block design, brain activations following motor imagery of a simple opening-closing hand movement performed by either the paretic or nonparetic hand was examined. During motor imagery tasks, patients with early right brain damages activated bilateral fronto-parietal network that comprise most of the nodes of the network well described in healthy subjects. Inversely, in patients with left early brain lesion brain activation following motor imagery tasks was reduced, compared to patients with right brain lesions. We found also a weak influence of the side of imagined hand movement. Decreased activations following motor imagery in patients with right unilateral cerebral palsy highlight the dominance of the left hemisphere during motor imagery tasks. This study gives neuronal substrate to propose motor imagery tasks in unilateral cerebral palsy rehabilitation at least for patients with right brain lesions.

Early monitoring of cerebral hypoperfusion in rats by laser speckle imaging and functional photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Wang, Hui; Yang, Xiaoquan; Wang, Zhen; Deng, Zilin; Gong, Hui; Luo, Qingming

2012-06-01

Because cerebral hypoperfusion brings damage to the brain, prevention of cerebrovascular diseases correlative to hypoperfusion by studying animal models makes great sense. Since complicated cerebrovascular adaptive changes in hypoperfusion could not be revealed only by cerebral blood flow (CBF) velocity imaging, we performed multi-parameter imaging by combining laser speckle imaging and functional photoacoustic microscopy. The changes in CBF, hemoglobin oxygen saturation (SO2), and total hemoglobin concentration (HbT) in single blood vessels of ipsilateral cortex were observed during transient cerebral hypoperfusion by ligating the unilateral common carotid artery in rats. CBF, SO2, and HbT, respectively, decreased to 37+/-3%, 71+/-7.5%, and 92+/-1.3% of baseline in 6 s immediately after occlusion, and then recovered to 77+/-4.8%, 84+/-8%, and 96+/-2% of baseline in 60 s. These parameters presented the decrease with different degree and the following recovery over time after ligation, the recovery of SO2 lagged behind those of CBF and HbT, which had the similar response. The results demonstrated that complete monitoring of both cerebral hemodynamic response and oxygen metabolic changes occurred at the earliest period of cerebral hypoperfusion was possible by using the two image modalities with high temporal and spatial resolution.

Prestroke Proteomic Changes in Cerebral Microvessels in Stroke-Prone, Transgenic[hCETP]-Hyperlipidemic, Dahl Salt-Sensitive Hypertensive Rats

PubMed Central

Bergerat, Agnes; Decano, Julius; Wu, Chang-Jiun; Choi, Hyungwon; Nesvizhskii, Alexey I; Moran, Ann Marie; Ruiz-Opazo, Nelson; Steffen, Martin; Herrera, Victoria LM

2011-01-01

Stroke is the third leading cause of death in the United States with high rates of morbidity among survivors. The search to fill the unequivocal need for new therapeutic approaches would benefit from unbiased proteomic analyses of animal models of spontaneous stroke in the prestroke stage. Since brain microvessels play key roles in neurovascular coupling, we investigated prestroke microvascular proteome changes. Proteomic analysis of cerebral cortical microvessels (cMVs) was done by tandem mass spectrometry comparing two prestroke time points. Metaprotein-pathway analyses of proteomic spectral count data were done to identify risk factor–induced changes, followed by QSPEC-analyses of individual protein changes associated with increased stroke susceptibility. We report 26 cMV proteome profiles from male and female stroke-prone and non–stroke-prone rats at 2 months and 4.5 months of age prior to overt stroke events. We identified 1,934 proteins by two or more peptides. Metaprotein pathway analysis detected age-associated changes in energy metabolism and cell-to-microenvironment interactions, as well as sex-specific changes in energy metabolism and endothelial leukocyte transmigration pathways. Stroke susceptibility was associated independently with multiple protein changes associated with ischemia, angiogenesis or involved in blood brain barrier (BBB) integrity. Immunohistochemical analysis confirmed aquaporin-4 and laminin-α1 induction in cMVs, representative of proteomic changes with >65 Bayes factor (BF), associated with stroke susceptibility. Altogether, proteomic analysis demonstrates significant molecular changes in ischemic cerebral microvasculature in the prestroke stage, which could contribute to the observed model phenotype of microhemorrhages and postischemic hemorrhagic transformation. These pathways comprise putative targets for translational research of much needed novel diagnostic and therapeutic approaches for stroke. PMID:21519634

Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia

PubMed Central

Chu, Hannah X; Kim, Hyun Ah; Lee, Seyoung; Moore, Jeffrey P; Chan, Christopher T; Vinh, Antony; Gelderblom, Mathias; Arumugam, Thiruma V; Broughton, Brad RS; Drummond, Grant R; Sobey, Christopher G

2014-01-01

We tested whether significant leukocyte infiltration occurs in a mouse model of permanent cerebral ischemia. C57BL6/J male mice underwent either permanent (3 or 24 hours) or transient (1 or 2 hours+22- to 23-hour reperfusion) middle cerebral artery occlusion (MCAO). Using flow cytometry, we observed ∼15,000 leukocytes (CD45+high cells) in the ischemic hemisphere as early as 3 hours after permanent MCAO (pMCAO), comprising ∼40% lymphoid cells and ∼60% myeloid cells. Neutrophils were the predominant cell type entering the brain, and were increased to ∼5,000 as early as 3 hours after pMCAO. Several cell types (monocytes, macrophages, B lymphocytes, CD8+ T lymphocytes, and natural killer cells) were also increased at 3 hours to levels sustained for 24 hours, whereas others (CD4+ T cells, natural killer T cells, and dendritic cells) were unchanged at 3 hours, but were increased by 24 hours after pMCAO. Immunohistochemical analysis revealed that leukocytes typically had entered and widely dispersed throughout the parenchyma of the infarct within 3 hours. Moreover, compared with pMCAO, there were ∼50% fewer infiltrating leukocytes at 24 hours after transient MCAO (tMCAO), independent of infarct size. Microglial cell numbers were bilaterally increased in both models. These findings indicate that a profound infiltration of inflammatory cells occurs in the brain early after focal ischemia, especially without reperfusion. PMID:24326388

Different Alterations of Cerebral Regional Homogeneity in Early-Onset and Late-Onset Parkinson's Disease

PubMed Central

Sheng, Ke; Fang, Weidong; Zhu, Yingcheng; Shuai, Guangying; Zou, Dezhi; Su, Meilan; Han, Yu; Cheng, Oumei

2016-01-01

HIGHLIGHTS Eighteen EOPD, 21 LOPD and 37 age-matched normal control subjects participated in the resting state fMRI scans.Age at onset of PD modulates the distribution of cerebral regional homogeneity during resting state.Disproportionate putamen alterations are more prominent in PD patients with a younger age of onset. Objective: Early-onset Parkinson's disease (EOPD) is distinct from late-onset PD (LOPD) as it relates to the clinical profile and response to medication. The objective of current paper is to investigate whether characteristics of spontaneous brain activity in the resting state are associated with the age of disease onset. Methods: We assessed the correlation between neural activity and age-at-onset in a sample of 39 PD patients (18 EOPD and 21 LOPD) and 37 age-matched normal control subjects. Regional homogeneity (ReHo) approaches were employed using ANOVA with two factors: PD and age. Results: In the comparisons between LOPD and EOPD, EOPD revealed lower ReHo values in the right putamen and higher ReHo values in the left superior frontal gyrus. Compared with age-matched control subjects, EOPD exhibited lower ReHo values in the right putamen and higher ReHo values in the left inferior temporal gyrus; However, LOPD showed lower ReHo values in the right putamen and left insula. The ReHo values were negatively correlated with the UPDRS total scores in the right putamen in LOPD, but a correlation between the ReHo value and UPDRS score was not detected in EOPD. Conclusions: Our findings support the notion that age at onset is associated with the distribution of cerebral regional homogeneity in the resting state and suggest that disproportionate putamen alterations are more prominent in patients with a younger age of onset. PMID:27462265

Hip Surveillance in Children with Cerebral Palsy.

PubMed

Huser, Aaron; Mo, Michelle; Hosseinzadeh, Pooya

2018-04-01

The hip is the second most common involved joint in cerebral palsy. Hip displacement occurs in more than 33% of children with cerebral palsy, with a higher prevalence in nonambulatory children. Hip displacement in this population is typically progressive. Hip dislocation can result in pain and difficulty with sitting and perineal care. Since early stage of hip displacement can be silent, and hip surveillance programs are recommended. Most programs use the degree of hip dysplasia and Growth Motor Function Classification System level for screening recommendations. Treatment depends on the degree of dysplasia, functional status of the patient, and patient's age. Copyright © 2017 Elsevier Inc. All rights reserved.

[Morphometrical analyze of the middle cerebral artery system at the 13-15 weeks fetuses].

PubMed

Macovei, Georgeta Nataşa; Varlam, H; St Antohe, D

2002-01-01

Tele-encephalization process is accompanied by the appearance and progressive complication of the middle cerebral artery system. The aim of our study is to analyze the morphometrical parameters of the middle cerebral artery branches in the beginning of the edification of its system. We used 162 cerebral hemispheres from 88 fetuses aged of 13-15 weeks. Middle cerebral artery system was injected with a gelatin-China ink mixture and images recorded by means of a Zeiss surgical microscope. Parameters evaluation (length, proximal and distal diameters, external surface, volume, angles of bifurcation) was realized with KS-300 program. At this early age middle cerebral artery system has only 4-5 generations of branches usually resulting from acute angle bifurcations.

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.

Cerebral sinovenous thrombosis associated with iron deficiency anemia secondary to severe menorrhagia: a case report.

PubMed

Corrales-Medina, Fernando F; Grant, Leon; Egas-Bejar, Daniela; Valdivia-Ascuna, Zoila; Rodriguez, Nidra; Mancias, Pedro

2014-09-01

Cerebral sinovenous thrombosis is a rare condition presenting with a wide spectrum of nonspecific symptoms that can make early diagnosis difficult. Cerebral sinovenous thrombosis has been associated with various etiologies. Iron deficiency anemia associated with cerebral sinovenous thrombosis in teenagers is rare. We present a teenage patient with complete thrombosis of the vein of Galen, straight sinus, and left internal cerebral vein associated with iron deficiency anemia due to severe menorrhagia. Mechanisms that can explain the association between iron deficiency anemia and thrombosis are discussed. © The Author(s) 2013.

Divergent regional patterns of cerebral hypoperfusion and gray matter atrophy in mild cognitive impairment patients.

PubMed

Wirth, Miranka; Pichet Binette, Alexa; Brunecker, Peter; Köbe, Theresa; Witte, A Veronica; Flöel, Agnes

2017-03-01

Reductions of cerebral blood flow and gray matter structure have been implicated in early pathogenesis of Alzheimer's disease, potentially providing complementary information. The present study evaluated regional patterns of cerebral hypoperfusion and atrophy in patients with mild cognitive impairment and healthy older adults. In each participant, cerebral perfusion and gray matter structure were extracted within selected brain regions vulnerable to Alzheimer's disease using magnetic resonance imaging. Measures were compared between diagnostic groups with/without adjustment for covariates. In mild cognitive impairment patients, cerebral blood flow was significantly reduced in comparison with healthy controls in temporo-parietal regions and the basal ganglia in the absence of local gray matter atrophy. By contrast, gray matter structure was significantly reduced in the hippocampus in the absence of local hypoperfusion. Both, cerebral perfusion and gray matter structure were significantly reduced in the entorhinal and isthmus cingulate cortex in mild cognitive impairment patients compared with healthy older adults. Our results demonstrated partly divergent patterns of temporo-parietal hypoperfusion and medial-temporal atrophy in mild cognitive impairment patients, potentially indicating biomarker sensitivity to dissociable pathological mechanisms. The findings support applicability of cerebral perfusion and gray matter structure as complementary magnetic resonance imaging-based biomarkers in early Alzheimer's disease detection, a hypothesis to be further evaluated in longitudinal studies.

Hypopituitarism in children with cerebral palsy.

PubMed

Uday, Suma; Shaw, Nick; Krone, Ruth; Kirk, Jeremy

2017-06-01

Poor growth and delayed puberty in children with cerebral palsy is frequently felt to be related to malnutrition. Although growth hormone deficiency is commonly described in these children, multiple pituitary hormone deficiency (MPHD) has not been previously reported. We present a series of four children with cerebral palsy who were born before 29 weeks gestation who were referred to the regional endocrinology service, three for delayed puberty and one for short stature, in whom investigations identified MPHD. All patients had a height well below -2 standard deviation score (2nd centile) at presentation and three who had MRI scans had an ectopic posterior pituitary gland. We therefore recommend that the possibility of MPHD should be considered in all children with cerebral palsy and poor growth or delayed puberty. Early diagnosis and treatment is essential to maximise growth and prevent associated morbidity and mortality. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Magnetic resonance features of cerebral malaria.

PubMed

Yadav, P; Sharma, R; Kumar, S; Kumar, U

2008-06-01

Cerebral malaria is a major health hazard, with a high incidence of mortality. The disease is endemic in many developing countries, but with a greater increase in tourism, occasional cases may be detected in countries where the disease in not prevalent. Early diagnosis and evaluation of cerebral involvement in malaria utilizing modern imaging modalities have an impact on the treatment and clinical outcome. To evaluate the magnetic resonance (MR) features of patients with cerebral malaria presenting with altered sensorium. We present the findings in three patients with cerebral malaria presenting with altered sensorium. MR imaging using a 1.5-Tesla unit was carried out. The sequences performed were 5-mm-thick T1-weighted, T2-weighted, fluid-attenuated inversion-recovery (FLAIR), and T2-weighted gradient-echo axial sequences, and sagittal and coronal FLAIR. Diffusion-weighted imaging was performed with b values of 0 and 1000 s/mm(2), and apparent diffusion coefficient (ADC) maps were obtained. Focal hyperintensities in the bilateral periventricular white matter, corpus callosum, occipital subcortex, and bilateral thalami were noticed on T2-weighted and FLAIR sequences. The lesions were more marked in the splenium of the corpus callosum. No enhancement on postcontrast T1-weighted MR images was observed. There was no evidence of restricted diffusion on the diffusion-weighted sequence and ADC map. MR is a sensitive imaging modality, with a role in the assessment of cerebral lesions in malaria. Focal white matter and corpus callosal lesions without any restricted diffusion were the key findings in our patients.

εPKC confers acute tolerance to cerebral ischemic reperfusion injury

PubMed Central

Bright, Rachel; Sun, Guo-Hua; Yenari, Midori A.; Steinberg, Gary K.; Mochly-Rosen, Daria

2008-01-01

In response to mild ischemic stress, the brain elicits endogenous survival mechanisms to protect cells against a subsequent lethal ischemic stress, referred to as ischemic tolerance. The molecular signals that mediate this protection are thought to involve the expression and activation of multiple kinases, including protein kinase C (PKC). Here we demonstrate that εPKC mediates cerebral ischemic tolerance in vivo. Systemic delivery of ψεRACK, an εPKC-selective peptide activator, confers neuroprotection against a subsequent cerebral ischemic event when delivered immediately prior to stroke. In addition, activation of εPKC by ψεRACK treatment decreases vascular tone in vivo, as demonstrated by a reduction in microvascular cerebral blood flow. Here we demonstrate the role of acute and transient εPKC in early cerebral tolerance in vivo and suggest that extra-parenchymal mechanisms, such as vasoconstriction, may contribute to the conferred protection. PMID:18586397

Early results of one-stage correction for hip instability in cerebral palsy.

PubMed

Kim, Hui Taek; Jang, Jae Hoon; Ahn, Jae Min; Lee, Jong Seo; Kang, Dong Joon

2012-06-01

We evaluated the clinical and radiological results of one-stage correction for cerebral palsy patients. We reviewed clinical outcomes and radiologic indices of 32 dysplastic hips in 23 children with cerebral palsy (13 males, 10 females; mean age, 8.6 years). Ten hips had dislocation, while 22 had subluxation. Preoperative Gross Motor Function Classification System (GMFCS) scores of the patients were as follows; level V (13 patients), level IV (9), and level III (1). Acetabular deficiency was anterior in 5 hips, superolateral in 7, posterior in 11 and mixed in 9, according to 3 dimensional computed tomography. The combined surgery included open reduction of the femoral head, release of contracted muscles, femoral shortening varus derotation osteotomy and the modified Dega osteotomy. Hip range of motion, GMFCS level, acetabular index, center-edge angle and migration percentage were measured before and after surgery. The mean follow-up period was 28.1 months. Hip abduction (median, 40°), sitting comfort and GMFCS level were improved after surgery, and pain was decreased. There were two cases of femoral head avascular necrosis, but no infection, nonunion, resubluxation or redislocation. All radiologic indices showed improvement after surgery. A single event multilevel surgery including soft tissue, pelvic and femoral side correction is effective in treating spastic dislocation of the hip in cerebral palsy.

Racial, Ethnic, and Socioeconomic Disparities in the Prevalence of Cerebral Palsy

PubMed Central

Xing, Guibo; Fuentes-Afflick, Elena; Danielson, Beate; Smith, Lloyd H.; Gilbert, William M.

2011-01-01

OBJECTIVE: Racial and ethnic disparities in cerebral palsy have been documented, but the underlying mechanism is poorly understood. We determined whether low birth weight accounts for ethnic disparities in the prevalence of cerebral palsy and whether socioeconomic factors impact cerebral palsy within racial and ethnic groups. METHODS: In a retrospective cohort of 6.2 million births in California between 1991 and 2001, we compared maternal and infant characteristics among 8397 infants with cerebral palsy who qualified for services from the California Department of Health Services and unaffected infants. RESULTS: Overall, black infants were 29% more likely to have cerebral palsy than white infants (relative risk: 1.29 [95% confidence interval: 1.19–1.39]). However, black infants who were very low or moderately low birth weight were 21% to 29% less likely to have cerebral palsy than white infants of comparable birth weight. After we adjusted for birth weight, there was no difference in the risk of cerebral palsy between black and white infants. In multivariate analyses, women of all ethnicities who did not receive any prenatal care were twice as likely to have infants with cerebral palsy relative to women with an early onset of prenatal care. Maternal education was associated with cerebral palsy in a dose-response fashion among white and Hispanic women. Hispanic adolescent mothers (aged <18 years) had increased risk of having a child with cerebral palsy. CONCLUSIONS: The increased risk of cerebral palsy among black infants is primarily related to their higher risk of low birth weight. Understanding how educational attainment and use of prenatal care impact the risk of cerebral palsy may inform new prevention strategies. PMID:21339278

Early pregnancy cerebral venous thrombosis and status epilepticus treated with levetiracetam and lacosamide throughout pregnancy.

PubMed

Ylikotila, Pauli; Ketola, Raimo A; Timonen, Susanna; Malm, Heli; Ruuskanen, Jori O

2015-11-01

Cerebral venous thrombosis (CVT) is an uncommon cause of stroke, accounting to less than 1% of all strokes. We describe a pregnant woman with a massive CVT in early pregnancy, complicated by status epilepticus. The mother was treated with levetiracetam, lacosamide, and enoxaparin throughout pregnancy. A male infant was born on pregnancy week 36, weighing 2.2kg. Both levetiracetam and and lacosamide were present in cord blood in levels similar to those in maternal blood. The infant was partially breast-fed and experienced poor feeding and sleepiness, starting to resolve after two first weeks. Milk samples were drawn 5 days after the delivery and a blood sample from the infant 3 days later. Lacosamide level in milk was low, resulting in an estimated relative infant dose of 1.8% of the maternal weight-adjusted daily dose in a fully breast-fed infant. This is the first case describing lacosamide use during pregnancy and lactation. Copyright © 2015 Elsevier Inc. All rights reserved.

Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology.

PubMed

Radde, Rebecca; Bolmont, Tristan; Kaeser, Stephan A; Coomaraswamy, Janaky; Lindau, Dennis; Stoltze, Lars; Calhoun, Michael E; Jäggi, Fabienne; Wolburg, Hartwig; Gengler, Simon; Haass, Christian; Ghetti, Bernardino; Czech, Christian; Hölscher, Christian; Mathews, Paul M; Jucker, Mathias

2006-09-01

We have generated a novel transgenic mouse model on a C57BL/6J genetic background that coexpresses KM670/671NL mutated amyloid precursor protein and L166P mutated presenilin 1 under the control of a neuron-specific Thy1 promoter element (APPPS1 mice). Cerebral amyloidosis starts at 6-8 weeks and the ratio of human amyloid (A)beta42 to Abeta40 is 1.5 and 5 in pre-depositing and amyloid-depositing mice, respectively. Consistent with this ratio, extensive congophilic parenchymal amyloid but minimal amyloid angiopathy is observed. Amyloid-associated pathologies include dystrophic synaptic boutons, hyperphosphorylated tau-positive neuritic structures and robust gliosis, with neocortical microglia number increasing threefold from 1 to 8 months of age. Global neocortical neuron loss is not apparent up to 8 months of age, but local neuron loss in the dentate gyrus is observed. Because of the early onset of amyloid lesions, the defined genetic background of the model and the facile breeding characteristics, APPPS1 mice are well suited for studying therapeutic strategies and the pathomechanism of amyloidosis by cross-breeding to other genetically engineered mouse models.

Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology

PubMed Central

Radde, Rebecca; Bolmont, Tristan; Kaeser, Stephan A; Coomaraswamy, Janaky; Lindau, Dennis; Stoltze, Lars; Calhoun, Michael E; Jäggi, Fabienne; Wolburg, Hartwig; Gengler, Simon; Haass, Christian; Ghetti, Bernardino; Czech, Christian; Hölscher, Christian; Mathews, Paul M; Jucker, Mathias

2006-01-01

We have generated a novel transgenic mouse model on a C57BL/6J genetic background that coexpresses KM670/671NL mutated amyloid precursor protein and L166P mutated presenilin 1 under the control of a neuron-specific Thy1 promoter element (APPPS1 mice). Cerebral amyloidosis starts at 6–8 weeks and the ratio of human amyloid (A)β42 to Aβ40 is 1.5 and 5 in pre-depositing and amyloid-depositing mice, respectively. Consistent with this ratio, extensive congophilic parenchymal amyloid but minimal amyloid angiopathy is observed. Amyloid-associated pathologies include dystrophic synaptic boutons, hyperphosphorylated tau-positive neuritic structures and robust gliosis, with neocortical microglia number increasing threefold from 1 to 8 months of age. Global neocortical neuron loss is not apparent up to 8 months of age, but local neuron loss in the dentate gyrus is observed. Because of the early onset of amyloid lesions, the defined genetic background of the model and the facile breeding characteristics, APPPS1 mice are well suited for studying therapeutic strategies and the pathomechanism of amyloidosis by cross-breeding to other genetically engineered mouse models. PMID:16906128

Cerebral Metabolic Alterations in Rats With Diabetic Ketoacidosis

PubMed Central

Glaser, Nicole; Yuen, Natalie; Anderson, Steven E.; Tancredi, Daniel J.; O'Donnell, Martha E.

2010-01-01

OBJECTIVE Cerebral edema is a life-threatening complication of diabetic ketoacidosis (DKA) in children. Recent data suggest that cerebral hypoperfusion and activation of cerebral ion transporters may be involved, but data describing cerebral metabolic alterations during DKA are lacking. RESEARCH DESIGN AND METHODS We evaluated 50 juvenile rats with DKA and 21 normal control rats using proton and phosphorus magnetic resonance spectroscopy (MRS). MRS measured cerebral intracellular pH and ratios of metabolites including ATP/inorganic phosphate (Pi), phosphocreatine (PCr)/Pi, N-acetyl aspartate (NAA)/creatine (Cr), and lactate/Cr before and during DKA treatment. We determined the effects of treatment with insulin and intravenous saline with or without bumetanide, an inhibitor of Na-K-2Cl cotransport, using ANCOVA with a 2 × 2 factorial study design. RESULTS Cerebral intracellular pH was decreased during DKA compared with control (mean ± SE difference −0.13 ± 0.03; P < 0.001), and lactate/Cr was elevated (0.09 ± 0.02; P < 0.001). DKA rats had lower ATP/Pi and NAA/Cr (−0.32 ± 0.10, P = 0.003, and −0.14 ± 0.04, P < 0.001, respectively) compared with controls, but PCr/Pi was not significantly decreased. During 2-h treatment with insulin/saline, ATP/Pi, PCr/Pi, and NAA/Cr declined significantly despite an increase in intracellular pH. Bumetanide treatment increased ATP/Pi and PCr/Pi and ameliorated the declines in these values with insulin/saline treatment. CONCLUSIONS These data demonstrate that cerebral metabolism is significantly compromised during DKA and that further deterioration occurs during early DKA treatment—consistent with possible effects of cerebral hypoperfusion and reperfusion injury. Treatment with bumetanide may help diminish the adverse effects of initial treatment with insulin/saline. PMID:20028943

In vivo MRI assessment of permanent middle cerebral artery occlusion by electrocoagulation: pitfalls of procedure

PubMed Central

2010-01-01

Permanent middle cerebral artery (MCA) occlusion (pMCAO) by electrocoagulation is a commonly used model but with potential traumatic lesions. Early MRI monitoring may assess pMCAO for non-specific brain damage. The surgical steps of pMCAO were evaluated for traumatic cerebral injury in 22 Swiss mice using diffusion and T2-weighted MRI (7T) performed within 1 h and 24 h after surgery. Temporal muscle cauterization without MCA occlusion produced an early T2 hyperintensity mimicking an infarct. No lesion was visible after temporal muscle incision or craniotomy. Early MRI monitoring is useful to identify non-specific brain injury that could hamper neuroprotective drugs assessment. PMID:20298536

Association Between Prolonged Seizures and Malignant Middle Cerebral Artery Infarction in Children With Acute Ischemic Stroke.

PubMed

Andrade, Andrea; Bigi, Sandra; Laughlin, Suzanne; Parthasarathy, Sujatha; Sinclair, Adriane; Dirks, Peter; Pontigon, Ann Marie; Moharir, Mahendranath; Askalan, Rand; MacGregor, Daune; deVeber, Gabrielle

2016-11-01

Malignant middle cerebral artery infarct syndrome is a potentially fatal complication of stroke that is poorly understood in children. We studied the frequency, associated characteristics, and outcomes of this condition in children. Children, aged two months to 18 years with acute middle cerebral artery infarct diagnosed at our center between January 2005 and December 2012 were studied. Associations with malignant middle cerebral artery infarct syndrome were sought, including age, seizures, neurological deficit severity (Pediatric National Institute of Health Stroke Severity Score), stroke etiology, fever, blood pressure, blood glucose, infarct location, infarct volume (modified pediatric Alberta Stroke Program Early Computed Tomography Score), and arterial occlusion. Death and neurological outcomes were determined. Among 66 children with middle cerebral artery stroke, 12 (18%) developed malignant middle cerebral artery infarct syndrome, fatal in three. Prolonged seizures during the first 24 hours (odds ratio, 25.51; 95% confidence interval, 3.10 to 334.81; P = 0.005) and a higher Pediatric National Institute of Health Stroke Severity Score (odds ratio, 1.22; 95% confidence interval, 1.08 to 1.45; P = 0.006) were independently associated with malignant middle cerebral artery infarct syndrome. All children aged greater than two years with a Pediatric National Institute of Health Stroke Severity Score ≥8 and initial seizures ≥5 minutes duration developed malignant middle cerebral artery infarct syndrome (100%). Malignant middle cerebral artery infarct syndrome affects nearly one in five children with acute middle cerebral artery stroke. Children with higher Pediatric National Institute of Health Stroke Severity Scores and prolonged initial seizures are at greatly increased risk for malignant middle cerebral artery infarct syndrome. Children with middle cerebral artery infarcts warrant intensive neuroprotective management and close monitoring to enable

Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease

PubMed Central

Wang, Fen; Gordon, Brian A.; Ryman, Davis C.; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M.; Cairns, Nigel J.; Marcus, Daniel S.; McDade, Eric; Ringman, John M.; Graff-Radford, Neill R.; Ghetti, Bernardino; Farlow, Martin R.; Sperling, Reisa; Salloway, Steve; Schofield, Peter R.; Masters, Colin L.; Martins, Ralph N.; Rossor, Martin N.; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A.S.; Morris, John C.; Bateman, Randall J.

2015-01-01

Objective: To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Methods: Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89–4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. Results: In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Conclusions: Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. PMID:26245925

Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease.

PubMed

Wang, Fen; Gordon, Brian A; Ryman, Davis C; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M; Cairns, Nigel J; Marcus, Daniel S; McDade, Eric; Ringman, John M; Graff-Radford, Neill R; Ghetti, Bernardino; Farlow, Martin R; Sperling, Reisa; Salloway, Steve; Schofield, Peter R; Masters, Colin L; Martins, Ralph N; Rossor, Martin N; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A S; Morris, John C; Benzinger, Tammie L S; Bateman, Randall J

2015-09-01

To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89-4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. © 2015 American Academy of Neurology.

Postischemic alterations of BDNF, NGF, HSP 70 and ubiquitin immunoreactivity in the gerbil hippocampus: pharmacological approach.

PubMed

Himeda, Toshiki; Tounai, Hiroko; Hayakawa, Natsumi; Araki, Tsutomu

2007-03-01

1. We investigated the immunohistochemical alterations of BDNF, NGF, HSP 70 and ubiquitin in the hippocampus 1 h to 14 days after transient cerebral ischemia in gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor pitavastatin against the changes of BDNF, NGF, HSP 70 and ubiquitin in the hippocampus after cerebral ischemia in the hippocampus after ischemia. 2. The transient cerebral ischemia was carried out by clamping the carotid arteries with aneurismal clips for 5 min. 3. In the present study, the alteration of HSP 70 and ubiquitin immunoreactivity in the hippocampal CA1 sector was more pronounced than that of BDNF and NGF immunoreactivity after transient cerebral ischemia. In double-labeled immunostainings, BDNF, NGF and ubiquitin immunostaining was observed both in GFAP-positive astrocytes and MRF-1-positive microglia in the hippocampal CA1 sector after ischemia. Furthermore, prophylactic treatment with pitavastatin prevented the damage of neurons with neurotrophic factor and stress proteins in the hippocampal CA1 sector after ischemia. 4. These findings suggest that the expression of stress protein including HSP 70 and ubiquitin may play a key role in the protection against the hippocampal CA1 neuronal damage after transient cerebral ischemia in comparison with the expression of neurotrophic factor such as BDNF and NGF. The present findings also suggest that the glial BDNF, NGF and ubiquitin may play some role for helping surviving neurons after ischemia. Furthermore, our present study indicates that prophylactic treatment with pitavastatin can prevent the damage of neurons with neurotrophic factor and stress proteins in the hippocampal CA1 sector after transient cerebral ischemia. Thus our study provides further valuable information for the pathogenesis after transient cerebral ischemia.

Rationale of cerebral protection devices in left atrial appendage occlusion.

PubMed

Meincke, Felix; Spangenberg, Tobias; Kreidel, Felix; Frerker, Christian; Virmani, Renu; Ladich, Elena; Kuck, Karl-Heinz; Ghanem, Alexander

2017-01-01

Aims of this case-series were to assess the feasibility of cerebral protection devices in interventional left atrial appendage occlusion (iLAAO) procedures and to yield insight into the pathomorphological correlate of early, procedural cerebral embolization during iLAAO. Five consecutive patients underwent iLLO flanked by the Sentinel CPS® (Claret Medical, Inc., Santa Rosa, CA) cerebral protection system. Placement and recapture of the Sentinel ® device as well as the iLAAO were successful and safe in all cases. Histomorphometric analysis of the collected filters showed embolized debris in all patients. Acute thrombus was found in three patients, organizing thrombus in four. Interestingly, two patients had endocardial or myocardial tissue in their filters. Cerebral protection during iLAAO with the Sentinel CPS ® device is feasible. Furthermore, this dataset identifies the formation and embolization of thrombus and cardiac tissue as emboligeneic sources and potential future targets to reduce procedural complications. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Reduced expression of IA channels is associated with post-ischemic seizures.

PubMed

Lei, Zhigang; Zhang, Hui; Liang, Yanling; Xu, Zao C

2016-08-01

Post-stroke seizures are considered as a major cause of epilepsy in adults. The pathophysiologic mechanisms resulting in post-stroke seizures are not fully understood. The present study attempted to reveal a new mechanism underlying neuronal hyperexcitability responsible to the seizure development after ischemic stroke. Transient global ischemia was produced in adult Wistar rats using the 4-vessel occlusion (4-VO) method. The spontaneous behavioral seizures were defined by the Racine scale III-V. The neuronal death in the brain was determined by hematoxylin-eosin staining. The expression levels of A-type potassium channels were analyzed by immunohistochemical staining and western blotting. We found that the incidence of spontaneous behavioral seizures increased according to the severity of ischemia with 0% after 15-min ischemia and ∼50% after 25-min ischemia. All behavioral seizures occurred with 48h after ischemia. Morphological analysis indicated that brain damage was not correlated with behavioral seizures. Immunohistochemical staining showed that the expression levels of the A-type potassium channel subunit Kv4.2 was significantly reduced in ischemic brains with behavioral seizures, but not in ischemic brains without seizures. In addition, rats failing to develop spontaneous behavioral seizures within 2days after ischemia were more sensitive to bicuculline-induced seizures at 2 months after ischemia than control rats. Meanwhile, Kv4.2 expression was decreased in brain at 2 months after ischemia. Our results demonstrated the reduction of Kv4.2 expression might contribute to the development of post-ischemic seizures and long-term increased seizure susceptibility after ischemia. The mechanisms underlying post-stroke seizures and epilepsy is unknown so far. The down-regulation of IA channels may explained the abnormal neuronal hyperexcitability responsible for the seizure development after ischemic stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

Cerebral aneurysm

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The tissue of the brain is supplied by a network of cerebral arteries. If the wall of a cerebral artery becomes weakened, a portion of the wall may balloon out forming an aneurysm. A cerebral aneurysm may enlarge until it bursts, sending blood ...

Pathogenesis of cerebral malaria: new diagnostic tools, biomarkers, and therapeutic approaches

PubMed Central

Sahu, Praveen K.; Satpathi, Sanghamitra; Behera, Prativa K.; Mishra, Saroj K.; Mohanty, Sanjib; Wassmer, Samuel Crocodile

2015-01-01

Cerebral malaria is a severe neuropathological complication of Plasmodium falciparum infection. It results in high mortality and post-recovery neuro-cognitive disorders in children, even after appropriate treatment with effective anti-parasitic drugs. While the complete landscape of the pathogenesis of cerebral malaria still remains to be elucidated, numerous innovative approaches have been developed in recent years in order to improve the early detection of this neurological syndrome and, subsequently, the clinical care of affected patients. In this review, we briefly summarize the current understanding of cerebral malaria pathogenesis, compile the array of new biomarkers and tools available for diagnosis and research, and describe the emerging therapeutic approaches to tackle this pathology effectively. PMID:26579500

Ultrasonic vocalization changes and FOXP2 expression after experimental stroke.

PubMed

Doran, Sarah J; Trammel, Cassandra; Benashaski, Sharon E; Venna, Venugopal Reddy; McCullough, Louise D

2015-04-15

Speech impairments affect one in four stroke survivors. However, animal models of post-ischemic vocalization deficits are limited. Male mice vocalize at ultrasonic frequencies when exposed to an estrous female mouse. In this study we assessed vocalization patterns and quantity in male mice after cerebral ischemia. FOXP2, a gene associated with verbal dyspraxia in humans, with known roles in neurogenesis and synaptic plasticity, was also examined after injury. Using a transient middle cerebral artery occlusion (MCAO) model, we assessed correlates of vocal impairment at several time-points after stroke. Further, to identify possible lateralization of vocalization deficits induced by left and right hemispheric strokes were compared. Significant differences in vocalization quantity were observed between stroke and sham animals that persisted for a month after injury. Injury to the left hemisphere reduced early vocalizations more profoundly than those to the right hemisphere. Nuclear expression of Foxp2 was elevated early after stroke (at 6h), but significantly decreased 24h after injury in both the nucleus and the cytoplasm. Neuronal Foxp2 expression increased in stroke mice compared to sham animals 4 weeks after injury. This study demonstrates that quantifiable deficits in ultrasonic vocalizations (USVs) are seen after stroke. USV may be a useful tool to assess chronic behavioral recovery in murine models of stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

Transcranial Doppler-based assessment of cerebral autoregulation in critically ill children during diabetic ketoacidosis treatment.

PubMed

Ma, Li; Roberts, Joan S; Pihoker, Catherine; Richards, Todd L; Shaw, Dennis W W; Marro, Ken I; Vavilala, Monica S

2014-10-01

Impaired cerebral autoregulation may be associated with poor outcome in diabetic ketoacidosis. We examined change in cerebral autoregulation during diabetic ketoacidosis treatment. Prospective observational cohort study. Tertiary care children's hospital. Children admitted to the ICU with diabetic ketoacidosis (venous pH < 7.3, glucose > 300 mg/dL, HCO3 < 15 mEq/L, and ketonuria) constituted cases, and children with type I diabetes without diabetic ketoacidosis constituted controls. None. Between 2005 and 2009, 32 cases and 50 controls were enrolled. Transcranial Doppler ultrasonography was used to measure middle cerebral artery flow velocities, and cerebral autoregulation testing was achieved via tilt-table testing. Cases underwent two and controls underwent one cerebral autoregulation test. Cerebral autoregulation was quantified by the autoregulatory index (autoregulatory index < 0.4 = impaired and autoregulatory index 0.4-1.0 = intact autoregulation). The first autoregulation test was obtained early (time 1, 12-24 hr; median [interquartile range], 8 hr [5-18 hr]) during diabetic ketoacidosis treatment, and a second autoregulation test was obtained during recovery (time 2, 36-72 hr; median [ interquartile range], 46 hr [40-59 hr]) from time 0 (defined as time of insulin start). Cases had lower autoregulatory index at time 1 than time 2 (p < 0.001) as well lower autoregulatory index than control subjects (p < 0.001). Cerebral autoregulation was impaired in 40% (n = 13) of cases at time 1 and in 6% (n = 2) of cases at time 2. Five cases (17%) showed persistent impairment of cerebral autoregulation between times 1 and 2 of treatment. All control subjects had intact cerebral autoregulation. Impaired cerebral autoregulation was common early during diabetic ketoacidosis treatment. Although the majority improved during diabetic ketoacidosis treatment, 17% of subjects had impairment between 36 and 72 hours after start of insulin therapy. The observed impaired cerebral

Diffusion tensor imaging of early changes in corpus callosum after acute cerebral hemisphere lesions in newborns.

PubMed

Righini, Andrea; Doneda, Chiara; Parazzini, Cecilia; Arrigoni, Filippo; Matta, Ursula; Triulzi, Fabio

2010-11-01

The main purpose was to investigate any early diffusion tensor imaging (DTI) changes in corpus callosum (CC) associated with acute cerebral hemisphere lesions in term newborns. We retrospectively analysed 19 cases of term newborns acutely affected by focal or multi-focal lesions: hypoxic-ischemic encephalopathy, hypoglycaemic encephalopathy, focal ischemic stroke and deep medullary vein associated lesions. DTI was acquired at 1.5 Tesla with dedicated neonatal coil. DTI metrics (apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial λ(∐) and radial λ(⟂) diffusivity) were measured in the hemisphere lesions and in the CC. The control group included seven normal newborns. The following significant differences were found between patients and normal controls in the CC: mean ADC was lower in patients (0.88 SD 0.23 versus 1.18 SD 0.07 μm(2)/s) and so was mean FA (0.50 SD 0.1 versus 0.67 SD 0.05) and mean λ(∐) value (1.61 SD 0.52 versus 2.36 SD 0.14 μm(2)/s). In CC the percentage of ADC always diminished independently of lesion age (with one exception), whereas in hemisphere lesions, it was negative in earlier lesions, but exceeded normal values in the older lesions. CC may undergo early DTI changes in newborns with acute focal or multi-focal hemisphere lesions of different aetiology. Although a direct insult to CC cannot be totally ruled out, DTI changes in CC (in particular λ(∐)) may also be compatible with very early Wallerian degeneration or pre-Wallerian degeneration.

Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain.

PubMed

Sakai, Tomoko; Matsui, Mie; Mikami, Akichika; Malkova, Ludise; Hamada, Yuzuru; Tomonaga, Masaki; Suzuki, Juri; Tanaka, Masayuki; Miyabe-Nishiwaki, Takako; Makishima, Haruyuki; Nakatsukasa, Masato; Matsuzawa, Tetsuro

2013-02-22

Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement.

Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain

PubMed Central

Sakai, Tomoko; Matsui, Mie; Mikami, Akichika; Malkova, Ludise; Hamada, Yuzuru; Tomonaga, Masaki; Suzuki, Juri; Tanaka, Masayuki; Miyabe-Nishiwaki, Takako; Makishima, Haruyuki; Nakatsukasa, Masato; Matsuzawa, Tetsuro

2013-01-01

Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement. PMID:23256194

Application of non-invasive cerebral electrical impedance measurement on brain edema in patients with cerebral infarction.

PubMed

He, Lan Ying; Wang, Jian; Luo, Yong; Dong, Wei Wei; Liu, Li Xu

2010-09-01

To investigate the change of brain edema in patients with cerebral infarction by non-invasive cerebral electrical impedance (CEI) measurements. An invariable secure current at a frequency of 50 kHz and an intensity of 0.1 mA was given into a person's brain. CEI values of the bilateral hemisphere of 200 healthy volunteers and 107 patients with cerebral infarction were measured by non-invasive brain edema monitor. The results of perturbative index (PI) converted from CEI were compared with the volumes of brain edema, which were calculated by an image analysing system according to magnetic resonance imaging or computed tomography. (1) In the healthy volunteers, PI values in the left and right hemisphere were 7.98 +/- 0.95 and 8.02 +/- 0.71 respectively, and there was no significant difference between the two sides (p>0.05). Age, gender and different measuring times did not obviously affect PI values (p>0.05). (2) In the cerebral infarction group, CEI measurements were more sensitive to the volumes of lesion, which were more than 20 ml. The positive ratio of PI was higher when the volumes of infarction were >20 ml (80.0%): the ratio of PI was 75.9% when the volumes of infarction were 20-50 ml and it was 83.3% when the volumes of lesion were more than 50 ml. PI was lower when the volumes were less than 20 ml. (3) PI of the infarction side increased obviously 3-5 days after onset; the difference of two sides was the most significant. There was a positive correlation between PI of the infarction side and volume of infarction. PI may be a sensitive parameter for non-invasive monitoring of the change of brain edema in patients with cerebral infarction. CEI is a valuable method for the early detection of brain edema.

[New developments in spastic unilateral cerebral palsy].

PubMed

Chabrier, S; Roubertie, A; Allard, D; Bonhomme, C; Gautheron, V

2010-01-01

Hemiplegic (or spastic unilateral) cerebral palsy accounts for about 30% of all cases of cerebral palsy. With a population prevalence of 0.6 per 1000 live births, it is the most common type of cerebral palsy among term-born children and the second most common type after diplegia among preterm infants. Many types of prenatal and perinatal brain injury can lead to congenital hemiplegia and brain MRI is the most useful tool to classify them with accuracy and to provide early prognostic information. Perinatal arterial ischemic stroke thus appears as the leading cause in term infants, whereas encephalopathy of prematurity is the most common cause in premature babies. Other causes include brain malformations, neonatal sinovenous thrombosis, parenchymal hemorrhage (for example due to coagulopathy or alloimmune thrombocytopenia) and the more recently described familial forms of porencephaly associated with mutations in the COL4A1 gene. In adjunction with pharmacologic treatment (botulinium neurotoxin injection), new evidence-based rehabilitational interventions, such as constraint-induced movement therapy and mirror therapy, are increasingly being used.

Partial eNOS deficiency causes spontaneous thrombotic cerebral infarction, amyloid angiopathy and cognitive impairment.

PubMed

Tan, Xing-Lin; Xue, Yue-Qiang; Ma, Tao; Wang, Xiaofang; Li, Jing Jing; Lan, Lubin; Malik, Kafait U; McDonald, Michael P; Dopico, Alejandro M; Liao, Francesca-Fang

2015-06-24

Cerebral infarction due to thrombosis leads to the most common type of stroke and a likely cause of age-related cognitive decline and dementia. Endothelial nitric oxide synthase (eNOS) generates NO, which plays a crucial role in maintaining vascular function and exerting an antithrombotic action. Reduced eNOS expression and eNOS polymorphisms have been associated with stroke and Alzheimer's disease (AD), the most common type of dementia associated with neurovascular dysfunction. However, direct proof of such association is lacking. Since there are no reports of complete eNOS deficiency in humans, we used heterozygous eNOS(+/-) mice to mimic partial deficiency of eNOS, and determine its impact on cerebrovascular pathology and perfusion of cerebral vessels. Combining cerebral angiography with immunohistochemistry, we found thrombotic cerebral infarctions in eNOS(+/-) mice as early as 3-6 months of age but not in eNOS(+/+) mice at any age. Remarkably, vascular occlusions in eNOS(+/-) mice were found almost exclusively in three areas: temporoparietal and retrosplenial granular cortexes, and hippocampus this distribution precisely matching the hypoperfused areas identified in preclinical AD patients. Moreover, progressive cerebral amyloid angiopaphy (CAA), blood brain barrier (BBB) breakdown, and cognitive impairment were also detected in aged eNOS(+/-) mice. These data provide for the first time the evidence that partial eNOS deficiency results in spontaneous thrombotic cerebral infarctions that increase with age, leading to progressive CAA and cognitive impairments. We thus conclude that eNOS(+/-) mouse may represent an ideal model of ischemic stroke to address early and progressive damage in spontaneously-evolving chronic cerebral ischemia and thus, study vascular mechanisms contributing to vascular dementia and AD.

Cerebral Palsy (For Parents)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Cerebral Palsy KidsHealth / For Parents / Cerebral Palsy What's in this ... Ahead Print en español Parálisis cerebral What Is Cerebral Palsy? Cerebral palsy (CP) is a disorder that affects ...

MRI-based in vivo assessment of early cerebral infarction in a mouse filament perforation model of subarachnoid hemorrhage.

PubMed

Sasaki, Kazumasu; Mutoh, Tatsushi; Nakamura, Kazuhiro; Kojima, Ikuho; Taki, Yasuyuki; Suarez, Jose Ignacio; Ishikawa, Tatsuya

2017-07-13

Experimental subarachnoid hemorrhage (SAH) by endovascular filament perforation method is used widely in mice, but it sometimes present acute cerebral infarctions with varied magnitude and anatomical location. This study aimed to determine the prevalence and location of the acute ischemic injury in this experimental model. Male C57BL/6 mice were subjected to SAH by endovascular perforation. Distribution of SAH was defined by T2*-weighted images within 1h after SAH. Prevalence and location of acute infarction were assessed by diffusion-weighted MR images on day 1 after the induction. Among 72 mice successfully acquired post-SAH MR images, 29 (40%) developed acute infarction. Location of the infarcts was classified into either single infarct (ipsilateral cortex, n=12; caudate putamen, n=3; hippocampus, n=1) or multiple lesions (cortex and caudate putamen, n=6; cortex and hippocampus, n=2; cortex, hippocampus and thalamus/hypothalamus, n=3; bilateral cortex, n=2). The mortality rate within 24h was significantly higher in mice with multiple infarcts than those with single lesion (30% versus 0%; P=0.03). Distribution of the ischemic lesion positively correlated with MRI-evidenced SAH grading (r 2 =0.31, P=0.0002). Experimental SAH immediately after the vessel perforation can induce acute cerebral infarction in varying vascular territories, resulting in increased mortality. The present model may in part, help researchers to interpret the mechanism of clinically-evidenced early multiple combined infarction. Copyright © 2017 Elsevier B.V. All rights reserved.

Positive affect predicts cerebral glucose metabolism in late middle-aged adults

PubMed Central

Nicholas, Christopher R.; Hoscheidt, Siobhan M.; Clark, Lindsay R.; Racine, Annie M.; Berman, Sara E.; Koscik, Rebecca L.; Maritza Dowling, N.; Asthana, Sanjay; Christian, Bradley T.; Sager, Mark A.

2017-01-01

Abstract Positive affect is associated with a number of health benefits; however, few studies have examined the relationship between positive affect and cerebral glucose metabolism, a key energy source for neuronal function and a possible index of brain health. We sought to determine if positive affect was associated with cerebral glucose metabolism in late middle-aged adults (n = 133). Participants completed the positive affect subscale of the Center for Epidemiological Studies Depression Scale at two time points over a two-year period and underwent 18F-fluorodeoxyglucose-positron emission tomography scanning. After controlling for age, sex, perceived health status, depressive symptoms, anti-depressant use, family history of Alzheimer’s disease, APOE ε4 status and interval between visits, positive affect was associated with greater cerebral glucose metabolism across para-/limbic, frontal, temporal and parietal regions. Our findings provide evidence that positive affect in late midlife is associated with greater brain health in regions involved in affective processing and also known to be susceptible to early neuropathological processes. The current findings may have implications for interventions aimed at increasing positive affect to attenuate early neuropathological changes in at-risk individuals. PMID:28402542

Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage.

PubMed

Malinova, Vesna; Dolatowski, Karoline; Schramm, Peter; Moerer, Onnen; Rohde, Veit; Mielke, Dorothee

2016-07-01

OBJECT This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI). METHODS Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)-measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated. RESULTS Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p < 0.0001). A repeated CTP was performed in 8 patients with a TCD-measured BFV increase > 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI. CONCLUSIONS Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD-measured BFV increase or persisting coma, do not contribute to information gain.

[Energy corrective and antioxidative actions of cytoflavin during postischemic period of human dermal fibroblasts in vitro].

PubMed

Tiuriaeva, I I; Kuranova, M L; Gonchar, I V; Rozanov, Iu M

2012-01-01

The influence of metabolic drug Cytoflavin (CF) with antihypoxic and antioxidative properties on human dermal fibroblasts in a model of ischemia-reoxygenation in vitro was studied. It was revealed that the restoration of ATP synthesis in fibroblasts in the postischemic period was considerably accelerated (in 2.1 times) by the addition of CF to the culture medium. The drug had a cell protective effect of reducing cell mortality during the reoxygenation after ischemia by 2-2.7 times. CF effectively reduced the level of reactive oxygen species (ROS) in fibroblasts after H2O2 treatment which allowed maintaining their survival at the level of control cells. Pretreatment of the cells with CF for one day ensured the maintenance of normal levels of ROS during the investigated time period in the fibroblasts subjected to H2O2 treatment, and reduced H2O2-induced cell death by almost a third compared to control cells. The introduction of CF in culture medium after ischemia showed no influence on Hsp70 synthesis, but led to decrease in GRP78 synthesis, raised after ischemia, to the control level, indicating a resolve of the endoplasmic reticulum (ER) stress and functional normalization of ER.

MRI of plaque characteristics and relationship with downstream perfusion and cerebral infarction in patients with symptomatic middle cerebral artery stenosis.

PubMed

Lu, Shan-Shan; Ge, Song; Su, Chun-Qiu; Xie, Jun; Mao, Jian; Shi, Hai-Bin; Hong, Xun-Ning

2017-10-30

Intracranial plaque characteristics are associated with stroke events. Differences in plaque features may explain the disconnect between stenosis severity and the presence of ischemic stroke. To investigate the relationship between plaque characteristics and downstream perfusion changes, and their contribution to the occurrence of cerebral infarction beyond luminal stenosis. Case control. Forty-six patients with symptomatic middle cerebral artery (MCA) stenosis (with acute cerebral infarction, n = 30; without acute cerebral infarction, n = 16). 3.0T with 3D turbo spin echo sequence (3D-SPACE). Luminal stenosis grade, plaque features including lesion T 2 and T 1 hyperintense components, plaque enhancement grade, and plaque distribution were assessed. Brain perfusion was evaluated on mean transient time maps based on the Alberta Stroke Program Early CT score (MTT-ASPECTS). Plaque features, grade of luminal stenosis, and MTT-ASPECTS were compared between two groups. The association between plaque features and MTT-ASPECTS were assessed using Spearman's correlation analysis. Multivariate logistic regression and receiver operating characteristic (ROC) curves were constructed to assess the effect of significant variables alone and their combination in determining the occurrence of cerebral infarction. Stronger enhanced plaques were associated with downstream lower MTT-ASPECTS (P = 0.010). Plaque enhancement grade (P = 0.039, odds ratio [OR] 5.9, 95% confidence interval [CI] 1.1-32) and MTT-ASPECTS (P = 0.003, OR 2.6, 95% CI 1.4-4.7) were associated with a recent cerebral infarction, whereas luminal stenosis grade was not (P = 0.128). The combination of MTT-ASPECTS and plaque enhancement grade provided incremental information beyond luminal stenosis grade alone. The area under the receiver operating characteristic curve (AUC) improved from 0.535 to 0.921 (P < 0.05). Strongly enhanced plaques are associated with a higher likelihood of downstream

Dominant inheritance of cerebral gigantism.

PubMed

Zonana, J; Sotos, J F; Romshe, C A; Fisher, D A; Elders, M J; Rimoin, D L

1977-08-01

Cerebral gigantism is a syndrome consisting of characteristic dysmorphic features, accelerated growth in early childhood, and variable degrees of mental retardation. Its etiology and pathogenesis have not been defined. Three families are presented with multiple affected members. The vertical transmission of the trait and equal expression in both sexes in these families indicates a genetic etiology with a dominant pattern of inheritance, probably autosomal. As in previously reported cases, extensive endocrine evaluation failed to define the pathogenesis of the accelerated growth present in this disorder.

Impact of an educational program on parental knowledge of cerebral palsy.

PubMed

Karande, Sunil; Patil, Shailesh; Kulkarni, Madhuri

2008-09-01

To investigate parental knowledge of cerebral palsy, and to evaluate the impact of an educational intervention on it. From May 2003 to April 2004, 26 parents of newly diagnosed children with cerebral palsy were interviewed. After the interview, each parent was administered a structured educational program and re-interviewed after three months. The pre and post intervention responses were compared using Chi-square test. After the intervention, there was a significant improvement in parental knowledge: (i) of the cause of the disorder (5/26 vs 20/26, P = 0.0001), (ii) that it is non-progressive (16/26 vs 24/26, P = 0.021), (iii) that it is not curable (10/26 vs 23/26, P = 0.0005), (iv) that it is treatable (12/26 vs 24/26, P=0.0009), (v) of the frequency and duration of therapy necessary to improve functional abilities (7/26 vs 17/26, P = 0.005), and, (vi) of the importance of following up regularly with a pediatrician (17/26 vs 26/26, P = 0.003). However, there was no significant improvement in parental knowledge: (i) of the meaning of the term 'cerebral palsy' (0/26 vs 5/26, P = 0.060), (ii) that 'early intervention therapy' given by a team of therapists is its recommended therapy (18/26 v 23/26, P = 0.174), (iii) of the meaning of the term 'early intervention therapy' (12/26 vs 17/26, P = 0.163), and (iv) that it is preventable with good medical care (8/26 vs 10/26, P = 0.560). Parental knowledge of cerebral palsy is inadequate. A single-session educational program can significantly improve parental knowledge about many 'core basic issues' regarding cerebral palsy.

Cerebral Palsy (For Teens)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Cerebral Palsy KidsHealth / For Teens / Cerebral Palsy What's in this ... do just what everyone else does. What Is Cerebral Palsy? Cerebral palsy (CP) is a disorder of the ...

Cerebral amyloid-beta protein accumulation with aging in cotton-top tamarins: a model of early Alzheimer's disease?

PubMed

Lemere, Cynthia A; Oh, Jiwon; Stanish, Heather A; Peng, Ying; Pepivani, Imelda; Fagan, Anne M; Yamaguchi, Haruyasu; Westmoreland, Susan V; Mansfield, Keith G

2008-04-01

Alzheimer's disease (AD) is the most common progressive form of dementia in the elderly. Two major neuropathological hallmarks of AD include cerebral deposition of amyloid-beta protein (Abeta) into plaques and blood vessels, and the presence of neurofibrillary tangles in brain. In addition, activated microglia and reactive astrocytes are often associated with plaques and tangles. Numerous other proteins are associated with plaques in human AD brain, including Apo E and ubiquitin. The amyloid precursor protein and its shorter fragment, Abeta, are homologous between humans and non-human primates. Cerebral Abeta deposition has been reported previously for rhesus monkeys, vervets, squirrel monkeys, marmosets, lemurs, cynomologous monkeys, chimpanzees, and orangutans. Here we report, for the first time, age-related neuropathological changes in cotton-top tamarins (CTT, Saguinus oedipus), an endangered non-human primate native to the rainforests of Colombia and Costa Rica. Typical lifespan is 13-14 years of age in the wild and 15-20+ years in captivity. We performed detailed immunohistochemical analyses of Abeta deposition and associated pathogenesis in archived brain sections from 36 tamarins ranging in age from 6-21 years. Abeta plaque deposition was observed in 16 of the 20 oldest tamarins (>12 years). Plaques contained mainly Abeta42, and in the oldest animals, were associated with reactive astrocytes, activated microglia, Apo E, and ubiquitin-positive dystrophic neurites, similar to human plaques. Vascular Abeta was detected in 14 of the 20 aged tamarins; Abeta42 preceded Abeta40 deposition. Phospho-tau labeled dystrophic neurites and tangles, typically present in human AD, were absent in the tamarins. In conclusion, tamarins may represent a model of early AD pathology.

Understanding Participation of Preschool-Age Children with Cerebral Palsy

ERIC Educational Resources Information Center

Chiarello, Lisa Ann; Palisano, Robert J.; Orlin, Margo N.; Chang, Hui-Ju; Begnoche, Denise; An, Mihee

2012-01-01

Participation in home, school, and community activities is a primary outcome of early intervention services for children with disabilities and their families. The objectives of this study were to (a) describe participation of preschool-age children with cerebral palsy (CP); (b) determine effects of sex, age, and gross motor function on intensity…

Cerebral Palsy Symptoms in Children Decreased Following Massage Therapy

ERIC Educational Resources Information Center

Hernandez-Reif, Maria; Field, Tiffany; Largie, Shay; Diego, Miguel; Manigat, Natasha; Seoanes, Jacqueline; Bornstein, Joan

2005-01-01

Twenty young children (mean age = 32 months) with cerebral palsy (CP) recruited from early intervention programs received 30 minutes of massage or reading twice weekly for 12 weeks. The children receiving massage therapy showed fewer physical symptoms including reduced spasticity, less rigid muscle tone overall and in the arms, and improved fine…

Postoperative Cerebral Vasospasm Following Transsphenoidal Pituitary Adenoma Surgery.

PubMed

Eseonu, Chikezie I; ReFaey, Karim; Geocadin, Romergryko G; Quinones-Hinojosa, Alfredo

2016-08-01

Cerebral vasospasm following a transsphenoidal resection of a pituitary adenoma is a devastating occurrence that can lead to delayed cerebral ischemia and poor neurologic outcome if not diagnosed and treated in a timely manner. The etiology of this condition is not well understood but can lead to significant arterial vasospasm that causes severe ischemic insults. In this paper, we identify common presenting symptoms and essential management strategies to treat this harmful disease. A retrospective case report and literature review of presentation, treatment, and outcome of cerebral vasospasm following transsphenoidal surgery. We present 1 case and review 12 known cases in the literature on vasospasm following transsphenoidal surgery. Mean age was 48 (±13.8) years. There were 46.2% male patients. Factors associated with vasospasm, such as cerebral spinal fluid leaks following surgery, were seen in 38.5% of cases, and postoperative subarachnoid hemorrhage (SAH) was seen in 84.6% of cases. Hemiparesis was the presenting symptom of delayed cerebral ischemia in 61.5% of cases. For management, maintaining at least a euvolemic volume status was used in 76.9%, induced hypertension was used in 61.5%, and nimodipine was administered in 46.2% of cases. Patients returned to their neurologic baseline in 61.5% of cases, had new permanent deficits in 7.7% of cases, and died in 30.8% of cases. Cerebral vasospasm following transsphenoidal surgery is a dangerous disease that can lead to a high likelihood of mortality if not identified and treated. Early postoperative events, such as peritumoral subarachnoid hemorrhage and hemiparesis, may be factors associated with post-transsphenoidal surgery vasospasm. Effective treatment options used in patients that regained complete neurologic recovery were by inducing hypertension, maintaining euvolemia, and administering nimodipine. Copyright © 2016 Elsevier Inc. All rights reserved.

Cerebral misery perfusion due to carotid occlusive disease

PubMed Central

Maddula, Mohana; Sprigg, Nikola; Bath, Philip M; Munshi, Sunil

2017-01-01

Purpose Cerebral misery perfusion (CMP) is a condition where cerebral autoregulatory capacity is exhausted, and cerebral blood supply in insufficient to meet metabolic demand. We present an educational review of this important condition, which has a range of clinical manifestations. Method A non-systematic review of published literature was undertaken on CMP and major cerebral artery occlusive disease, using Pubmed and Sciencedirect. Findings Patients with CMP may present with strokes in watershed territories, collapses and transient ischaemic attacks or episodic movements associated with an orthostatic component. While positron emission tomography is the gold standard investigation for misery perfusion, advanced MRI is being increasingly used as an alternative investigation modality. The presence of CMP increases the risk of strokes. In addition to the devastating effect of stroke, there is accumulating evidence of impaired cognition and quality of life with carotid occlusive disease (COD) and misery perfusion. The evidence for revascularisation in the setting of complete carotid occlusion is weak. Medical management constitutes careful blood pressure management while addressing other vascular risk factors. Discussion The evidence for the management of patients with COD and CMP is discussed, together with recommendations based on our local experience. In this review, we focus on misery perfusion due to COD. Conclusion Patients with CMP and COD may present with a wide-ranging clinical phenotype and therefore to many specialties. Early identification of patients with misery perfusion may allow appropriate management and focus on strategies to maintain or improve cerebral blood flow, while avoiding potentially harmful treatment. PMID:28959496

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.

PTEN inhibition enhances angiogenesis in an in vitro model of ischemic injury by promoting Akt phosphorylation and subsequent hypoxia inducible factor-1α upregulation.

PubMed

Xue, Lixia; Huang, Jiankang; Zhang, Ting; Wang, Xiuzhe; Fu, Jianliang; Geng, Zhi; Zhao, Yuwu; Chen, Hao

2018-06-24

Angiogenesis is an important pathophysiological response to cerebral ischemia. PTEN is a lipid phosphatase whose loss activates PI3K/Akt signaling, which is related to HIF-1α upregulation and enhanced angiogenesis in human cancer cells. However, the specific roles of PTEN in endothelial cell functions and angiogenesis after cerebral ischemia remain unknown. Therefore, we sought to examine the potential effects of PTEN inhibition on post-ischemic angiogenesis in human blood vessel cells and to determine the underlying mechanism. In this present study, human umbilical vein endothelial cells (HUVECs) were exposed to oxygen-glucose deprivation (OGD), cell proliferation, migration and apoptosis, in vitro tube formation and expression of PTEN/Akt pathway and angiogenic factors were examined in HUVECs after treatment with PTEN inhibitor bisperoxovanadium (bpV) at different doses. The results showed that bpV significantly increased the cell proliferation and reduced cell apoptosis indicating that the drug exerts a cytoprotective effect on HUVECs with OGD exposure. bpV also enhanced cell migration and tube formation in HUVECs following OGD, and upregulated HIF-1α and VEGF expressions, but attenuated endostatin expression. Additionally, western blotting analysis demonstrated that Akt phosphorylation in HUVECs was significantly increased after bpV treatment. These findings suggest that PTEN inhibition promotes post-ischemic angiogenesis in HUVECs after exposure to OGD and this enhancing effect might be achieved through activation of the Akt signal cascade.

Cerebral ischemia and neuroregeneration

PubMed Central

Lee, Reggie H. C.; Lee, Michelle H. H.; Wu, Celeste Y. C.; Couto e Silva, Alexandre; Possoit, Harlee E.; Hsieh, Tsung-Han; Minagar, Alireza; Lin, Hung Wen

2018-01-01

Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke (a form of cerebral ischemia)-related costs are expected to reach 240.67 billion dollars by 2030, options for treatment against cerebral ischemia/stroke are limited. All therapies except anti-thrombolytics (i.e., tissue plasminogen activator) and hypothermia have failed to reduce neuronal injury, neurological deficits, and mortality rates following cerebral ischemia, which suggests that development of novel therapies against stroke/cerebral ischemia are urgently needed. Here, we discuss the possible mechanism(s) underlying cerebral ischemia-induced brain injury, as well as current and future novel therapies (i.e., growth factors, nicotinamide adenine dinucleotide, melatonin, resveratrol, protein kinase C isozymes, pifithrin, hypothermia, fatty acids, sympathoplegic drugs, and stem cells) as it relates to cerebral ischemia. PMID:29623912

High-altitude cerebral oedema mimicking stroke.

PubMed

Yanamandra, Uday; Gupta, Amul; Patyal, Sagarika; Varma, Prem Prakash

2014-03-26

High-altitude cerebral oedema (HACO) is the most fatal high-altitude illness seen by rural physicians practising in high-altitude areas. HACO presents clinically with cerebellar ataxia, features of raised intracranial pressure (ICP) and coma. Early identification is important as delay in diagnosis can be fatal. We present two cases of HACO presenting with focal deficits mimicking stroke. The first patient presented with left-sided hemiplegia associated with the rapid deterioration in the sensorium. Neuroimaging revealed features suggestive of vasogenic oedema. The second patient presented with monoplegia of the lower limb. Neuroimaging revealed perfusion deficit in anterior cerebral artery territory. Both patients were managed with dexamethasone and they improved dramatically. Clinical picture and neuroimaging closely resembled acute ischaemic stroke in both cases. Thrombolysis in these patients would have been disastrous. Recent travel to high altitude, young age, absence of atherosclerotic risk factors and features of raised ICP concomitantly directed the diagnosis to HACO.

Neuroprotective Effect of TAT-14-3-3ε Fusion Protein against Cerebral Ischemia/Reperfusion Injury in Rats

PubMed Central

Liu, Xiaoyan; Hu, Wenhui; Wang, Yinye

2014-01-01

Stroke is the major cause of death and disability worldwide, and the thrombolytic therapy currently available was unsatisfactory. 14-3-3ε is a well characterized member of 14-3-3 family, and has been reported to protect neurons against apoptosis in cerebral ischemia. However, it cannot transverse blood brain barrier (BBB) due to its large size. A protein transduction domain (PTD) of HIV TAT protein, is capable of delivering a large variety of proteins into the brain. In this study, we generated a fusion protein TAT-14-3-3ε, and evaluated its potential neuroprotective effect in rat focal ischemia/reperfusion (I/R) model. Western blot analysis validated the efficient transduction of TAT-14-3-3ε fusion protein into brain via a route of intravenous injection. TAT-14-3-3ε pre-treatment 2 h before ischemia significantly reduced cerebral infarction volume and improved neurologic score, while post-treatment 2 h after ischemia was less effective. Importantly, pre- or post-ischemic treatment with TAT-14-3-3ε significantly increased the number of surviving neurons as determined by Nissl staining, and attenuated I/R-induced neuronal apoptosis as showed by the decrease in apoptotic cell numbers and the inhibition of caspase-3 activity. Moreover, the introduction of 14-3-3ε into brain by TAT-mediated delivering reduced the formation of autophagosome, attenuated LC3B-II upregulation and reversed p62 downregulation induced by ischemic injury. Such inhibition of autophagy was reversed by treatment with an autophagy inducer rapamycin (RAP), which also attenuated the neuroprotective effect of TAT-14-3-3ε. Conversely, autophagy inhibitor 3-methyladenine (3-MA) inhibited I/R-induced the increase in autophagic activity, and attenuated I/R-induced brain infarct. These results suggest that TAT-14-3-3ε can be efficiently transduced into brain and exert significantly protective effect against brain ischemic injury through inhibiting neuronal apoptosis and autophagic activation. PMID

Cerebral Palsy

MedlinePlus

Cerebral palsy is a group of disorders that affect a person's ability to move and to maintain balance ... do not get worse over time. People with cerebral palsy may have difficulty walking. They may also have ...

Changes in cerebral glucose metabolism during early abstinence from chronic methamphetamine abuse.

PubMed

Berman, S M; Voytek, B; Mandelkern, M A; Hassid, B D; Isaacson, A; Monterosso, J; Miotto, K; Ling, W; London, E D

2008-09-01

Changes in brain function during the initial weeks of abstinence from chronic methamphetamine abuse may substantially affect clinical outcome, but are not well understood. We used positron emission tomography with [F-18]fluorodeoxyglucose (FDG) to quantify regional cerebral glucose metabolism, an index of brain function, during performance of a vigilance task. A total of 10 methamphetamine-dependent subjects were tested after 5-9 days of abstinence, and after 4 additional weeks of supervised abstinence. A total of 12 healthy control subjects were tested at corresponding times. Global glucose metabolism increased between tests (P=0.01), more in methamphetamine-dependent (10.9%, P=0.02) than control subjects (1.9%, NS). Glucose metabolism did not change in subcortical regions of methamphetamine-dependent subjects, but increased in neocortex, with maximal increase (>20%) in parietal regions. Changes in reaction time and self-reports of negative affect varied more in methamphetamine-dependent than in control subjects, and correlated both with the increase in parietal glucose metabolism, and decrease in relative activity (after scaling to the global mean) in some regions. A robust relationship between change in self-reports of depressive symptoms and relative activity in the ventral striatum may have great relevance to treatment success because of the role of this region in drug abuse-related behaviors. Shifts in cortical-subcortical metabolic balance either reflect new processes that occur during early abstinence, or the unmasking of effects of chronic methamphetamine abuse that are obscured by suppression of cortical glucose metabolism that continues for at least 5-9 days after cessation of methamphetamine self-administration.

[Etiology of cerebral palsy].

PubMed

Jaisle, F

1996-01-01

The "perinatal asphyxia" is regarded to be one of the causes of cerebral palsy, though in the very most of the children with cerebral palsy there is found no hypoxia during labour. It should be mentioned, that the definition of "perinatal" and "asphyxia" neither are unic nor concret. And also there is no correlation between nonreassuring fetal heart rate patterns and acidosis in fetal blood with the incidence of cerebral palsy. Numerous studies in pregnant animals failed in proving an acute intrapartal hypoxia to be the origin of the cerebral palsy. Myers (1975) describes four patterns of anatomic brain damage after different injuries. Only his so called oligo-acidotic hypoxia, which is protracted and lasts over a longer time is leading to brain injury, which can be regarded in analogy to the injury of children with cerebral palsy. Summarising the update publications about the causes of cerebral palsy and the studies in pregnant animals there is no evidence that hypoxia during labour may be the cause of cerebral palsy. There is a great probability of a pre(and post-)natal origin of brain injury (for instance a periventricular leucomalacia found after birth) which leads to cerebral palsy. Short after labour signs of a so called "asphyxia" may occur in addition to this preexisting injury and misrepresent the cause of cerebral palsy. Finally the prepartal injury may cause both: Cerebral palsy and hypoxia.

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

Genetic modification of cerebral arterial wall: implications for prevention and treatment of cerebral vasospasm.

PubMed

Vijay, Anantha; Santhanam, R; Katusic, Zvonimir S

2006-10-01

Genetic modification of cerebral vessels represents a promising and novel approach for prevention and/or treatment of various cerebral vascular disorders, including cerebral vasospasm. In this review, we focus on the current understanding of the use of gene transfer to the cerebral arteries for prevention and/or treatment of cerebral vasospasm following subarachnoid hemorrhage (SAH). We also discuss the recent developments in vascular therapeutics, involving the autologous use of progenitor cells for repair of damaged vessels, as well as a cell-based gene delivery approach for the prevention and treatment of cerebral vasospasm.

Cerebral Atrophy

MedlinePlus

... Alzheimer’s disease, Pick’s disease, and fronto-temporal dementia cerebral palsy , in which lesions (damaged areas) may impair motor ... Alzheimer’s disease, Pick’s disease, and fronto-temporal dementia cerebral palsy , in which lesions (damaged areas) may impair motor ...

Longitudinal Cerebral Blood Flow Changes during Speech in Hereditary Ataxia

ERIC Educational Resources Information Center

Sidtis, John J.; Strother, Stephen C.; Naoum, Ansam; Rottenberg, David A.; Gomez, Christopher

2010-01-01

The hereditary ataxias constitute a group of degenerative diseases that progress over years or decades. With principal pathology involving the cerebellum, dysarthria is an early feature of many of the ataxias. Positron emission tomography was used to study regional cerebral blood flow changes during speech production over a 21 month period in a…

Cerebral and non-cerebral coenurosis: on the genotypic and phenotypic diversity of Taenia multiceps.

PubMed

Christodoulopoulos, Georgios; Dinkel, Anke; Romig, Thomas; Ebi, Dennis; Mackenstedt, Ute; Loos-Frank, Brigitte

2016-12-01

We characterised the causative agents of cerebral and non-cerebral coenurosis in livestock by determining the mitochondrial genotypes and morphological phenotypes of 52 Taenia multiceps isolates from a wide geographical range in Europe, Africa, and western Asia. Three studies were conducted: (1) a morphological comparison of the rostellar hooks of cerebral and non-cerebral cysts of sheep and goats, (2) a morphological comparison of adult worms experimentally produced in dogs, and (3) a molecular analysis of three partial mitochondrial genes (nad1, cox1, and 12S rRNA) of the same isolates. No significant morphological or genetic differences were associated with the species of the intermediate host. Adult parasites originating from cerebral and non-cerebral cysts differed morphologically, e.g. the shape of the small hooks and the distribution of the testes in the mature proglottids. The phylogenetic analysis of the mitochondrial haplotypes produced three distinct clusters: one cluster including both cerebral isolates from Greece and non-cerebral isolates from tropical and subtropical countries, and two clusters including cerebral isolates from Greece. The majority of the non-cerebral specimens clustered together but did not form a monophyletic group. No monophyletic groups were observed based on geography, although specimens from the same region tended to cluster. The clustering indicates high intraspecific diversity. The phylogenetic analysis suggests that all variants of T. multiceps can cause cerebral coenurosis in sheep (which may be the ancestral phenotype), and some variants, predominantly from one genetic cluster, acquired the additional capacity to produce non-cerebral forms in goats and more rarely in sheep.

Cerebral Palsy. Fact Sheet = La Paralisis Cerebral. Hojas Informativas Sobre Discapacidades.

ERIC Educational Resources Information Center

National Information Center for Children and Youth with Disabilities, Washington, DC.

This fact sheet on cerebral palsy is written in both English and Spanish. First, it provides a definition of cerebral palsy and considers various causes (e.g., an insufficient amount of oxygen reaching the fetal or newborn brain). The fact sheet then offers incidence figures and explains characteristics of the three main types of cerebral palsy:…

Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation.

PubMed

Allende, Maria L; Cook, Emily K; Larman, Bridget C; Nugent, Adrienne; Brady, Jacqueline M; Golebiowski, Diane; Sena-Esteves, Miguel; Tifft, Cynthia J; Proia, Richard L

2018-03-01

Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of β-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB -corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB -corrected organoids, accumulated GM2 ganglioside and exhibited increased size and cellular proliferation compared with the HEXB -corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses.

Initial experience of coiling cerebral aneurysms using the new Comaneci device

PubMed Central

Lawson, Aimee Louise Deborah; Chandran, Arun; Puthuran, Mani; Goddard, Tony; Nahser, Hans; Patankar, Tufail

2015-01-01

We present our initial patient experience with an innovative temporary bridging device, the Comaneci (Rapid Medical, Israel), to assist in the coiling of cerebral aneurysms. The Comaneci device confers the same benefits as balloon remodeling but without the risks of parent artery occlusion. This alleviates time pressure on the clinician, and could reduce the risk of parent artery thrombosis. Three patients were treated with the Comaneci device. Two patients had acute ruptured posterior communicating aneurysms and one patient was treated electively for a carotico-ophthalmic aneurysm. Excellent occlusion of all three aneurysms was obtained. One patient developed a distal middle cerebral artery clot, that was treated with intravenous aspirin, with minor neurological consequences. These early results show that the Comaneci device can be used to achieve good cerebral aneurysm occlusion. Vessel patency is maintained throughout the procedure with potential advantages over conventional balloon assisted coiling. PMID:26123460

APC sets the Wnt tone necessary for cerebral cortical progenitor development.

PubMed

Nakagawa, Naoki; Li, Jingjun; Yabuno-Nakagawa, Keiko; Eom, Tae-Yeon; Cowles, Martis; Mapp, Tavien; Taylor, Robin; Anton, E S

2017-08-15

Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC-β-catenin pathway indicates that the maintenance of appropriate β-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates β-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. β-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of β-catenin or inhibition of β-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated β-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development. © 2017 Nakagawa et al.; Published by Cold Spring Harbor Laboratory Press.

APC sets the Wnt tone necessary for cerebral cortical progenitor development

PubMed Central

Nakagawa, Naoki; Li, Jingjun; Yabuno-Nakagawa, Keiko; Eom, Tae-Yeon; Cowles, Martis; Mapp, Tavien; Taylor, Robin; Anton, E.S.

2017-01-01

Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC–β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical progenitor development, a necessary early step in cerebral cortical formation. Radial progenitor-specific inactivation of the APC–β-catenin pathway indicates that the maintenance of appropriate β-catenin-mediated Wnt tone is necessary for the orderly differentiation of cortical progenitors and the resultant formation of the cerebral cortex. APC deletion deregulates β-catenin, leads to high Wnt tone, and disrupts Notch1 signaling and primary cilium maintenance necessary for radial progenitor functions. β-Catenin deregulation directly disrupts cilium maintenance and signaling via Tulp3, essential for intraflagellar transport of ciliary signaling receptors. Surprisingly, deletion of β-catenin or inhibition of β-catenin activity in APC-null progenitors rescues the APC-null phenotype. These results reveal that APC-regulated β-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development. PMID:28916710

Effects of antenatal magnesium sulfate treatment for neonatal neuro-protection on cerebral oxygen kinetics.

PubMed

Stark, Michael J; Hodyl, Nicolette A; Andersen, Chad C

2015-09-01

The underlying neuro-protective mechanisms of antenatal magnesium sulfate (MgSO(4)) in infants born preterm remain poorly understood. Early neonatal brain injury may be preceded by low cerebral blood flow (CBF) and elevated cerebral fractional tissue oxygen extraction (cFTOE). This study investigated the effect of antenatal MgSO(4) on cerebral oxygen delivery, consumption, and cFTOE in preterm infants. CBF and tissue oxygenation index were measured, and oxygen delivery, consumption, and cFTOE calculated within 24 h of birth and at 48 and 72 h of life in 36 infants ≤ 30 wk gestation exposed to MgSO(4) and 29 unexposed infants. Total internal carotid blood flow and cerebral oxygen delivery did not differ between the groups at the three study time-points. Cerebral oxygen consumption and cFTOE were lower in infants exposed to antenatal MgSO(4) (P = 0.012) compared to unexposed infants within 24 h of delivery. This difference was not evident by 48 h of age. Fewer infants in the MgSO(4) group developed P/IVH by 72 h of age (P = 0.03). Infants exposed to MgSO(4) had similar systemic and cerebral hemodynamics but lower cFTOE compared to nonexposed. These findings suggest reduced cerebral metabolism maybe a component of the neuro-protective actions of antenatal MgSO(4).

The Effect of Otitis Media on Articulation in Children with Cerebral Palsy.

ERIC Educational Resources Information Center

Van der Vyver, Marguerite; And Others

1988-01-01

A study involving 20 Afrikaans-speaking children with cerebral palsy found that recurrent otitis media in early childhood had a negative effect on articulation abilities of the 7 to 11-year-old children but that other factors such as intelligence also played a role. (JDD)

[Cerebral metabolism and permeability of the hemato-encephalic barrier in an experimental model for brain radiotherapy].

PubMed

Cicciarello, R; Russi, E; Albiero, F; Mesiti, M; Torre, E; D'Aquino, A; Raffaele, L; Bertolani, S; D'Avella, D

1990-11-01

Whole brain irradiation (WBR) can produce acute and chronic neurological adverse effects, which are usually divided into acute, early delayed and late delayed reactions according to the time of onset. To assess the impact of WBR on brain functional parameters during the early-delayed phase, we employed the [14C]-2-deoxyglucose (2-DG) and the [14C]-alfa-aminoisobutyric (AIB) acid quantitative autoradiographic techniques to study local cerebral glucose utilization and blood-brain barrier permeability, respectively. Sprague-Dowley albino rats were exposed to conventional fractionation (200 Gy/day 5 days a week) for a total dose of 4000 Gy. Experiments were made 3 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased following irradiation. As a rule, brain areas with the highest basal metabolic rates showed the highest percentage drop in glucose utilization. Changes in blood-brain barrier function, as assessed by an increased transcapillary transport of AIB, were also demonstrated in specific brain regions. This study illustrates how moderate doses of WBR induce well-defined changes in brain metabolism and BBB function, which are possibly involved in the pathogenesis of the early-delayed radiation-induced cerebral dysfunction in humans.

Fatal Cerebral Edema With Status Epilepticus in Children With Dravet Syndrome: Report of 5 Cases.

PubMed

Myers, Kenneth A; McMahon, Jacinta M; Mandelstam, Simone A; Mackay, Mark T; Kalnins, Renate M; Leventer, Richard J; Scheffer, Ingrid E

2017-04-01

Dravet syndrome (DS) is a well-recognized developmental and epileptic encephalopathy associated with SCN1A mutations and 15% mortality by 20 years. Although over half of cases succumb to sudden unexpected death in epilepsy, the cause of death in the remainder is poorly defined. We describe the clinical, radiologic, and pathologic characteristics of a cohort of children with DS and SCN1A mutations who developed fatal cerebral edema causing mass effect after fever-associated status epilepticus. Cases were identified from a review of children with DS enrolled in the Epilepsy Genetics Research Program at The University of Melbourne, Austin Health, who died after fever-associated status epilepticus. Five children were identified, all of whom presented with fever-associated convulsive status epilepticus, developed severe brain swelling, and died. All had de novo SCN1A mutations. Fever of 40°C or greater was measured in all cases. Signs of brainstem dysfunction, indicating cerebral herniation, were first noted 3 to 5 days after initial presentation in 4 patients, though were apparent as early as 24 hours in 1 case. When MRI was performed early in a patient's course, focal regions of cortical diffusion restriction were noted. Later MRI studies demonstrated diffuse cytotoxic edema, with severe cerebral herniation. Postmortem studies revealed diffuse brain edema and widespread neuronal damage. Laminar necrosis was seen in 1 case. Cerebral edema leading to fatal brain herniation is an important, previously unreported sequela of status epilepticus in children with DS. This potentially remediable complication may be a significant contributor to the early mortality of DS. Copyright © 2017 by the American Academy of Pediatrics.

Effects of hyperglycemia and effects of ketosis on cerebral perfusion, cerebral water distribution, and cerebral metabolism.

PubMed

Glaser, Nicole; Ngo, Catherine; Anderson, Steven; Yuen, Natalie; Trifu, Alexandra; O'Donnell, Martha

2012-07-01

Diabetic ketoacidosis (DKA) may cause brain injuries in children. The mechanisms responsible are difficult to elucidate because DKA involves multiple metabolic derangements. We aimed to determine the independent effects of hyperglycemia and ketosis on cerebral metabolism, blood flow, and water distribution. We used magnetic resonance spectroscopy to measure ratios of cerebral metabolites (ATP to inorganic phosphate [Pi], phosphocreatine [PCr] to Pi, N-acetyl aspartate [NAA] to creatine [Cr], and lactate to Cr) and diffusion-weighted imaging and perfusion-weighted imaging to assess cerebral water distribution (apparent diffusion coefficient [ADC] values) and cerebral blood flow (CBF) in three groups of juvenile rats (hyperglycemic, ketotic, and normal control). ATP-to-Pi ratio was reduced in both hyperglycemic and ketotic rats in comparison with controls. PCr-to-Pi ratio was reduced in the ketotic group, and there was a trend toward reduction in the hyperglycemic group. No significant differences were observed in NAA-to-Cr or lactate-to-Cr ratio. Cortical ADC was reduced in both groups (indicating brain cell swelling). Cortical CBF was also reduced in both groups. We conclude that both hyperglycemia and ketosis independently cause reductions in cerebral high-energy phosphates, CBF, and cortical ADC values. These effects may play a role in the pathophysiology of DKA-related brain injury.

Accumulation of intimal platelets in cerebral arteries following experimental subarachnoid hemorrhage in cats

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

Haining, J.L.; Clower, B.R.; Honma, Y.

From 2 hours to 23 days following experimental subarachnoid hemorrhage, the accumulation of indium-111-labeled platelets on the intimal surface of the middle cerebral artery was studied in 23 cats. Subarachnoid hemorrhage was produced by transorbital rupture of the right middle cerebral artery. Of the 23 cats, 17 exhibited right middle cerebral artery/left middle cerebral artery radioactivity ratios of greater than 1.25. When these results were compared with those of 12 control cats, 0.001 less than p less than 0.005 (chi2 test). Thus, the results from the control and experimental groups are significantly different and indicate early (after 2 hours) preferentialmore » accumulation of intimal platelets in the ruptured right middle cerebral artery compared with the unruptured left middle cerebral artery and new platelet deposition continuing for up to 23 days. However, the experimental group did not reveal a clear pattern for platelet accumulation following subarachnoid hemorrhage. There was no simple correlation between the magnitude of the radioactivity ratios and the time after hemorrhage when the cats were killed although the ratios for 2 hours to 7 days seemed greater than those for 8 to 23 days. Assuming the pivotal role of platelets in the angiopathy of subarachnoid hemorrhage, the administration of antiplatelet agents as soon as possible following its occurrence may be of value.« less

Iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET-1 balance.

PubMed

Kawashima, Masahiro; Nakamura, Takayuki; Schneider, Sven; Vollmar, Brigitte; Lausberg, Henning F; Bauer, Michael; Menger, Michael D; Schäfers, Hans-Joachim

2003-07-01

Ischemia-reperfusion (I/R) injury of the lung involves increased pulmonary vascular resistance. Prostaglandins are thought to have a beneficial effect in lung transplantation, but their mechanism in I/R injury is unknown. We investigated whether iloprost, a stable prostacyclin analogue, prevents I/R-associated pulmonary vascular dysfunction and whether it affects endothelin-1 (ET-1) balance. In an isolated blood-perfusion model, we subjected lungs of Lewis rats to 45 minutes of ischemia at 37 degrees C and randomly allocated the lungs to 3 groups (n = 6 each): iloprost (33.3 nmol/liter) added to the perfusate before ischemia and reperfusion (ILO+IR), iloprost (33.3 nmol/liter) given only before reperfusion (ILO+R), and controls without iloprost treatment (ILO-). Reperfusion induced marked pulmonary edema in non-treated controls (ILO-), which was attenuated in ILO+R lungs and completely prevented in ILO+IR lungs. At 60 minutes reperfusion, arterial oxygen tension was significantly greater in both ILO+R and ILO+IR lungs compared with ILO- controls. Mean pulmonary artery pressure and pulmonary vascular resistance were slightly decreased in the ILO+R and significantly decreased in the ILO+IR group compared with the ILO- controls. Plasma levels of big ET-1, measured in both afferent and efferent blood, showed that I/R results in increased pulmonary venous levels of big ET-1. Interestingly, the increased venoarterial ET-1 gradient in ILO- lungs decreased significantly in the ILO+IR group. We demonstrated in an isolated lung perfusion model that iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET-1 balance.

Cerebral palsy - resources

MedlinePlus

Resources - cerebral palsy ... The following organizations are good resources for information on cerebral palsy : National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope- ...

Importance of Speech Production for Phonological Awareness and Word Decoding: The Case of Children with Cerebral Palsy

ERIC Educational Resources Information Center

Peeters, Marieke; Verhoeven, Ludo; de Moor, Jan; van Balkom, Hans

2009-01-01

The goal of this longitudinal study was to investigate the precursors of early reading development in 52 children with cerebral palsy at kindergarten level in comparison to 65 children without disabilities. Word Decoding was measured to investigate early reading skills, while Phonological Awareness, Phonological Short-term Memory (STM), Speech…

Differential diagnoses of cerebral hemiatrophy in childhood: a review of literature with illustrative report of two cases.

PubMed

Uduma, Felix Uduma; Emejulu, Jude-Kennedy C; Motah, Mathieu; Okere, Philip C N; Ongolo, Pierre C; Muna, W

2013-03-20

Childhood cerebral hemiatrophy is an uncommon clinical entity. Its aetiologies are diverse but can generally be grouped into congenital and acquired. The congenital type is intrauterine in origin while the acquired type occurs early in life, usually before two year of life. When childhood cerebral hemiatrophy occurs, it evokes a spectrum of compensatory calvarial sequlae. These include ipsilateral calvarial thickening, diploe widening, hyper-pneumatization of paranasal sinues/ mastoids, elevation of petrous bone and small middle cranial fossa. MRI is very effective in high lightening brain atrophy, associated parenchymal changes and even the above enumerated skull changes. Our two case reports of left hemi-cerebral atrophy in male Cameroonian children seen in our MRI practice aptly demonstrated some of the aforementioned radiological features of childhood cerebral hemiatrophy noted in literature review.

Cerebral arteriovenous malformation

MedlinePlus

AVM - cerebral; Arteriovenous hemangioma; Stroke - AVM; Hemorrhagic stroke - AVM ... The cause of cerebral AVM is unknown. An AVM occurs when arteries in the brain connect directly to nearby veins without having the ...

Epilepsy after cerebral infection: review of the literature and the potential for surgery.

PubMed

Ramantani, Georgia; Holthausen, Hans

2017-06-01

The risk of unprovoked seizures in population-based cohorts of cerebral infection survivors is 7-8% in developed countries, rising to considerably higher rates in resource-poor countries. The main risk factors for epilepsy after cerebral infection, besides acute seizures, are infection-associated brain lesions and status epilepticus during the acute phase. Despite the high prevalence of pharmacoresistant epilepsies after cerebral infections, especially in patients with MRI-identifiable lesions, only a small minority undergoes epilepsy surgery. However, excellent surgical candidates are particularly those with a history of meningitis or encephalitis in early childhood, hippocampal sclerosis on MRI, as well as a history, seizure semiology, and EEG-findings compatible with the diagnosis of a mesial temporal lobe epilepsy syndrome. More challenging are patients with neocortical/extratemporal lobe epilepsies post cerebral infection. Finally, patients with a severe hemispheric injury with contralateral hemiparesis are candidates for hemispherectomy/hemispherotomy. This review attempts to shed some light on this frequent cause of symptomatic focal epilepsy, with an emphasis on the chances offered by epilepsy surgery.

Fractal dimension values of cerebral and cerebellar activity in rats loaded with aluminium.

PubMed

Kekovic, Goran; Culic, Milka; Martac, Ljiljana; Stojadinovic, Gordana; Capo, Ivan; Lalosevic, Dusan; Sekulic, Slobodan

2010-07-01

Aluminium interferes with a variety of cellular metabolic processes in the mammalian nervous system and its intake might increase a risk of developing Alzheimer's disease (AD). While cerebral involvement even at the early stages of intoxication is well known, the role of cerebellum is underestimated. Our aim was to investigate cerebral and cerebellar electrocortical activity in adult male rats exposed to chronic aluminium treatment by nonlinear analytic tools. The adult rats in an aluminium-treated group were injected by AlCl(3), intraperitoneally (2 mg Al/kg, daily for 4 weeks). Fractal analysis of brain activity was performed off-line using Higuchi's algorithm. The average fractal dimension of electrocortical activity in aluminium-treated animals was lower than the average fractal dimension of electrocortical activity in the control rats, at cerebral but not at cerebellar level. The changes in the stationary and nonlinear properties of time series were more expressed in cerebral electrocortical activity than in cerebellar activity. This can be useful for developing effective diagnostic and therapeutic strategies in neurodegenerative diseases.

Brainstem Involvement as a Cause of Central Sleep Apnea: Pattern of Microstructural Cerebral Damage in Patients with Cerebral Microangiopathy

PubMed Central

Duning, Thomas; Deppe, Michael; Brand, Eva; Stypmann, Jörg; Becht, Charlotte; Heidbreder, Anna; Young, Peter

2013-01-01

Background The exact underlying pathomechanism of central sleep apnea with Cheyne-Stokes respiration (CSA-CSR) is still unclear. Recent studies have demonstrated an association between cerebral white matter changes and CSA. A dysfunction of central respiratory control centers in the brainstem was suggested by some authors. Novel MR-imaging analysis tools now allow far more subtle assessment of microstructural cerebral changes. The aim of this study was to investigate whether and what severity of subtle structural cerebral changes could lead to CSA-CSR, and whether there is a specific pattern of neurodegenerative changes that cause CSR. Therefore, we examined patients with Fabry disease (FD), an inherited, lysosomal storage disease. White matter lesions are early and frequent findings in FD. Thus, FD can serve as a "model disease" of cerebral microangiopathy to study in more detail the impact of cerebral lesions on central sleep apnea. Patients and Methods Genetically proven FD patients (n = 23) and age-matched healthy controls (n = 44) underwent a cardio-respiratory polysomnography and brain MRI at 3.0 Tesla. We applied different MR-imaging techniques, ranging from semiquantitative measurement of white matter lesion (WML) volumes and automated calculation of brain tissue volumes to VBM of gray matter and voxel-based diffusion tensor imaging (DTI) analysis. Results In 5 of 23 Fabry patients (22%) CSA-CSR was detected. Voxel-based DTI analysis revealed widespread structural changes in FD patients when compared to the healthy controls. When calculated as a separate group, DTI changes of CSA-CSR patients were most prominent in the brainstem. Voxel-based regression analysis revealed a significant association between CSR severity and microstructural DTI changes within the brainstem. Conclusion Subtle microstructural changes in the brainstem might be a neuroanatomical correlate of CSA-CSR in patients at risk of WML. DTI is more sensitive and specific than

Aging and Cerebral Palsy.

ERIC Educational Resources Information Center

Networker, 1993

1993-01-01

This special edition of "The Networker" contains several articles focusing on aging and cerebral palsy (CP). "Aging and Cerebral Palsy: Pathways to Successful Aging" (Jenny C. Overeynder) reports on the National Invitational Colloquium on Aging and Cerebral Palsy held in April 1993. "Observations from an Observer" (Kathleen K. Barrett) describes…

Life-threatening Cerebral Edema Caused by Acute Occlusion of a Superior Vena Cava Stent

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

Sofue, Keitaro, E-mail: keitarosofue@yahoo.co.jp; Takeuchi, Yoshito, E-mail: yotake62@qg8.so-net.ne.jp; Arai, Yasuaki, E-mail: arai-y3111@mvh.biglobe.ne.jp

A71-year-old man with advanced lung cancer developed a life-threatening cerebral edema caused by the acute occlusion of a superior vena cava (SVC) stent and was successfully treated by an additional stent placement. Although stent occlusion is a common early complication, no life-threatening situations have been reported until now. Our experience highlights the fact that acute stent occlusion can potentially lead to the complete venous shutdown of the SVC, resulting in life-threatening cerebral edema, after SVC stent placement. Immediate diagnosis and countermeasures are required.

Ursolic Acid Ameliorates Inflammation in Cerebral Ischemia and Reperfusion Injury Possibly via High Mobility Group Box 1/Toll-Like Receptor 4/NFκB Pathway.

PubMed

Wang, Yanzhe; Li, Lei; Deng, Shumin; Liu, Fang; He, Zhiyi

2018-01-01

Toll-like receptors (TLRs) play key roles in cerebral ischemia and reperfusion injury by inducing the production of inflammatory mediators, such as interleukins (ILs) and tumor necrosis factor-alpha (TNF-α). According to recent studies, ursolic acid (UA) regulates TLR signaling and exhibits notable anti-inflammatory properties. In the present study, we explored the mechanism by which UA regulates inflammation in the rat middle cerebral artery occlusion and reperfusion (MCAO/R) model. The MCAO/R model was induced in male Sprague-Dawley rats (MCAO for 2 h, followed by reperfusion for 48 h). UA was administered intragastrically at 0.5, 24, and 47 h after reperfusion. The direct high mobility group box 1 (HMGB1) inhibitor glycyrrhizin (GL) was injected intravenously after 0.5 h of ischemia as a positive control. The degree of brain damage was estimated using the neurological deficit score, infarct volume, histopathological changes, and neuronal apoptosis. We assessed IL-1β, TNF-α, and IL-6 levels to evaluate post-ischemic inflammation. HMGB1 and TLR4 expression and phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) were also examined to explore the underlying mechanism. UA (10 and 20 mg/kg) treatment significantly decreased the neurological deficit scores, infarct volume, apoptotic cells, and IL-1β, TNF-α, and IL-6 concentrations. The infarct area ratio was reduced by (33.07 ± 1.74), (27.05 ± 1.13), (27.49 ± 1.87), and (39.74 ± 2.14)% in the 10 and 20 mg/kg UA, GL, and control groups, respectively. Furthermore, UA (10 and 20 mg/kg) treatment significantly decreased HMGB1 release and the TLR4 level and inactivated NFκB signaling. Thus, the effects of intragastric administration of 20 mg/kg of UA and 10 mg/kg of GL were similar. We provide novel evidence that UA reduces inflammatory cytokine production to protect the brain from cerebral ischemia and reperfusion injury possibly through the

Effects of Red Palm Oil on Myocardial Antioxidant Enzymes, Nitric Oxide Synthase and Heart Function in Spontaneously Hypertensive Rats.

PubMed

Katengua-Thamahane, Emma; Szeiffova Bacova, Barbara; Bernatova, Iveta; Sykora, Matus; Knezl, Vladimir; Van Rooyen, Jacques; Tribulova, Narcis

2017-11-21

The purpose of this study was to investigate the effect of antioxidants rich red palm oil (RPO) supplementation on cardiac oxidative stress known as crucial factor deteriorating heart function in hypertension. 3-month-old, male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were fed standard rat chow without or with RPO (0.2 mL/day/5 weeks). General characteristic of rats were registered. Left ventricular tissue (LV) was used to determine expression of superoxide dismutases (SOD1, SOD2) and glutathione peroxidases (Gpx) as well as activity of nitric oxide synthase (NOS). Functional parameters of the heart were examined during basal conditions and at the early-phase of post-ischemic reperfusion using Langendorff-perfused system. RPO intake significantly reduced elevated blood pressure and total NOS activity as well as increased lowered expression of mitochondrial SOD2 in SHR hearts during basal condition. Moreover, RPO supplementation resulted in suppression of elevated heart rate, increase of reduced coronary flow and enhancement of systolic and diastolic heart function at the early-phase of post-ischemic reperfusion. It is concluded that SHR benefit from RPO intake due to decrease of blood pressure, amelioration of oxidative stress and protection of heart function that was deteriorated by post-ischemic reperfusion.

Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy.

PubMed

Eichler, Florian; Duncan, Christine; Musolino, Patricia L; Orchard, Paul J; De Oliveira, Satiro; Thrasher, Adrian J; Armant, Myriam; Dansereau, Colleen; Lund, Troy C; Miller, Weston P; Raymond, Gerald V; Sankar, Raman; Shah, Ami J; Sevin, Caroline; Gaspar, H Bobby; Gissen, Paul; Amartino, Hernan; Bratkovic, Drago; Smith, Nicholas J C; Paker, Asif M; Shamir, Esther; O'Meara, Tara; Davidson, David; Aubourg, Patrick; Williams, David A

2017-10-26

In X-linked adrenoleukodystrophy, mutations in ABCD1 lead to loss of function of the ALD protein. Cerebral adrenoleukodystrophy is characterized by demyelination and neurodegeneration. Disease progression, which leads to loss of neurologic function and death, can be halted only with allogeneic hematopoietic stem-cell transplantation. We enrolled boys with cerebral adrenoleukodystrophy in a single-group, open-label, phase 2-3 safety and efficacy study. Patients were required to have early-stage disease and gadolinium enhancement on magnetic resonance imaging (MRI) at screening. The investigational therapy involved infusion of autologous CD34+ cells transduced with the elivaldogene tavalentivec (Lenti-D) lentiviral vector. In this interim analysis, patients were assessed for the occurrence of graft-versus-host disease, death, and major functional disabilities, as well as changes in neurologic function and in the extent of lesions on MRI. The primary end point was being alive and having no major functional disability at 24 months after infusion. A total of 17 boys received Lenti-D gene therapy. At the time of the interim analysis, the median follow-up was 29.4 months (range, 21.6 to 42.0). All the patients had gene-marked cells after engraftment, with no evidence of preferential integration near known oncogenes or clonal outgrowth. Measurable ALD protein was observed in all the patients. No treatment-related death or graft-versus-host disease had been reported; 15 of the 17 patients (88%) were alive and free of major functional disability, with minimal clinical symptoms. One patient, who had had rapid neurologic deterioration, had died from disease progression. Another patient, who had had evidence of disease progression on MRI, had withdrawn from the study to undergo allogeneic stem-cell transplantation and later died from transplantation-related complications. Early results of this study suggest that Lenti-D gene therapy may be a safe and effective alternative to

[Aortic and cerebral trombosis caused by hypernatremic dehydration in an exclusively breast-fed infant].

PubMed

Iglesias Fernández, C; Chimenti Camacho, P; Vázquez López, P; Guerrero Soler, M; Blanco Bravo, D

2006-10-01

Complete aortic thrombosis is rare in neonates. Because it carries high morbidity and mortality, this entity requires aggressive and early treatment. This report describes an 8-day-old healthy and exclusively breast-fed infant, without specific coagulopathy, who developed complete aortic and cerebral venous thrombosis, which was attributed to inadequate breast-feeding and severe hypernatremic dehydration. Early systemic anticoagulation and thrombolytic therapy allowed complete resolution of the problem.

Spectral analysis-based risk score enables early prediction of mortality and cerebral performance in patients undergoing therapeutic hypothermia for ventricular fibrillation and comatose status

PubMed Central

Filgueiras-Rama, David; Calvo, Conrado J.; Salvador-Montañés, Óscar; Cádenas, Rosalía; Ruiz-Cantador, Jose; Armada, Eduardo; Rey, Juan Ramón; Merino, J.L.; Peinado, Rafael; Pérez-Castellano, Nicasio; Pérez-Villacastín, Julián; Quintanilla, Jorge G.; Jiménez, Santiago; Castells, Francisco; Chorro, Francisco J.; López-Sendón, J.L.; Berenfeld, Omer; Jalife, José; López de Sá, Esteban; Millet, José

2017-01-01

Background Early prognosis in comatose survivors after cardiac arrest due to ventricular fibrillation (VF) is unreliable, especially in patients undergoing mild hypothermia. We aimed at developing a reliable risk-score to enable early prediction of cerebral performance and survival. Methods Sixty-one out of 239 consecutive patients undergoing mild hypothermia after cardiac arrest, with eventual return of spontaneous circulation (ROSC), and comatose status on admission fulfilled the inclusion criteria. Background clinical variables, VF time and frequency domain fundamental variables were considered. The primary and secondary outcomes were a favorable neurological performance (FNP) during hospitalization and survival to hospital discharge, respectively. The predictive model was developed in a retrospective cohort (n=32; September 2006–September 2011, 48.5 ± 10.5 months of follow-up) and further validated in a prospective cohort (n = 29; October 2011–July 2013, 5 ± 1.8 months of follow-up). Results FNP was present in 16 (50.0%) and 21 patients (72.4%) in the retrospective and prospective cohorts, respectively. Seventeen (53.1%) and 21 patients (72.4%), respectively, survived to hospital discharge. Both outcomes were significantly associated (p < 0.001). Retrospective multivariate analysis provided a prediction model (sensitivity= 0.94, specificity = 1) that included spectral dominant frequency, derived power density and peak ratios between high and low frequency bands, and the number of shocks delivered before ROSC. Validation on the prospective cohort showed sensitivity = 0.88 and specificity = 0.91. A model-derived risk-score properly predicted 93% of FNP. Testing the model on follow-up showed a c-statistic ≥ 0.89. Conclusions A spectral analysis-based model reliably correlates time-dependent VF spectral changes with acute cerebral injury in comatose survivors undergoing mild hypothermia after cardiac arrest. PMID:25828128

Cerebral hemodynamics at altitude: effects of hyperventilation and acclimatization on cerebral blood flow and oxygenation.

PubMed

Sanborn, Matthew R; Edsell, Mark E; Kim, Meeri N; Mesquita, Rickson; Putt, Mary E; Imray, Chris; Yow, Heng; Wilson, Mark H; Yodh, Arjun G; Grocott, Mike; Martin, Daniel S

2015-06-01

Alterations in cerebral blood flow (CBF) and cerebral oxygenation are implicated in altitude-associated diseases. We assessed the dynamic changes in CBF and peripheral and cerebral oxygenation engendered by ascent to altitude with partial acclimatization and hyperventilation using a combination of near-infrared spectroscopy, transcranial Doppler ultrasound, and diffuse correlation spectroscopy. Peripheral (Spo2) and cerebral (Scto2) oxygenation, end-tidal carbon dioxide (ETCO2), and cerebral hemodynamics were studied in 12 subjects using transcranial Doppler and diffuse correlation spectroscopy (DCS) at 75 m and then 2 days and 7 days after ascending to 4559 m above sea level. After obtaining baseline measurements, subjects hyperventilated to reduce baseline ETCO2 by 50%, and a further set of measurements were obtained. Cerebral oxygenation and peripheral oxygenation showed a divergent response, with cerebral oxygenation decreasing at day 2 and decreasing further at day 7 at altitude, whereas peripheral oxygenation decreased on day 2 before partially rebounding on day 7. Cerebral oxygenation decreased after hyperventilation at sea level (Scto2 from 68.8% to 63.5%; P<.001), increased after hyperventilation after 2 days at altitude (Scto2 from 65.6% to 69.9%; P=.001), and did not change after hyperventilation after 7 days at altitude (Scto2 from 62.2% to 63.3%; P=.35). An intensification of the normal cerebral hypocapnic vasoconstrictive response occurred after partial acclimatization in the setting of divergent peripheral and cerebral oxygenation. This may help explain why hyperventilation fails to improve cerebral oxygenation after partial acclimatization as it does after initial ascent. The use of DCS is feasible at altitude and provides a direct measure of CBF indices with high temporal resolution. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Early childhood obesity is associated with compromised cerebellar development.

PubMed

Miller, Jennifer L; Couch, Jessica; Schwenk, Krista; Long, Michelle; Towler, Stephen; Theriaque, Douglas W; He, Guojun; Liu, Yijun; Driscoll, Daniel J; Leonard, Christiana M

2009-01-01

As part of a study investigating commonalities between Prader-Willi syndrome (PWS-a genetic imprinting disorder) and early-onset obesity of unknown etiology (EMO) we measured total cerebral and cerebellar volume on volumetric magnetic resonance imaging (MRI) images. Individuals with PWS (N = 16) and EMO (N = 12) had smaller cerebellar volumes than a control group of 15 siblings (p = .02 control vs. EMO; p = .0005 control vs. PWS), although there was no difference among the groups in cerebral volume. Individuals with PWS and EMO also had impaired cognitive function: general intellectual ability (GIA): PWS 65 +/- 25; EMO 81 +/- 19; and Controls 112 +/- 13 (p < .0001 controls vs. PWS and controls vs. EMO). As both conditions are characterized by early-onset obesity and slowed cognitive development, these results raise the possibility that early childhood obesity retards both cerebellar and cognitive development.

Technology-Aided Assessment of Sensorimotor Function in Early Infancy

PubMed Central

Allievi, Alessandro G.; Arichi, Tomoki; Gordon, Anne L.; Burdet, Etienne

2014-01-01

There is a pressing need for new techniques capable of providing accurate information about sensorimotor function during the first 2 years of childhood. Here, we review current clinical methods and challenges for assessing motor function in early infancy, and discuss the potential benefits of applying technology-assisted methods. We also describe how the use of these tools with neuroimaging, and in particular functional magnetic resonance imaging (fMRI), can shed new light on the intra-cerebral processes underlying neurodevelopmental impairment. This knowledge is of particular relevance in the early infant brain, which has an increased capacity for compensatory neural plasticity. Such tools could bring a wealth of knowledge about the underlying pathophysiological processes of diseases such as cerebral palsy; act as biomarkers to monitor the effects of possible therapeutic interventions; and provide clinicians with much needed early diagnostic information. PMID:25324827

A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment.

PubMed

Xie, Long; Dolui, Sudipto; Das, Sandhitsu R; Stockbower, Grace E; Daffner, Molly; Rao, Hengyi; Yushkevich, Paul A; Detre, John A; Wolk, David A

2016-01-01

Arterial spin labeled perfusion magnetic resonance imaging (ASL MRI) provides non-invasive quantification of cerebral blood flow, which can be used as a biomarker of brain function due to the tight coupling between cerebral blood flow (CBF) and brain metabolism. A growing body of literature suggests that regional CBF is altered in neurodegenerative diseases. Here we examined ASL MRI CBF in subjects with amnestic mild cognitive impairment (n = 65) and cognitively normal healthy controls (n = 62), both at rest and during performance of a memory-encoding task. As compared to rest, task-enhanced ASL MRI improved group discrimination, which supports the notion that physiologic measures during a cognitive challenge, or "stress test", may increase the ability to detect subtle functional changes in early disease stages. Further, logistic regression analysis demonstrated that ASL MRI and concomitantly acquired structural MRI provide complementary information of disease status. The current findings support the potential utility of task-enhanced ASL MRI as a biomarker in early Alzheimer's disease.

Blood-brain barrier transport of an essential amino acid after cerebral ischemia reperfusion injury.

PubMed

Suzuki, Toyofumi; Miyazaki, Yumiko; Ohmuro, Aya; Watanabe, Masaki; Furuishi, Takayuki; Fukami, Toshiro; Tomono, Kazuo

2013-01-01

Under pathophysiological conditions such as -cerebral ischemia-reperfusion (IR), damage to cerebrovascular endothelial cells causes alterations in the blood-brain barrier (BBB) function that can exacerbate neuronal cell injury and death. Clarifying changes in BBB transport in the early period of IR is important for understanding BBB function during therapy after cerebral ischemia. The present study was aimed at clarifying changes during IR in the BBB transport of L-phenylalanine (Phe) as a substrate of L-type amino acid transporter 1. An IR model was produced in mice by blood recirculation following occlusion of the middle cerebral artery. Permeability of the BBB to [(3)H]Phe was measured after IR injury using the brain perfusion method. Confocal microscopy of the IR injury showed no brain penetration of fluorescent tracer, thus confirming BBB integrity during 45 min of ischemia. Tight junction opening was not observed at 30 min after reperfusion following ischemia for 45 min. At the time of IR, [(3)H]Phe uptake into the brain appeared saturated. The Michaelis constant and maximum transport velocity in the IR group was reduced by 22 % compared with those in controls. These results suggest that the intrinsic transport clearance of Phe is slightly decreased in the early phase of IR.

Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation[S

PubMed Central

Allende, Maria L.; Cook, Emily K.; Larman, Bridget C.; Nugent, Adrienne; Brady, Jacqueline M.; Golebiowski, Diane; Sena-Esteves, Miguel; Tifft, Cynthia J.

2018-01-01

Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of β-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB-corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB-corrected organoids, accumulated GM2 ganglioside and exhibited increased size and cellular proliferation compared with the HEXB-corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses. PMID:29358305

Early prediction of cerebral palsy by computer-based video analysis of general movements: a feasibility study.

PubMed

Adde, Lars; Helbostad, Jorunn L; Jensenius, Alexander R; Taraldsen, Gunnar; Grunewaldt, Kristine H; Støen, Ragnhild

2010-08-01

The aim of this study was to investigate the predictive value of a computer-based video analysis of the development of cerebral palsy (CP) in young infants. A prospective study of general movements used recordings from 30 high-risk infants (13 males, 17 females; mean gestational age 31wks, SD 6wks; range 23-42wks) between 10 and 15 weeks post term when fidgety movements should be present. Recordings were analysed using computer vision software. Movement variables, derived from differences between subsequent video frames, were used for quantitative analyses. CP status was reported at 5 years. Thirteen infants developed CP (eight hemiparetic, four quadriparetic, one dyskinetic; seven ambulatory, three non-ambulatory, and three unknown function), of whom one had fidgety movements. Variability of the centroid of motion had a sensitivity of 85% and a specificity of 71% in identifying CP. By combining this with variables reflecting the amount of motion, specificity increased to 88%. Nine out of 10 children with CP, and for whom information about functional level was available, were correctly predicted with regard to ambulatory and non-ambulatory function. Prediction of CP can be provided by computer-based video analysis in young infants. The method may serve as an objective and feasible tool for early prediction of CP in high-risk infants.

Evaluation of cerebral function after carotid endarterectomy.

PubMed

Uclés, P; Almárcegui, C; Lorente, S; Romero, F; Marco, M

1997-05-01

Neuroimaging methods have failed to disclose correlation between degree of cerebral atrophy and blood flow in carotid artery stenosis patients. Moreover, intellectual improvement after carotid endarterectomy does not correlate fully with neuroimaging data in such patients. We performed brain electrical activity mapping and psychological testing before and 4 weeks after operation in 28 patients with symptomatic, high-grade, carotid stenosis. Postoperatively, electroencephalographic (EEG) mean frequency and absolute theta power improved significantly (p < 0.01). Mean frequency increased >1 Hz in most areas while power decreased dramatically, mainly because of resolution of high-voltage foci in 8 patients. Differences were conspicuous in both frontal lobes irrespective of the operated side, which suggests changes in perfusion affecting the whole brain. This is a positive effect of endarterectomy. Mini-Mental test and Set Test for verbal fluency had a positive correlation with the qEEG changes. Quantitative EEG as a measure of cerebral function has disclosed discriminative improvement in the early postoperative period. Our results support the thesis of improvement subsequent to endarterectomy.

Twenty-seven Years of Cerebral Pyruvate Recycling.

PubMed

Cerdán, Sebastián

2017-06-01

Cerebral pyruvate recycling is a metabolic pathway deriving carbon skeletons and reducing equivalents from mitochondrial oxaloacetate and malate, to the synthesis of mitochondrial and cytosolic pyruvate, lactate and alanine. The pathway allows both, to provide the tricarboxylic acid cycle with pyruvate molecules produced from alternative substrates to glucose and, to generate reducing equivalents necessary for the operation of NADPH requiring processes. At the cellular level, pyruvate recycling involves the activity of malic enzyme, or the combined activities of phosphoenolpyruvate carboxykinase and pyruvate kinase, as well as of those transporters of the inner mitochondrial membrane exchanging the corresponding intermediates. Its cellular localization between the neuronal or astrocytic compartments of the in vivo brain has been controversial, with evidences favoring either a primarily neuronal or glial localizations, more recently accepted to occur in both environments. This review provides a brief history on the detection and characterization of the pathway, its relations with the early developments of cerebral high resolution 13 C NMR, and its potential neuroprotective functions under hypoglycemic conditions or ischemic redox stress.

Impaired Voluntary Movement Control and Its Rehabilitation in Cerebral Palsy.

PubMed

Gordon, Andrew M

2016-01-01

Cerebral palsy is caused by early damage to the developing brain, as the most common pediatric neurological disorder. Hemiplegia (unilateral spastic cerebral palsy) is the most common subtype, and the resulting impairments, lateralized to one body side, especially affect the upper extremity, limiting daily function. This chapter first describes the pathophysiology and mechanisms underlying impaired upper extremity control of cerebral palsy. It will be shown that the severity of impaired hand function closely relates to the integrity of the corticospinal tract innervating the affected hand. It will also shown that the developing corticospinal tract can reorganize its connectivity depending on the timing and location of CNS injury, which also has implications for the severity of hand impairments and rehabilitation. The mechanisms underlying impaired motor function will be highlighted, including deficits in movement execution and planning and sensorimotor integration. It will be shown that despite having unimanual hand impairments, bimanual movement control deficits and mirror movements also impact function. Evidence for motor learning-based therapies including Constraint-Induced Movement Therapy and Bimanual Training, and the possible pathophysiological predictors of treatment outcome and plasticity will be described. Finally, future directions for rehabilitations will be presented.

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

Revisiting cerebral thromboangiitis obliterans.

PubMed

Hurelbrink, Carrie B; Barnett, Yael; Buckland, Michael E; Wilkinson, Mark; Leicester, Jon; Anderson, Craig; Brennan, Jeffrey; Barnett, Michael

2012-06-15

We describe a 56-year-old patient with progressive cognitive decline in the context of heavy tobacco use and migraine, and imaging evidence of an occlusive terminal cerebral vasculopathy. The results of brain biopsy recapitulated the pathological features described by Lindenberg and Spatz in their classic 1939 treatise on cerebral thromboangiitis obliterans, or cerebral Buerger's disease. Although the condition is associated with heavy smoking, the identification of a hypercoagulable state in our patient suggests a multifactorial pathogenesis. The diagnosis of cerebral thromboangiitis obliterans in life is facilitated by modern neuroimaging and should prompt immediate cessation of smoking and a search for an underlying prothrombotic tendency. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

Epileptiform abnormalities predict delayed cerebral ischemia in subarachnoid hemorrhage.

PubMed

Kim, J A; Rosenthal, E S; Biswal, S; Zafar, S; Shenoy, A V; O'Connor, K L; Bechek, S C; Valdery Moura, J; Shafi, M M; Patel, A B; Cash, S S; Westover, M B

2017-06-01

To identify whether abnormal neural activity, in the form of epileptiform discharges and rhythmic or periodic activity, which we term here ictal-interictal continuum abnormalities (IICAs), are associated with delayed cerebral ischemia (DCI). Retrospective analysis of continuous electroencephalography (cEEG) reports and medical records from 124 patients with moderate to severe grade subarachnoid hemorrhage (SAH). We identified daily occurrence of seizures and IICAs. Using survival analysis methods, we estimated the cumulative probability of IICA onset time for patients with and without delayed cerebral ischemia (DCI). Our data suggest the presence of IICAs indeed increases the risk of developing DCI, especially when they begin several days after the onset of SAH. We found that all IICA types except generalized rhythmic delta activity occur more commonly in patients who develop DCI. In particular, IICAs that begin later in hospitalization correlate with increased risk of DCI. IICAs represent a new marker for identifying early patients at increased risk for DCI. Moreover, IICAs might contribute mechanistically to DCI and therefore represent a new potential target for intervention to prevent secondary cerebral injury following SAH. These findings imply that IICAs may be a novel marker for predicting those at higher risk for DCI development. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Cerebral Asymmetry of fMRI-BOLD Responses to Visual Stimulation

PubMed Central

Hougaard, Anders; Jensen, Bettina Hagström; Amin, Faisal Mohammad; Rostrup, Egill; Hoffmann, Michael B.; Ashina, Messoud

2015-01-01

Hemispheric asymmetry of a wide range of functions is a hallmark of the human brain. The visual system has traditionally been thought of as symmetrically distributed in the brain, but a growing body of evidence has challenged this view. Some highly specific visual tasks have been shown to depend on hemispheric specialization. However, the possible lateralization of cerebral responses to a simple checkerboard visual stimulation has not been a focus of previous studies. To investigate this, we performed two sessions of blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in 54 healthy subjects during stimulation with a black and white checkerboard visual stimulus. While carefully excluding possible non-physiological causes of left-to-right bias, we compared the activation of the left and the right cerebral hemispheres and related this to grey matter volume, handedness, age, gender, ocular dominance, interocular difference in visual acuity, as well as line-bisection performance. We found a general lateralization of cerebral activation towards the right hemisphere of early visual cortical areas and areas of higher-level visual processing, involved in visuospatial attention, especially in top-down (i.e., goal-oriented) attentional processing. This right hemisphere lateralization was partly, but not completely, explained by an increased grey matter volume in the right hemisphere of the early visual areas. Difference in activation of the superior parietal lobule was correlated with subject age, suggesting a shift towards the left hemisphere with increasing age. Our findings suggest a right-hemispheric dominance of these areas, which could lend support to the generally observed leftward visual attentional bias and to the left hemifield advantage for some visual perception tasks. PMID:25985078

Physical therapy interventions for patients with movement disorders due to cerebral palsy.

PubMed

Barry, M J

1996-11-01

The purpose of this paper is to present evidence of the efficacy of physical therapy interventions for patients with cerebral palsy and identify goals for these patients. Studies suggest that neurodevelopmental treatment and Vojta techniques improve postural control. Little evidence supports the efficacy of early intervention, but researchers have not yet studied effects on the family. Strengthening, electrical stimulation, the use of orthoses, and seating show positive effects in studies of small numbers of subjects. For severely involved children, ease of care and comfort are important goals, as well as prevention of deformity, which is important for all children. To the extent possible, therapy should prepare a child for independent adult life. In early intervention through school age, therapy focuses on promoting communication, self-care, and mobility. Independence is a key issue for adolescents transitioning into adulthood. The rehabilitation and health needs of adults with cerebral palsy need to be addressed. Research needs to determine the effects of physical therapy not only on impairment but also on function and disability.

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome.

PubMed

Naess, Halvor; Romi, Fredrik

2011-01-01

To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis.

Comparing patients with spinal cord infarction and cerebral infarction: clinical characteristics, and short-term outcome

PubMed Central

Naess, Halvor; Romi, Fredrik

2011-01-01

Background: To compare the clinical characteristics, and short-term outcome of spinal cord infarction and cerebral infarction. Methods: Risk factors, concomitant diseases, neurological deficits on admission, and short-term outcome were registered among 28 patients with spinal cord infarction and 1075 patients with cerebral infarction admitted to the Department of Neurology, Haukeland University Hospital, Bergen, Norway. Multivariate analyses were performed with location of stroke (cord or brain), neurological deficits on admission, and short-term outcome (both Barthel Index [BI] 1 week after symptom onset and discharge home or to other institution) as dependent variables. Results: Multivariate analysis showed that patients with spinal cord infarction were younger, more often female, and less afflicted by hypertension and cardiac disease than patients with cerebral infarction. Functional score (BI) was lower among patients with spinal cord infarctions 1 week after onset of symptoms (P < 0.001). Odds ratio for being discharged home was 5.5 for patients with spinal cord infarction compared to cerebral infarction after adjusting for BI scored 1 week after onset (P = 0.019). Conclusion: Patients with spinal cord infarction have a risk factor profile that differs significantly from that of patients with cerebral infarction, although there are some parallels to cerebral infarction caused by atherosclerosis. Patients with spinal cord infarction were more likely to be discharged home when adjusting for early functional level on multivariate analysis. PMID:21915166

Socioeconomic characteristics of patients undergoing ambulatory diagnostic cerebral angiography in four US States.

PubMed

Bekelis, K; Missios, S; Eskey, C; Labropoulos, N

2014-02-01

Several groups have demonstrated the safety of ambulatory cerebral angiography, with no patients experiencing complications related to early discharge. Although this practice appears to be safe, the socioeconomic characteristics factoring in the selection of the patients have not been investigated. We performed a retrospective cohort study involving 45,226 patients undergoing outpatient and 159,046 undergoing inpatient cerebral angiography, who were registered in the State Ambulatory Surgery Databases (SASD) and State Inpatient Databases (SID) respectively for 4 US States (New York, California, Florida, North Carolina). In a multivariate analysis of diagnostic cerebral angiography, Caucasian race (OR 1.36, 95% CI, 1.31, 1.42) and male gender (OR 1.36, 95% CI, 1.31, 1.41), were significantly associated with outpatient procedures. Higher Charlson Comorbidity Index (CCI) (OR 0.60, 95% CI, 0.54, 0.67), high income (OR 0.70, 95% CI, 0.67, 0.73), high volume hospitals (OR 0.69, 95% CI, 0.66, 0.73), and coverage by Medicare/Medicaid (OR 0.96, 95% CI, 0.92, 0.99) were associated with a decreased chance of outpatient procedures. Institutional charges were significantly less for outpatient cerebral angiography. The median charge for inpatient diagnostic cerebral angiography was $26,968 as compared to $16,151 in the outpatient setting (P < 0.0001, Student's t-test). Access to ambulatory diagnostic cerebral angiography appears to be more common for patients with private insurance and less comorbidities, in the setting of lower volume hospitals. Further investigation is needed in the direction of mapping these disparities in resource utilization.

Effects of intermittent theta burst stimulation on cerebral blood flow and cerebral vasomotor reactivity.

PubMed

Pichiorri, Floriana; Vicenzini, Edoardo; Gilio, Francesca; Giacomelli, Elena; Frasca, Vittorio; Cambieri, Chiara; Ceccanti, Marco; Di Piero, Vittorio; Inghilleri, Maurizio

2012-08-01

To determine whether intermittent theta burst stimulation influences cerebral hemodynamics, we investigated changes induced by intermittent theta burst stimulation on the middle cerebral artery cerebral blood flow velocity and vasomotor reactivity to carbon dioxide (CO(2)) in healthy participants. The middle cerebral artery flow velocity and vasomotor reactivity were monitored by continuous transcranial Doppler sonography. Changes in cortical excitability were tested by transcranial magnetic stimulation. In 11 healthy participants, before and immediately after delivering intermittent theta burst stimulation, we tested cortical excitability measured by the resting motor threshold and motor evoked potential amplitude over the stimulated hemisphere and vasomotor reactivity to CO(2) bilaterally. The blood flow velocity was monitored in both middle cerebral arteries throughout the experimental session. In a separate session, we tested the effects of sham stimulation under the same experimental conditions. Whereas the resting motor threshold remained unchanged before and after stimulation, motor evoked potential amplitudes increased significantly (P = .04). During and after stimulation, middle cerebral artery blood flow velocities also remained bilaterally unchanged, whereas vasomotor reactivity to CO(2) increased bilaterally (P = .04). The sham stimulation left all variables unchanged. The expected intermittent theta burst stimulation-induced changes in cortical excitability were not accompanied by changes in cerebral blood flow velocities; however, the bilateral increased vasomotor reactivity suggests that intermittent theta burst stimulation influences the cerebral microcirculation, possibly involving subcortical structures. These findings provide useful information on hemodynamic phenomena accompanying intermittent theta burst stimulation, which should be considered in research aimed at developing this noninvasive, low-intensity stimulation technique for safe

Centripetal Propagation of Vasoconstriction at the Time of Headache Resolution in Patients with Reversible Cerebral Vasoconstriction Syndrome.

PubMed

Shimoda, M; Oda, S; Hirayama, A; Imai, M; Komatsu, F; Hoshikawa, K; Shigematsu, H; Nishiyama, J; Osada, T

2016-09-01

Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache and diffuse segmental vasoconstriction that resolves spontaneously within 3 months. Previous reports have proposed that vasoconstriction first involves small distal arteries and then progresses toward major vessels at the time of thunderclap headache remission. The purpose of this study was to confirm centripetal propagation of vasoconstriction on MRA at the time of thunderclap headache remission compared with MRA at the time of reversible cerebral vasoconstriction syndrome onset. Of the 39 patients diagnosed with reversible cerebral vasoconstriction syndrome at our hospital during the study period, participants comprised the 16 patients who underwent MR imaging, including MRA, within 72 hours of reversible cerebral vasoconstriction syndrome onset (initial MRA) and within 48 hours of thunderclap headache remission. In 14 of the 16 patients (87.5%), centripetal propagation of vasoconstriction occurred from the initial MRA to remission of thunderclap headache, with typical segmental vasoconstriction of major vessels. These mainly involved the M1 portion of the MCA (10 cases), P1 portion of the posterior cerebral artery (10 cases), and A1 portion of the anterior cerebral artery (5 cases). This study found evidence of centripetal propagation of vasoconstriction on MRA obtained at the time of thunderclap headache remission, compared with MRA obtained at the time of reversible cerebral vasoconstriction syndrome onset. If clinicians remain unsure of the diagnosis during early-stage reversible cerebral vasoconstriction syndrome, this time point represents the best opportunity to diagnose reversible cerebral vasoconstriction syndrome with confidence. © 2016 by American Journal of Neuroradiology.

Risk Factors for Developing Scoliosis in Cerebral Palsy: A Cross-Sectional Descriptive Study.

PubMed

Bertoncelli, Carlo M; Solla, Federico; Loughenbury, Peter R; Tsirikos, Athanasios I; Bertoncelli, Domenico; Rampal, Virginie

2017-06-01

This study aims to identify the risk factors leading to the development of severe scoliosis among children with cerebral palsy. A cross-sectional descriptive study of 70 children (aged 12-18 years) with severe spastic and/or dystonic cerebral palsy treated in a single specialist unit is described. Statistical analysis included Fisher exact test and logistic regression analysis to identify risk factors. Severe scoliosis is more likely to occur in patients with intractable epilepsy ( P = .008), poor gross motor functional assessment scores ( P = .018), limb spasticity ( P = .045), a history of previous hip surgery ( P = .048), and nonambulatory patients ( P = .013). Logistic regression model confirms the major risk factors are previous hip surgery ( P = .001), moderate to severe epilepsy ( P = .007), and female gender ( P = .03). History of previous hip surgery, intractable epilepsy, and female gender are predictors of developing severe scoliosis in children with cerebral palsy. This knowledge should aid in the early diagnosis of scoliosis and timely referral to specialist services.

Sodium transport through the cerebral sodium-glucose transporter exacerbates neuron damage during cerebral ischaemia.

PubMed

Yamazaki, Yui; Harada, Shinichi; Wada, Tetsuyuki; Yoshida, Shigeru; Tokuyama, Shogo

2016-07-01

We recently demonstrated that the cerebral sodium-glucose transporter (SGLT) is involved in postischaemic hyperglycaemia-induced exacerbation of cerebral ischaemia. However, the associated SGLT-mediated mechanisms remain unclear. Thus, we examined the involvement of cerebral SGLT-induced excessive sodium ion influx in the development of cerebral ischaemic neuronal damage. [Na+]i was estimated according to sodium-binding benzofuran isophthalate fluorescence. In the in vitro study, primary cortical neurons were prepared from fetuses of ddY mice. Primary cortical neurons were cultured for 5 days before each treatment with reagents, and these survival rates were assessed using biochemical assays. In in vivo study, a mouse model of focal ischaemia was generated using middle cerebral artery occlusion (MCAO). In these experiments, treatment with high concentrations of glucose induced increment in [Na+]i, and this phenomenon was suppressed by the SGLT-specific inhibitor phlorizin. SGLT-specific sodium ion influx was induced using a-methyl-D-glucopyranoside (a-MG) treatments, which led to significant concentration-dependent declines in neuronal survival rates and exacerbated hydrogen peroxide-induced neuronal cell death. Moreover, phlorizin ameliorated these effects. Finally, intracerebroventricular administration of a-MG exacerbated the development of neuronal damage induced by MCAO, and these effects were ameliorated by the administration of phlorizin. Hence, excessive influx of sodium ions into neuronal cells through cerebral SGLT may exacerbate the development of cerebral ischaemic neuronal damage. © 2016 Royal Pharmaceutical Society.

[Cerebral missile injuries in civilian practice (author's transl)].

PubMed

Kretschmer, H

1980-01-01

Over a 10 year period we have treated 63 cases of cerebral gunshot injuries, most of them attempted suicides. Following the presentation of ballistic data, and the classification and pathophysiology of the clinical symptoms, early and late complications are reported in detail and recommendations for therapy given. The mortality rate of all admitted patients in our material was 60.9%; a direct relation between the severity of primary brain damage (recognizable in the degree of initial unconsciousness) and the chance of survival was found.

Evaluation of cerebral vasomotor reactivity in Parkinson's disease: is there any association with orthostatic hypotension?

PubMed

Zamani, Babak; Mehrabani, Mehrnoush; Fereshtehnejad, Seyed-Mohammad; Rohani, Mohammad

2011-06-01

Our aim was to look for a probable relationship between cerebral vasomotor reactivity (VMR) and orthostatic hypotension (OH) in Parkinson's disease (PD). This study was conducted on 44 patients with PD. Assessment of cerebral VMR was performed by means of transcranial Doppler (TCD) of middle cerebral artery (MCA) before and after a vasodilatory stimulus, carbon dioxide test. Moreover, orthostatic hypotension was evaluated. OH was presented in 12 (27.3%) Parkinson's patients. The average resting blood flow velocity (BFV) in the MCA was 30.20 (SD=9.58)cms(-1) which significantly increased to 46.25 (SD=16.23)cms(-1) after carbon dioxide test (P<0.001). Impaired VMR was observed in 15 (34.1%) of the subjects, while it was not associated with the presence of OH (P=0.770). Evaluation of VMR in patients affected by PD, could assist in early diagnosis of cerebral autonomic dysfunction and prevent its serious consequences prior and more valid to OH. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Methylmercury poisoning in common marmosets--a study of selective vulnerability within the cerebral cortex.

PubMed

Eto, K; Yasutake, A; Kuwana, T; Korogi, Y; Akima, M; Shimozeki, T; Tokunaga, H; Kaneko, Y

2001-01-01

Neuropathological lesions found in chronic human Minamata disease tend to be localized in the calcarine cortex of occipital lobes, the pre- and postcentral lobuli, and the temporal gyri. The mechanism for the selective vulnerability is still not clear, though several hypotheses have been proposed. One hypothesis is vascular and postulates that the lesions are the result of ischemia secondary to compression of sulcal arteries from methylmercury-induced cerebral edema. To test this hypothesis, we studied common marmosets because the cerebrum of marmosets has 2 distinct deep sulci, the calcarine and Sylvian fissures. MRI analysis, mercury assays of tissue specimens, histologic and histochemical studies of the brain are reported and discussed. Brains sacrificed early after exposure to methylmercury showed high contents of methylmercury and edema of the cerebral white matter. These results may explain the selective cortical degeneration along the deep cerebral fissures or sulci.

Initial experience of a novel sheath guide for transbrachial coil embolization of cerebral aneurysms in the anterior cerebral circulation.

PubMed

Iwata, Tomonori; Mori, Takahisa; Tajiri, Hiroyuki; Miyazaki, Yuichi; Nakazaki, Masahito; Mizokami, Koji

2013-03-01

The transfemoral approach is a common technique for coil embolization of cerebral aneurysms in the anterior cerebral circulation. However, it is difficult to advance a guiding catheter into the carotid artery via the femoral route in patients with a tortuous aortic arch, an unfavorable supra-aortic takeoff, aortic diseases, or occlusion of the femoral artery. To report our initial experiences of coil embolization of cerebral aneurysms in the anterior cerebral circulation with a novel sheath guide for transbrachial carotid cannulation. A sheath guide designed specifically for transbrachial carotid cannulation was developed; transbrachial coil embolization for cerebral aneurysms began in May 2011. Included for analysis were patients who underwent transbrachial coil embolization for cerebral aneurysms in the anterior cerebral circulation from May 2011 to January 2012. Adjuvant techniques, angiographic results, procedural success, and periprocedural complications were investigated. Ten patients underwent transbrachial coil embolization of cerebral aneurysms in the anterior cerebral circulation. All procedures were successful using the brachial route. No periprocedural complications occurred. Patients were permitted to get seated immediately after coil embolization even during hemostasis. The sheath guide specifically designed for transbrachial carotid cannulation was useful for coil embolization of cerebral aneurysms in the anterior cerebral circulation.

Electroencephalographic Response to Sodium Nitrite May Predict Delayed Cerebral Ischemia After Severe Subarachnoid Hemorrhage.

PubMed

Garry, Payashi S; Rowland, Matthew J; Ezra, Martyn; Herigstad, Mari; Hayen, Anja; Sleigh, Jamie W; Westbrook, Jon; Warnaby, Catherine E; Pattinson, Kyle T S

2016-11-01

Aneurysmal subarachnoid hemorrhage often leads to death and poor clinical outcome. Injury occurring during the first 72 hours is termed "early brain injury," with disruption of the nitric oxide pathway playing an important pathophysiologic role in its development. Quantitative electroencephalographic variables, such as α/δ frequency ratio, are surrogate markers of cerebral ischemia. This study assessed the quantitative electroencephalographic response to a cerebral nitric oxide donor (intravenous sodium nitrite) to explore whether this correlates with the eventual development of delayed cerebral ischemia. Unblinded pilot study testing response to drug intervention. Neuroscience ICU, John Radcliffe Hospital, Oxford, United Kingdom. Fourteen World Federation of Neurosurgeons grades 3, 4, and 5 patients (mean age, 52.8 yr [range, 41-69 yr]; 11 women). IV sodium nitrite (10 μg/kg/min) for 1 hour. Continuous electroencephalographic recording for 2 hours. The alpha/delta frequency ratio was measured before and during IV sodium nitrite infusion. Seven of 14 patients developed delayed cerebral ischemia. There was a +30% to +118% (range) increase in the alpha/delta frequency ratio in patients who did not develop delayed cerebral ischemia (p < 0.0001) but an overall decrease in the alpha/delta frequency ratio in those patients who did develop delayed cerebral ischemia (range, +11% to -31%) (p = 0.006, multivariate analysis accounting for major confounds). Administration of sodium nitrite after severe subarachnoid hemorrhage differentially influences quantitative electroencephalographic variables depending on the patient's susceptibility to development of delayed cerebral ischemia. With further validation in a larger sample size, this response may be developed as a tool for risk stratification after aneurysmal subarachnoid hemorrhage.

Cervical spondylotic radiculo-myelopathy in patients with athetoid-dystonic cerebral palsy: clinical evaluation and surgical treatment.

PubMed Central

Hirose, G; Kadoya, S

1984-01-01

The acute onset of symptoms of severe cervical radiculo-myelopathy in four patients with athetoid-dystonic cerebral palsy is reported. Neurological and radiological examination showed that the spondylotic changes of the cervical spine were responsible for new neurological deficits leading to the patients being bedridden. Dystonic-athetoid neck movements may cause excessive axial neck rotation as well as flexion and extension movements of the spine. These repetitive exaggerated movements may result in early degenerative changes of the vertebrae which may enhance the radiculo-myelopathy. The four patients were treated with an anterior discectomy with interbody fusion. They were bedridden pre-operatively but all have since been able to walk with or without a cane. It is concluded that early anterior decompression with interbody fusion is a treatment of choice for cervical spondylotic radiculo-myelopathy in association with athetoid cerebral palsy. Images PMID:6470718

Therapeutic interventions in cerebral palsy.

PubMed

Patel, Dilip R

2005-11-01

Various therapeutic interventions have been used in the management of children with cerebral palsy. Traditional physiotherapy and occupational therapy are widely used interventions and have been shown to be of benefit in the treatment of cerebral palsy. Evidence in support of the effectiveness of the neurodevelopmental treatment is equivocal at best. There is evidence to support the use and effectiveness of neuromuscular electrical stimulation in children with cerebral palsy. The effectiveness of many other interventions used in the treatment of cerebral palsy has not been clearly established based on well-controlled trials. These include: sensory integration, body-weight support treadmill training, conductive education, constraint-induced therapy, hyperbaric oxygen therapy, and the Vojta method. This article provides an overview of salient aspects of popular interventions used in the management of children with cerebral palsy.

Cerebral Palsy Litigation

PubMed Central

Sartwelle, Thomas P.

2015-01-01

The cardinal driver of cerebral palsy litigation is electronic fetal monitoring, which has continued unabated for 40 years. Electronic fetal monitoring, however, is based on 19th-century childbirth myths, a virtually nonexistent scientific foundation, and has a false positive rate exceeding 99%. It has not affected the incidence of cerebral palsy. Electronic fetal monitoring has, however, increased the cesarian section rate, with the expected increase in mortality and morbidity risks to mothers and babies alike. This article explains why electronic fetal monitoring remains endorsed as efficacious in the worlds’ labor rooms and courtrooms despite being such a feeble medical modality. It also reviews the reasons professional organizations have failed to condemn the use of electronic fetal monitoring in courtrooms. The failures of tort reform, special cerebral palsy courts, and damage limits to stem the escalating litigation are discussed. Finally, the authors propose using a currently available evidence rule—the Daubert doctrine that excludes “junk science” from the courtroom—as the beginning of the end to cerebral palsy litigation and electronic fetal monitoring’s 40-year masquerade as science. PMID:25183322

Deficiency in Serine Protease Inhibitor Neuroserpin Exacerbates Ischemic Brain Injury by Increased Postischemic Inflammation

PubMed Central

Ludewig, Peter; Bernreuther, Christian; Krasemann, Susanne; Arunachalam, Priyadharshini; Gerloff, Christian; Glatzel, Markus; Magnus, Tim

2013-01-01

The only approved pharmacological treatment for ischemic stroke is intravenous administration of plasminogen activator (tPA) to re-canalize the occluded cerebral vessel. Not only reperfusion but also tPA itself can induce an inflammatory response. Microglia are the innate immune cells of the central nervous system and the first immune cells to become activated in stroke. Neuroserpin, an endogenous inhibitor of tPA, is up-regulated following cerebral ischemia. To examine neuroserpin-dependent mechanisms of neuroprotection in stroke, we studied neuroserpin deficient (Ns−/−) mice in an animal model of temporal focal ischemic stroke. Infarct size and neurological outcome were worse in neuroserpin deficient mice even though the fibrinolytic activity in the ischemic brain was increased. The increased infarct size was paralleled by a selective increase in proinflammatory microglia activation in Ns−/− mice. Our results show excessive microglial activation in Ns−/− mice mediated by an increased activity of tPA. This activation results in a worse outcome further underscoring the potential detrimental proinflammatory effects of tPA. PMID:23658802

Effects of hyperbaric oxygen on intracranial pressure and cerebral blood flow in experimental cerebral oedema1

PubMed Central

Miller, J. D.; Ledingham, I. McA.; Jennett, W. B.

1970-01-01

Increased intracranial pressure was induced in anaesthetized dogs by application of liquid nitrogen to the dura mater. Intracranial pressure and cerebral blood flow were measured, together with arterial blood pressure and arterial and cerebral venous blood gases. Carbon dioxide was administered intermittently to test the responsiveness of the cerebral circulation, and hyperbaric oxygen was delivered at intervals in a walk-in hyperbaric chamber, pressurized to two atmospheres absolute. Hyperbaric oxygen caused a 30% reduction of intracranial pressure and a 19% reduction of cerebral blood flow in the absence of changes in arterial PCO2 or blood pressure, but only as long as administration of carbon dioxide caused an increase in both intracranial pressure and cerebral blood flow. When carbon dioxide failed to influence intracranial pressure or cerebral blood flow then hyperbaric oxygen had no effect. This unresponsive state was reached at high levels of intracranial pressure. Images PMID:5497875

[A case of severe asthma exacerbation complicated with cerebral edema and diffuse multiple cerebral micro-bleeds].

PubMed

Ohkura, Noriyuki; Fujimura, Masaki; Sakai, Asao; Fujita, Kentaro; Katayama, Nobuyuki

2009-08-01

A 36-year-old woman was admitted to the Intensive Care Unit for the treatment of severe asthma exacerbation. Her condition of asthma improved with systemic glucocorticosteroids, inhaled beta2-agonist, intravenous theophylline and inhaled anesthesia (isoflurane) under mechanical ventilation. Her consciousness was disturbed even after terminating isoflurane. Brain CT and MRI scan showed cerebral edema and diffuse multiple cerebral micro-bleeds. Glyceol, a hyperosmotic diuretic solution consisting of 10% glycerol and 5% fructose in saline, was administered to decrease cerebral edema. Her consciousness disturbance gradually recovered. Cerebral edema and hemorrhage improved. On the 69th hospital day, she was discharged from hospital without sequelae. This case is a rare one in which severe asthma exacerbation was complicated with cerebral edema and diffuse multiple cerebral hemorrhage. Inhaled anesthesia for asthma exacerbation should be used carefully to avoid delay of diagnosis of central nervous system complications.

Magnetic resonance imaging of post-ischemic blood-brain barrier damage with PEGylated iron oxide nanoparticles

NASA Astrophysics Data System (ADS)

Liu, Dong-Fang; Qian, Cheng; An, Yan-Li; Chang, Di; Ju, Sheng-Hong; Teng, Gao-Jun

2014-11-01

Blood-brain barrier (BBB) damage during ischemia may induce devastating consequences like cerebral edema and hemorrhagic transformation. This study presents a novel strategy for dynamically imaging of BBB damage with PEGylated supermagnetic iron oxide nanoparticles (SPIONs) as contrast agents. The employment of SPIONs as contrast agents made it possible to dynamically image the BBB permeability alterations and ischemic lesions simultaneously with T2-weighted MRI, and the monitoring could last up to 24 h with a single administration of PEGylated SPIONs in vivo. The ability of the PEGylated SPIONs to highlight BBB damage by MRI was demonstrated by the colocalization of PEGylated SPIONs with Gd-DTPA after intravenous injection of SPION-PEG/Gd-DTPA into a mouse. The immunohistochemical staining also confirmed the leakage of SPION-PEG from cerebral vessels into parenchyma. This study provides a novel and convenient route for imaging BBB alteration in the experimental ischemic stroke model.

Regulatory effect of Dimethyl Sulfoxide (DMSO) on astrocytic reactivity in a murine model of cerebral infarction by arterial embolization

PubMed Central

Rengifo Valbuena, Carlos Augusto; Ávila Rodríguez, Marco Fidel; Céspedes Rubio, Angel

2013-01-01

Introduction: The pathophysiology of cerebral ischemia is essential for early diagnosis, neurologic recovery, the early onset of drug treatment and the prognosis of ischemic events. Experimental models of cerebral ischemia can be used to evaluate the cellular response phenomena and possible neurological protection by drugs. Objective: To characterize the cellular changes in the neuronal population and astrocytic response by the effect of Dimethyl Sulfoxide (DMSO) on a model of ischemia caused by cerebral embolism. Methods: Twenty Wistar rats were divided into four groups (n= 5). The infarct was induced with α-bovine thrombin (40 NIH/Unit.). The treated group received 90 mg (100 μL) of DMSO in saline (1:1 v/v) intraperitoneally for 5 days; ischemic controls received only NaCl (placebo) and two non-ischemic groups (simulated) received NaCl and DMSO respectively. We evaluated the neuronal (anti-NeuN) and astrocytic immune-reactivity (anti-GFAP). The results were analyzed by densitometry (NIH Image J-Fiji 1.45 software) and analysis of variance (ANOVA) with the Graph pad software (Prism 5). Results: Cerebral embolism induced reproducible and reliable lesions in the cortex and hippocampus (CA1)., similar to those of focal models. DMSO did not reverse the loss of post-ischemia neuronal immune-reactivity, but prevented the morphological damage of neurons, and significantly reduced astrocytic hyperactivity in the somato-sensory cortex and CA1 (p <0.001). Conclusions: The regulatory effect of DMSO on astrocyte hyperreactivity and neuronal-astroglial cytoarchitecture , gives it potential neuroprotective properties for the treatment of thromboembolic cerebral ischemia in the acute phase. PMID:24892319

Baroreflex sensitivity to predict malignant middle cerebral artery infarction.

PubMed

Sykora, Marek; Steiner, Thorsten; Rocco, Andrea; Turcani, Peter; Hacke, Werner; Diedler, Jennifer

2012-03-01

Hemicraniectomy has been shown to be an effective treatment of life-threatening edema (LTE) in malignant middle cerebral artery infarction when performed early. Identifying patients who will develop LTE is therefore imperative. We hypothesize that autonomic shift toward sympathetic dominance may relate to LTE formation. We aimed to investigate the predictive potential of baroreflex sensitivity (BRS) as a marker of autonomic balance for calculating the course of large middle cerebral artery infarction. Patients with middle cerebral artery infarction >2/3 of the territory and BRS measurement at admission were analyzed. BRS was estimated using the cross-correlational method. Demographic, clinical, and radiological data including stroke severity, infarct size, and basal ganglia involvement were recorded. Malignant course with LTE was defined as clinical deterioration and midline shift ≥5 mm in the first 48 hours. Eighteen (62.8%) patients developed LTE. Patients with LTE had lower BRS (2.3 versus 4.4 mm Hg/ms, P=0.007), larger infarcts (214 versus 144 mL, P=0.03), more frequent involvement of the basal ganglia (14 versus 4, P=0.03), and more often underwent thrombolysis combined with endovascular intervention (6 versus 0, P=0.04). In a multivariate model, BRS (OR, 0.36; CI, 0.14-0.93; P=0.03) and basal ganglia involvement (OR, 11.53; CI, 1.15-115.9; P=0.04) were independent predictors for LTE. This model correctly classified 86.2% of the malignant cases. Decreased BRS, mirroring sympathetic activation, and basal ganglia involvement were associated with development of malignant course with LTE in large middle cerebral artery infarction. The predictive relevance of our findings needs to be confirmed in further studies.

Differential diagnosis of regional cerebral hyperfixation of TC-99m HMPAO on SPECT imaging

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

Shirazi, P.; Konopka, L.; Crayton, J.W.

1994-05-01

Accurate diagnostic evaluation of patients with neurologic and neuropsychiatric disease is important because early treatment may halt disease progression and prevent impairment or disability. Cerebral hyperfixation of HMPAO has been ascribed to luxury perfusion following ischemic infarction. The present study sought to identify other conditions that also display radiotracer hyperfixation in order to develop a differential diagnosis of this finding on SPECT imaging. Two hundred fifty (n=250) successive cerebral SPECT images were reviewed for evidence of HMPAO hyperfixation. Hyperfixation was defined as enhanced focal perfusion surrounded by a zone of diminished or normal cerebral perfusion. All patients were scanned aftermore » intravenous injection of 25 mCi Tc-99m HMPAO. Volume-rendered and oblique images were obtained with a Trionix triple-head SPECT system using ultra high resolution fan beam collimators. Thirteen (13/250; 5%) of the patients exhibited regions of HMPAO hyperfixation. CT or MRI abnormalities were detected in 6/13 cases. Clinical diagnoses in these patients included intractable psychosis, post-traumatic stress disorder, alcohol and narcotic dependence, major depression, acute closed-head trauma, hypothyroidism, as well as subacute ischemic infarction. A wide variety of conditions may be associated with cerebral hyperfixation of HMPAO. These conditions include neurologic and psychiatric diagnoses, and extend the consideration of hyperfixation beyond ischemic infarction. Consequently, a differential diagnosis of HMPAO hyperfixation may be broader than originally considered, and this may suggest a fundamental role for local cerebral hyperperfusion. Elucidation of the fundamental mechanism(s) for cerebral hyperperfusion requires further investigation.« less

Cerebral Palsy (For Kids)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Cerebral Palsy KidsHealth / For Kids / Cerebral Palsy What's in this ... the things that kids do every day. What's CP? Some kids with CP use wheelchairs and others ...

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

Vascular Endothelial Function Assessed by Postischemic Diastolic Blood Pressure Is Associated with Acclimatization and Acute Mountain Sickness.

PubMed

He, Lipeng; Jiang, Yu; Su, Hai; Li, Juxiang; Cheng, Xiaoshu

2016-03-01

This study assessed whether the brachial diastolic blood pressure (DBP) decline induced by 5-minute arm ischemia is associated with acclimatization and acute mountain sickness (AMS). Forty-two age- and body mass index-matched young male residents at sea level (<400 m) or moderate altitude (1000-2000 m above sea level) were enrolled. All subjects had never been to 3200 m before. Brachial BP was measured at a station at 1380 m altitude before and 1, 5, and 10 minutes after right arm ischemia. AMS score was evaluated after 3-day training at a high altitude of 3200 m. In moderate altitude versus sea-level residents: (1) systolic BP curves for both arms overlapped well; (2) mean right arm DBP decline post right arm ischemia was larger, while left arm, which was not subjected to ischemia, did not show DBP decline in either group; and (3) AMS scores were significantly lower (3.19 ± 2.16 vs. 5.52 ± 4.58, p = 0.043) in those residing at moderate altitude compared to those from low altitude. There was a low negative correlation between AMS score and right arm area between curves-DBP (r = -0.320, p = 0.039). Moderate altitude relative to sea-level residents had a larger mean postischemic DBP decline in weak but significant association with lower mean AMS score at 3200 m. These data suggest that differences in vascular endothelial function related to altitude of residence persist during travel to high altitude and might contribute to AMS risk.

A diagnostic approach for cerebral palsy in the genomic era.

PubMed

Lee, Ryan W; Poretti, Andrea; Cohen, Julie S; Levey, Eric; Gwynn, Hilary; Johnston, Michael V; Hoon, Alexander H; Fatemi, Ali

2014-12-01

An ongoing challenge in children presenting with motor delay/impairment early in life is to identify neurogenetic disorders with a clinical phenotype, which can be misdiagnosed as cerebral palsy (CP). To help distinguish patients in these two groups, conventional magnetic resonance imaging of the brain has been of great benefit in "unmasking" many of these genetic etiologies and has provided important clues to differential diagnosis in others. Recent advances in molecular genetics such as chromosomal microarray and next-generation sequencing have further revolutionized the understanding of etiology by more precisely classifying these disorders with a molecular cause. In this paper, we present a review of neurogenetic disorders masquerading as cerebral palsy evaluated at one institution. We have included representative case examples children presenting with dyskinetic, spastic, and ataxic phenotypes, with the intent to highlight the time-honored approach of using clinical tools of history and examination to focus the subsequent etiologic search with advanced neuroimaging modalities and molecular genetic tools. A precise diagnosis of these masqueraders and their differentiation from CP is important in terms of therapy, prognosis, and family counseling. In summary, this review serves as a continued call to remain vigilant for current and other to-be-discovered neurogenetic masqueraders of cerebral palsy, thereby optimizing care for patients and their families.

Relative cerebral blood volume as a marker of durable tissue-at-risk viability in hyperacute ischemic stroke.

PubMed

Cortijo, Elisa; Calleja, Ana Isabel; García-Bermejo, Pablo; Mulero, Patricia; Pérez-Fernández, Santiago; Reyes, Javier; Muñoz, Ma Fe; Martínez-Galdámez, Mario; Arenillas, Juan Francisco

2014-01-01

Selection of best responders to reperfusion therapies could be aided by predicting the duration of tissue-at-risk viability, which may be dependant on collateral circulation status. We aimed to identify the best predictor of good collateral circulation among perfusion computed tomography (PCT) parameters in middle cerebral artery (MCA) ischemic stroke and to analyze how early MCA response to intravenous thrombolysis and PCT-derived markers of good collaterals interact to determine stroke outcome. We prospectively studied patients with acute MCA ischemic stroke treated with intravenous thrombolysis who underwent PCT before treatment showing a target mismatch profile. Collateral status was assessed using a PCT source image-based score. PCT maps were quantitatively analyzed. Cerebral blood volume (CBV), cerebral blood flow, and Tmax were calculated within the hypoperfused volume and in the equivalent region of unaffected hemisphere. Occluded MCAs were monitored by transcranial Duplex to assess early recanalization. Main outcome variables were brain hypodensity volume and modified Rankin scale score at day 90. One hundred patients with MCA ischemic stroke imaged by PCT received intravenous thrombolysis, and 68 met all inclusion criteria. A relative CBV (rCBV) >0.93 emerged as the only predictor of good collaterals (odds ratio, 12.6; 95% confidence interval, 2.9-55.9; P=0.001). Early MCA recanalization was associated with better long-term outcome and lower infarct volume in patients with rCBV<0.93, but not in patients with high rCBV. None of the patients with rCBV<0.93 achieved good outcome in absence of early recanalization. High rCBV was the strongest marker of good collaterals and may characterize durable tissue-at-risk viability in hyperacute MCA ischemic stroke.

A Perceptual Motor Intervention Improves Play Behavior in Children with Moderate to Severe Cerebral Palsy

ERIC Educational Resources Information Center

Ryalls, Brigette O.; Harbourne, Regina; Kelly-Vance, Lisa; Wickstrom, Jordan; Stergiou, Nick; Kyvelidou, Anastasia

2016-01-01

For children with moderate or severe cerebral palsy (CP), a foundational early goal is independent sitting. Sitting offers additional opportunities for object exploration, play and social engagement. The achievement of sitting coincides with important milestones in other developmental areas, such as social engagement with others, understanding of…

[The cerebral hemodynamics in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy].

PubMed

Jin, De-xin; Chen, Xiu-yun; Huang, He; Zhang, Xu

2006-12-01

To investigate the cerebral hemodynamics in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The blood flow velocity of cerebral arteries was measured by using transcranial Doppler ultrasound (TCD) in 6 cases with CADASIL and a quite number of age and sex matched control subjects. All patients (4 were symptomatic and 2 asymptomatic), being an established CADASIL family with the diagnosis confirmed by clinical characteristics, neuroimaging, pathology and molecular genetics, had abnormal mark signals on MR imagining and no history of hypertension, diabetes, heart disease and migraine. A routinely TCD detection, including peak-systolic velocity (Vp), end-diastolic velocity (Vd), mean velocity (Vm) and pulsatility index (PI), was carried out on the bilateral middle cerebral arteries (MCA), anterior cerebral arteries (ACA), posterior cerebral arteries (PCA) and vertebral arteries (VA) as well as the basilar artery (BA). A comparison between the cases and controls was made. Then, the changes of flow velocity in middle cerebral arteries (MCA) of the patients with CADASIL were observed before and after breathholding tests. In addition, brain CT perfusion imaging (CTP) was carried out in all the cases by using 16-slice spiral CT. The appearances of frequency spectrum were nearly normal in all the cases and there was no abnormality between the two sides on velocity (P > 0.05). As compared with the controls, the bilateral Vp, Vd and Vm in ACA and PCA were decreased obviously (P < 0.05). The velocity parameters of MCA with the exception of left Vm and right PI showed changes (P < 0.05) and there were no changes of PI in the bilateral ACA, PCA and Left MCA (P > 0.05). Moreover, there were marked changes in MCA (including Vm, Vd and PI) of all the cases as compared with the controls after breathholding (P < 0.01). Brain perfusion imaging showing the regional cerebral blood flow and regional cerebral blood volume in frontal

Molecular pathophysiology of cerebral edema

PubMed Central

Gerzanich, Volodymyr; Simard, J Marc

2015-01-01

Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. PMID:26661240

Symptomatic Cerebral Vasospasm and Delayed Cerebral Ischemia Following Transsphenoidal Resection of a Craniopharyngioma.

PubMed

Ricarte, Irapuá Ferreira; Funchal, Bruno F; Miranda Alves, Maramélia A; Gomes, Daniela L; Valiente, Raul A; Carvalho, Flávio A; Silva, Gisele S

2015-09-01

Vasospasm has been rarely described as a complication associated with craniopharyngioma surgery. Herein we describe a patient who developed symptomatic vasospasm and delayed cerebral ischemia after transsphenoidal surgery for a craniopharyngioma. A 67-year-old woman became drowsy 2 weeks after a transsphenoidal resection of a craniopharyngioma. A head computed tomography (CT) was unremarkable except for postoperative findings. Electroencephalogram and laboratory studies were within the normal limits. A repeated CT scan 48 hours after the initial symptoms showed bilateral infarcts in the territory of the anterior cerebral arteries (ACA). Transcranial Doppler (TCD) showed increased blood flow velocities in both anterior cerebral arteries (169 cm/second in the left ACA and 145 cm/second in the right ACA) and right middle cerebral artery (164 cm/second) compatible with vasospasm. A CT angiography confirmed the findings. She was treated with induced hypertension and her level of consciousness improved. TCD velocities normalized after 2 weeks. Cerebral vasospasm should be considered in the differential diagnosis of patients with altered neurologic status in the postoperative period following a craniopharyngioma resection. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Enhanced contractility of intraparenchymal arterioles after global cerebral ischaemia in rat - new insights into the development of delayed cerebral hypoperfusion.

PubMed

Spray, S; Johansson, S E; Radziwon-Balicka, A; Haanes, K A; Warfvinge, K; Povlsen, G K; Kelly, P A T; Edvinsson, L

2017-08-01

Delayed cerebral hypoperfusion is a secondary complication found in the days after transient global cerebral ischaemia that worsens the ischaemic damage inflicted by the initial transient episode of global cerebral ischaemia. A recent study demonstrated increased cerebral vasoconstriction in the large arteries on the brain surface (pial arteries) after global cerebral ischaemia. However, smaller arterioles inside the brain (parenchymal arterioles) are equally important in the regulation of cerebral blood flow and yet their pathophysiology after global cerebral ischaemia is largely unknown. Therefore, we investigated whether increased contractility occurs in the intraparenchymal arterioles. Global cerebral ischaemia was induced in male Wistar rats by bilateral common carotid occlusion for 15 min combined with hypovolaemia. Regional cerebral blood flow was determined by quantitative autoradiography. Intraparenchymal arterioles were isolated and pressurized, and concentration-response curves to endothelin-1 with and without the endothelin B receptor-selective antagonist BQ788 was generated. Endothelin B receptor expression was investigated by quantitative flow cytometry and immunohistochemistry. We observed increased endothelin-1-mediated contractility of parenchymal arterioles correlating with reduced cerebral blood flow of the cortex, hippocampus and caudate nucleus 48 h after global cerebral ischaemia. The increased endothelin-1-mediated contractility was abolished by BQ788, and the vascular smooth muscle cell-specific expression of endothelin B receptors was significantly increased after global cerebral ischaemia. Increased endothelin-1-mediated contractility and expression of endothelin B receptors in the intraparenchymal vasculature contributes to the development of delayed cerebral hypoperfusion after global cerebral ischaemia in combination with vascular changes of the pial vasculature. © 2016 Scandinavian Physiological Society. Published by John Wiley

Cerebral Blood Flow Velocity and Neurodevelopmental Outcome in Infants Undergoing Surgery for Congenital Heart Disease

PubMed Central

Cheng, Henry H.; Wypij, David; Laussen, Peter C.; Bellinger, David C.; Stopp, Christian D.; Soul, Janet S.; Newburger, Jane W.; Kussman, Barry D.

2014-01-01

Background Cerebral blood flow velocity (CBFV) measured by transcranial Doppler sonography has provided information on cerebral perfusion in patients undergoing infant heart surgery, but no studies have reported a relationship to early postoperative and long-term neurodevelopmental outcomes. Methods CBFV was measured in infants undergoing biventricular repair without aortic arch reconstruction as part of a trial of hemodilution during cardiopulmonary bypass (CPB). CBFV (Vm, mean; Vs, systolic; Vd, end-diastolic) in the middle cerebral artery and change in Vm (rVm) were measured intraoperatively and up to 18 hours post-CPB. Neurodevelopmental outcomes, measured at 1 year of age, included the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development-II. Results CBFV was measured in 100 infants: 43 with D-transposition of the great arteries, 36 with tetralogy of Fallot, and 21 with ventricular septal defects. Lower Vm, Vs, Vd, and rVm at18 hours post-CPB were independently related to longer ICU duration of stay (P<0.05). In the 85 patients who returned for neurodevelopmental testing, lower Vm, Vs, Vd and rVm at 18 hours post-CPB were independently associated with lower PDI (P<0.05) and MDI (P<0.05, except Vs: P=0.06) scores. Higher Vs and rVm at 18 hours post-CPB were independently associated with increased incidence of brain injury on MRI in 39 patients. Conclusions Postoperative CBFV after biventricular repair is related to early postoperative and neurodevelopmental outcomes at 1 year of age, possibly indicating that low CBFV is a marker of suboptimal postoperative hemodynamics and cerebral perfusion. PMID:24820395

Simple retrograde cerebral perfusion is as good as complex antegrade cerebral perfusion for hemiarch replacement.

PubMed

Tanaka, Akiko; Estrera, Anthony L

2018-01-01

Cerebral complication is a major concern after aortic arch surgery, which may lead to death. Thus, cerebral protection strategy plays the key role to obtain respectable results in aortic arch repair. Deep hypothermic circulatory arrest was introduced in 1970s to decrease the ischemic insults to the brain. However, safe duration of circulatory arrest time was limited to 30 minutes. The 1990s was the decade of evolution for cerebral protection, in which two adjuncts for deep hypothermic circulatory arrest were introduced: retrograde and antegrade cerebral perfusion (ACP) techniques. These two cerebral perfusion techniques significantly decreased incidence of postoperative neurological dysfunction and mortality after aortic arch surgery. Although there are no large prospective studies that demonstrate which perfusion technique provide better outcomes, multiple retrospective studies implicate that ACP may decrease cerebral complications compared to retrograde cerebral perfusion (RCP) when a long circulatory arrest time is required during aortic arch reconstructions. To date, many surgeons favor ACP over RCP during a complex aortic arch repair, such as total arch replacement and hybrid arch replacement. However, the question is whether the use of ACP is necessary during a short, limited circulatory arrest time, such as hemiarch replacement? There is a paucity of data that proves the advantages of a complex ACP over a simple RCP for a short circulatory arrest time. RCP with deep hypothermic circulatory arrest is the simple, efficient cerebral protection technique with minimal interference to the surgical field-and it potentially allows to flush atheromatous debris out from the arch vessels. Thus, it is the preferred adjunct to deep hypothermic circulatory arrest during hemiarch replacement in our institution.

Simple retrograde cerebral perfusion is as good as complex antegrade cerebral perfusion for hemiarch replacement

PubMed Central

Tanaka, Akiko

2018-01-01

Cerebral complication is a major concern after aortic arch surgery, which may lead to death. Thus, cerebral protection strategy plays the key role to obtain respectable results in aortic arch repair. Deep hypothermic circulatory arrest was introduced in 1970s to decrease the ischemic insults to the brain. However, safe duration of circulatory arrest time was limited to 30 minutes. The 1990s was the decade of evolution for cerebral protection, in which two adjuncts for deep hypothermic circulatory arrest were introduced: retrograde and antegrade cerebral perfusion (ACP) techniques. These two cerebral perfusion techniques significantly decreased incidence of postoperative neurological dysfunction and mortality after aortic arch surgery. Although there are no large prospective studies that demonstrate which perfusion technique provide better outcomes, multiple retrospective studies implicate that ACP may decrease cerebral complications compared to retrograde cerebral perfusion (RCP) when a long circulatory arrest time is required during aortic arch reconstructions. To date, many surgeons favor ACP over RCP during a complex aortic arch repair, such as total arch replacement and hybrid arch replacement. However, the question is whether the use of ACP is necessary during a short, limited circulatory arrest time, such as hemiarch replacement? There is a paucity of data that proves the advantages of a complex ACP over a simple RCP for a short circulatory arrest time. RCP with deep hypothermic circulatory arrest is the simple, efficient cerebral protection technique with minimal interference to the surgical field—and it potentially allows to flush atheromatous debris out from the arch vessels. Thus, it is the preferred adjunct to deep hypothermic circulatory arrest during hemiarch replacement in our institution. PMID:29682460

Caffeine induced changes in cerebral circulation

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

Mathew, R.J.; Wilson, W.H.

1985-09-01

While the caffeine induced cerebral vasoconstriction is well documented, the effects of oral ingestion of the drug in a dose range comparable to the quantities in which it is usually consumed and the intensity and duration of the associated reduction in cerebral circulation are unknown. Cerebral blood flow was measured via the TTXenon inhalation technique before and thirty and ninety minutes after the oral administration of 250 mg of caffeine or a placebo, under double-blind conditions. Caffeine ingestion was found to be associated with significant reductions in cerebral perfusion thirty and ninety minutes later. The placebo group showed no differencesmore » between the three sets of cerebral blood flow values.« less

What makes children with cerebral palsy vulnerable to malnutrition? Findings from the Bangladesh cerebral palsy register (BCPR).

PubMed

Jahan, Israt; Muhit, Mohammad; Karim, Tasneem; Smithers-Sheedy, Hayley; Novak, Iona; Jones, Cheryl; Badawi, Nadia; Khandaker, Gulam

2018-04-16

To assess the nutritional status and underlying risk factors for malnutrition among children with cerebral palsy in rural Bangladesh. We used data from the Bangladesh Cerebral Palsy Register; a prospective population based surveillance of children with cerebral palsy aged 0-18 years in a rural subdistrict of Bangladesh (i.e., Shahjadpur). Socio-demographic, clinical and anthropometric measurements were collected using Bangladesh Cerebral Palsy Register record form. Z scores were calculated using World Health Organization Anthro and World Health Organization AnthroPlus software. A total of 726 children with cerebral palsy were registered into the Bangladesh Cerebral Palsy Register (mean age 7.6 years, standard deviation 4.5, 38.1% female) between January 2015 and December 2016. More than two-third of children were underweight (70.0%) and stunted (73.1%). Mean z score for weight for age, height for age and weight for height were -2.8 (standard deviation 1.8), -3.1 (standard deviation 2.2) and -1.2 (standard deviation 2.3) respectively. Moderate to severe undernutrition (i.e., both underweight and stunting) were significantly associated with age, monthly family income, gross motor functional classification system and neurological type of cerebral palsy. The burden of undernutrition is high among children with cerebral palsy in rural Bangladesh which is augmented by both poverty and clinical severity. Enhancing clinical nutritional services for children with cerebral palsy should be a public health priority in Bangladesh. Implications for Rehabilitation Population-based surveillance data on nutritional status of children with cerebral palsy in Bangladesh indicates substantially high burden of malnutrition among children with CP in rural Bangladesh. Children with severe form of cerebral palsy, for example, higher Gross Motor Function Classification System (GMFCS) level, tri/quadriplegic cerebral palsy presents the highest proportion of severe malnutrition; hence, these

Cerebral Arterial Occlusion Did Not Promote the Prevalence of Cerebral Amyloid Angiopathy.

PubMed

Honda, Kazuhiro

2016-08-01

An impairment of amyloid-β (Aβ) clearance has been suggested in Alzheimer's disease. Perivascular drainage along cerebrovascular vessels is considered an important amyloid clearance pathway. This study examined the effect of reduced arterial pulsation that could cause an impairment in cerebral amyloid drainage on the prevalence of cortical microbleeds (CMBs), a surrogate marker for cerebral amyloid angiopathy (CAA). Patients who lost depiction of either side of the carotid artery or the middle cerebral artery on magnetic resonance angiography were studied. Those who showed acute cerebral infarction or a previous cortical cerebral infarction were excluded. The number of CMBs was counted on the occluded and non-occluded sides of the brain in each subject. The number of subjects who showed more CMBs on the occluded side of the brain was compared with the number of subjects who showed more CMBs on the non-occluded side of the brain. Twenty-eight patients were studied. The extent of lacunar infarction and white matter lesions was not different, irrespective of the occluded vessels or the distribution of CMBs. The prevalence of CMBs was not different between the occluded and non-occluded sides of the brain. In this cross-sectional study, reduction of arterial pulsation was not associated with a higher prevalence of CAA. Therefore, reduced arterial pulsation alone may not be enough to promote CAA.

Neonatal interventions for preventing cerebral palsy: an overview of Cochrane Systematic Reviews.

PubMed

Shepherd, Emily; Salam, Rehana A; Middleton, Philippa; Han, Shanshan; Makrides, Maria; McIntyre, Sarah; Badawi, Nadia; Crowther, Caroline A

2018-06-20

); interventions for neonates born preterm and/or at low or very low birthweight (33); and interventions for other specific groups of 'at risk' neonates (7). Quality of evidence (GRADE) ranged from very low to high.Interventions for neonates with perinatal asphyxia or with evidence of neonatal encephalopathyEffective interventions: high-quality evidence of effectivenessResearchers found a reduction in cerebral palsy following therapeutic hypothermia versus standard care for newborns with hypoxic ischaemic encephalopathy (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.54 to 0.82; seven trials; 881 children).No conclusions possible: very low-quality evidenceOne review observed no clear differences in cerebral palsy following therapeutic hypothermia versus standard care.Interventions for neonates born preterm and/or at low or very low birthweightPossibly effective interventions: moderate-quality evidence of effectivenessResearchers found a reduction in cerebral palsy with prophylactic methylxanthines (caffeine) versus placebo for endotracheal extubation in preterm infants (RR 0.54, 95% CI 0.32 to 0.92; one trial; 644 children).Probably ineffective interventions: moderate-quality evidence of harmResearchers reported an increase in cerebral palsy (RR 1.45, 95% CI 1.06 to 1.98; 12 trials; 1452 children) and cerebral palsy in assessed survivors (RR 1.50, 95% CI 1.13 to 2.00; 12 trials; 959 children) following early (at less than eight days of age) postnatal corticosteroids versus placebo or no treatment for preventing chronic lung disease in preterm infants.Probably ineffective interventions: moderate-quality evidence of lack of effectivenessTrial results showed no clear differences in cerebral palsy following ethamsylate versus placebo for prevention of morbidity and mortality in preterm or very low birthweight infants (RR 1.13, 95% CI 0.64 to 2.00; three trials, 532 children); volume expansion versus no treatment (RR 0.76, 95% CI 0.48 to 1.20; one trial; 604 children); gelatin

[Advances in genetic research of cerebral palsy].

PubMed

Wang, Fang-Fang; Luo, Rong; Qu, Yi; Mu, De-Zhi

2017-09-01

Cerebral palsy is a group of syndromes caused by non-progressive brain injury in the fetus or infant and can cause disabilities in childhood. Etiology of cerebral palsy has always been a hot topic for clinical scientists. More and more studies have shown that genetic factors are closely associated with the development of cerebral palsy. With the development and application of various molecular and biological techniques such as chromosome microarray analysis, genome-wide association study, and whole exome sequencing, new achievements have been made in the genetic research of cerebral palsy. Chromosome abnormalities, copy number variations, susceptibility genes, and single gene mutation associated with the development of cerebral palsy have been identified, which provides new opportunities for the research on the pathogenesis of cerebral palsy. This article reviews the advances in the genetic research on cerebral palsy in recent years.

Video training and certification program improves reliability of postischemic neurologic deficit measurement in the rat.

PubMed

Taninishi, Hideki; Pearlstein, Molly; Sheng, Huaxin; Izutsu, Miwa; Chaparro, Rafael E; Goldstein, Larry B; Warner, David S

2016-12-01

Scoring systems are used to measure behavioral deficits in stroke research. Video-assisted training is used to standardize stroke-related neurologic deficit scoring in humans. We hypothesized that a video-assisted training and certification program can improve inter-rater reliability in assessing neurologic function after middle cerebral artery occlusion in rats. Three expert raters scored neurologic deficits in post-middle cerebral artery occlusion rats using three published systems having different complexity levels (3, 18, or 48 points). The system having the highest point estimate for the correlation between neurologic score and infarct size was selected to create a video-assisted training and certification program. Eight trainee raters completed the video-assisted training and certification program. Inter-rater agreement ( Κ: score) and agreement with expert consensus scores were measured before and after video-assisted training and certification program completion. The 48-point system correlated best with infarct size. Video-assisted training and certification improved agreement with expert consensus scores (pretraining = 65 ± 10, posttraining = 87 ± 14, 112 possible scores, P < 0.0001), median number of trainee raters with scores within ±2 points of the expert consensus score (pretraining = 4, posttraining = 6.5, P < 0.01), categories with Κ:  > 0.4 (pretraining = 4, posttraining = 9), and number of categories with an improvement in the Κ: score from pretraining to posttraining (n = 6). Video-assisted training and certification improved trainee inter-rater reliability and agreement with expert consensus behavioral scores in rats after middle cerebral artery occlusion. Video-assisted training and certification may be useful in multilaboratory preclinical studies. © The Author(s) 2015.

Direct visualization of minimal cerebral capillary flow during retrograde cerebral perfusion: an intravital fluorescence microscopy study in pigs.

PubMed

Duebener, Lennart F; Hagino, Ikuo; Schmitt, Katharina; Sakamoto, Takahiko; Stamm, Christof; Zurakowski, David; Schäfers, Hans-Joachim; Jonas, Richard A

2003-04-01

Retrograde cerebral perfusion (RCP) is used in some centers during aortic arch surgery for brain protection during hypothermic circulatory arrest. It is still unclear however whether RCP provides adequate microcirculatory blood flow at a capillary level. We used intravital microscopy to directly visualize the cerebral capillary blood flow in a piglet model of RCP. Twelve pigs (weight 9.7 +/- 0.9 kg) were divided into two groups (n = 6 each): deep hypothermic circulatory arrest (DHCA) and RCP. After the creation of a window over the parietal cerebral cortex, pigs underwent 10 minutes of normothermic bypass and 40 minutes of cooling to 15 degrees C on cardiopulmonary bypass ([CPB] pH-stat, hemocrit 30%, pump flow 100 mL x kg(-1) x min(-1)). This was followed by 45 minutes of DHCA and rewarming on CPB to 37 degrees C. In the RCP group the brain was retrogradely perfused (pump flow 30 mL x kg(-1) x min(-1)) during DHCA through the superior vena cava after inferior vena cava occlusion. Plasma was labeled with fluorescein-isothiocyanate-dextran for assessing microvascular diameter and functional capillary density (FCD), defined as total length of erythrocyte-perfused capillaries per observation area. Cerebral tissue oxygenation was determined by nicotinamide adenine dinucleotide hydrogen (NADH) autofluorescence, which increases during tissue ischemia. During normothermic and hypothermic antegrade cerebral perfusion the FCD did not significantly change from base line (97% +/- 14% and 96% +/- 12%, respectively). During retrograde cerebral perfusion the FCD decreased highly significantly to 2% +/- 2% of base line values (p < 0.001). Thus there was no evidence of significant capillary blood flow during retrograde cerebral perfusion. The microvascular diameter of cerebral arterioles that were slowly perfused significantly decreased to 27% +/- 6% of base line levels during RCP. NADH fluorescence progressively and significantly increased during RCP, indicating poorer tissue

Microvolt T-wave alternans and beat-to-beat variability of repolarization during early postischemic remodeling in a pig heart.

PubMed

Floré, Vincent; Claus, Piet; Antoons, Gudrun; Oosterhoff, Peter; Holemans, Patricia; Vos, Marc A; Sipido, Karin R; Willems, Rik

2011-07-01

Repolarization variability is considered to predict sudden cardiac death. T-wave alternans (TWA) has been the subject of exhaustive research, whereas beat-to-beat variability of repolarization (BVR) is a new parameter that possibly predicts proarrhythmia. How these parameters interact has not been tested. The purpose of this study was to compare TWA and BVR as predictors of proarrhythmic substrate early after myocardial infarction (MI). In nine pigs, MI was induced by 1-hour occlusion of the left anterior descending coronary artery. Cardiac magnetic resonance imaging was performed at day 21. Six sham pigs served as control. Spectral TWA was tested during right atrial pacing before induction of MI and after 21 days. BVR was calculated from 60 consecutive QT intervals. Magnetic resonance imaging showed transmural MI. TWA was negative in all pigs at clinical threshold rate and equally present in MI versus sham pigs at higher rates (170 bpm: 55% vs 50% positive TWA). In MI pigs, BVR of QT intervals increased significantly during acute ischemia (2.44 ± 0.43 ms vs 3.55 ± 0.41 ms, P <.01) and even more on day 21 (5.80 ± 1.12 ms), but it differed significantly from sham (2.14 ± 0.54 ms, P <.01). A clinical ventricular tachycardia induction protocol was positive in 2 of 8 MI pigs and in none of 6 shams. In early remodeling after MI, BVR at intrinsic heart rate was a consistent phenomenon, whereas TWA during atrial pacing or baseline QT-interval changes were not. TWA and BVR could reflect different post-MI remodeling processes. BVR may be a new technique for predicting a potentially proarrhythmic substrate in the early postinfarction period. Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Cerebral Lateralization and Aggression.

ERIC Educational Resources Information Center

Hillbrand, Marc; And Others

1994-01-01

A resurgence of interest in the relationship between cerebral lateralization (the functional asymmetry of the cerebral cortex) and aggression has occurred. Most recent studies have found that individuals with abnormal patterns of lateralization are overrepresented among violent individuals. Intervening variables (such as drug and alcohol abuse)…

Puerarin Attenuates Cerebral Damage by Improving Cerebral Microcirculation in Spontaneously Hypertensive Rats

PubMed Central

Wu, Xu-Dong; Wang, Chen; Zhang, Zhen-Ying; Fu, Yan; Liu, Feng-Ying; Liu, Xiu-Hua

2014-01-01

Puerariae Lobatae Radix (Gegen in Chinese) is the dried root of Pueraria lobata, a semiwoody, perennial, and leguminous vine native to China. Puerarin is one of the effective components of isoflavones isolated from the root of Pueraria lobata. Previous studies showed that extracts derived from the root of Pueraria lobata possessed antihypertensive effect. Our study is to investigate whether puerarin contributes to prevention of stroke by improving cerebral microcirculation in rats. Materials and Methods. Video microscopy and laser Doppler perfusion imaging on the pia mater were used to measure the diameter of microvessel and blood perfusion in 12-week old spontaneously hypertensive rats (SHRs) and age-matched normotensive WKY rats. Histological alterations were observed by hematoxylin and eosin staining, and microvessel density in cerebral tissue was measured by immunohistochemical analysis with anti-Factor VIII antibody. Cell proliferation was detected by [3H]-TdR incorporation, and activities of p42/44 mitogen activated protein kinases (p42/44 MAPKs) were detected by western blot analysis in cultured cerebral microvascular endothelial cells (MECs). Results. Intravenous injection of puerarin relaxed arterioles and increased the blood flow perfusion in the pia mater in SHRs. Puerarin treatment for 14 days reduced the blood pressure to a normal level in SHRs (P < 0.05) and increased the arteriole diameter in the pia mater significantly as compared with vehicle treatment. Arteriole remodeling, edema, and ischemia in cerebral tissue were attenuated in puerarin-treated SHRs. Microvessel density in cerebral tissue was greater with puerarin than with vehicle treatment. Puerarin-treated MECs showed greater proliferation and p42/44 MAPKs activities than vehicle treatment. Conclusions. Puerarin possesses effects of antihypertension and stroke prevention by improved microcirculation in SHRs, which results from the increase in cerebral blood perfusion both by arteriole

ABCD2 score and BNP level in patients with TIA and cerebral stroke.

PubMed

Mortezabeigi, H R; Taghizadeh, A; Talebi, M; Amini, K; Goldust, M

2013-11-01

Scoring systems have been designed to help physicians in early prediction of cerebral stroke following Transitional Ischemic Attack (TIA). ABCD2 system is one of these scoring systems. Considering increase of brain natriuretic peptide following cerebral ischemic stroke, BNP level may be associated with incidence of ischemic stroke following TIA. The present study evaluates ABCD2 score, BNP level in patients with TIA and incidence of cerebral stroke. This cross sectional-analytical study evaluated 78 patients with TIA. ABCD2 score was calculated for all patients based on some criteria including age, blood pressure, clinical manifestations (speech/motor disorder), symptoms duration and diabetes. BNP level was measured at the reference laboratory when the patient referred to the treatment center. The patients were followed up for 6 months considering incidence of cerebral stroke and TIA. Mean age of the patients was 66.53 +/- 13.08 years and the sample was consisted of 62.8% male and 37.2% female patients. Mean BNP level and mean ABCD2 score was 611.31 +/- 125.61 and 4.61 +/- 10.99 in all patients, respectively. During follow-up period, TIA recurrence and cerebral stroke were, respectively seen in 11.5 and 3.8% of cases. Mortality was reported in 5.1% of the patients. BNP was significantly higher in cases with recursive TIA (p = 0.03). But, there was not any difference considering ABCD2 score (p = 0.38). BNP is capable of predicting TIA recurrence following first TIA and it can be used in this case.

Predictive value of early amplitude-integrated electroencephalography for later diagnosed cerebral white matter damage in preterm infants.

PubMed

Song, Juan; Zhu, Changlian; Xu, Falin; Guo, Jiajia; Zhang, Yanhua

2014-10-01

 The aim of the article is to assess the predictive value of amplitude-integrated electroencephalogram (aEEG) for cerebral white matter damage (WMD) in preterm infants. Patients and  Preterms ≤ 32 weeks' gestational age (GA) born between March 2012 and December 2012 were enrolled. The aEEG patterns within 72 hours were classified and recorded to predict their neurodevelopmental prognosis and the predictive results were used to compare with the results by cerebral ultrasound examination. Neurobehavioral disorder (neonatal behavioral neurological assessment score < 35, dyskinesia or dysgnosia) or death was thought as poor neurodevelopmental prognosis. Psychomotor development index (PDI) or mental development index (MDI) ≤ 79 was regarded as dyskinesia or dysgnosia, respectively.  Of the 63 preterms, 3.2% were born < 27 weeks' gestation and 96.8% at 27 to 32 weeks' gestation. The median GA was 29.3 weeks and the median birth weight was 1,030 g. On the basis of the aEEG results, normal, mildly abnormal, and severely abnormal cases were 10, 24, and 29; whereas determined by cerebral ultrasound, normal, mild, and severe cases were 17, 20, and 26, respectively. The aEEG degree showed significantly positive correlations with both WMD and poor neurodevelopmental prognosis (p < 0.01).  Abnormal aEEG of preterm infants within 72 hours after birth may imply WMD occurrence and poor neurodevelopmental prognosis. Georg Thieme Verlag KG Stuttgart · New York.

EEG as an Indicator of Cerebral Functioning in Postanoxic Coma.

PubMed

Juan, Elsa; Kaplan, Peter W; Oddo, Mauro; Rossetti, Andrea O

2015-12-01

Postanoxic coma after cardiac arrest is one of the most serious acute cerebral conditions and a frequent cause of admission to critical care units. Given substantial improvement of outcome over the recent years, a reliable and timely assessment of clinical evolution and prognosis is essential in this context, but may be challenging. In addition to the classic neurologic examination, EEG is increasingly emerging as an important tool to assess cerebral functions noninvasively. Although targeted temperature management and related sedation may delay clinical assessment, EEG provides accurate prognostic information in the early phase of coma. Here, the most frequently encountered EEG patterns in postanoxic coma are summarized and their relations with outcome prediction are discussed. This article also addresses the influence of targeted temperature management on brain signals and the implication of the evolution of EEG patterns over time. Finally, the article ends with a view of the future prospects for EEG in postanoxic management and prognostication.

The Influence of Neurodevelopmental Treatment on Transforming Growth Factor-β1 Levels and Neurological Remodeling in Children With Cerebral Palsy.

PubMed

Tao, Weiyuan; Lu, Zuneng; Wen, Fang

2016-11-01

Neurodevelopmental treatment is an advanced therapeutic approach for the neural rehabilitation of children with cerebral palsy. Cerebral palsy represents a spectrum of neurological disorders primarily affecting gross motor function. The authors investigated the effects of neurodevelopmental treatment on serum levels of transforming growth factor-β1 (TGF-β1), a neuroprotective cytokine, and improvements to motor skills. Serum TGF-β1 levels and total score of the Gross Motor Function Measure-88 (GMFM-88) were significantly higher in children with cerebral palsy who underwent neurodevelopmental treatment compared to untreated patients (P < .01). Furthermore, the improved GMFM-88 total scores after neurodevelopmental treatment were significantly higher in children under the age of 3 with cerebral palsy than in older patients (P < .01). The authors demonstrate that the integration of TGF-β1 levels and GMFM-88 total score could be used to assess the efficacy of neurodevelopmental treatment. Moreover, the findings provide further scientific support for the early intervention and neurological rehabilitation of young children with cerebral palsy. © The Author(s) 2016.

Cerebral Hypoperfusion Precedes Nausea During Centrifugation

NASA Technical Reports Server (NTRS)

Serrador, Jorge M.; Schlegel, Todd T.; Black, F. Owen; Wood, Scott J.

2004-01-01

Nausea and motion sickness are important operational concerns for aviators and astronauts. Understanding underlying mechanisms associated with motion sickness may lead to new treatments. The goal of this work was to determine if cerebral blood flow changes precede the development of nausea in motion sick susceptible subjects. Cerebral flow velocity in the middle cerebral artery (transcranial Doppler), blood pressure (Finapres) and end-tidal CO2 were measured while subjects were rotated on a centrifuge (250 degrees/sec). Following 5 min of rotation, subjects were translated 0.504 m off-center, creating a +lGx centripetal acceleration in the nasal-occipital plane. Ten subjects completed the protocol without symptoms while 5 developed nausea (4 while 6ff-center and 1 while rotating on-center). Prior to nausea, subjects had significant increases in blood pressure (+13plus or minus 3 mmHg, P less than 0.05) and cerebrovascular resistance (+46 plus or minus 17%, P less than 0.05) and decreases in cerebral flow velocity both in the second (-13 plus or minus 4%) and last minute (-22 plus or minus 5%) before symptoms (P less than 0.05). In comparison, controls demonstrated no change in blood pressure or cerebrovascular resistance in the last minute of off-center rotation and only a 7 plus or minus 2% decrease in cerebral flow velocity. All subjects had significant hypocapnia (-3.8 plus or minus 0.4 mmHg, P less than 0.05), however this hypocapnia could not fully explain the cerebral hypoperfusion associated with the development of nausea. These data indicate that reductions in cerebral blood flow precede the development of nausea. Further work is necessary to determine what role cerebral hypoperfusion plays in motion sickness and whether cerebral hypoperfusion can be used to predict the development of nausea in susceptible individuals.

Spatially extended versus frontal cerebral near-infrared spectroscopy during cardiac surgery: a case series identifying potential advantages

NASA Astrophysics Data System (ADS)

Rummel, Christian; Basciani, Reto; Nirkko, Arto; Schroth, Gerhard; Stucki, Monika; Reineke, David; Eberle, Balthasar; Kaiser, Heiko A.

2018-01-01

Stroke due to hypoperfusion or emboli is a devastating adverse event of cardiac surgery, but early detection and treatment could protect patients from an unfavorable postoperative course. Hypoperfusion and emboli can be detected with transcranial Doppler of the middle cerebral artery (MCA). The measured blood flow velocity correlates with cerebral oxygenation determined clinically by near-infrared spectroscopy (NIRS) of the frontal cortex. We tested the potential advantage of a spatially extended NIRS in detecting critical events in three cardiac surgery patients with a whole-head fiber holder of the FOIRE-3000 continuous-wave NIRS system. Principle components analysis was performed to differentiate between global and localized hypoperfusion or ischemic territories of the middle and anterior cerebral arteries. In one patient, we detected a critical hypoperfusion of the right MCA, which was not apparent in the frontal channels but was accompanied by intra- and postoperative neurological correlates of ischemia. We conclude that spatially extended NIRS of temporal and parietal vascular territories could improve the detection of critically low cerebral perfusion. Even in severe hemispheric stroke, NIRS of the frontal lobe may remain normal because the anterior cerebral artery can be supplied by the contralateral side directly or via the anterior communicating artery.

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.

Autism Spectrum Disorder Phenotype in Children with Ambulatory Cerebral Palsy: A Descriptive Cross-Sectional Study

ERIC Educational Resources Information Center

Smile, S.; Dupuis, A.; MacArthur, C.; Roberts, W.; Fehlings, D.

2013-01-01

The current study aims to describe the cognitive profile, autism profile, medical and behavioral presentation of children with a dual diagnosis of cerebral palsy (CP) and autism spectrum disorder (ASD). Little is known about the dual presentation of CP and ASD. Timely diagnosis is imperative as early intervention may impact a child's developmental…

Comparable Cerebral Blood Flow in Both Hemispheres During Regional Cerebral Perfusion in Infant Aortic Arch Surgery.

PubMed

Rüffer, André; Tischer, Philip; Münch, Frank; Purbojo, Ariawan; Toka, Okan; Rascher, Wolfgang; Cesnjevar, Robert Anton; Jüngert, Jörg

2017-01-01

Cerebral protection during aortic arch repair can be provided by regional cerebral perfusion (RCP) through the innominate artery. This study addresses the question of an adequate bilateral blood flow in both hemispheres during RCP. Fourteen infants (median age 11 days [range, 3 to 108]; median weight, 3.6 kg [range, 2.8 to 6.0 kg]) undergoing RCP (flow rate 54 to 60 mL · kg -1 · min -1 ) were prospectively included. Using combined transfontanellar/transtemporal two- and three-dimensional power/color Doppler sonography, cerebral blood flow intensity in the main cerebral vessels was displayed. Mean time average velocities were measured with combined pulse-wave Doppler in the basilar artery, and both sides of the internal carotid, anterior, and medial cerebral arteries. In addition, bifrontal regional cerebral oximetry (rSO 2 ) was assessed. Comparing both hemispheres, measurements were performed at target temperature (28°C) during full-flow total body perfusion (TBP) and RCP. A regular circle of Willis with near-symmetric blood flow intensity to both hemispheres was visualized in all infants during both RCP and TBP. In the left internal carotid artery, blood flow direction was mixed (retrograde, n = 5; antegrade, n = 8) during TBP and retrograde during RCP. Comparison between sides showed comparable cerebral time average velocities and rSO 2 , except for higher time average velocities in the right internal carotid artery (TBP p = 0.019, RCP p = 0.09). Unilateral comparison between perfusion methods revealed significantly higher rSO 2 in the right hemisphere during TBP (82% ± 9%) compared with RCP (74% ± 11%, p = 0.036). Bilateral assessment of cerebral rSO 2 and time average velocity in the main great cerebral vessels suggests that RCP is associated with near-symmetric blood flow intensity to both hemispheres. Further neurodevelopmental studies are necessary to verify RCP for neuroprotection during aortic arch repair. Copyright © 2017 The Society of

Cerebral blood flow velocity and neurodevelopmental outcome in infants undergoing surgery for congenital heart disease.

PubMed

Cheng, Henry H; Wypij, David; Laussen, Peter C; Bellinger, David C; Stopp, Christian D; Soul, Janet S; Newburger, Jane W; Kussman, Barry D

2014-07-01

Cerebral blood flow velocity (CBFV) measured by transcranial Doppler sonography has provided information on cerebral perfusion in patients undergoing infant heart surgery, but no studies have reported a relationship to early postoperative and long-term neurodevelopmental outcomes. CBFV was measured in infants undergoing biventricular repair without aortic arch reconstruction as part of a trial of hemodilution during cardiopulmonary bypass (CPB); CBFV (Vm, mean; Vs, systolic; Vd, end-diastolic) in the middle cerebral artery and change in Vm (rVm) were measured intraoperatively and up to 18 hours post-CPB. Neurodevelopmental outcomes, measured at 1 year of age, included the psychomotor development index (PDI) and mental development index (MDI) of the Bayley Scales of Infant Development-II. CBFV was measured in 100 infants; 43 with D-transposition of the great arteries, 36 with tetralogy of Fallot, and 21 with ventricular septal defects. Lower Vm, Vs, Vd, and rVm at 18 hours post-CPB were independently related to longer intensive care unit duration of stay (p<0.05). In the 85 patients who returned for neurodevelopmental testing, lower Vm, Vs, Vd, and rVm at 18 hours post-CPB were independently associated with lower PDI (p<0.05) and MDI (p<0.05, except Vs: p=0.06) scores. Higher Vs and rVm at 18 hours post-CPB were independently associated with increased incidence of brain injury on magnetic resonance imaging in 39 patients. Postoperative CBFV after biventricular repair is related to early postoperative and neurodevelopmental outcomes at 1 year of age, possibly indicating that low CBFV is a marker of suboptimal postoperative hemodynamics and cerebral perfusion. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Narcolepsy: regional cerebral blood flow during sleep and wakefulness

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

Sakai, F.; Meyer, J.S.; Karacan, I.

Serial measurements of regional cerebral blood flow were made by the 135Xe inhalation method during the early stages of sleep and wakefulness in eight normal volunteers and 12 patients with narcolepsy. Electroencephalogram, electro-oculogram, and submental electromyogram were recorded simultaneously. In normals, mean hemispheric gray matter blood flow (Fg) during stages I and II sleep was significantly less than waking values. Maximum regional blood flow decreases during sleep occurred in the brainstem-cerebellar, right inferior temporal, and bilateral frontal regions. In patients with narcolepsy, mean hemispheric Fg while awake was 80.5 +- 13 ml per 100 gm brain per minute. During REMmore » sleep, mean hemispheric Fg increased concurrently with large increases in brainstem-cerebellar region flow. During stages I and II sleep without REM, there were significant increases in mean hemispheric Fg and brainstem-cerebellar Fg, just the opposite of changes in normals. In narcolepsy, there appears to be a reversal of normal cerebral deactivation patterns, particularly involving the brainstem, during stages I and II sleep.« less

A Diagnostic Approach for Cerebral Palsy in the Genomic Era

PubMed Central

Lee, Ryan W.; Poretti, Andrea; Cohen, Julie S.; Levey, Eric; Gwynn, Hilary; Johnston, Michael V.; Hoon, Alexander H.; Fatemi, Ali

2014-01-01

An ongoing challenge in children presenting with motor delay/impairment early in life is to identify neurogenetic disorders with a clinical phenotype which can be misdiagnosed as cerebral palsy (CP). To help distinguish patients in these two groups, conventional magnetic resonance imaging (MRI) of the brain has been of great benefit in “unmasking” many of these genetic etiologies and has provided important clues to differential diagnosis in others. Recent advances in molecular genetics such as chromosomal microarray and next generation sequencing have further revolutionized the understanding of etiology by more precisely classifying these disorders with a molecular cause. In this paper, we present a review of neurogenetic disorders masquerading as cerebral palsy evaluated at one institution. We have included representative case examples children presenting with dyskinetic, spastic and ataxic phenotypes, with the intent to highlight the time honored approach of using clinical tools of history and examination to focus the subsequent etiologic search with advanced neuroimaging modalities and molecular genetic tools. A precise diagnosis of these masqueraders and their differentiation from CP is important in terms of therapy, prognosis, and family counseling. In summary, this review serves as a continued call to remain vigilant for current and other to-be-discovered neurogenetic masqueraders of cerebral palsy, thereby optimizing care for patients and their families. PMID:25280894

Impact of extracranial contamination on regional cerebral oxygen saturation: a comparison of three cerebral oximetry technologies.

PubMed

Davie, Sophie N; Grocott, Hilary P

2012-04-01

Cerebral oximetry is a noninvasive technology using near-infrared spectroscopy (NIRS) to estimate regional cerebral oxygen saturation. Although NIRS cerebral oximetry is being increasingly used in many clinical settings, interdevice technologic differences suggest potential variation in the ability to accurately acquire brain oxygenation signals. The primary objective of this study was to determine if NIRS-derived regional cerebral oxygen saturation measurements accurately account for oxygen saturation contamination from extracranial tissue. Twelve healthy volunteers had each of three NIRS devices (FORE-SIGHT [CAS Medical Systems Inc; Brandford, CT], INVOS 5100C-PB [Covidien; Boulder, CO], and EQUANOX Classic 7600 [Nonin Medical Inc; Plymouth, MN]) randomly applied to the forehead. After this, a circumferential pneumatic head cuff was positioned such that when inflated, hypoxia-ischemia would be produced in the extracranial scalp tissue beneath the NIRS cerebral oximeters. Comparisons among the three devices were made of the NIRS measurements before and following hypoxia-ischemia produced in the scalp tissue with inflation of the head cuff. The induction of extracranial hypoxia-ischemia resulted in a significant reduction in regional cerebral oxygen saturation measurements in all three NIRS devices studied. At 5 min postinflation of the pneumatic head cuff, the INVOS demonstrated a 16.6 ± 9.6% (mean ± SD) decrease from its baseline (P = 0.0001), the FORE-SIGHT an 11.8 ± 5.3% decrease from its baseline (P < 0.0001), and the EQUANOX a 6.8 ± 6.0% reduction from baseline (P = 0.0025). Extracranial contamination appears to significantly affect NIRS measurements of cerebral oxygen saturation. Although the clinical implications of these apparent inaccuracies require further study, they suggest that the oxygen saturation measurements provided by cerebral oximetry do not solely reflect that of the brain alone.

White Matter Integrity Linked To Functional Impairments in Aging and Early Alzheimer’s Disease

PubMed Central

Kavcic, Voyko; Ni, Hongyan; Zhu, Tong; Zhong, Jianhui; Duffy, Charles J.

2008-01-01

Background Alzheimer’s disease (AD) is associated with changes in cerebral white matter (WM) but the functional significance of such findings is not yet established. We hypothesized that diffusion tensor imaging (DTI) might reveal links between regional WM changes and specific neuropsychologically and psychophysically defined impairments in early AD. Methods Older adult control subjects (OA, n=18) and mildly impaired AD patients (n=14) underwent neuropsychological and visual perceptual testing along with DTI of cerebral WM. DTI yielded factional anisotropy (FA) and mean diffusivity () maps for nine ROIs in three brain regions that were then compared to the performance measures. Results AD patients showed non-significant trends toward lower FAs in the posterior region’s callosal and sub-cortical ROIs. However, posterior callosal FA was significantly correlated with verbal fluency and figural memory impairments, whereas posterior subcortical FA was correlated with delayed verbal memory, figural memory, and optic flow perceptual impairments. Conclusions WM changes in early AD are concentrated in posterior cerebral areas with distributions that correspond to specific functional impairments. DTI can be used to assess regional pathology related to individual’s deficits in early AD. PMID:19012862

Body mass index in ambulatory cerebral palsy patients.

PubMed

Feeley, Brian T; Gollapudi, Kiran; Otsuka, Norman Y

2007-05-01

Malnutrition is a common problem in children with cerebral palsy. Although malnutrition is often recognized in patients with severe cerebral palsy, it can be unrecognized in less severely affected patients. The consequences of malnutrition are serious, and include decreased muscle strength, poor immune status, and depressed cerebral functioning. Low body mass index has been used as a marker for malnutrition. The purpose of this study was to determine which patients in an ambulatory cerebral palsy patient population were at risk for low body mass index. A retrospective chart review was performed on 75 patients. Age, sex, height, weight, type of cerebral palsy, and functional status [gross motor functional classification system (GMFCS) level] was recorded from the chart. Descriptive statistics with bivariate and multivariate regression analyses were performed. Thirty-eight boys and 37 girls with an average age of 8.11 years were included in the study. Unique to our patient population, all cerebral palsy patients were independent ambulators. Patients with quadriplegic cerebral palsy had a significantly lower body mass index than those with diplegic and hemiplegic cerebral palsy. Patients with a GMFCS III had significantly lower body mass index than those with GMFCS I and II. When multivariate regression analysis to control for age and sex was performed, low body mass index remained associated with quadriplegic cerebral palsy and GMFCS III. Malnutrition is a common health problem in patients with cerebral palsy, leading to significant morbidity in multiple organ systems. We found that in an ambulatory cerebral palsy population, patients with lower functional status or quadriplegia had significantly lower body mass index, suggesting that even highly functioning ambulatory cerebral palsy patients are at risk for malnutrition.

Cerebral Microcirculation during Experimental Normovolaemic Anemia

PubMed Central

Bellapart, Judith; Cuthbertson, Kylie; Dunster, Kimble; Diab, Sara; Platts, David G.; Raffel, O. Christopher; Gabrielian, Levon; Barnett, Adrian; Paratz, Jenifer; Boots, Rob; Fraser, John F.

2016-01-01

Anemia is accepted among critically ill patients as an alternative to elective blood transfusion. This practice has been extrapolated to head injury patients with only one study comparing the effects of mild anemia on neurological outcome. There are no studies quantifying microcirculation during anemia. Experimental studies suggest that anemia leads to cerebral hypoxia and increased rates of infarction, but the lack of clinical equipoise, when testing the cerebral effects of transfusion among critically injured patients, supports the need of experimental studies. The aim of this study was to quantify cerebral microcirculation and the potential presence of axonal damage in an experimental model exposed to normovolaemic anemia, with the intention of describing possible limitations within management practices in critically ill patients. Under non-recovered anesthesia, six Merino sheep were instrumented using an intracardiac transeptal catheter to inject coded microspheres into the left atrium to ensure systemic and non-chaotic distribution. Cytometric analyses quantified cerebral microcirculation at specific regions of the brain. Amyloid precursor protein staining was used as an indicator of axonal damage. Animals were exposed to normovolaemic anemia by blood extractions from the indwelling arterial catheter with simultaneous fluid replacement through a venous central catheter. Simultaneous data recording from cerebral tissue oxygenation, intracranial pressure, and cardiac output was monitored. A regression model was used to examine the effects of anemia on microcirculation with a mixed model to control for repeated measures. Homogeneous and normal cerebral microcirculation with no evidence of axonal damage was present in all cerebral regions, with no temporal variability, concluding that acute normovolaemic anemia does not result in short-term effects on cerebral microcirculation in the ovine brain. PMID:26869986

Prediction of early neurological deterioration using diffusion- and perfusion-weighted imaging in hyperacute middle cerebral artery ischemic stroke.

PubMed

Arenillas, Juan F; Rovira, Alex; Molina, Carlos A; Grivé, Elisenda; Montaner, Joan; Alvarez-Sabín, José

2002-09-01

Early neurological deterioration (END) occurs in approximately one third of all ischemic stroke patients and is associated with a poor outcome. Our study sought to assess the value of ultra-early MRI in the prediction of END in stroke patients. Between August 1999 and November 2001, 38 stroke patients with a proven middle cerebral artery (MCA) or intracranial internal carotid artery (ICA) occlusion on MR angiography underwent perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) within 6 hours after onset, and 30 fulfilled all inclusion criteria. Control DWI and MR angiography were performed between days 3 and 5. Cranial CT was performed to rule out hemorrhagic transformation. Vascular risk factors, temperature, blood pressure, glycemia, and blood count were assessed on admission. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and at 6, 12, 24, and 48 hours. At the same time points, transcranial Doppler (TCD) examinations were conducted to assess arterial recanalization. END was defined as an increase in the NIHSS score >4. A logistic regression model was applied to detect independent predictors of END. The Kruskal-Wallis test was used to evaluate the relationship between infarct growth and duration of vessel occlusion. Initial MR angiography showed an occlusion of intracranial ICA in 7 patients (23.3%), of proximal MCA in 14 (46.6%), and of distal MCA in the remaining 9 (30%). A PWI-DWI mismatch >20% was observed in 28 patients (93.3%). END occurred in 7 patients (23.3%). Baseline NIHSS score (P=0.05), proximal site of occlusion (P=0.002), initial DWI (P=0.002) and PWI (P=0.003) volumes, and reduced PWI-DWI mismatch (P=0.038) were associated with END in the univariate analysis. Only hyperacute DWI volume remained as a predictor of END when a logistic regression model was applied (odds ratio, 11.5; 95% CI, 2.31 to 57.10; P=0.0028). A receiver operator characteristic curve identified a cutoff point of DWI >89 cm(3

Intraoperative Magnetic Resonance Imaging of Cerebral Oxygen Metabolism During Resection of Brain Lesions.

PubMed

Stadlbauer, Andreas; Merkel, Andreas; Zimmermann, Max; Sommer, Björn; Buchfelder, Michael; Meyer-Bäse, Anke; Rössler, Karl

2017-04-01

Tissue oxygen tension is an important parameter for brain tissue viability and its noninvasive intraoperative monitoring in the whole brain is of highly clinical relevance. The purpose of this study was the introduction of a multiparametric quantitative blood oxygenation dependent magnetic resonance imaging (MRI) approach for intraoperative examination of oxygen metabolism during the resection of brain lesions. Sixteen patients suffering from brain lesions were examined intraoperatively twice (before craniotomy and after gross-total resection) via the quantitative blood oxygenation dependent technique and a 1.5-Tesla MRI scanner, which is installed in an operating room. The MRI protocol included T2*- and T2 mapping and dynamic susceptibility weighted perfusion. Data analysis was performed with a custom-made, in-house MatLab software for calculation of maps of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) as well as of cerebral blood volume and cerebral blood flow. Perilesional edema showed a significant increase in both perfusion (cerebral blood volume +21%, cerebral blood flow +13%) and oxygen metabolism (OEF +32%, CMRO 2  +16%) after resection of the lesions. In perilesional nonedematous tissue only, however, oxygen metabolism (OEF +19%, CMRO 2  +11%) was significantly increased, but not perfusion. No changes were found in normal brain. Fortunately, no neurovascular adverse events were observed. This approach for intraoperative examination of oxygen metabolism in the whole brain is a new application of intraoperative MRI additionally to resection control (residual tumor detection) and updating of neuronavigation (brain shift detection). It may help to detect neurovascular adverse events early during surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased regional cerebral glucose uptake in an APP/PS1 model of Alzheimer’s disease

PubMed Central

Poisnel, Géraldine; Hérard, Anne-Sophie; El Tannir El Tayara, Nadine; Bourrin, Emmanuel; Volk, Andreas; Kober, Frank; Delatour, Benoit; Delzescaux, Thierry; Debeir, Thomas; Rooney, Thomas; Benavides, Jésus; Hantraye, Philippe; Dhenain, Marc

2013-01-01

Alzheimer’s disease (AD), the most common age-related neurodegenerative disorder, is characterized by the invariant cerebral accumulation of β-amyloid peptide. This event occurs early in the disease process. In humans, [18F]-Fluoro-2-deoxy-D-Glucose-Positron Emission Tomography ([18F]-FDG-PET) is largely used to follow-up in vivo cerebral glucose utilisation (CGU) and brain metabolism modifications associated to the AD pathology. Here, [18F]-FDG-PET was used to study age-related changes of CGU under resting conditions in 3, 6 and 12-month-old APPSweLon/PS1M146L, a mouse model of amyloidosis. We showed an age-dependent increase of glucose uptake in several brain regions of APP/PS1 mice but not in control animals and a higher [18F]-FDG uptake in the cortex and the hippocampus of 12-month-old APP/PS1 mice as compared to age-matched control mice. We then developed a method of 3D-microscopic autoradiography to evaluate glucose uptake at the level of amyloid plaques and showed an increased glucose uptake close to the plaques rather than in amyloid-free cerebral tissues. These data suggest a macroscopic and microscopic reorganisation of glucose uptake in relation to cerebral amyloidosis. PMID:22079157

Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease

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

van Duinen, S.G.; Castano, E.M.; Prelli, F.

1987-08-01

Hereditary cerebral hemorrhage with amyloidosis in Dutch patients is an autosomal dominant form of vascular amyloidosis restricted to the leptomeninges and cerebral cortex. Clinically the disease is characterized by cerebral hemorrhages leading to an early death. Immunohistochemical studies of five patients revealed that the vascular amyloid deposits reacted intensely with an antiserum raised against a synthetic peptide homologous to the Alzheimer disease-related ..beta..-protein. Silver stain-positive, senile plaque-like structures were also labeled by the antiserum, yet these lesions lacked the dense amyloid cores present in typical plaques of Alzheimer disease. No neurofibrillary tangles were present. Amyloid fibrils were purified from themore » leptomeningeal vessels of one patient who clinically had no signs of dementia. The protein had a molecular weight of approx. 4000 and its partial amino acid sequence to position 21 showed homology to the ..beta..-protein of Alzheimer disease and Down syndrome. These results suggest that hereditary cerebral hemorrhage with amyloidosis of Dutch origin is pathogenetically related to Alzheimer disease and support the concept that the initial amyloid deposition in this disorder occurs in the vessel walls before damaging the brain parenchyma. Thus, deposition of ..beta..-protein in brain tissue seems to be related to a spectrum of diseases involving vascular syndromes, progressive dementia, or both.« less

Mineralocorticoid receptor activation causes cerebral vessel remodeling and exacerbates the damage caused by cerebral ischemia.

PubMed

Dorrance, Anne M; Rupp, Nikki C; Nogueira, Edson F

2006-03-01

Mineralocorticoid receptor antagonists protect against ischemic cerebrovascular disease; this appears to be caused by changes in cerebral vessel structure that would promote blood flow. Therefore, we hypothesized that mineralocorticoid receptor activation with deoxycorticosterone acetate would cause deleterious remodeling of the cerebral vasculature and exacerbate the damage caused by cerebral ischemia. Six-week-old male Wistar rats were treated with deoxycorticosterone acetate (200 mg/kg) for 6 weeks. At 12 weeks of age, the deoxycorticosterone acetate-treated rats had elevated systolic blood pressure compared with age-matched controls (157+/-5.9 versus 124+/-3.1 mm Hg deoxycorticosterone acetate versus control; P<0.05). The area of ischemic damage resulting from middle cerebral artery occlusion was greater in the deoxycorticosterone acetate-treated rats than control (63.5+/-3.72 versus 46.6+/-5.52% of the hemisphere infarcted, deoxycorticosterone acetate versus control; P<0.05). Middle cerebral artery structure was assessed using a pressurized arteriograph under calcium-free conditions. Over a range of intralumenal pressures, the lumen and ODs of the middle cerebral arteries were smaller in the deoxycorticosterone acetate-treated rats than the control rats (P<0.05). There was also an increase in the wall thickness and wall:lumen ratio in the vessels from deoxycorticosterone acetate-treated rats (P<0.05). The vessels from the deoxycorticosterone acetate-treated rats were stiffer than those from control rats as evidenced by a leftward shift in the stress/strain curve. These novel data suggest that mineralocorticoid receptor activation without salt loading and nephrectomy is sufficient to elicit deleterious effects on the cerebral vasculature that lead to inward hypertrophic remodeling and an increase in the ischemic damage in the event of a stroke.

Revisiting Hemicraniectomy: Late Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Stroke and the Role of Infarct Growth Rate

PubMed Central

Akhtar, Naveed; Salam, Abdul; Alboudi, Ayman; Kamran, Kainat; Ahmed, Arsalan; Khan, Rabia A.; Mirza, Mohsin K.; Inshasi, Jihad

2017-01-01

Objective and Methods. The outcome in late decompressive hemicraniectomy in malignant middle cerebral artery stroke and the optimal timings of surgery has not been addressed by the randomized trials and pooled analysis. Retrospective, multicenter, cross-sectional study to measure outcome following DHC under 48 or over 48 hours using the modified Rankin scale [mRS] and dichotomized as favorable ≤4 or unfavorable >4 at three months. Results. In total, 137 patients underwent DHC. Functional outcome analyzed as mRS 0–4 versus mRS 5-6 showed no difference in this split between early and late operated on patients [P = 0.140] and mortality [P = 0.975]. Multivariate analysis showed that age ≥ 55 years, MCA with additional infarction, septum pellucidum deviation ≥1 cm, and uncal herniation were independent predictors of poor functional outcome at three months. In the “best” multivariate model, second infarct growth rate [IGR2] >7.5 ml/hr, MCA with additional infarction, and patients with temporal lobe involvement were independently associated with surgery under 48 hours. Both first infarct growth rate [IGR1] and second infarct growth rate [IGR2] were nearly double [P < 0.001] in patients with early surgery [under 48 hours]. Conclusions. The outcome and mortality in malignant middle cerebral artery stroke patients operated on over 48 hours of stroke onset were comparable to those of patients operated on less than 48 hours after stroke onset. Our data identifies IGR, temporal lobe involvement, and middle cerebral artery with additional infarct as independent predictors for early surgery. PMID:28409051

Revisiting Hemicraniectomy: Late Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Stroke and the Role of Infarct Growth Rate.

PubMed

Kamran, Saadat; Akhtar, Naveed; Salam, Abdul; Alboudi, Ayman; Kamran, Kainat; Ahmed, Arsalan; Khan, Rabia A; Mirza, Mohsin K; Inshasi, Jihad; Shuaib, Ashfaq

2017-01-01

Objective and Methods. The outcome in late decompressive hemicraniectomy in malignant middle cerebral artery stroke and the optimal timings of surgery has not been addressed by the randomized trials and pooled analysis. Retrospective, multicenter, cross-sectional study to measure outcome following DHC under 48 or over 48 hours using the modified Rankin scale [mRS] and dichotomized as favorable ≤4 or unfavorable >4 at three months. Results. In total, 137 patients underwent DHC. Functional outcome analyzed as mRS 0-4 versus mRS 5-6 showed no difference in this split between early and late operated on patients [ P = 0.140] and mortality [ P = 0.975]. Multivariate analysis showed that age ≥ 55 years, MCA with additional infarction, septum pellucidum deviation ≥1 cm, and uncal herniation were independent predictors of poor functional outcome at three months. In the "best" multivariate model, second infarct growth rate [IGR2] >7.5 ml/hr, MCA with additional infarction, and patients with temporal lobe involvement were independently associated with surgery under 48 hours. Both first infarct growth rate [IGR1] and second infarct growth rate [IGR2] were nearly double [ P < 0.001] in patients with early surgery [under 48 hours]. Conclusions. The outcome and mortality in malignant middle cerebral artery stroke patients operated on over 48 hours of stroke onset were comparable to those of patients operated on less than 48 hours after stroke onset. Our data identifies IGR, temporal lobe involvement, and middle cerebral artery with additional infarct as independent predictors for early surgery.

Unilateral glaucoma in Sotos syndrome (cerebral gigantism).

PubMed

Yen, M T; Gedde, S J; Flynn, J T

2000-12-01

To report a patient with unilateral glaucoma associated with Sotos syndrome. Sotos syndrome (cerebral gigantism) is a disorder of growth and development with characteristic facial changes and normal endocrine function. Ocular manifestations may also include megalocornea, iris hypoplasia, cataracts, megalophthalmos, strabismus, nystagmus, and retinal dystrophy. Case report. A 50 year-old man with the clinical features of Sotos syndrome presented with complaints of decreased vision in the left eye. Ophthalmologic examination revealed bilateral megalocornea, megalophthalmos, iris hypoplasia and transillumination defects, cataracts, and unilateral glaucoma. Intraocular pressure was lowered, and visual field loss was stabilized with topical medications. Sotos syndrome patients should be examined routinely to allow for early detection and treatment of potential ocular problems, including glaucoma.

Early Cerebral Blood Volume Changes Predict Progression After Convection-Enhanced Delivery of Topotecan for Recurrent Malignant Glioma.

PubMed

Surapaneni, Krishna; Kennedy, Benjamin C; Yanagihara, Ted K; DeLaPaz, Robert; Bruce, Jeffrey N

2015-07-01

To assess whether early changes in enhancing tumor volume (eTV) and relative cerebral blood volume (rCBV) 1 month after convection-enhanced delivery of topotecan in patients with recurrent malignant glioma correlated with 6-month disease progression status. Sixteen patients were enrolled in a Phase Ib trial of convection-enhanced delivery of topotecan for recurrent malignant glioma. Each patient was evaluated with serial follow-up magnetic resonance imaging at baseline and at 4- to 8-week intervals. Changes at 1 month compared with baseline in eTV and rCBV were evaluated as potential predictors of 6-month progression status, classified as either progressive disease or nonprogressive disease. Relationships between percent changes in eTV and rCBV at 1 month with the probability of progressive disease at 6 months were estimated by the use of logistic regression analysis. Receiver operating characteristic curves for varying percent change thresholds in eTV and rCBV were evaluated by the use of 6-month progressive disease as the reference. There was a significant difference in the percent change in rCBV at 1 month in patients with progressive disease compared with those with nonprogressive disease at 6 months (+12% vs. -29%, P = 0.02). Logistic regression analysis demonstrated on average that a 10% increase in rCBV at 1 month after convection-enhanced delivery of topotecan was associated with 1.7 times the odds of developing progressive disease at 6 months (95% confidence interval [CI] 1.0-2.9 P = 0.05). Receiver operating characteristic analysis for determining progressive disease at 6 months showed a greater area under the curve with rCBV (0.867; 95% CI 0.66-1.00) than with change in enhancing tumor volume (0.767; 95% CI 0.51-1.00). In this selected population of patients with recurrent malignant glioma treated with convection-enhanced delivery of topotecan, early changes in rCBV at 4 weeks after therapy may help predict progression status at 6 months. Copyright �

Indocyanine Green Liposomes for Diagnosis and Therapeutic Monitoring of Cerebral Malaria.

PubMed

Portnoy, Emma; Vakruk, Natalia; Bishara, Ameer; Shmuel, Miriam; Magdassi, Shlomo; Golenser, Jacob; Eyal, Sara

2016-01-01

Cerebral malaria (CM) is a major cause of death of Plasmodium falciparum infection. Misdiagnosis of CM often leads to treatment delay and mortality. Conventional brain imaging technologies are rarely applicable in endemic areas. Here we address the unmet need for a simple, non-invasive imaging methodology for early diagnosis of CM. This study presents the diagnostic and therapeutic monitoring using liposomes containing the FDA-approved fluorescent dye indocyanine green (ICG) in a CM murine model. Increased emission intensity of liposomal ICG was demonstrated in comparison with free ICG. The Liposomal ICG's emission was greater in the brains of the infected mice compared to naïve mice and drug treated mice (where CM was prevented). Histological analyses suggest that the accumulation of liposomal ICG in the cerebral vasculature is due to extensive uptake mediated by activated phagocytes. Overall, liposomal ICG offers a valuable diagnostic tool and a biomarker for effectiveness of CM treatment, as well as other diseases that involve inflammation and blood vessel occlusion.

Non operative management of cerebral abscess

NASA Astrophysics Data System (ADS)

Batubara, C. A.

2018-03-01

Cerebral abscess is a focal intracerebral infection that begins as a localized area of cerebritis and develops into a collection of pus surrounded by a well-vascularized capsule. Patients typically present with varying combinations of aheadache, progressive neurologic deficits, seizures, and evidence of infection. Computed Tomography and Magnetic Resonance Imagingare the most important diagnostic tools in diagnosing cerebral abscess. The treatment of cerebral abscess has been a challenge. Small cerebralabscesses (< 2.5 cm) have been treated empirically with antibiotics. Elevation of intracranial pressure and threatening herniation can be managed by the use of intravenous mannitol (or hypertonic saline) and dexamethasone. Acute seizures should be terminated with the administration of intravenous benzodiazepines or by intravenous fosphenytoin. Anticonvulsants prophylaxis must be initiated immediately and continued at least one year due to high risk in the cerebral abscesses. Easier detection of underlying conditions, monitoring of the therapeutic progress, and recognition of complications have probably contributed to the improved prognosis.

A reappraisal of retrograde cerebral perfusion.

PubMed

Ueda, Yuichi

2013-05-01

Brain protection during aortic arch surgery by perfusing cold oxygenated blood into the superior vena cava was first reported by Lemole et al. In 1990 Ueda and associates first described the routine use of continuous retrograde cerebral perfusion (RCP) in thoracic aortic surgery for the purpose of cerebral protection during the interval of obligatory interruption of anterograde cerebral flow. The beneficial effects of RCP may be its ability to sustain brain hypothermia during hypothermic circulatory arrest (HCA) and removal of embolic material from the arterial circulation of the brain. RCP can offer effective brain protection during HCA for about 40 to 60 minutes. Animal experiments revealed that RCP provided inadequate cerebral perfusion and that neurological recovery was improved with selective antegrade cerebral perfusion (ACP), however, both RCP and ACP provide comparable clinical outcomes regarding both the mortality and stroke rates by risk-adjusted and case-matched comparative study. RCP still remains a valuable adjunct for brain protection during aortic arch repair in particular pathologies and patients.

[Characteristics of cerebral glucose metabolism in patients with cognitive impairment in Parkinson's disease].

PubMed

Homenko, Ju G; Susin, D S; Kataeva, G V; Irishina, Ju A; Zavolokov, I G

To study the relationship between early cognitive impairment symptoms and cerebral glucose metabolism in different brain regions (according to the positron emission tomography (PET) data) in Parkinson's disease (PD) in order to increase the diagnostic and treatment efficacy. Two groups of patients with PD (stage I-III), including 11 patients without cognitive disorders and 13 with mild cognitive impairment (MCI), were examined. The control group included 10 age-matched people with normal cognition. To evaluate cognitive state, the Mini mental state examination (MMSE), the Frontal assessment battery (FAB) and the 'clock drawing test' were used. The regional cerebral glucose metabolism rate (CMRglu) was assessed using PET with 18F-fluorodeoxyglucose (FDG). In PD patients, CMRglu were decreased in the frontal (Brodmann areas (BA) 9, 10, 11, 46, 47), occipital (BA 19) and parietal (BA 39), temporal (BA 20, 37), and cingulate cortex (BA 32) compared to the control group. Cerebral glucose metabolism was decreased in the frontal (BA 8, 9, 10, 45, 46, 47), parietal (BA 7, 39, 40) and cingulate cortex (BA 23, 24, 31, 32) in the group of PD patients with MCI compared to PD patients with normal cognition. Hypometabolism in BA 7, 8, 23, 24, 31, 40 was revealed only in comparison of PD and PD-MCI groups, and did not appear in case of comparison of cognitively normal PD patients with the control group. It is possible to suggest that the mentioned above brain areas were associated with cognitive impairment. The revealed glucose hypometabolism pattern possibly has the diagnostic value for the early and preclinical diagnosis of MCI in PD and control of treatment efficacy.

Characteristic CT and MR imaging findings of cerebral paragonimiasis.

PubMed

Xia, Yong; Chen, Jing; Ju, Yan; You, Chao

2016-06-01

The early diagnosis of cerebral paragonimiasis (CP) is essential for a good prognosis. We seek to provide references for early diagnosis by analyzing the imaging characteristics of cerebral paragonimiasis. Images of 27 patients with CP (22 males and 5 females; median age 20.3 years; range: 4 to 47 years) were retrospectively evaluated. All patients underwent head computed tomography (CT) scans; 22 patients underwent conventional magnetic resonance imaging (MRI) sequences, including contrast-enhanced MRI for 20 patients and diffusion-weighted-imaging (DWI) for 1 patient. The diagnosis was confirmed based on a positive antibody test using enzyme-linked immunosorbent assay (ELISA) for paragonimiasis in the serum. The most common imaging findings of CP were isodense or hypodense lesions combined with extensive hypodense areas of perilesional edema on CT scans and a large mass composed of multiple ring-shaped lesions with surrounding edema on MRI images. The conglomeration of multiple ring-shaped lesions (n=11 patients), "tunnel signs" (n=12 patients) and worm-eaten signs (n=5 patients) were characteristic of most CP images. In 14 patients, contrast-enhanced MRI showed varying degrees of contrast enhancement combined with adjacent meningeal enhancement (n=10). A large mass comprising multiple ring-shaped lesions of different sizes, "tunnel signs" and worm-eaten signs with surrounding edema are the most characteristic features of CP. Extensive invasions of the adjacent meninges and ventricular wall (19 patients), multiple intracerebral lesions, bilateral hemispheric involvement, and lesion migration are other noteworthy imaging characteristics. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Acute seizures in cerebral venous sinus thrombosis: What predicts it?

PubMed

Mahale, Rohan; Mehta, Anish; John, Aju Abraham; Buddaraju, Kiran; Shankar, Abhinandan K; Javali, Mahendra; Srinivasa, Rangasetty

2016-07-01

Seizures are the presenting feature of cerebral venous sinus thrombosis (CVST) in 12-31.9% of patients. 44.3% of patients have seizures in the early stage of the disease. Acute seizures (AS), refers to seizures which take place before the diagnosis or during the first 2 weeks afterward. To report the predictors of acute seizures in cerebral venous sinus thrombosis (CVST). 100 patients with CVST were included in the study. The occurrence of acute seizures was noted. The predictors of acute seizure were evaluated by univariate analysis including the demographic (gender, age), clinical (headache, focal neurological deficit, papilloedema, GCS score), type and number of risk factors, MRI findings (Type of lesion: hemorrhagic infarction or hematoma, location of lesion) and MRV findings (superficial or deep sinus, cortical veins). A total of 46 patients had acute seizures. On univariate analysis, altered mental status (p<0.001), paresis (p=0.03), GCS score <8 (p=0.009), hemorrhagic infarct on imaging (p=0.04), involvement of frontal lobe (p=0.02), superior sagittal sinus (p=0.008), and high D-dimer levels (p=0.03) were significantly associated with acute seizure. On multivariate analysis, the hemorrhagic infarct on MRI and high D-dimer was independently predictive for early seizure. The predictive factors for the acute seizures are altered mental status (GCS<8), focal deficits, hemorrhagic infarct, involvement of frontal lobe and superior sagittal sinus with high D-dimer levels. Copyright © 2016 Elsevier B.V. All rights reserved.

Digestive tract neural control and gastrointestinal disorders in cerebral palsy.

PubMed

Araújo, Liubiana A; Silva, Luciana R; Mendes, Fabiana A A

2012-01-01

To examine the neural control of digestive tract and describe the main gastrointestinal disorders in cerebral palsy (CP), with attention to the importance of early diagnosis to an efficient interdisciplinary treatment. Systematic review of literature from 1997 to 2012 from Medline, Lilacs, Scielo, and Cochrane Library databases. The study included 70 papers, such as relevant reviews, observational studies, controlled trials, and prevalence studies. Qualitative studies were excluded. The keywords used were: cerebral palsy, dysphagia, gastroesophageal reflux disease, constipation, recurrent respiratory infections, and gastrostomy. The appropriate control of the digestive system depends on the healthy functioning and integrity of the neural system. Since CP patients have structural abnormalities of the central and peripheral nervous system, they are more likely to develop eating disorders. These range from neurological immaturity to interference in the mood and capacity of caregivers. The disease has, therefore, a multifactorial etiology. The most prevalent digestive tract disorders are dysphagia, gastroesophageal reflux disease, and constipation, with consequent recurrent respiratory infections and deleterious impact on nutritional status. Patients with CP can have neurological abnormalities of digestive system control; therefore, digestive problems are common. The issues raised in the present study are essential for professionals within the interdisciplinary teams that treat patients with CP, concerning the importance of comprehensive anamnesis and clinical examination, such as detailed investigation of gastrointestinal disorders. Early detection of these digestive problems may lead to more efficient rehabilitation measures in order to improve patients' quality of life.

Physiology, intervention, and outcome: three critical questions about cerebral tissue oxygen saturation monitoring.

PubMed

Meng, Lingzhong; Gruenbaum, Shaun E; Dai, Feng; Wang, Tianlong

2018-05-01

The balance between cerebral tissue oxygen consumption and supply can be continuously assessed by cerebral tissue oxygen saturation (SctO2) monitor. A construct consisting of three sequential questions, targeting the physiology monitored, the intervention implemented, and the outcomes affected, is proposed to critically appraise this monitor. The impact of the SctO2-guided care on patient outcome was examined through a systematic literature search and meta-analysis. We concluded that the physiology monitored by SctO2 is robust and dynamic, fragile (prone to derangement), and adversely consequential when deranged. The inter-individual variability of SctO2 measurement advocates for an intervention threshold based on a relative, not absolute, change. The intra-individual variability has multiple determinants which is the foundation of intervention. A variety of therapeutic options are available; however, none are 100% efficacious in treating cerebral dys-oxygenation. The therapeutic efficacy likely depends on both an appropriate differential diagnosis and the functional status of the regulatory mechanisms of cerebral blood flow. Meta-analysis based on five randomized controlled trials suggested a reduced incidence of early postoperative cognitive decline after major surgeries (RR= 0.53; 95% CI: 0.33-0.87; I2 =82%; P=0.01). However, its effects on other neurocognitive outcomes remain unclear. These results need to be interpreted with caution due to the high risks of bias. Quality RCTs based on improved intervention protocols and standardized outcome assessment are warranted in the future.

Unique Transcriptional Profile of Sustained Ligand-Activated Preconditioning in Pre- and Post-Ischemic Myocardium

PubMed Central

Ashton, Kevin J.; Tupicoff, Amanda; Williams-Pritchard, Grant; Kiessling, Can J.; See Hoe, Louise E.; Headrick, John P.; Peart, Jason N.

2013-01-01

Background Opioidergic SLP (sustained ligand-activated preconditioning) induced by 3–5 days of opioid receptor (OR) agonism induces persistent protection against ischemia-reperfusion (I-R) injury in young and aged hearts, and is mechanistically distinct from conventional preconditioning responses. We thus applied unbiased gene-array interrogation to identify molecular effects of SLP in pre- and post-ischemic myocardium. Methodology/Principal Findings Male C57Bl/6 mice were implanted with 75 mg morphine or placebo pellets for 5 days. Resultant SLP did not modify cardiac function, and markedly reduced dysfunction and injury in perfused hearts subjected to 25 min ischemia/45 min reperfusion. Microarray analysis identified 14 up- and 86 down-regulated genes in normoxic hearts from SLP mice (≥1.3-fold change, FDR≤5%). Induced genes encoded sarcomeric/contractile proteins (Myh7, Mybpc3,Myom2,Des), natriuretic peptides (Nppa,Nppb) and stress-signaling elements (Csda,Ptgds). Highly repressed genes primarily encoded chemokines (Ccl2,Ccl4,Ccl7,Ccl9,Ccl13,Ccl3l3,Cxcl3), cytokines (Il1b,Il6,Tnf) and other proteins involved in inflammation/immunity (C3,Cd74,Cd83, Cd86,Hla-dbq1,Hla-drb1,Saa1,Selp,Serpina3), together with endoplasmic stress proteins (known: Dnajb1,Herpud1,Socs3; putative: Il6, Gadd45g,Rcan1) and transcriptional controllers (Egr2,Egr3, Fos,Hmox1,Nfkbid). Biological themes modified thus related to inflammation/immunity, together with cellular/cardiovascular movement and development. SLP also modified the transcriptional response to I-R (46 genes uniquely altered post-ischemia), which may influence later infarction/remodeling. This included up-regulated determinants of cellular resistance to oxidant (Mgst3,Gstm1,Gstm2) and other forms of stress (Xirp1,Ankrd1,Clu), and repression of stress-response genes (Hspa1a,Hspd1,Hsp90aa,Hsph1,Serpinh1) and Txnip. Conclusions Protection via SLP is associated with transcriptional repression of inflammation/immunity, up

Changes in Cerebral Compartmental Compliances during Mild Hypocapnia in Patients with Traumatic Brain Injury

PubMed Central

Steiner, Luzius A.; Castellani, Gianluca; Smielewski, Peter; Zweifel, Christian; Haubrich, Christina; Pickard, John D.; Menon, David K.; Czosnyka, Marek

2011-01-01

Abstract The benefit of induced hyperventilation for intracranial pressure (ICP) control after severe traumatic brain injury (TBI) is controversial. In this study, we investigated the impact of early and sustained hyperventilation on compliances of the cerebral arteries and of the cerebrospinal (CSF) compartment during mild hyperventilation in severe TBI patients. We included 27 severe TBI patients (mean 39.5 ± 3.4 years, 6 women) in whom an increase in ventilation (20% increase in respiratory minute volume) was performed during 50 min as part of a standard clinical CO2 reactivity test. Using a new mathematical model, cerebral arterial compliance (Ca) and CSF compartment compliance (Ci) were calculated based on the analysis of ICP, arterial blood pressure, and cerebral blood flow velocity waveforms. Hyperventilation initially induced a reduction in ICP (17.5 ± 6.6 vs. 13.9 ± 6.2 mmHg; p < 0.001), which correlated with an increase in Ci (r2 = 0.213; p = 0.015). Concomitantly, the reduction in cerebral blood flow velocities (CBFV, 74.6 ± 27.0 vs. 62.9 ± 22.9 cm/sec; p < 0.001) marginally correlated with the reduction in Ca (r2 = 0.209; p = 0.017). During sustained hyperventilation, ICP increased (13.9 ± 6.2 vs. 15.3 ± 6.4 mmHg; p < 0.001), which correlated with a reduction in Ci (r2 = 0.297; p = 0.003), but no significant changes in Ca were found during that period. The early reduction in Ca persisted irrespective of the duration of hyperventilation, which may contribute to the lack of clinical benefit of hyperventilation after TBI. Further studies are needed to determine whether monitoring of arterial and CSF compartment compliances may detect and prevent an adverse ischemic event during hyperventilation. PMID:21204704

Early detection of cerebral microbleeds following traumatic brain injury using MRI in the hyper-acute phase.

PubMed

Lawrence, Tim P; Pretorius, Pieter M; Ezra, Martyn; Cadoux-Hudson, Tom; Voets, Natalie L

2017-08-10

Traumatic brain injury (TBI) is a leading cause of death and disability in people under 45. Advanced imaging techniques to identify injury and classify severity in the first few hours and days following trauma could improve patient stratification and aid clinical decision making. Traumatic cerebral microbleeds (TCMBs), detectable on magnetic resonance susceptibility weighted imaging (SWI), can be used as markers of long-term clinical outcome. However, the relationship between TCMBs and injury severity in the first few hours after injury, and their natural evolution, is unknown. We obtained SWI scans in 10 healthy controls, and 13 patients scanned 3-24h following TBI and again at 7-15days. TCMBs were identified and total volume quantified for every lesion in each scan. TCMBs were present in 6 patients, all with more severe injury classified by GCS. No lesions were identified in patients with an initial GCS of 15. Improvement in GCS in the first 15days following injury was significantly associated with a reduction in microbleed volume over the same time-period. MRI is feasible in severely injured patients in the first 24h after trauma. Detection of TCMBs using SWI provides an objective early marker of injury severity following trauma. TCMBs revealed in this time frame, offer the potential to help determine the degree of injury, improving stratification, in order to identify patients who require admission to hospital, transfer to a specialist center, or an extended period of intubation on intensive care. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Cerebellar malformations alter regional cerebral development.

PubMed

Bolduc, Marie-Eve; Du Plessis, Adre J; Evans, Alan; Guizard, Nicolas; Zhang, Xun; Robertson, Richard L; Limperopoulos, Catherine

2011-12-01

The aim of this study was to compare total and regional cerebral volumes in children with isolated cerebellar malformations (CBMs) with those in typically developing children, and to examine the extent to which cerebellar volumetric reductions are associated with total and regional cerebral volumes. This is a case-control study of children diagnosed with isolated CBMs. Each child was matched on age and sex to two typically developing children. Using advanced three-dimensional volumetric magnetic resonance imaging, the cerebrum was segmented into tissue classes and partitioned into eight regions. Analysis of variance was used to compare cerebral volumes between children with CBMs and control children, and linear regressions to examine the impact of cerebellar volume reduction on cerebral volumes. Magnetic resonance imaging was performed at a mean age of 27 months in 20 children (10 males, 10 females) with CBMs and 40 typically developing children. Children with CBMs showed significantly smaller deep grey matter nuclei (p < 0.001), subgenual white matter (p = 0.03), midtemporal white matter (p = 0.02), and inferior occipital grey matter (p = 0.03) volumes than typically developing children. Greater cerebellar volumetric reduction in children with CBMs was associated with decreased total cerebral volume and deep grey matter nuclei (p = 0.02), subgenual white/grey matter (p = 0.001), midtemporal white (p = 0.02) and grey matter (p = 0.01), and parieto-occipital grey matter (p = 0.004). CBMs are associated with impaired regional cerebral growth, suggesting deactivation of principal cerebello-cerebral pathways. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

Early Evidence of Sepsis-Associated Hyperperfusion-A Study of Cerebral Blood Flow Measured With MRI Arterial Spin Labeling in Critically Ill Septic Patients and Control Subjects.

PubMed

Masse, Marie-Hélène; Richard, Marie Anne; D'Aragon, Frédérick; St-Arnaud, Charles; Mayette, Michael; Adhikari, Neill K J; Fraser, William; Carpentier, André; Palanchuck, Steven; Gauthier, David; Lanthier, Luc; Touchette, Matthieu; Lamontagne, Albert; Chénard, Jean; Mehta, Sangeeta; Sansoucy, Yanick; Croteau, Etienne; Lepage, Martin; Lamontagne, François

2018-04-06

Mechanisms underlying sepsis-associated encephalopathy remain unclear, but reduced cerebral blood flow, alone or in conjunction with altered autoregulation, is reported as a potential contributor. We compared cerebral blood flow of control subjects and vasopressor-dependent septic patients. Randomized crossover study. MRI with arterial spin labeling. Ten sedated septic patients on mechanical ventilation (four with controlled chronic hypertension) and 12 control subjects (six with controlled chronic hypertension) were enrolled. Mean ± SD ages were 61.4 ± 10.2 and 44.2 ± 12.8 years, respectively (p = 0.003). Mean Acute Physiology and Chronic Health Evaluation II score of septic patients at ICU admission was 27.7 ± 6.6. To assess the potential confounding effects of sedation and mean arterial pressure, we measured cerebral blood flow with and without sedation with propofol in control subjects and at a target mean arterial pressure of 65 mm Hg and greater than or equal to 75 mm Hg in septic patients. The sequence of sedation versus no sedation and mean arterial pressure targets were randomized. In septic patients, cerebral blood flow measured at a mean arterial pressure target of 65 mm Hg (40.4 ± 10.9 mL/100 g/min) was not different from cerebral blood flow measured at a mean arterial pressure target of greater than or equal to 75 mm Hg (41.3 ± 9.8 mL/100 g/min; p = 0.65). In control subjects, we observed no difference in cerebral blood flow measured without and with sedation (24.8 ± 4.2 vs 24.9 ± 5.9 mL/100 g/min; p = 0.93). We found no interaction between chronic hypertension and the effect of sedation or mean arterial pressure targets. Cerebral blood flow measured in sedated septic patients (mean arterial pressure target 65 mm Hg) was 62% higher than in sedated control subjects (p = 0.001). In septic patients, cerebral blood flow was higher than in sedated control subjects and did not vary with mean arterial pressure targets. Further research is required to

Neonatal cerebral sinovenous thrombosis: Two cases, two different gene polymorphisms and risk factors.

PubMed

Turan, Özden; Anuk-İnce, Deniz; Olcay, Lale; Sezer, Taner; Gülleroğlu, Kaan; Yılmaz-Çelik, Zerrin; Ecevit, Ayşe

2017-01-01

Turan Ö, Anuk-İnce D, Olcay L, Sezer T, Gülleroğlu K, Yılmaz-Çelik Z, Ecevit A. Neonatal cerebral sinovenous thrombosis: Two cases, two different gene polymorphisms and risk factors. Turk J Pediatr 2017; 59: 71-75. Cerebral sinovenous thrombosis (CSVT) is a rare disease in the neonatal period and also the greatest risk of neonatal mortality and morbidity. In this report, we presented two cases with CSVT and different risk factors. One of these cases had methylenetetrahydrofolate reductase (MTHFR) C677T homozygous polymorphism and the other case had both MTHFR A1298C homozygous polymorphism, plasminogen activator inhibitor-1 (PAI-1) 4G/ 5G polymorphism and elevated lipoprotein a. Early diagnosis and prompt initiation of therapy of neonatal CSVT may prevent neonatal mortality and poor long-term neurodevelopmental outcomes.

Effect of x-radiation to brain on cerebral glucose utilization in the rat.

PubMed

D'Aquino, S; Cicciarello, R; D'Avella, D; Mesiti, M; Albiero, F; Princi, P; Gagliardi, M E; Russi, E; D'Aquino, A

1990-01-01

We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of whole-brain x-radiation on local cerebral glucose utilization in the rat brain. Animals were exposed to conventional fractionation (200 +/- cGy/day given 5 days a week) to a total dose of 4000 cGy. Metabolic experiments were made 2 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased following irradiation. Statistically significant decreases in metabolic activity were observed in 13 of 27 brain regions studied. In general, brain areas with the highest basal metabolic rates showed the greatest percentage drop of glucose utilization. Post-irradiation metabolic alterations possibly provide an explanation for the syndrome of early delayed deterioration observed in humans after whole-brain radiotherapy.

Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

PubMed Central

2010-01-01

Background Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. Methods The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Results Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. Conclusions These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis. PMID:20955613

Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats.

PubMed

Liu, Zhenquan; Li, Pengtao; Zhao, Dan; Tang, Huiling; Guo, Jianyou

2010-10-19

Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis.

Optoacoustic mapping of cerebral blood oxygenation in humans

NASA Astrophysics Data System (ADS)

Petrov, Yuriy; Prough, Donald S.; Petrov, Irene Y.; Richardson, C. Joan; Fonseca, Rafael A.; Robertson, Claudia S.; Esenaliev, Rinat O.

2017-03-01

Noninvasive, transcranial mapping, monitoring, and imaging are highly important for detection and management of cerebral abnormalities and neuroscience research. Mapping, imaging, and monitoring of cerebral blood oxygenation are necessary for diagnostics and management of patients with traumatic brain injury, stroke, and other neurological conditions. We proposed to use optoacoustic technology for noninvasive, transcranial monitoring and imaging. In this work, we developed optoacoustic systems for mapping of cerebral blood oxygenation in humans and tested them in adults and neonates. The systems provide noninvasive, transcranial optoacoustic measurements in the transmission (forward) and reflection (backward) modes in the near infrared spectral range. Novel, ultra-sensitive probes were built for detection of optoacoustic signals and measurement of blood oxygenation in neonates and adults. Cerebral oxygenation was measured at different lateral sites from the superior sagittal sinus (SSS), a large central cerebral vein, located immediately beneath the midline of the human skull. In neonates, cerebral oxygenation was measured through open anterior and posterior fontanelles. Optoacoustic signal detection at different locations allowed for mapping of cerebral blood oxygenation. Our future studies will be focused on 3D mapping of cerebral blood oxygenation.

Endothelin-1-induced focal cerebral ischemia in the growth hormone/IGF-1 deficient Lewis Dwarf rat.

PubMed

Yan, Han; Mitschelen, Matthew; Toth, Peter; Ashpole, Nicole M; Farley, Julie A; Hodges, Erik L; Warrington, Junie P; Han, Song; Fung, Kar-Ming; Csiszar, Anna; Ungvari, Zoltan; Sonntag, William E

2014-11-01

Aging is a major risk factor for cerebrovascular disease. Growth hormone (GH) and its anabolic mediator, insulin-like growth factor (IGF)-1, decrease with advancing age and this decline has been shown to promote vascular dysfunction. In addition, lower GH/IGF-1 levels are associated with higher stroke mortality in humans. These results suggest that decreased GH/IGF-1 level is an important factor in increased risk of cerebrovascular diseases. This study was designed to assess whether GH/IGF-1-deficiency influences the outcome of cerebral ischemia. We found that endothelin-1-induced middle cerebral artery occlusion resulted in a modest but nonsignificant decrease in cerebral infarct size in GH/IGF-1 deficient dw/dw rats compared with control heterozygous littermates and dw/dw rats with early-life GH treatment. Expression of endothelin receptors and endothelin-1-induced constriction of the middle cerebral arteries were similar in the three experimental groups. Interestingly, dw/dw rats exhibited reduced brain edema and less astrocytic infiltration compared with their heterozygous littermates and this effect was reversed by GH-treatment. Because reactive astrocytes are critical for the regulation of poststroke inflammatory processes, maintenance of the blood-brain barrier and neural repair, further studies are warranted to determine the long-term functional consequences of decreased astrocytic activation in GH/IGF-1 deficient animals after cerebral ischemia. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

Cerebral intolerance during flow arrested carotid angioplasty.

PubMed

St Louis, Myron; Park, Brian D; Dahn, Michael; Bozeman, Patricia

2012-01-01

The use of flow arrest as a means of providing cerebral protection during carotid angioplasty offers the advantages of improved efficiency of debris removal and the ability to provide protection under unfavorable (tortuous) anatomic circumstances. However, in contrast to the filtration methods of cerebral protection, this modality requires complete interruption of antegrade carotid artery flow during balloon angioplasty and stent deployment. We report our experience with 9 patients undergoing carotid angioplasty with the Mo.Ma device, which utilizes common and external carotid artery balloon occlusion during the angioplasty procedure. We assessed the clinical outcomes and intraprocedural hemodynamic data. The average duration of carotid occlusion was 8.3 minutes. Of the 9 patients, 2 patients (22%) experienced cerebral intolerance. No stroke occurred in this patient cohort. There appeared to be a poor relationship between procedure intolerance and the presence of significant contralateral stenosis or low carotid back pressure. Furthermore, the incidence of postangioplasty hypotension was not clearly related to cerebral intolerance. Carotid angioplasty with stenting can be safely conducted with flow arrest as an alternative to filter-type cerebral protection devices. However, because cerebral intolerance is not an infrequent occurrence with this approach, clinicians must be cognizant of management strategies for transient cerebral intolerance.

Neuroevolutional Approach to Cerebral Palsy and Speech.

ERIC Educational Resources Information Center

Mysak, Edward D.

Intended for cerebral palsy specialists, the book emphasizes the contribution that a neuroevolutional approach to therapy can make to habilitation goals of the child with cerebral palsy and applies the basic principles of the Bobath approach to therapy. The first section discusses cerebral palsy as a reflection of disturbed neuro-ontogenisis and…

Soluble guanylate cyclase activation during ischemic injury in mice protects against postischemic inflammation at the mitochondrial level.

PubMed

Wang, Derek Z; Jones, Allan W; Wang, Walter Z; Wang, Meifang; Korthuis, Ronald J

2016-05-01

The aim was to determine whether treatment with BAY 60-2770, a selective activator of oxidized soluble guanylate cyclase (sGC), near the end of an ischemic event would prevent postischemic inflammation and mitochondrial dysfunction in wild-type (WT) and heme oxygenase-1 KO (HO-1(-/-)) mice. This protocol prevented increases in leukocyte rolling (LR) and adhesion (LA) to intestinal venules along with elevated TNFα and circulating neutrophil levels that accompany ischemia-reperfusion (I/R) in both animal models. We further hypothesized that a component of BAY 60-2770 treatment involves maintenance of mitochondrial membrane integrity during I/R. Measurements on isolated enterocytes of calcein fluorescence (mitochondrial permeability) and JC-1 fluorescence ratio (mitochondrial membrane potential) were reduced by I/R, indicating formation of mitochondrial permeability transition pores (mPTP). These effects were abrogated by BAY 60-2770 as well as cyclosporin A and SB-216763, which prevented mPTP opening and inhibited glycogen synthase kinase-3β (GSK-3β), respectively. Western blots of WT and HO-1(-/-) enterocytes indicated that GSK-3β phosphorylation on Ser(9) (inhibitory site) was reduced by half following I/R alone (increased GSK-3β activity) and increased by one-third (reduced GSK-3β activity) following BAY 60-2770. Other investigators have associated phosphorylation of the GSK-3β substrate cyclophilin D (pCyPD) with mPTP formation. We observed a 60% increase in pCyPD after I/R, whereas BAY 60-2770 treatment of sham and I/R groups reduced pCyPD by about 20%. In conclusion, selective activation of oxidized sGC of WT and HO-1(-/-) during ischemia protects against I/R-induced inflammation and preserves mucosal integrity in part by reducing pCyPD production and mPTP formation. Copyright © 2016 the American Physiological Society.

Antecedent hydrogen sulfide elicits an anti-inflammatory phenotype in postischemic murine small intestine: role of BK channels

PubMed Central

Zuidema, Mozow Y.; Yang, Yan; Wang, Meifang; Kalogeris, Theodore; Liu, Yajun; Meininger, Cynthia J.; Hill, Michael A.; Davis, Michael J.

2010-01-01

The objectives of this study were to determine the role of calcium-activated, small (SK), intermediate (IK), and large (BK) conductance potassium channels in initiating the development of an anti-inflammatory phenotype elicited by preconditioning with an exogenous hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS). Intravital microscopy was used to visualize rolling and firmly adherent leukocytes in vessels of the small intestine of mice preconditioned with NaHS (in the absence and presence of SK, IK, and BK channel inhibitors, apamin, TRAM-34, and paxilline, respectively) or SK/IK (NS-309) or BK channel activators (NS-1619) 24 h before ischemia-reperfusion (I/R). I/R induced marked increases in leukocyte rolling and adhesion, effects that were largely abolished by preconditioning with NaHS, NS-309, or NS-1619. The postischemic anti-inflammatory effects of NaHS-induced preconditioning were mitigated by BKB channel inhibitor treatment coincident with NaHS, but not by apamin or TRAM-34, 24 h before I/R. Confocal imaging and immunohistochemistry were used to demonstrate the presence of BKα subunit staining in both endothelial and vascular smooth muscle cells of isolated, pressurized mesenteric venules. Using patch-clamp techniques, we found that BK channels in cultured endothelial cells were activated after exposure to NaHS. Bath application of the same concentration of NaHS used in preconditioning protocols led to a rapid increase in a whole cell K+ current; specifically, the component of K+ current blocked by the selective BK channel antagonist iberiotoxin. The activation of BK current by NaHS could also be demonstrated in single channel recording mode where it was independent of a change in intracellular Ca+ concentration. Our data are consistent with the concept that H2S induces the development of an anti-adhesive state in I/R in part mediated by a BK channel-dependent mechanism. PMID:20833953

Cerebral versus Ocular Visual Impairment: The Impact on Developmental Neuroplasticity.

PubMed

Martín, Maria B C; Santos-Lozano, Alejandro; Martín-Hernández, Juan; López-Miguel, Alberto; Maldonado, Miguel; Baladrón, Carlos; Bauer, Corinna M; Merabet, Lotfi B

2016-01-01

Cortical/cerebral visual impairment (CVI) is clinically defined as significant visual dysfunction caused by injury to visual pathways and structures occurring during early perinatal development. Depending on the location and extent of damage, children with CVI often present with a myriad of visual deficits including decreased visual acuity and impaired visual field function. Most striking, however, are impairments in visual processing and attention which have a significant impact on learning, development, and independence. Within the educational arena, current evidence suggests that strategies designed for individuals with ocular visual impairment are not effective in the case of CVI. We propose that this variance may be related to differences in compensatory neuroplasticity related to the type of visual impairment, as well as underlying alterations in brain structural connectivity. We discuss the etiology and nature of visual impairments related to CVI, and how advanced neuroimaging techniques (i.e., diffusion-based imaging) may help uncover differences between ocular and cerebral causes of visual dysfunction. Revealing these differences may help in developing future strategies for the education and rehabilitation of individuals living with visual impairment.

Cerebral versus Ocular Visual Impairment: The Impact on Developmental Neuroplasticity

PubMed Central

Martín, Maria B. C.; Santos-Lozano, Alejandro; Martín-Hernández, Juan; López-Miguel, Alberto; Maldonado, Miguel; Baladrón, Carlos; Bauer, Corinna M.; Merabet, Lotfi B.

2016-01-01

Cortical/cerebral visual impairment (CVI) is clinically defined as significant visual dysfunction caused by injury to visual pathways and structures occurring during early perinatal development. Depending on the location and extent of damage, children with CVI often present with a myriad of visual deficits including decreased visual acuity and impaired visual field function. Most striking, however, are impairments in visual processing and attention which have a significant impact on learning, development, and independence. Within the educational arena, current evidence suggests that strategies designed for individuals with ocular visual impairment are not effective in the case of CVI. We propose that this variance may be related to differences in compensatory neuroplasticity related to the type of visual impairment, as well as underlying alterations in brain structural connectivity. We discuss the etiology and nature of visual impairments related to CVI, and how advanced neuroimaging techniques (i.e., diffusion-based imaging) may help uncover differences between ocular and cerebral causes of visual dysfunction. Revealing these differences may help in developing future strategies for the education and rehabilitation of individuals living with visual impairment. PMID:28082927

Mullen scales of early learning: the utility in assessing children diagnosed with autism spectrum disorders, cerebral palsy, and epilepsy.

PubMed

Burns, Thomas G; King, Tricia Z; Spencer, Katherine S

2013-01-01

A group of 47 patients diagnosed with neurodevelopmental disorders were compared to 47 age-, gender-, and racially matched typically developing children to examine the frequency of impairment across domains of the Mullen Scales of Early Learning (MSEL). The MSEL is a comprehensive measure of cognitive functioning designed to assess infants and preschool children between the ages of birth to 68 months. In the neurodevelopmental group, the sample was composed of children 2 to 4 years of age who were diagnosed with autism spectrum disorders (ASD; n = 19), cerebral palsy (CP; n = 14), and epilepsy (EPI; n = 14). A sample of 47 matched controls, taken from the normative sample of the MSEL, was used as a comparison group. Each one of the clinical groups comprising the neurodevelopmental sample demonstrated statistically significant delays across domains relative to the respective matched control group (p < .001). Children failed to demonstrate a "signature" profile for a diagnosis of ASD, CP, or EPI. The clinical sensitivity of the MSEL and the need for obtaining specific intervention services for children diagnosed with these conditions are presented. Finally, these results are discussed within the context of the clinical sensitivity of the MSEL in working with these clinical populations.

Dopamine D2 receptor status assessed by IBZM SPECT - A sensitive indicator for cerebral hypoxia

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

Tatsch, K.; Schwarz, J.; Welz, A.

1995-05-01

The striatum is highly sensitive to tissue hypoxia. Thus, it may be suggested that cerebral hypoxia could affect the integrity of the striatal receptor system. Purpose of the current SPECT investigations with IBZM was to evaluate whether hypoxic conditions cause detectable changes in the D2 receptor status. 25 controls and 30 pts with history of cerebral hypoxia (resuscitation after cardiac arrest: n=19, CABG surgery under cardiopulmonary bypass: n=11) were investigated with SPECT 2h p.i. of 185 MBq I-123 IBZM. For semiquant, evaluation transverse slices corrected for attenuation were used to calculate striatal to frontal cortex (S/FC) ratios. In 13/19 ptsmore » with cerebral hypoxia due to cardiac arrest IBZM binding was severely reduced after successful resuscitation. 7 died, 5 were in a vegetative state, 1 remained severely disabled. In 6/19 S/FC ratios were normal/mildly reduced, 2 of them had a good outcome, 4 were moderatley disabled. In pts with CABG IBZM binding was preoperatively normal. After hypoxia due to cardiac surgery striatal S/FC ratios decreased slightly, persisting on this level even 6 months after surgery. Neuropsychological/psychiatric testing showed only minor or transient changes in this group of patients. The striatal D2 receptor status seems to be a sensitive indicator for cerebral hypoxia. After hypoxia due to cardiac arrest IBZM results well correlate (in contrast to morphological or SEP findings) with the clinical outcome and thus may serve as early predictor of the individual prognosis. The moderate decline in IBZM binding following CABG surgery suggests mild cerebral hypoxia despite of protective hypothermia. Sensitively indicating cerebral hypoxia changes in the D2 receptor status assessed by IBZM SPECT may serve as a valuable diagnostic tool for testing neuroprotective drugs or modified surgical techniques.« less

Monitoring cerebral oxygen saturation during cardiopulmonary bypass using near-infrared spectroscopy: the relationships with body temperature and perfusion rate.

PubMed

Teng, Yichao; Ding, Haishu; Gong, Qingcheng; Jia, Zaishen; Huang, Lan

2006-01-01

During cardiopulmonary bypass (CPB) because of weak arterial pulsation, near-IR spectroscopy (NIRS) is almost the only available method to monitor cerebral oxygenation noninvasively. Our group develops a NIRS oximeter to monitor regional cerebral oxygenation especially its oxygen saturation (rScO2). To achieve optimal coupling between the sensor and human brain, the distances between the light source and the detectors on it are properly chosen. The oximeter is calibrated by blood gas analysis, and the results indicate that its algorithm is little influenced by either background absorption or overlying tissue. We used it to measure the rScO2 of 15 patients during CPB. It is shown that rScO2 is negatively correlated with body temperature and positively with perfusion rate. There are two critical stages during CPB when rScO2 might be relatively low: one is the low-perfusion-rate stage, the other is the early rewarming stage. During cooling, the changes of total hemoglobin concentration (C(tHb)) compared with its original value is also monitored. It is shown that C(tHb) decreases to a small extent, which may mainly reflect cerebral vasoconstriction induced by cooling. All these results indicate that NIRS can be used to monitor cerebral oxygenation to protect cerebral tissue during CPB.

Cerebral responses and role of the prefrontal cortex in conditioned pain modulation: an fMRI study in healthy subjects

PubMed Central

Bogdanov, Volodymyr B.; Viganò, Alessandro; Noirhomme, Quentin; Bogdanova, Olena V.; Guy, Nathalie; Laureys, Steven; Renshaw, Perry F.; Dallel, Radhouane; Phillips, Christophe; Schoenen, Jean

2017-01-01

The mechanisms underlying conditioned pain modulation (CPM) are multifaceted. We searched for a link between individual differences in prefrontal cortex activity during multi-trial heterotopic noxious cold conditioning and modulation of the cerebral response to phasic heat pain. In 24 healthy female subjects, we conditioned laser heat stimuli to the left hand by applying alternatively ice-cold or lukewarm compresses to the right foot. We compared pain ratings with cerebral fMRI BOLD responses. We also analyzed the relation between CPM and BOLD changes produced by the heterotopic cold conditioning itself, as well as the impact of anxiety and habituation of cold-pain ratings. Specific cerebral activation was identified in precuneus and left posterior insula/SII, respectively, during early and sustained phases of cold application. During cold conditioning, laser pain decreased (n = 7), increased (n = 10) or stayed unchanged (n = 7). At the individual level, the psychophysical effect was directly proportional to the cold-induced modulation of the laser-induced BOLD response in left posterior insula/SII. The latter correlated with the BOLD response recorded 80 s earlier during the initial 10-s phase of cold application in anterior cingulate, orbitofrontal and lateral prefrontal cortices. High anxiety and habituation of cold pain were associated with greater laser heat-induced pain during heterotopic cold stimulation. The habituation was also linked to the early cold-induced orbitofrontal responses. We conclude that individual differences in conditioned pain modulation are related to different levels of prefrontal cortical activation by the early part of the conditioning stimulus, possibly due to different levels in trait anxiety. PMID:25461267

[Indication for exercise therapy in infancy in the prevention of childhood cerebral palsy].

PubMed

Weber, S

1983-01-01

As in physiotherapy of cerebral palsy early therapy is desired, if possible even in early infancy, a period, when a safe diagnosis does not yet exist, infants at risk have to be identified. The resulting difficulties in early diagnosis and inevitability of treating a considerable number of not affected infants are discussed. The most common methods of physiotherapy are briefly described and evaluated critically concerning possible side effects as well. Superiority in effectivity improving motor efficiency of one method over another cannot be proven. It is shown, however, that in the Vojta method adverse psychological side effects cannot be excluded. Therefore, physiotherapy being a purely prophylactic and not a therapeutic procedure in the multitude of cases should be considered in ordering and selecting a particular method and the one according to Bobath should be favoured.

A reappraisal of retrograde cerebral perfusion

PubMed Central

2013-01-01

Brain protection during aortic arch surgery by perfusing cold oxygenated blood into the superior vena cava was first reported by Lemole et al. In 1990 Ueda and associates first described the routine use of continuous retrograde cerebral perfusion (RCP) in thoracic aortic surgery for the purpose of cerebral protection during the interval of obligatory interruption of anterograde cerebral flow. The beneficial effects of RCP may be its ability to sustain brain hypothermia during hypothermic circulatory arrest (HCA) and removal of embolic material from the arterial circulation of the brain. RCP can offer effective brain protection during HCA for about 40 to 60 minutes. Animal experiments revealed that RCP provided inadequate cerebral perfusion and that neurological recovery was improved with selective antegrade cerebral perfusion (ACP), however, both RCP and ACP provide comparable clinical outcomes regarding both the mortality and stroke rates by risk-adjusted and case-matched comparative study. RCP still remains a valuable adjunct for brain protection during aortic arch repair in particular pathologies and patients. PMID:23977600

Cerebral palsy

MedlinePlus

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Effects of rapamycin on cerebral oxygen supply and consumption during reperfusion after cerebral ischemia.

PubMed

Chi, O Z; Barsoum, S; Vega-Cotto, N M; Jacinto, E; Liu, X; Mellender, S J; Weiss, H R

2016-03-01

Activation of the mammalian target of rapamycin (mTOR) leads to cell growth and survival. We tested the hypothesis that inhibition of mTOR would increase infarct size and decrease microregional O2 supply/consumption balance after cerebral ischemia-reperfusion. This was tested in isoflurane-anesthetized rats with middle cerebral artery blockade for 1h and reperfusion for 2h with and without rapamycin (20mg/kg once daily for two days prior to ischemia). Regional cerebral blood flow was determined using a C(14)-iodoantipyrine autoradiographic technique. Regional small-vessel arterial and venous oxygen saturations were determined microspectrophotometrically. The control ischemic-reperfused cortex had a similar blood flow and O2 consumption to the contralateral cortex. However, microregional O2 supply/consumption balance was significantly reduced in the ischemic-reperfused cortex. Rapamycin significantly increased cerebral O2 consumption and further reduced O2 supply/consumption balance in the reperfused area. This was associated with an increased cortical infarct size (13.5±0.8% control vs. 21.5±0.9% rapamycin). We also found that ischemia-reperfusion increased AKT and S6K1 phosphorylation, while rapamycin decreased this phosphorylation in both the control and ischemic-reperfused cortex. This suggests that mTOR is important for not only cell survival, but also for the control of oxygen balance after cerebral ischemia-reperfusion. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Early-life Sodium-exposure Unmasks Susceptibility to Stroke in hyperlipidemic-hypertensive Tg[hCETP]25-Rats

PubMed Central

Decano, Julius L.; Viereck, Jason C.; McKee, Ann C.; Hamilton, James A.; Ruiz-Opazo, Nelson; Herrera, Victoria L.M.

2009-01-01

Background Early-life risk factor exposure increases aortic atherosclerosis and blood pressure in humans and animal models, however, limited insight has been made into end-organ complications. Methods and Results We investigated the effects of early-life Na-exposure (0.23% vs 0.4%NaCl regular-rat chow) on vascular disease outcomes using the inbred, transgenic[hCETP]25 Dahl salt-sensitive hypertensive rat model of male-predominant coronary atherosclerosis, Tg25. Rather than the expected increased coronary heart disease, fetal 0.4%Na-exposure (≤2g-Na/2000cal/diet/day) induced adult-onset stroke in both sexes (ANOVA P<0.0001), with earlier stroke-onset in Tg25-females. Analysis of later onsets of 0.4%Na-exposure resulted in decreased stroke-risk and later stroke-onsets, despite longer 0.4%Na-exposure durations, indicating increasing risk with earlier onsets of 0.4%Na-exposure. Histological analysis of stroke+rat brains revealed cerebral cortical hemorrhagic infarctions, microhemorrhages, neuronal ischemia, microvascular injury. Ex-vivo MRI of stroke+ rat brains detected cerebral hemorrhages, microhemorrhages and ischemia with middle cerebral artery-distribution, and cerebellar non-involvement. Ultrasound micro-imaging detected carotid artery disease. Pre-stroke analysis detected neuronal ischemia, and decreased mass of isolated cerebral, but not cerebellar, microvessels. Conclusions Early-life Na-exposure exacerbated hypertension and unmasked stroke susceptibility with greater female vulnerability in hypertensive-hyperlipidemic Tg25-rats. The reproducible modeling in Tg25sp rats of carotid artery disease, cerebral hemorrhagic-infarctions, neuronal ischemia, microhemorrhages, and microvascular alterations suggests a pathogenic spectrum with causal interrelationships. This “mixed-stroke” spectrum could represent paradigms of ischemic-hemorrhagic transformation, and/or a microangiopathic basis for the association of ischemic-lesions, microhemorrhages, and strokes

Sonographic assessment of normal and abnormal patterns of fetal cerebral lamination.

PubMed

Pugash, D; Hendson, G; Dunham, C P; Dewar, K; Money, D M; Prayer, D

2012-12-01

Prenatal development of the brain is characterized by gestational age-specific changes in the laminar structure of the brain parenchyma before 30 gestational weeks. Cerebral lamination patterns of normal fetal brain development have been described histologically, by postmortem in-vitro magnetic resonance imaging (MRI) and by in-vivo fetal MRI. The purpose of this study was to evaluate the sonographic appearance of laminar organization of the cerebral wall in normal and abnormal brain development. This was a retrospective study of ultrasound findings in 92 normal fetuses and 68 fetuses with abnormal cerebral lamination patterns for gestational age, at 17-38 weeks' gestation. We investigated the visibility of the subplate zone relative to the intermediate zone and correlated characteristic sonographic findings of cerebral lamination with gestational age in order to evaluate transient structures. In the normal cohort, the subplate zone-intermediate zone interface was identified as early as 17 weeks, and in all 57 fetuses examined up to 28 weeks. In all of these fetuses, the subplate zone appeared anechoic and the intermediate zone appeared homogeneously more echogenic than did the subplate zone. In the 22 fetuses between 28 and 34 weeks, there was a transition period when lamination disappeared in a variable fashion. The subplate zone-intermediate zone interface was not identified in any fetus after 34 weeks (n=13). There were three patterns of abnormal cerebral lamination: (1) no normal laminar pattern before 28 weeks (n=32), in association with severe ventriculomegaly, diffuse ischemia, microcephaly, teratogen exposure or lissencephaly; (2) focal disruption of lamination before 28 weeks (n=24), associated with hemorrhage, porencephaly, stroke, migrational abnormalities, thanatophoric dysplasia, meningomyelocele or encephalocele; (3) increased prominence and echogenicity of the intermediate zone before 28 weeks and/or persistence of a laminar pattern beyond 33 weeks

Early physiotherapy ad modum Vojta or Bobath in infants with suspected neuromotor disturbance.

PubMed

d'Avignon, M; Norén, L; Arman, T

1981-08-01

Thirty children with early signs of cerebral neuromotor disturbances according to "Vojta criteria" were followed until the age of thirty-three months to six years. Twelve children were treated with early physiotherapy according to Bobath, ten children were treated according to Vojta and eight constituted a control group. The infants tended for early physical therapy were divided by random into two different groups. The neonatal risk factors, however, proved to be unevenly distributed among the infants in the Vojta- and the Bobath-treated groups - the latter being more heavily burdened in this respect. Vojta has claimed that his method of early physiotherapy is able to prevent the development of cerebral palsy (cp) of "uncomplicated" (but not of "complicated") type. At follow-up we found one child out of nine with "uncomplicated" cp in the Vojta group against three out of six in the Bobath- and two out of six in the control group. These differences, however, are not statistically significant. Further detailed studies with greater groups of children seem necessary to help us to clarify these problems. The psychological aspects of early physiotherapy should be thoroughly considered and this is particularly important in connection with the Vojta method.

Cerebral perfusion and oxygenation after the Norwood procedure: comparison of right ventricle-pulmonary artery conduit with modified Blalock-Taussig shunt.

PubMed

Kussman, Barry D; Gauvreau, Kimberlee; DiNardo, James A; Newburger, Jane W; Mackie, Andrew S; Booth, Karen L; del Nido, Pedro J; Roth, Stephen J; Laussen, Peter C

2007-03-01

The proposed physiologic advantage of the modified Norwood procedure using a right ventricle-pulmonary artery conduit to supply pulmonary blood flow, compared with a modified Blalock-Taussig shunt, is reduced runoff from the systemic-to-pulmonary circulation during diastole, resulting in a higher diastolic blood pressure and improved systemic perfusion. We hypothesized that the modified Norwood procedure is associated with improved cerebral perfusion and oxygenation. Transcranial Doppler sonography and near-infrared spectroscopy were performed in neonates undergoing the Norwood procedure with either a modified Blalock-Taussig shunt (n = 14) or right ventricle-pulmonary artery conduit (n = 13). Diastolic blood pressure was significantly higher in the right ventricle-pulmonary artery group at 6 hours after bypass (46 +/- 7 vs 40 +/- 4 mm Hg; P = .03), on postoperative day 1 (45 +/- 6 vs 37 +/- 5 mm Hg; P = .002), and on postoperative day 2 (46 +/- 7 vs 37 +/- 4 mm Hg; P = .001). Cerebral diastolic blood flow velocity did not differ significantly between groups at any time point or over time, but cerebral systolic blood flow velocity was higher over time in the Blalock-Taussig group (P = .01). No significant differences in regional cerebral oxygen saturation were found between groups at baseline or after bypass. Blood flow velocities and cerebral oxygen saturation did not differ significantly according to use of regional low-flow perfusion. The higher diastolic blood pressure after the modified Norwood procedure is not associated with higher cerebral blood flow velocities or regional cerebral oxygen saturation. This may imply an equal vulnerability to the cerebral injury associated with hemodynamic instability in the early postoperative period.

[Amyotrophy and neuronal depopulation of cerebral origin].

PubMed

Serratrice, G; Gastaut, J L; Pellissier, J F; Baret, J; Roux, H; Cartouzou, G

1975-03-01

Amyotrophy of cerebral origin was analyzed in 12 hemiplegics by means of comparative histological, histoenzymological, histographic and biochemical analysis of biopsies carried out in symmetrical zones. In the 6 cases in which atrophy predominated on the paralyzed side, it occurred early, the deficiency affecting the upper limb in particular and the sensory disturbance being irregular. Attempted numeration of the motor units remaining, according to the "incremential" method of stimulation, suggests a numerical reduction on the hemipelgic side. Despite reservations and general criticisms of this method, its comparative value, although approximate, must be acknowledged. However, although amyotrophy presumes a transsynaptic change in trophic function to have taken place in the peripheral neurone, neuronal depopulation--if one accepts it--cannot be other than functional.

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.

Management of delayed cerebral ischemia after subarachnoid hemorrhage.

PubMed

Francoeur, Charles L; Mayer, Stephan A

2016-10-14

For patients who survive the initial bleeding event of a ruptured brain aneurysm, delayed cerebral ischemia (DCI) is one of the most important causes of mortality and poor neurological outcome. New insights in the last decade have led to an important paradigm shift in the understanding of DCI pathogenesis. Large-vessel cerebral vasospasm has been challenged as the sole causal mechanism; new hypotheses now focus on the early brain injury, microcirculatory dysfunction, impaired autoregulation, and spreading depolarization. Prevention of DCI primarily relies on nimodipine administration and optimization of blood volume and cardiac performance. Neurological monitoring is essential for early DCI detection and intervention. Serial clinical examination combined with intermittent transcranial Doppler ultrasonography and CT angiography (with or without perfusion) is the most commonly used monitoring paradigm, and usually suffices in good grade patients. By contrast, poor grade patients (WFNS grades 4 and 5) require more advanced monitoring because stupor and coma reduce sensitivity to the effects of ischemia. Greater reliance on CT perfusion imaging, continuous electroencephalography, and invasive brain multimodality monitoring are potential strategies to improve situational awareness as it relates to detecting DCI. Pharmacologically-induced hypertension combined with volume is the established first-line therapy for DCI; a good clinical response with reversal of the presenting deficit occurs in 70 % of patients. Medically refractory DCI, defined as failure to respond adequately to these measures, should trigger step-wise escalation of rescue therapy. Level 1 rescue therapy consists of cardiac output optimization, hemoglobin optimization, and endovascular intervention, including angioplasty and intra-arterial vasodilator infusion. In highly refractory cases, level 2 rescue therapies are also considered, none of which have been validated. This review provides an overview of

A Study on Cerebral Embolism in Mitral Stenosis

PubMed Central

Kwon, Osun; Kim, Myung Hwan; Kim, Kwon Sam; Bae, Jong Hoa; Kim, Myung Shick; Song, Jung Sang

1986-01-01

To evaluate the significance of episodes of cerebral embolism in patients with mitral valve disease in Korea, 128 patients with echocardiographic diagnosis of mitral valve disease were examined. Among these, 82 patients had predominant mitral stenosis. The clinical features of 82 patients with mitral stenosis have been reviewed to elucidate the factors favoring cerebral embolism which occurred in 19 patients, i.e., incidence of 23.2%.Atrial fibrillation was present in 16 of 19 patients with cerebral embolism (84.2%). Cerebral embolic episodes occurred in 16 of 47 patients with atrial fibrillation (34.0%).The mean age (55.3 ± 12.1 years) of patients without cerebral embolism was significantly older than that (43.2 ± 14.6 years) of patients without cerebral embolism (P<0.005).There was no significant relationship between the incidence of embolism and sex, left atrial thrombi, left atrium/aortic root diameter, mitral valvular orifice area, mitral valvular vegetation or calcification, left ventricular enddiastolic dimension or left ventricular posterior wall thickness. Cerebral embolism is common in patients with mitral stenosis in our country. The presence of atrial fibrillation and low cardiac output increase the attack of cerebral emboli whereas the severity of mitral stenosis, as judged by valve area, may not correlate with the occurrence of emboli. The best treatment for cerebral embolism is prevention. Therefore, we believe that more vigorous treatment of patients with mitral valve disease who are old or associated with atrial fibrillation as well as previous embolic history is indicated. PMID:15759378

A Virtual Environment to Improve the Detection of Oral-Facial Malfunction in Children with Cerebral Palsy.

PubMed

Martín-Ruiz, María-Luisa; Máximo-Bocanegra, Nuria; Luna-Oliva, Laura

2016-03-26

The importance of an early rehabilitation process in children with cerebral palsy (CP) is widely recognized. On the one hand, new and useful treatment tools such as rehabilitation systems based on interactive technologies have appeared for rehabilitation of gross motor movements. On the other hand, from the therapeutic point of view, performing rehabilitation exercises with the facial muscles can improve the swallowing process, the facial expression through the management of muscles in the face, and even the speech of children with cerebral palsy. However, it is difficult to find interactive games to improve the detection and evaluation of oral-facial musculature dysfunctions in children with CP. This paper describes a framework based on strategies developed for interactive serious games that is created both for typically developed children and children with disabilities. Four interactive games are the core of a Virtual Environment called SONRIE. This paper demonstrates the benefits of SONRIE to monitor children's oral-facial difficulties. The next steps will focus on the validation of SONRIE to carry out the rehabilitation process of oral-facial musculature in children with cerebral palsy.

Brain region-selective mechanisms contribute to the progression of cerebral alterations in acute liver failure in rats.

PubMed

Cauli, Omar; López-Larrubia, Pilar; Rodrigo, Regina; Agusti, Ana; Boix, Jordi; Nieto-Charques, Laura; Cerdán, Sebastián; Felipo, Vicente

2011-02-01

Patients with acute liver failure (ALF) often die of intracranial pressure (IP) and cerebral herniation. Main contributors to increased IP are ammonia, glutamine, edema, and blood flow. The sequence of events and underlying mechanisms, as well as the temporal pattern, regional distribution, and contribution of each parameter to the progression of neurologic deterioration and IP, are unclear. We studied rats with ALF to follow the progression of changes in ammonia, glutamine, grade and type (vasogenic or cytotoxic) of edema, blood-brain barrier permeability, cerebral blood flow, and IP. We assessed whether the changes in these parameters were similar between frontal cortex and cerebellum and evaluated the presence, type, and progression of edema in 12 brain areas. ALF was induced by injection of galactosamine. The grade and type of edema was assessed by measuring the apparent diffusion coefficient by magnetic resonance imaging. Cerebral blood flow was measured by magnetic resonance and blood-brain barrier permeability by Evans blue-albumin extravasation. Increased IP arises from an early increase of blood-brain barrier permeability in certain areas (including cerebellum but not frontal cortex) followed by vasogenic edema. Ammonia and glutamine then increase progressively, leading to cytotoxic edema in many areas. Alterations in lactate and cerebral blood flow are later events that further increase IP. Different mechanisms in specific regions of the brain contribute, with different temporal patterns, to the progression of cerebral alterations and IP in ALF. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Duplicated middle cerebral artery

PubMed Central

Perez, Jesus; Machado, Calixto; Scherle, Claudio; Hierro, Daniel

2009-01-01

Duplicated middle cerebral artery (DMCA) is an anomalous vessel arising from the internal carotid artery. The incidence DMCA is relatively law, and an association between this anomaly and cerebral aneurysms has been documented. There is a controversy whether DMCA may have perforating arteries. This is an important fact to consider in aneurysm surgery. We report the case of a 34-year-old black woman who suffered a subarachnoid hemorrhage and the angiography a left DMCA, and an aneurysm in an inferior branch of the main MCA. The DMCA and the MCA had perforating arteries. The aneurysm was clipped without complications. The observation of perforating arteries in our patient confirms that the DMCA may have perforating arteries. This is very important to be considered in cerebral aneurysms surgery. Moreover, the DMCA may potentially serve as a collateral blood supply to the MCA territory in cases of MCA occlusion. PMID:22140405

Cerebral specialization. [greater performance efficiency for certain mental abilities or processes by one cerebral hemisphere over another

NASA Technical Reports Server (NTRS)

Morris, Robin D.; Hopkins, William D.; Rumbaugh, Duane M.

1991-01-01

The concept of greater performance efficiency for certain mental abilities or processes in one cerebral hemisphere rather than the other is referred to as 'cerebral lateralization'. The experimental paradigm for lateralization research involves the study of patients with one damaged hemisphere, which prevents their performance of a certain task or function; this approach, however, presents many difficulties in extrapolating to brain function in normal patients. Attention is presently given to gender differences in lateralization, cerebral asymmetries in other species, and the evolutionary bases of hemispheric specialization.

The hypothalamus and pituitary in cerebral gigantism. A clinicopathologic and immunocytochemical study.

PubMed

Whitaker, M D; Scheithauer, B W; Hayles, A B; Okazaki, H

1985-07-01

Cerebral gigantism, or Sotos' disease, is a rare disorder of unknown cause characterized by the early onset of excessive growth, acromegalic features, and some degree of mental retardation. Although several endocrinologic abnormalities have been described in such patients, none has been specific or sufficient to explain the clinical features. Our report of the endocrinologic and pathologic aspects in a young woman with Sotos' disease includes the first microanatomic study of the hypothalamus and immunocytochemical examination of the pituitary gland in this disorder.

Early neuroprotection after cardiac arrest.

PubMed

Dell'anna, Antonio M; Scolletta, Sabino; Donadello, Katia; Taccone, Fabio S

2014-06-01

Many efforts have been made in the last decades to improve outcome in patients who are successfully resuscitated from sudden cardiac arrest. Despite some advances, postanoxic encephalopathy remains the most common cause of death among those patients and several investigations have focused on early neuroprotection in this setting. Therapeutic hypothermia is the only strategy able to provide effective neuroprotection in clinical practice. Experimental studies showed that therapeutic hypothermia was even more effective when it was started immediately after the ischemic event. In human studies, the use of prehospital hypothermia was able to reduce the time to target temperature but did not result in higher survival rate or neurological recovery in patients with out-of-hospital cardiac arrest, when compared with standard in-hospital therapeutic hypothermia. Thus, intra-arrest hypothermia (i.e., initiated during cardiopulmonary resuscitation) may be a valid alternative to improve the effectiveness of therapeutic hypothermia in this setting; however, more clinical data are needed to demonstrate any potential benefit of such intervention on neurological outcome. Together with cooling, early hemodynamic optimization should be considered to improve cerebral perfusion in cardiac arrest patients and minimize any secondary brain injury. Nevertheless, only scarce data are available on the impact of early hemodynamic optimization on the development of organ dysfunction and neurological recovery in such patients. Some new protective strategies, including inhaled gases (i.e., xenon, argon, nitric oxide) and intravenous drugs (i.e., erythropoietin) are emerging in experimental studies as promising tools to improve neuroprotection, especially when combined with therapeutic hypothermia. Early cooling may contribute to enhance neuroprotection after cardiac arrest. Hemodynamic optimization is mandatory to avoid cerebral hypoperfusion in this setting. The combination of such

Modelling of Cerebral Tuberculosis: Hope for Continuous Research in Solving the Enigma of the Bottom Billion’s Disease

PubMed Central

Hernández Pando, Rogelio

2011-01-01

Cerebral tuberculosis is a severe type of extrapulmonary disease that is highly predominant in children. It is thought that meningeal tuberculosis, the most common form of cerebral tuberculosis, begins with respiratory infection followed by early haematogenous dissemination to extrapulmonary sites involving the brain. Host genetic susceptibility factors and specific mycobacteria substrains could be involved in the development of this serious form of tuberculosis. In this editorial the different animal models of cerebral tuberculosis are commented, highlighting a recently described murine model in which BALB/c mice were infected by the intratracheal route with clinical isolates, which exhibited rapid dissemination and brain infection. These strains were isolated from the cerebrospinal fluid of patients with meningeal tuberculosis; they showed specific genotype and induced a peculiar immune response in the infected brain. This model could be a useful tool to study host and bacilli factors involved in the pathogenesis of the most severe form of tuberculosis. PMID:22135568

Cerebral Palsy

MedlinePlus

... her strength. Recommend on Facebook Tweet Share Compartir Cerebral palsy (CP) is a group of disorders that affect a ... ability to move and maintain balance and posture. CP is the most common motor disability in childhood. ...

Early Detection and Quantification of Cerebral Venous Thrombosis by Magnetic Resonance Black Blood Thrombus Imaging (MRBTI)

PubMed Central

Yang, Qi; Duan, Jiangang; Fan, Zhaoyang; Qu, Xiaofeng; Xie, Yibin; Nguyen, Christopher; Du, Xiangying; Bi, Xiaoming; Li, Kuncheng; Ji, Xunming; Li, Debiao

2015-01-01

Background and Purpose Early diagnosis of cerebral venous and sinus thrombosis (CVT) is currently a major clinical challenge. We proposed a novel MR black-blood thrombus imaging technique(MRBTI) for detection and quantification of CVT. Methods MRBTI was performed on 23 patients with proven CVT and 24 patients with negative CVT confirmed by conventional imaging techniques. Patients were divided into two groups based on the duration of clinical onset: ≤ 7 days (group 1); between 7 and 30 days (group 2). Signal-to-noise ratio (SNR) was calculated for the detected thrombus and contrast-to-noise ratio (CNR) was measured between thrombus and lumen, and also between thrombus and brain tisssue. The feasibility of using MRBTI for thrombus volume measurement was explored and total thrombus volume was calculated for each patient. Results In 23 patients with proven CVT, MRBTI correctly identified 113 out of 116 segments with a sensitivity of 97.4%. Thrombus SNR was 153±57 and 261±95 for group 1(n=10) and group 2(n=13), respectively(P<0.01). Thrombus to lumen CNR was 149±57 and 256±94 for group 1 and group 2. Thrombus to brain tissue CNR was 41±36 and 120±63 (P<0.01), respectively. Quantification of thrombus volume was successfully conducted in all patients with CVT, and mean volume of thrombus was 10.5±6.9cc. Conclusions The current findings support that with effectively suppressed blood signal, MRBTI allows selective visualization of thrombus as opposed to indirect detection of venous flow perturbation and can be used as a promising first line diagnostic imaging tool. PMID:26670082

Predictors of early infection in cerebral ischemic stroke.

PubMed

Ashour, Wmr; Al-Anwar, A D; Kamel, A E; Aidaros, M A

2016-01-01

Infection is the most common complication of stroke. To determine the risk factors and predictors of post-stroke infection (PSI), which developed within 7 days from the onset of acute ischemic stroke. The study included 60 ischemic stroke patients admitted in the Neurology Department of Zagazig University, Egypt, who were subdivided into: [Non Stroke Associated Infection group (nSAI); 30 patients having stroke without any criteria of infection within 7 days from the onset and Stroke Associated Infection group (SAI); 30 patients having stroke with respiratory tract infection (RTI) or urinary tract infection within 7 days], in addition to 30 healthy sex and age-matching subjects as control. All the patients had a detailed history taking, thorough clinical general and neurological examination, laboratory tests (Urine analysis & urine culture, blood sugar, lipid profile and serum tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10), a chest radiography to assess RTI and brain computed tomography (CT) to exclude the hemorrhagic stroke and to confirm the ischemic stroke. SAI patients were found to be significantly older with higher baseline blood glucose level. Also the number of patients with tube feeding, lower conscious level, more stroke severity and more large size infarcts were significantly higher in SAI patients. There was a significant elevation in the IL-10, a significant decrease in the TNF-α and a significant decrease in the TNF-α/ IL-10 ratio, in the SAI group. The baseline serum level of IL-10 ≥ 14.5 pg/ ml and size of infarct area > 3.5 cm3 were found to be the independent predictors of PSI. Patients with older age, tube feeding, lower conscious level, worse baseline stroke severity, large cerebral infarcts in CT scan, and increased IL-10 serum level were more susceptible to infection. The baseline serum level of IL-10 ≥ 14.5 pg/ ml and the size of infarct area > 3.5 cm3 were the independent predictors of PSI.

Predictors of early infection in cerebral ischemic stroke

PubMed Central

Ashour, WMR; Al-Anwar, AD; Kamel, AE; Aidaros, MA

2016-01-01

Background: Infection is the most common complication of stroke. Aim: To determine the risk factors and predictors of post-stroke infection (PSI), which developed within 7 days from the onset of acute ischemic stroke. Subjects: The study included 60 ischemic stroke patients admitted in the Neurology Department of Zagazig University, Egypt, who were subdivided into: [Non Stroke Associated Infection group (nSAI); 30 patients having stroke without any criteria of infection within 7 days from the onset and Stroke Associated Infection group (SAI); 30 patients having stroke with respiratory tract infection (RTI) or urinary tract infection within 7 days], in addition to 30 healthy sex and age-matching subjects as control. Methods: All the patients had a detailed history taking, thorough clinical general and neurological examination, laboratory tests (Urine analysis & urine culture, blood sugar, lipid profile and serum tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10), a chest radiography to assess RTI and brain computed tomography (CT) to exclude the hemorrhagic stroke and to confirm the ischemic stroke. Results: SAI patients were found to be significantly older with higher baseline blood glucose level. Also the number of patients with tube feeding, lower conscious level, more stroke severity and more large size infarcts were significantly higher in SAI patients. There was a significant elevation in the IL-10, a significant decrease in the TNF-α and a significant decrease in the TNF-α/ IL-10 ratio, in the SAI group. The baseline serum level of IL-10 ≥ 14.5 pg/ ml and size of infarct area > 3.5 cm3 were found to be the independent predictors of PSI. Conclusion: Patients with older age, tube feeding, lower conscious level, worse baseline stroke severity, large cerebral infarcts in CT scan, and increased IL-10 serum level were more susceptible to infection. The baseline serum level of IL-10 ≥ 14.5 pg/ ml and the size of infarct area > 3.5 cm3 were the

Effects of ischemic stroke on dynamics of cerebral autoregulation

NASA Astrophysics Data System (ADS)

Chen, Zhi; Ivanov, Plamen Ch; Hu, Kun; Stanley, Eugene; Novak, Vera

2004-03-01

Cerebral vasoregulation involves several complex mechanisms adapting blood flow to fluctuations of systemic blood pressure (BP). Autonomic BP and metabolic vasoregulation are impaired after stroke and cerebral blood flow depends on systemic BP. To probe the mechanisms of cerebral autoregulation we study levels of nonlinear synchronization between cerebral blood flow velocity (BFV) and peripheral BP. We quantify the instantaneous phase of each signal employing analytic signal approach and Hilbert transform. As a marker of synchronization, we introduce a measure of cross-correlation between the instantaneous phase increments of the BFV and BP signals at different time lags. We have studied 12 subjects with minor chronic ischemic stroke and 11 matched normotensive controls (age<65years). BFV and BP of these subjects are continuously recorded during supine baseline, head-up tilt, hyperventilation and CO2 rebreathing. For control subjects we find significant synchronization between cerebral BFV and peripheral BP only for short time lags of up to 5-6 seconds, suggesting a rapid return to a steady cerebral blood flow after initial blood pressure perturbations. In contrast, for stroke subjects BFV/BP we find enhanced synchronization over longer time lags of up to 20 seconds, suggesting entrainment of cerebral blood flow velocity by slow vasomotor rhythms. These findings suggest that cerebral vasoregulation is impaired and cerebral blood flow follows the fluctuations of systemic BP in a synchronous manner. Our analysis shows that cerebral autoregulation is impaired in 10 out of the 12 stroke subjects, which is typically difficult to diagnose with conventional methods. Thus, our novel synchronization approach offers a new tool sensitive for evaluation of changes in the dynamics of cerebral autoregulation under stroke.

Effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with pre-existing cerebral ischemia.

PubMed

Xu, Lili; Hu, Zhiyong; Shen, Jianjun; McQuillan, Patrick M

2015-04-01

Cerebral injury caused by hypoperfusion during the perioperative period is one of the main causes of disability and death in patients after major surgery. No effective protective or preventative strategies have been identified. This study was designed to evaluate the effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with known, pre-existing cerebral ischemia. Sixty ASA (American Society of Anesthesiologists) II-III patients, diagnosed with vertebral artery ischemia by transcranial Doppler ultrasonography (TCD), and scheduled for elective total hip replacement surgery, were enrolled in the study. They were randomly allocated to receive either 1mg/kg Ginkgo biloba extract (G group n=30) or normal saline (D group n=30) after induction of anesthesia. Blood samples were collected from radial artery and jugular venous bulb catheters for blood gas analysis and determination of glucose and lactate concentrations preoperatively, before surgical incision, at the end of surgery, and on post-op day 1. Arterial O2 content (CaO2), jugular venous O2 content (CjvO2), arteriovenous O2 content difference (Da-jvO2), cerebral oxygen extraction rate (CEO2), and arteriovenous glucose and lactate content differences (Da-jvGlu and Da-jvLac) were calculated. There were no significant differences in CaO2 or Da-jvGlu during surgery between groups (p>0.05). However, the Ginkgo group had higher CjvO2, internal jugular venous oxygen saturation (SjvO2) and lower CEO2, Da-jvO2 and Da-jvLac at the end of surgery (T2) and on post-op day 1 (T3) than those in the control group (p<0.05). Ginkgo biloba extract can improve cerebral oxygen supply, decrease cerebral oxygen extraction rate and consumption, and help maintain the balance between cerebral oxygen supply and consumption. It has no effect, however, on cerebral glucose metabolism in elderly patients with known, pre-existing cerebral ischemia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Group characteristics of children with cerebral and spinal cord tumours.

PubMed

Stewart, A M; Lennox, E L; Sanders, B M

1973-12-01

A study of 2072 children who developed cerebral or spinal cord tumours of varying degrees of malignancy before 15 years of age has shown that there is equally good representation of fatal and non-fatal cases in official registrations. Attack rates are higher for boys than girls and the prognosis is better for girls than boys. The risk of an early death is negatively correlated with age at diagnosis, and the risk of a late death shows the opposite relationship. These observations and a relatively high incidence of hindbrain tumours are suggestive of an embryonic origin for most of the cases.

Changes in intracranial pressure gradients between the cerebral hemispheres in patients with intracerebral hematomas in one cerebral hemisphere.

PubMed

Qiu, Wusi; Jiang, Qizhou; Xiao, Guoming; Wang, Weiming; Shen, Hong

2014-01-01

Intracranial-pressure (ICP) monitoring is useful for patients with increased ICP following hemorrhagic stroke. In this study, the changes in pressure gradients between the two cerebral hemispheres were investigated after hemorrhagic stroke of one side, and after a craniotomy. Twenty-four patients with acute cerebral hemorrhages and intracerebral hematomas who exhibited mass effect and midline shift to the contralateral side on computed tomography were selected for this study. After admission, both sides of the cranium were drilled, and optical fiber sensors were implanted to monitor the brain parenchyma pressure (BPP) in both cerebral hemispheres. All patients underwent surgical hematoma evacuations. The preoperative and postoperative BPP data from both cerebral hemispheres were collected at various time points and compared pairwise. There were statistically significant differences (P < 0.01) in the preoperative BPP values between the two hemispheres at three different time points. Differences in the BPP values between the two hemispheres at the time of surgery, and 24 and 48 h after surgery, were not statistically significant (P > 0.05). The posteroperative BPPs of both hemispheres were statistically significantly lower than preoperative recordings. BPP sensors should be applied to the injured cerebral hemisphere, because this becomes the source of increased ICP. Hematoma evacuation surgery effectively decreases ICP and eliminates pressure gradients between the two cerebral hemispheres, consequently enabling brain shift correction.

Cerebral glucose deficiency versus oxygen deficiency in neonatal encephalopathy.

PubMed

Rudolph, A M

2018-04-24

Hypoxic-ischemic encephalopathy (HIE) in newborn infants is generally considered to result from decreased arterial oxygen content or cerebral blood flow. Cerebral injury similar to that of HIE has been noted with hypoglycemia. Studies in fetal lambs have shown that ventilation with 3% oxygen did not change cerebral blood flow, but ventilation with 100% oxygen resulted in marked reduction in cerebral blood flow, glucose delivery and glucose consumption. Blood glucose concentration falls markedly after birth; this, associated with the fall in cerebral blood flow, greatly reduces glucose supply to the brain. In preterm infants, blood glucose levels tend to be very low. Also persistent patency of the ductus arteriosus may reduce cerebral flow in diastole, thus exaggerating the decrease in glucose supply. I propose that glycopenic-ischemic encephalopathy is a more appropriate term for the cerebral insult. We should consider more aggressive management of the low blood glucose concentrations in the neonate, and particularly in preterm infants. Administration of high levels of oxygen in inspired air should be avoided to reduce the enhancement of cerebral vasoconstriction and decreased flow that normally occurs after birth.

The evolution of invasive cerebral vasospasm treatment in patients with spontaneous subarachnoid hemorrhage and delayed cerebral ischemia-continuous selective intracarotid nimodipine therapy in awake patients without sedation.

PubMed

Paľa, Andrej; Schneider, Max; Brand, Christine; Pedro, Maria Teresa; Özpeynirci, Yigit; Schmitz, Bernd; Wirtz, Christian Rainer; Kapapa, Thomas; König, Ralph; Braun, Michael

2018-05-26

Cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) are major factors that limit good outcome in patients with spontaneous subarachnoid hemorrhage (SAH). Continuous therapy with intra-arterial calcium channel blockers has been introduced as a new step in the invasive treatment cascade of CV and DCI. Sedation is routinely necessary for this procedure. We report about the feasibility to apply this therapy in awake compliant patients without intubation and sedation. Out of 67 patients with invasive endovascular treatment of cerebral vasospasm due to spontaneous SAH, 5 patients underwent continuous superselective intracarotid nimodipine therapy without intubation and sedation. Complications, neurological improvement, and outcome at discharge were summarized. Very good outcome was achieved in all 5 patients. The Barthel scale was 100 and the modified Rankin scale 0-1 in all cases at discharge. We found no severe complications and excellent neurological monitoring was possible in all cases due to patients' alert status. Symptoms of DCI resolved within 24 h in all 5 cases. We could demonstrate the feasibility and safety of selective intracarotid arterial nimodipine treatment in awake, compliant patients with spontaneous SAH and symptomatic CV and DCI. Using this method, an excellent monitoring of neurological function as well as early detection of other complications is possible. It might be an important step in the risk reduction of invasive CV therapy to improve the outcome with CV and DCI after SAH in selected patients.

Human cerebral autoregulation before, during and after spaceflight.

PubMed

Iwasaki, Ken-ichi; Levine, Benjamin D; Zhang, Rong; Zuckerman, Julie H; Pawelczyk, James A; Diedrich, André; Ertl, Andrew C; Cox, James F; Cooke, William H; Giller, Cole A; Ray, Chester A; Lane, Lynda D; Buckey, Jay C; Baisch, Friedhelm J; Eckberg, Dwain L; Robertson, David; Biaggioni, Italo; Blomqvist, C Gunnar

2007-03-15

Exposure to microgravity alters the distribution of body fluids and the degree of distension of cranial blood vessels, and these changes in turn may provoke structural remodelling and altered cerebral autoregulation. Impaired cerebral autoregulation has been documented following weightlessness simulated by head-down bed rest in humans, and is proposed as a mechanism responsible for postspaceflight orthostatic intolerance. In this study, we tested the hypothesis that spaceflight impairs cerebral autoregulation. We studied six astronauts approximately 72 and 23 days before, after 1 and 2 weeks in space (n = 4), on landing day, and 1 day after the 16 day Neurolab space shuttle mission. Beat-by-beat changes of photoplethysmographic mean arterial pressure and transcranial Doppler middle cerebral artery blood flow velocity were measured during 5 min of spontaneous breathing, 30 mmHg lower body suction to simulate standing in space, and 10 min of 60 deg passive upright tilt on Earth. Dynamic cerebral autoregulation was quantified by analysis of the transfer function between spontaneous changes of mean arterial pressure and cerebral artery blood flow velocity, in the very low- (0.02-0.07 Hz), low- (0.07-0.20 Hz) and high-frequency (0.20-0.35 Hz) ranges. Resting middle cerebral artery blood flow velocity did not change significantly from preflight values during or after spaceflight. Reductions of cerebral blood flow velocity during lower body suction were significant before spaceflight (P < 0.05, repeated measures ANOVA), but not during or after spaceflight. Absolute and percentage reductions of mean (+/- s.e.m.) cerebral blood flow velocity after 10 min upright tilt were smaller after than before spaceflight (absolute, -4 +/- 3 cm s(-1) after versus -14 +/- 3 cm s(-1) before, P = 0.001; and percentage, -8.0 +/- 4.8% after versus -24.8 +/- 4.4% before, P < 0.05), consistent with improved rather than impaired cerebral blood flow regulation. Low-frequency gain decreased

CT and MRI Findings in Cerebral Aspergilloma.

PubMed

Gärtner, Friederike; Forstenpointner, Julia; Ertl-Wagner, Birgit; Hooshmand, Babak; Riedel, Christian; Jansen, Olav

2017-11-20

Purpose  Invasive aspergillosis usually affects immunocompromised patients. It carries a high risk of morbidity and mortality and usually has a nonspecific clinical presentation. Early diagnosis is essential in order to start effective treatment and improve clinical outcome. Materials and Methods  In a retrospective search of the PACS databases from two medical centers, we identified 9 patients with histologically proven cerebral aspergilloma. We systematically analyzed CT and MRI imaging findings to identify typical imaging appearances of cerebral aspergilloma. Results  CT did not show a typical appearance of the aspergillomas. In 100 % (9/9) there was a rim-attenuated diffusion restriction on MRI imaging. Multiple hypointense layers in the aspergillus wall, especially on the internal side, were detected in 100 % on T2-weighted imaging (9/9). Aspergillomas were T1-hypointense in 66 % of cases (6/9) and partly T1-hyperintense in 33 % (3/9). In 78 % (7/9) of cases, a rim-attenuated diffusion restriction was detected after contrast agent application. Conclusion  Nine cases were identified. Whereas CT features were less typical, we observed the following imaging features on MRI: A strong, rim-attenuated diffusion restriction (9/9); onion layer-like hypointense zones, in particular in the innermost part of the abscess wall on T2-weighted images (9/9). Enhancement of the lesion border was present in the majority of the cases (7/9). Key points   · There are typical MRI imaging features of aspergillomas.. · However, these findings could be affected by the immune status of the patient.. · Swift identification of aspergilloma imaging patterns is essential to allow for adequate therapeutic decision making.. Citation Format · Gärtner F, Forstenpointner J, Ertl-Wagner B et al. CT and MRI Findings in Cerebral Aspergilloma. Fortschr Röntgenstr 2017; DOI: 10.1055/s-0043-120766. © Georg Thieme Verlag KG Stuttgart · New York.

Comparison between antegrade and retrograde cerebral perfusion or profound hypothermia as brain protection strategies during repair of type A aortic dissection.

PubMed

Stamou, Sotiris C; Rausch, Laura A; Kouchoukos, Nicholas T; Lobdell, Kevin W; Khabbaz, Kamal; Murphy, Edward; Hagberg, Robert C

2016-07-01

The goal of this study was to compare early postoperative outcomes and actuarial-free survival between patients who underwent repair of acute type A aortic dissection by the method of cerebral perfusion used. A total of 324 patients from five academic medical centers underwent repair of acute type A aortic dissection between January 2000 and December 2010. Of those, antegrade cerebral perfusion (ACP) was used for 84 patients, retrograde cerebral perfusion (RCP) was used for 55 patients, and deep hypothermic circulatory arrest (DHCA) was used for 184 patients during repair. Major morbidity, operative mortality, and 5-year actuarial survival were compared between groups. Multivariate logistic regression was used to determine predictors of operative mortality and Cox Regression hazard ratios were calculated to determine the predictors of long term mortality. Operative mortality was not influenced by the type of cerebral protection (19% for ACP, 14.5% for RCP and 19.1% for DHCA, P=0.729). In multivariable logistic regression analysis, hemodynamic instability [odds ratio (OR) =19.6, 95% confidence intervals (CI), 0.102-0.414, P<0.001] and CPB time >200 min(OR =4.7, 95% CI, 1.962-1.072, P=0.029) emerged as independent predictors of operative mortality. Actuarial 5-year survival was unchanged by cerebral protection modality (48.8% for ACP, 61.8% for RCP and 66.8% for no cerebral protection, log-rank P=0.844). During surgical repair of type A aortic dissection, ACP, RCP or DHCA are safe strategies for cerebral protection in selected patients with type A aortic dissection.

The active metabolite of prasugrel, R-138727, improves cerebral blood flow and reduces cerebral infarction and neurologic deficits in a non-human primate model of acute ischaemic stroke.

PubMed

Sugidachi, Atsuhiro; Mizuno, Makoto; Ohno, Kousaku; Jakubowski, Joseph A; Tomizawa, Atsuyuki

2016-10-05

Previously, we showed preventive effects of prasugrel, a P2Y12 antagonist, in a non-human primate model of thrombotic middle cerebral artery occlusion (MCAO); however, it remains unclear if P2Y12 inhibition after MCAO reduces cerebral injury and dysfunction. Here we investigated the effects of R-138727, the major active metabolite of prasugrel, on ex vivo platelet aggregation at 5min, 15min, 60min, and 24h after administration to non-human primates (n=3). A single intravenous dose of R-138727 (0.03-0.3mg/kg) resulted in significant and sustained dose-related effects on platelets for up to 24h. R-138727 was administered 1h after MCAO induction, and its effects on thrombosis, cerebral infarction, and neurological deficits were determined (n=8-10). R-138727 (0.3mg/kg) significantly increased total patency rate of the MCA (P=0.0211). Although there was no effect on the patency rate before R-138727 dosing (P=0.3975), it increased 1h after dosing (P=0.0114). R-138727 significantly reduced total ischaemic infarction volumes (P=0.0147), including those of basal ganglia (P=0.0028), white matter (P=0.0393), and haemorrhagic infarction (P=0.0235). Additionally, treatment with R-138727 reduced overall neurological deficits (P=0.0019), including the subcategories of consciousness (P=0.0042), sensory system (P=0.0045), motor system (P=0.0079) and musculoskeletal coordination (P=0.0082). These findings support the possible utility of P2Y12 inhibition during early-onset MCAO to limit the progression and degree of cerebral ischaemia and infarction and also associated neurological deficits. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

[The Cerebral Function Monitor. Description, functioning and interpretation principles].

PubMed

Roujas, F; Bertrand, C; Hrouda, P; Laborit, G; Lang, G; Rivet, P

1979-01-01

The Monitor of Cerebral Function enables continuous monitoring of the cerebral electrical activity and this over long periods due to the slow recording speeds. The cerebral electrical signals picked up by the electrodes attached to the scalp are registered in the form of a curve which fluctuates to a greater or lesser extent depending on the recording speed. The examination of the height of the curve with respect to zero and its amplitude indicates the voltage of the cerebral activity and yields information regarding polymorphism. It is thus possible to monitor variations in cerebral activity over a prolonged period during anaesthesia as well as during the revival phase with the Monitor of Cerebral Function, the electroencephalogram being reserved as an aid to precise diagnosis and for localization and close scruting of the anomalies.

Decreased cerebral perfusion in Duchenne muscular dystrophy patients.

PubMed

Doorenweerd, Nathalie; Dumas, Eve M; Ghariq, Eidrees; Schmid, Sophie; Straathof, Chiara S M; Roest, Arno A W; Wokke, Beatrijs H; van Zwet, Erik W; Webb, Andrew G; Hendriksen, Jos G M; van Buchem, Mark A; Verschuuren, Jan J G M; Asllani, Iris; Niks, Erik H; van Osch, Matthias J P; Kan, Hermien E

2017-01-01

Duchenne muscular dystrophy is caused by dystrophin gene mutations which lead to the absence of the protein dystrophin. A significant proportion of patients suffer from learning and behavioural disabilities, in addition to muscle weakness. We have previously shown that these patients have a smaller total brain and grey matter volume, and altered white matter microstructure compared to healthy controls. Patients with more distal gene mutations, predicted to affect dystrophin isoforms Dp140 and Dp427, showed greater grey matter reduction. Now, we studied if cerebral blood flow in Duchenne muscular dystrophy patients is altered, since cerebral expression of dystrophin also occurs in vascular endothelial cells and astrocytes associated with cerebral vasculature. T1-weighted anatomical and pseudo-continuous arterial spin labeling cerebral blood flow images were obtained from 26 patients and 19 age-matched controls (ages 8-18 years) on a 3 tesla MRI scanner. Group comparisons of cerebral blood flow were made with and without correcting for grey matter volume using partial volume correction. Results showed that patients had a lower cerebral blood flow than controls (40.0 ± 6.4 and 47.8 ± 6.3 mL/100 g/min respectively, p = 0.0002). This reduction was independent of grey matter volume, suggesting that they are two different aspects of the pathophysiology. Cerebral blood flow was lowest in patients lacking Dp140. There was no difference in CBF between ambulant and non-ambulant patients. Only three patients showed a reduced left ventricular ejection fraction. No correlation between cerebral blood flow and age was found. Our results indicate that cerebral perfusion is reduced in Duchenne muscular dystrophy patients independent of the reduced grey matter volume. Copyright © 2016 Elsevier B.V. All rights reserved.

Cerebral toxoplasmosis in patients with acquired immune deficiency syndrome in the neurological emergency department of a tertiary hospital.

PubMed

de Oliveira, Gabriela Brito; da Silva, Maria Almerice Lopes; Wanderley, Leandro Batista; da Cunha Correia, Carolina; Ferreira, Eduardo Caetano Brandão; de Medeiros, Zulma Maria; Filho, José Luiz Lima; de Melo, Fábio Lopes; de Araújo, Paulo Sérgio Ramos; Santos, Alfredo Henrique Cecílio Marins

2016-11-01

Cerebral toxoplasmosis is the most common cause of space occupying brain lesion in patients with HIV/AIDS in Brazil. In the post-HAART era, it is responsible for high rates of morbidity and mortality worldwide. This study consists of a case series of 56 patients diagnosed with cerebral toxoplasmosis whose clinical features, brain imaging and cerebrospinal fluid aspects were analyzed. Cerebral toxoplasmosis led to the diagnosis of infection by the human immunodeficiency virus (HIV) in 27 (48.2%) of the patients, while 29 (51.2%) others already knew to be HIV seropositive. However, at the time of diagnosis of cerebral toxoplasmosis, only 9 (16.6%) reported being under antiretroviral therapy and 5 (8.9%) were receiving primary prophylaxis for toxoplasmosis. Headache, strength deficit and fever were the most frequent signs and symptoms throughout the study. Fifty-three patients showed changes consistent with toxoplasmosis in CT or MRI. Thirty-four (60.7%) CSF samples were positive in the indirect haemagglutination test and for the reaction of Toxoplasma gondii IgG ELISA, while 31 (55.4%) were positive in the direct haemagglutination test. Fifty (89.3%) patients underwent first-line treatment for toxoplasmosis. Cerebral toxoplasmosis is still a very relevant neurological disease in individuals with AIDS admitted to neurology emergency departments. Early diagnosis and initiation of empiric treatment and antiretroviral therapy are important for good prognosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Time-of-Flight MR Angiography for Detection of Cerebral Hyperperfusion Syndrome after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis in Moyamoya Disease.

PubMed

Sato, K; Yamada, M; Kuroda, H; Yamamoto, D; Asano, Y; Inoue, Y; Fujii, K; Kumabe, T

2016-07-01

Cerebral hyperperfusion syndrome is a potential complication of superficial temporal artery-MCA anastomosis for Moyamoya disease. In this study, we evaluated whether TOF-MRA could assess cerebral hyperperfusion syndrome after superficial temporal artery-MCA anastomosis for this disease. This retrospective study included patients with Moyamoya disease who underwent superficial temporal artery-MCA single anastomosis. TOF-MRA and SPECT were performed before and 1-6 days after anastomosis. Bilateral ROIs on the source image of TOF-MRA were manually placed directly on the parietal branch of the superficial temporal artery just after branching the frontal branch of the superficial temporal artery and on the contralateral superficial temporal artery on the same axial image, respectively. The change ratio of the maximum signal intensity of the superficial temporal artery on TOF-MRA was calculated by using the following formula: (Postoperative Ipsilateral/Postoperative Contralateral)/(Preoperative Ipsilateral/Preoperative Contralateral). Of 23 patients (26 sides) who underwent the operation, 5 sides showed cerebral hyperperfusion syndrome postoperatively. There was a significant difference in the change ratio of signal intensity on TOF-MRA observed between the cerebral hyperperfusion syndrome and non-cerebral hyperperfusion syndrome groups (cerebral hyperperfusion syndrome group: 1.88 ± 0.32; non-cerebral hyperperfusion syndrome group: 1.03 ± 0.20; P = .0009). The minimum ratio value for the cerebral hyperperfusion syndrome group was 1.63, and the maximum ratio value for the non-cerebral hyperperfusion syndrome group was 1.30. Thus, no overlap was observed between the 2 groups for the change ratio of signal intensity on TOF-MRA. Diagnosis of cerebral hyperperfusion syndrome is indicated by an increase in the change ratio of signal intensity on TOF-MRA by more than approximately 1.5 times the preoperative levels. © 2016 by American Journal of Neuroradiology.

Reversible cerebral vasoconstriction syndrome: a comprehensive update.

PubMed

Mehdi, Ali; Hajj-Ali, Rula A

2014-09-01

Reversible cerebral vasoconstriction syndrome (RCVS) is a clinico-radiological syndrome characterized by recurrent thunderclap headache, with or without neurologic symptoms, and reversible vasoconstriction of cerebral arteries. RCVS affects patients in various racial and ethnic groups and in all age groups, although most commonly in the fourth decade of life. Many conditions and exposures have been linked to RCVS, including vasoactive drugs and the peripartum period. Disturbance of the cerebral vascular tone is thought to contribute to the disease's pathophysiology. RCVS generally follows a monophasic course. Associated strokes and cerebral hemorrhages are not uncommon. In this review we will attempt to provide a comprehensive overview of RCVS, with emphasis on the controversies in the field and the newest findings in the reported literature.

Cerebral Autoregulation in Hypertension and Ischemic Stroke: A Mini Review

PubMed Central

Shekhar, Shashank; Liu, Ruen; Travis, Olivia K; Roman, Richard J; Fan, Fan

2017-01-01

Aging and chronic hypertension are associated with dysfunction in vascular smooth muscle, endothelial cells, and neurovascular coupling. These dysfunctions induce impaired myogenic response and cerebral autoregulation, which diminish the protection of cerebral arterioles to the cerebral microcirculation from elevated pressure in hypertension. Chronic hypertension promotes cerebral focal ischemia in response to reductions in blood pressure that are often seen in sedentary elderly patients on antihypertensive therapy. Cerebral autoregulatory dysfunction evokes Blood-Brain Barrier (BBB) leakage, allowing the circulating inflammatory factors to infiltrate the brain to activate glia. The impaired cerebral autoregulation-induced inflammatory and ischemic injury could cause neuronal cell death and synaptic dysfunction which promote cognitive deficits. In this brief review, we summarize the pathogenesis and signaling mechanisms of cerebral autoregulation in hypertension and ischemic stroke-induced cognitive deficits, and discuss our new targets including 20-Hydroxyeicosatetraenoic acid (20-HETE), Gamma-Adducin (Add3) and Matrix Metalloproteinase-9 (MMP-9) that may contribute to the altered cerebral vascular function. PMID:29333537

Cerebral Oximetry Monitoring to Maintain Normal Cerebral Oxygen Saturation during High-risk Cardiac Surgery: A Randomized Controlled Feasibility Trial.

PubMed

Deschamps, Alain; Hall, Richard; Grocott, Hilary; Mazer, C David; Choi, Peter T; Turgeon, Alexis F; de Medicis, Etienne; Bussières, Jean S; Hudson, Christopher; Syed, Summer; Seal, Doug; Herd, Stuart; Lambert, Jean; Denault, André; Deschamps, Alain; Mutch, Alan; Turgeon, Alexis; Denault, Andre; Todd, Andrea; Jerath, Angela; Fayad, Ashraf; Finnegan, Barry; Kent, Blaine; Kennedy, Brent; Cuthbertson, Brian H; Kavanagh, Brian; Warriner, Brian; MacAdams, Charles; Lehmann, Christian; Fudorow, Christine; Hudson, Christopher; McCartney, Colin; McIsaac, Dan; Dubois, Daniel; Campbell, David; Mazer, David; Neilpovitz, David; Rosen, David; Cheng, Davy; Drapeau, Dennis; Dillane, Derek; Tran, Diem; Mckeen, Dolores; Wijeysundera, Duminda; Jacobsohn, Eric; Couture, Etienne; de Medicis, Etienne; Alam, Fahad; Abdallah, Faraj; Ralley, Fiona E; Chung, Frances; Lellouche, Francois; Dobson, Gary; Germain, Genevieve; Djaiani, George; Gilron, Ian; Hare, Gregory; Bryson, Gregory; Clarke, Hance; McDonald, Heather; Roman-Smith, Helen; Grocott, Hilary; Yang, Homer; Douketis, James; Paul, James; Beaubien, Jean; Bussières, Jean; Pridham, Jeremy; Armstrong, J N; Parlow, Joel; Murkin, John; Gamble, Jonathan; Duttchen, Kaylene; Karkouti, Keyvan; Turner, Kim; Baghirzada, Leyla; Szabo, Linda; Lalu, Manoj; Wasowicz, Marcin; Bautista, Michael; Jacka, Michael; Murphy, Michael; Schmidt, Michael; Verret, Michaël; Perrault, Michel-Antoine; Beaudet, Nicolas; Buckley, Norman; Choi, Peter; MacDougall, Peter; Jones, Philip; Drolet, Pierre; Beaulieu, Pierre; Taneja, Ravi; Martin, Rene; Hall, Richard; George, Ronald; Chun, Rosa; McMullen, Sarah; Beattie, Scott; Sampson, Sonia; Choi, Stephen; Kowalski, Stephen; McCluskey, Stuart; Syed, Summer; Boet, Sylvain; Ramsay, Tim; Saha, Tarit; Mutter, Thomas; Chowdhury, Tumul; Uppal, Vishal; Mckay, William

2016-04-01

Cerebral oxygen desaturation during cardiac surgery has been associated with adverse perioperative outcomes. Before a large multicenter randomized controlled trial (RCT) on the impact of preventing desaturations on perioperative outcomes, the authors undertook a randomized prospective, parallel-arm, multicenter feasibility RCT to determine whether an intervention algorithm could prevent desaturations. Eight Canadian sites randomized 201 patients between April 2012 and October 2013. The primary outcome was the success rate of reversing cerebral desaturations below 10% relative to baseline in the intervention group. Anesthesiologists were blinded to the cerebral saturation values in the control group. Intensive care unit personnel were blinded to cerebral saturation values for both groups. Secondary outcomes included the area under the curve of cerebral desaturation load, enrolment rates, and a 30-day follow-up for adverse events. Cerebral desaturations occurred in 71 (70%) of the 102 intervention group patients and 56 (57%) of the 99 control group patients (P = 0.04). Reversal was successful in 69 (97%) of the intervention group patients. The mean cerebral desaturation load (SD) in the operating room was smaller for intervention group patients compared with control group patients (104 [217] %.min vs. 398 [869] %.min, mean difference, -294; 95% CI, -562 to -26; P = 0.03). This was also true in the intensive care unit (P = 0.02). There were no differences in adverse events between the groups. Study sites were successful in reversal of desaturation, patient recruitment, randomization, and follow-up in cardiac surgery, supporting the feasibility of conducting a large multicenter RCT.

[Acetabuloplasty in cerebral palsy patients].

PubMed

Schejbalová, A; Chládek, P

2007-12-01

Acetabuloplasty as an isolated surgical procedure is one of the options allowing for hip joint realignment in cerebral palsy patients. Also, it is often involved in combined techniques used for hip joint reconstruction. In the years 2004-2005, 20 cerebral palsy patients, aged from 4 to 13 years, were indicated for acetabuloplasty. The group included children with varying degrees of locomotor disability, ranging from inability even to crawl to ability to move without support (stages 2 to 7 on the Vojta scale). Clinical and X-ray findings were evaluated at 2 and 6 months after surgical treatment and then every 6 months of follow- up. The X-ray finding was described by means of CE angle (Wiberg) values and hip migration percentage. Of 21 hips (in 20 patients) treated by acetabuloplasty in our modification during the two years, one developed recurrent dorsal dislocation which was possible to deal with by conservative treatment. All hips pre-operatively categorized as group B or group C were post-operatively assessed as group A hips. Subsequent migration of the acetabulum occurred within a year in two patients with distinct original asymmetry. Surgery on bones comprising the hip joint in cerebral palsy patients is indicated according to the degree of lateral migration and changes in hip joint geometry involving the proximal femur or pelvis, or in combination with open reduction. Acetabuloplasty is indicated as an isolated procedure or as part of combined techniques leading to a better coverage of the hip joint. It is recommended for children up to 10 years of age, but also older ones, in whom the flexibility of child bones enables us to do without internal osteosynthesis. Acetabuloplasty is indicated as an isolated surgical procedure for hip joint subluxation in cerebral palsy children. It has no adverse effects on hip abductors that, in cerebral palsy patients, are 85 % insufficient. It improves hip joint symmetry and helps to avoid more demanding reconstructive or

Apparent diffusion coefficient evaluation for secondary changes in the cerebellum of rats after middle cerebral artery occlusion

PubMed Central

Yang, Yunjun; Gao, Lingyun; Fu, Jun; Zhang, Jun; Li, Yuxin; Yin, Bo; Chen, Weijian; Geng, Daoying

2013-01-01

Supratentorial cerebral infarction can cause functional inhibition of remote regions such as the cerebellum, which may be relevant to diaschisis. This phenomenon is often analyzed using positron emission tomography and single photon emission CT. However, these methods are expensive and radioactive. Thus, the present study quantified the changes of infarction core and remote regions after unilateral middle cerebral artery occlusion using apparent diffusion coefficient values. Diffusion-weighted imaging showed that the area of infarction core gradually increased to involve the cerebral cortex with increasing infarction time. Diffusion weighted imaging signals were initially increased and then stabilized by 24 hours. With increasing infarction time, the apparent diffusion coefficient value in the infarction core and remote bilateral cerebellum both gradually decreased, and then slightly increased 3–24 hours after infarction. Apparent diffusion coefficient values at remote regions (cerebellum) varied along with the change of supratentorial infarction core, suggesting that the phenomenon of diaschisis existed at the remote regions. Thus, apparent diffusion coefficient values and diffusion weighted imaging can be used to detect early diaschisis. PMID:25206615

Cerebral oxygenation in the beach chair position for shoulder surgery in regional anesthesia: impact on cerebral blood flow and neurobehavioral outcome.

PubMed

Aguirre, José A; Märzendorfer, Olivia; Brada, Muriel; Saporito, Andrea; Borgeat, Alain; Bühler, Philipp

2016-12-01

Beach chair position is considered a potential risk factor for central neurological events particularly if combined with low blood pressure. The aim of this study was to assess the impact of regional anesthesia on cerebral blood flow and neurobehavioral outcome. This is a prospective, assessor-blinded observational study evaluating patients in the beach chair position undergoing shoulder surgery under regional anesthesia. University hospital operating room. Forty patients with American Society of Anesthesiologists classes I-II physical status scheduled for elective shoulder surgery. Cerebral saturation and blood flow of the middle cerebral artery were measured prior to anesthesia and continued after beach chair positioning until discharge to the postanesthesia care unit. The anesthesiologist was blinded for these values. Controlled hypotension with systolic blood pressure≤100mm Hg was maintained during surgery. Neurobehavioral tests and values of regional cerebral saturation, bispectral index, the mean maximal blood flow of the middle cerebral artery, and invasive blood pressure were measured prior to regional anesthesia, and measurements were repeated after placement of the patient on the beach chair position and every 20 minutes thereafter until discharge to postanesthesia care unit. The neurobehavioral tests were repeated the day after surgery. The incidence of cerebral desaturation events was 5%. All patients had a significant blood pressure drop 5 minutes after beach chair positioning, measured at the heart as well as the acoustic meatus levels, when compared with baseline values (P<.05). There was no decrease in either the regional cerebral saturation (P=.136) or the maximal blood flow of the middle cerebral artery (P=.212) at the same time points. Some neurocognitive tests showed an impairment 24 hours after surgery (P<.001 for 2 of 3 tests). Beach chair position in patients undergoing regional anesthesia for shoulder surgery had no major impact on

The influence of systemic hemodynamics and oxygen transport on cerebral oxygen saturation in neonates after the Norwood procedure.

PubMed

Li, Jia; Zhang, Gencheng; Holtby, Helen; Guerguerian, Anne-Marie; Cai, Sally; Humpl, Tilman; Caldarone, Christopher A; Redington, Andrew N; Van Arsdell, Glen S

2008-01-01

Ischemic brain injury is an important morbidity in neonates after the Norwood procedure. Its relationship to systemic hemodynamic oxygen transport is poorly understood. Sixteen neonates undergoing the Norwood procedure were studied. Continuous cerebral oxygen saturation was measured by near-infrared spectroscopy. Continuous oxygen consumption was measured by respiratory mass spectrometry. Pulmonary and systemic blood flow, systemic vascular resistance, oxygen delivery, and oxygen extraction ratio were derived with measurements of arterial, and superior vena cava and pulmonary venous gases and pressures at 2- to 4-hour intervals during the first 72 hours in the intensive care unit. Mean cerebral oxygen saturation was 66% +/- 12% before the operation, reduced to 51% +/- 13% on arrival in the intensive care unit, and remained low during the first 8 hours; it increased to 56% +/- 9% at 72 hours, still significantly lower than the preoperative level (P < .05). Postoperatively, cerebral oxygen saturation was closely and positively correlated with systemic arterial pressure, arterial oxygen saturation, and arterial oxygen tension and negatively with oxygen extraction ratio (P < .0001 for all). Cerebral oxygen saturation was moderately and positively correlated with systemic blood flow and oxygen delivery (P < .0001 for both). It was weakly and positively correlated with pulmonary blood flow (P = .001) and hemoglobin (P = .02) and negatively correlated with systemic vascular resistance (P = .003). It was not correlated with oxygen consumption (P > .05). Cerebral oxygen saturation decreased significantly in neonates during the early postoperative period after the Norwood procedure and was significantly influenced by systemic hemodynamic and metabolic events. As such, hemodynamic interventions to modify systemic oxygen transport may provide further opportunities to reduce the risk of cerebral ischemia and improve neurodevelopmental outcomes.

Cerebral infarction in association with Ecstasy abuse.

PubMed

Manchanda, S; Connolly, M J

1993-11-01

A previously fit 35 year old man presented with a right hemiparesis and dysphasia 36 hours after abuse of Ecstasy (3,4-methylenedioxymethamphetamine). Computerized axial tomography scan demonstrated an extensive acute left cerebral infarction and carotid digital subtraction angiogram, 2 days after admission, revealed left middle cerebral artery occlusion. There were no other known risk factors and all other investigations were negative. The patient made a partial recovery. We propose an association between Ecstasy abuse and cerebral infarction.

Regional cerebral blood flow changes associated with focal electrically administered seizure therapy (FEAST).

PubMed

Chahine, George; Short, Baron; Spicer, Ken; Schmidt, Matthew; Burns, Carol; Atoui, Mia; George, Mark S; Sackeim, Harold A; Nahas, Ziad

2014-01-01

Use of electroconvulsive therapy (ECT) is limited by cognitive disturbance. Focal electrically-administered seizure therapy (FEAST) is designed to initiate focal seizures in the prefrontal cortex. To date, no studies have documented the effects of FEAST on regional cerebral blood flow (rCBF). A 72 year old depressed man underwent three single photon emission computed tomography (SPECT) scans to capture the onset and resolution of seizures triggered with right unilateral FEAST. We used Bioimage Suite for within-subject statistical analyses of perfusion differences ictally and post-ictally compared with the baseline scan. Early ictal increases in regional cerebral blood flow (rCBF) were limited to the right prefrontal cortex. Post-ictally, perfusion was reduced in bilateral frontal and occipital cortices and increased in left motor and precuneus cortex. FEAST appears to triggers focal onsets of seizure activity in the right prefrontal cortex with subsequent generalization. Future studies are needed on a larger sample. Copyright © 2014 Elsevier Inc. All rights reserved.

Acute effect of coffee drinking on dynamic cerebral autoregulation.

PubMed

Sasaki, Hiroyuki; Hirasawa, Ai; Washio, Takuro; Ogoh, Shigehiko

2016-05-01

Drinking coffee causes caffeine-induced physiological alterations such as increases in arterial blood pressure, sympathetic nerve activity, cerebral vasoconstriction, etc., and these physiological alterations may be associated with a reduced risk of cerebral vascular disease. However, the effect of coffee drinking on dynamic cerebral blood flow (CBF) regulation remains unclear. The aim of this study was to test our hypothesis that coffee drinking enhances dynamic cerebral autoregulation. Twelve healthy young subjects participated in the present study. After a 5 min baseline measurement in a semi-recumbent position on the hospital bed, each subject drank water (CON) as a placebo condition or coffee beverage (Coffee INT). Arterial blood pressure and middle cerebral artery blood velocity (MCAv) were measured continuously throughout the experiment. At 30 min after the intake of either water or coffee, dynamic cerebral autoregulation was examined using a thigh cuffs occlusion and release technique. Each condition was randomly performed on a different day. Under Coffee INT condition, mean arterial blood pressure was increased (P = 0.01) and mean MCAv was decreased (P = 0.01) from the baseline. The rate of regulation (RoR), as an index of dynamic cerebral autoregulation, during coffee condition was significantly higher than that during CON (P = 0.0009). The findings of the present study suggest that coffee drinking augments dynamic CBF regulation with cerebral vasoconstriction. This phenomenon may be associated with a reduction in the risk of cerebral vascular disease.

Global Cerebral Ischemia: Synaptic and Cognitive Dysfunction

PubMed Central

Neumann, Jake T.; Cohan, Charles H.; Dave, Kunjan R.; Wright, Clinton B.; Perez-Pinzon, Miguel A.

2018-01-01

Cardiopulmonary arrest is one of the leading causes of death and disability, primarily occurring in the aged population. Numerous global cerebral ischemia animal models induce neuronal damage similar to cardiac arrest. These global cerebral ischemia models range from vessel occlusion to total cessation of cardiac function, both of which have allowed for the investigation of this multifaceted disease and detection of numerous agents that are neuroprotective. Synapses endure a variety of alterations after global cerebral ischemia from the resulting excitotoxicity and have been a major target for neuroprotection; however, neuroprotective agents have proven unsuccessful in clinical trials, as neurological outcomes have not displayed significant improvements in patients. A majority of these neuroprotective agents have specific neuronal targets, where the success of future neuroprotective agents may depend on non-specific targets and numerous cognitive improvements. This review focuses on the different models of global cerebral ischemia, neuronal synaptic alterations, synaptic neuroprotection and behavioral tests that can be used to determine deficits in cognitive function after global cerebral ischemia. PMID:23170794

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.

Individual variability of cerebral autoregulation, posterior cerebral circulation and white matter hyperintensity.

PubMed

Liu, Jie; Tseng, Benjamin Y; Khan, Muhammad Ayaz; Tarumi, Takashi; Hill, Candace; Mirshams, Niki; Hodics, Timea M; Hynan, Linda S; Zhang, Rong

2016-06-01

Cerebral autoregulation (CA) is a key mechanism to protect brain perfusion in the face of changes in arterial blood pressure, but little is known about individual variability of CA and its relationship to the presence of brain white matter hyperintensity (WMH) in older adults, a type of white matter lesion related to cerebral small vessel disease (SVD). This study demonstrated the presence of large individual variability of CA in healthy older adults during vasoactive drug-induced changes in arterial pressure assessed at the internal carotid and vertebral arteries. We also observed, unexpectedly, that it was the 'over-' rather than the 'less-reactive' CA measured at the vertebral artery that was associated with WMH severity. These findings challenge the traditional concept of CA and suggest that the presence of cerebral SVD, manifested as WMH, is associated with posterior brain hypoperfusion during acute increase in arterial pressure. This study measured the individual variability of static cerebral autoregulation (CA) and determined its associations with brain white matter hyperintensity (WMH) in older adults. Twenty-seven healthy older adults (13 females, 66 ± 6 years) underwent assessment of CA during steady-state changes in mean arterial pressure (MAP) induced by intravenous infusion of sodium nitroprusside (SNP) and phenylephrine. Cerebral blood flow (CBF) was measured using colour-coded duplex ultrasonography at the internal carotid (ICA) and vertebral arteries (VA). CA was quantified by a linear regression slope (CA slope) between percentage changes in cerebrovascular resistance (CVR = MAP/CBF) and MAP relative to baseline values. Periventricular and deep WMH volumes were measured with T2-weighted magnetic resonance imaging. MAP was reduced by -11 ± 7% during SNP, and increased by 21 ± 8% during phenylephrine infusion. CA demonstrated large individual variability with the CA slopes ranging from 0.37 to 2.20 at the ICA and from 0.17 to 3.18 at the

Cerebral complexity preceded enlarged brain size and reduced olfactory bulbs in Old World monkeys

PubMed Central

Gonzales, Lauren A.; Benefit, Brenda R.; McCrossin, Monte L.; Spoor, Fred

2015-01-01

Analysis of the only complete early cercopithecoid (Old World monkey) endocast currently known, that of 15-million-year (Myr)-old Victoriapithecus, reveals an unexpectedly small endocranial volume (ECV) relative to body size and a large olfactory bulb volume relative to ECV, similar to extant lemurs and Oligocene anthropoids. However, the Victoriapithecus brain has principal and arcuate sulci of the frontal lobe not seen in the stem catarrhine Aegyptopithecus, as well as a distinctive cercopithecoid pattern of gyrification, indicating that cerebral complexity preceded encephalization in cercopithecoids. Since larger ECVs, expanded frontal lobes, and reduced olfactory bulbs are already present in the 17- to 18-Myr-old ape Proconsul these features evolved independently in hominoids (apes) and cercopithecoids and much earlier in the former. Moreover, the order of encephalization and brain reorganization was apparently different in hominoids and cercopithecoids, showing that brain size and cerebral organization evolve independently. PMID:26138795

Examination of the Pattern of Growth of Cerebral Tissue Volumes From Hospital Discharge to Early Childhood in Very Preterm Infants.

PubMed

Monson, Brian B; Anderson, Peter J; Matthews, Lillian G; Neil, Jeffrey J; Kapur, Kush; Cheong, Jeanie L Y; Doyle, Lex W; Thompson, Deanne K; Inder, Terrie E

2016-08-01

Smaller cerebral volumes at hospital discharge in very preterm (VPT) infants are associated with poor neurobehavioral outcomes. Brain growth from the newborn period to middle childhood has not been explored because longitudinal data have been lacking. To examine the pattern of growth of cerebral tissue volumes from hospital discharge to childhood in VPT infants and to determine perinatal risk factors for impaired brain growth and associations with neurobehavioral outcomes at 7 years. Prospective cohort study of VPT infants (<30 weeks' gestation or <1250 g) born between April 11, 2001, and April 26, 2004, and followed up at 7 years' corrected age. The setting was The Royal Women's Hospital and The Royal Children's Hospital, Melbourne, Australia. Of 224 VPT infants and 46 full-term (FT) infants, usable magnetic resonance imaging data at either infancy or 7 years were collected for 214 VPT children (95.5%) and 46 FT children (100%), while 126 VPT children (56.3%) and 31 FT children (67.4%) had usable magnetic resonance imaging data at both time points. Follow-up was conducted from April 28, 2008, to August 9, 2011. Our final analysis was on March 3, 2016. Prematurity. Absolute tissue growth, defined as change in absolute tissue volume, between infancy and 7 years was calculated for cortical gray matter volume (GMV), white matter volume (WMV), and subcortical GMV. IQ, language, and motor function were measured at 7 years. The study cohort comprised 260 participants. Their mean (SD) age was 7.5 (0.2) years, and 49.2% (128 of 260) were female. Early GMV deficits in VPT infants were magnified by 7 years, with less growth than FT controls. Growth differences were 31.4 (95% CI, 14.8-48.1) cm3 for cortical GMV and 1.7 (95% CI, 0.5-2.8) cm3 for subcortical GMV. Within the VPT group, greater growth was observed in boys for cortical GMV (31.9; 95% CI, 16.8-46.9 cm3), WMV (31.7; 95% CI, 19.7-43.7 cm3), and subcortical GMV (1.8; 95% CI, 0.8-2.8 cm3). After controlling for sex and

Blood transfusions increase cerebral, splanchnic, and renal oxygenation in anemic preterm infants.

PubMed

Dani, Carlo; Pratesi, Simone; Fontanelli, Giulia; Barp, Jacopo; Bertini, Giovanna

2010-06-01

Multiprobe near infrared spectroscopy (NIRS) has been used to study regional cerebral (rSO(2)C), splanchnic (rSO(2)S), and renal (rSO(2)R) tissue oxygenation in newborns. We used this method to study the effects of red blood cell (RBC) transfusions in anemic preterm infants to assess if thresholds for transfusions were appropriate for recognizing a clinical condition permitting tissue oxygenation improvement. Multiprobe NIRS (INVOS 5100, Somanetics) was applied during transfusion to 15 preterm infants with symptomatic anemia of prematurity (hematocrit level of <25%). rSO(2)C, rSO(2)S, and rSO(2)R were recorded at selected times, and then fractional oxygen cerebral extraction ratio [FOEC: (SaO(2)-rSO(2)C)/SaO(2)], fractional oxygen splanchnic extraction ratio [FOES: (SaO(2)-rSO(2)S)/SaO(2)], fractional oxygen renal extraction ratio [FOER: (SaO(2)-rSO(2)R)/SaO(2)], cerebrosplanchnic oxygenation ratio [CSOR: (rSO(2)S/rSO(2)C)], and cerebrorenal oxygenation ratio [CROR: (rSO(2)R/rSO(2)C)] were calculated. In addition, we used Doppler ultrasonography for evaluating cerebral blood flow (CBF), splanchnic blood flow (SBF), and renal blood flow (RBF) velocity. rSO(2)C, rSO(2)S, and rSO(2)R significantly increased during transfusions, while FOEC, FOES, and FOER decreased. CSOR and CROR increased during transfusions. CBF velocity decreased during the study period, while SBF and RBF velocities did not vary. RBC transfusions performed at used thresholds permitted an increase in cerebral, splanchnic, and renal oxygenation. The associated decreases in oxygen tissue extraction might suggest that transfusions were well timed for preventing tissue hypoxia or too early and theoretically prooxidant. Further studies could help to clarify this issue.

β-adrenergic receptor inhibition affects cerebral glucose metabolism, motor performance, and inflammatory response after traumatic brain injury.

PubMed

Ley, Eric J; Clond, Morgan A; Bukur, Marko; Park, Ryan; Chervonski, Michael; Dagliyan, Grant; Margulies, Dan R; Lyden, Patrick D; Conti, Peter S; Salim, Ali

2012-07-01

The purpose of this study was to evaluate how β-adrenergic receptor inhibition after traumatic brain injury (TBI) alters changes in early cerebral glucose metabolism and motor performance, as well as cerebral cytokine and heat shock protein (HSP) expression. Mouse cerebral glucose metabolism was measured by microPET fluorodeoxyglucose uptake and converted into standardized uptake values (SUV). Four groups of C57/Bl6 mice (wild type [WT]) were initially evaluated: sham or TBI, followed by tail vein injection of either saline or a nonselective β-adrenergic receptor inhibitor (propranolol, 4 mg/kg). Then motor performance, cerebral cytokine, and HSP70 expression were studied at 12 hours and 24 hours after sham injury or TBI in WT mice treated with saline or propranolol and in β1-adrenergic/β2-adrenergic receptor knockout (BARKO) mice treated with saline. Cerebral glucose metabolism was significantly reduced after TBI (mean SUV TBI, 1.63 vs. sham 1.97, p < 0.01) and propranolol attenuated this reduction (mean SUV propranolol, 1.89 vs. saline 1.63, p < 0.01). Both propranolol and BARKO reduced motor deficits at 24 hours after injury, but only BARKO had an effect at 12 hours after injury. TBI WT mice treated with saline performed worse than propranolol mice at 24 hours after injury on rotarod (23 vs. 44 seconds, p < 0.01) and rearing (130 vs. 338 events, p = 0.01) results. At 24 hours after injury, sham BARKO and TBI BARKO mice were similar on rotarod (21 vs. 19 seconds, p = 0.53), ambulatory testing (2,891 vs. 2,274 events, p = 0.14), and rearing (129 vs. 64 events, p = 0.09) results. Interleukin 1β expression was affected by BARKO and propranolol after TBI; attenuation of interleukin 6 and increased HSP70 expression were noted only with BARKO. β-adrenergic receptor inhibition affects cerebral glucose metabolism, motor performance, as well as cerebral cytokine and HSP expression after TBI.

[Oral motor dysfunction, feeding problems and nutritional status in children with cerebral palsy].

PubMed

Hou, Mei; Fu, Ping; Zhao, Jian-hui; Lan, Kun; Zhang, Hong

2004-10-01

This study was undertaken to investigate the clinical features of oral motor dysfunction and feeding problems as well as the nutritional status of children with cerebral palsy (CP). Fifty-nine CP children, 39 boys and 20 girls, mean age 31 months (20 to 72 months), were recruited. Their parents were interviewed for high risk factors and feeding history. Each case was assessed for oral motor and feeding problems based on oral motor and feeding skill score; for nutritional status by measurement of weight, height; neurologically for type of cerebral palsy and for developmental age by Gesell's developmental scale. Equal number of age and sex matched controls were included for comparison of nutritional status, oral motor and feeding skill score. Among 59 patients, 51 cases had oral motor dysfunction and 55 cases had feeding problems including all athtosis, spastic tetraplegia, and 16 had spastic diplegia. The scores of both the mean oral motor function and feeding skill of CP children were significantly lower than those of the controls (P < 0.001). Main food of children with cerebral palsy consisted of liquid and semisolid diet. Body weight and height below the 25th percentile were found in 13 cases and 19 cases, respectively. The majority of the children with cerebral palsy had oral motor dysfunction and feeding problems which appeared in early age and disturbed the growth and nutritional status. Thorough assessment for oral motor function, feeding problems and nutritional status of CP children is indicated in order to start timely rehabilitation and nutritional interventions which can significantly improve their nutritional status and quality of life.

Cerebral infarction in association with Ecstasy abuse.

PubMed Central

Manchanda, S.; Connolly, M. J.

1993-01-01

A previously fit 35 year old man presented with a right hemiparesis and dysphasia 36 hours after abuse of Ecstasy (3,4-methylenedioxymethamphetamine). Computerized axial tomography scan demonstrated an extensive acute left cerebral infarction and carotid digital subtraction angiogram, 2 days after admission, revealed left middle cerebral artery occlusion. There were no other known risk factors and all other investigations were negative. The patient made a partial recovery. We propose an association between Ecstasy abuse and cerebral infarction. PMID:7904748

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.

Keyhole Approach Combined With External Ventricular Drainage for Ruptured, Poor-Grade, Anterior Circulation Cerebral Aneurysms

PubMed Central

Zheng, Shu-Fa; Yao, Pei-Sen; Yu, Liang-Hong; Kang, De-Zhi

2015-01-01

Abstract Poor-grade ruptured anterior circulation cerebral aneurysms are frequently associated with severe vasospasm and high morbidity rates despite recent remarkable advances in endovascular coiling. Here, we explored the feasibility of keyhole approach combined with external ventricular drainage for ruptured, poor-grade, anterior circulation cerebral aneurysms. We retrospectively assessed the records of 103 patients with ruptured, Hunt and Hess grade IV or V, anterior circulation cerebral aneurysms. The patients were divided into 2 groups (conservative group and surgical group). In surgical group, patients were divided into 2 subgroups according to surgical time (within 24 hours and at 24–48 hours). Clinical outcome was assessed at the 6-month follow-up and categorized according to modified Rankin Scale (mRS) score. Twenty percent of patients (9/44) in conservative group obtained good outcome, while 54% (32/54) in surgical group (P < 0.05). Mortality was 73% in conservative group and 40% in surgical group, respectively. In surgical group, age, Hunt and Hess grade (IV or V), and timing of intervention (<24 hours or later) influenced the clinical outcome of the patients (P < 0.05), while sex, Fisher grade, hydrocephalus, the location of aneurysms, and cerebral vasospasm (CVS) not (P > 0.05). Furthermore, 65% of patients (22/34) operated within 24 hours after onset of hemorrhage had a good outcome compared with 20% of patients (5/25) operated at 24 to 48 hours in surgical group (P < 0.05). The results indicate that keyhole approach combined with external ventricular drainage is a safe and reliable treatment for ruptured, poor-grade, anterior circulation cerebral aneurysms in early stage, which will reduce mortality. PMID:26705215

Cerebral Effect of Intratracheal Aerosolized Surfactant Versus Bolus Therapy in Preterm Lambs.

PubMed

Rey-Santano, Carmen; Mielgo, Victoria E; López-de-Heredia-y-Goya, Jon; Murgia, Xabier; Valls-i-Soler, Adolfo

2016-04-01

Aerosolization has been proposed as a useful alternative to rapid intratracheal instillation for the delivery of exogenous surfactant in neonatal respiratory distress syndrome. However, there is a lack of information regarding the likely safety of this new therapeutic approach for the neonatal brain. We aimed to compare the cerebral effects of aerosolized versus bolus surfactant administration in premature lambs with respiratory distress syndrome. Prospective randomized study. BioCruces Institute Animal Research Facility. Fourteen intensively monitored and mechanically ventilated preterm lambs. Preterm lambs were randomly assigned to receive intratracheal aerosolized surfactant or bolus surfactant. Brain hemodynamics (cerebral and regional cerebral blood flow) and cerebral oxygen metabolism (cerebral oxygen delivery, cerebral metabolic rate of oxygen, and oxygen extraction fraction) were measured every 30 minutes for 6 hours. We also performed cerebral biochemical and histological analysis. In preterm lambs with respiratory distress syndrome, cerebral blood flow, regional cerebral blood flow, cerebral oxygen delivery, and cerebral metabolic rate of oxygen increased significantly in the bolus surfactant group during the first 5 minutes, without changes in cerebral oxygen extraction fraction. By 60 minutes, all parameters had decreased in both groups, cerebral blood flow and regional cerebral blood flow (in inner and cerebellum brainstem regions) remaining higher in the bolus surfactant than in the aerosolized surfactant group. Overall, the impact of aerosol surfactant was not significantly different to that of bolus surfactant in terms of cerebral necrosis, edema, inflammation, hemorrhage, infarct, apoptosis, or oxidative stress. In preterm lambs with severe respiratory distress syndrome, aerosol surfactant administration seems to be as safe as bolus administration, showing more stable cerebral hemodynamics and cerebral oxygen metabolism to the same dose of

Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused by mitofusin2 mutations.

PubMed

Brockmann, Knut; Dreha-Kulaczewski, Steffi; Dechent, Peter; Bönnemann, Carsten; Helms, Gunther; Kyllerman, Marten; Brück, Wolfgang; Frahm, Jens; Huehne, Kathrin; Gärtner, Jutta; Rautenstrauss, Bernd

2008-07-01

Mutations in the mitofusin 2 (MFN2) gene are a major cause of primary axonal Charcot- Marie-Tooth (CMT) neuropathy. This study aims at further characterization of cerebral white matter alterations observed in patients with MFN2 mutations. Molecular genetic, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) investigations were performed in four unrelated patients aged 7 to 38 years with early onset axonal CMT neuropathy. Three distinct and so far undescribed MFN2 mutations were detected. Two patients had secondary macrocephaly and mild diffuse predominantly periventricular white matter alterations on MRI. In addition, one boy had symmetrical T2-hyperintensities in both thalami. Two patients had optic atrophy, one of them with normal MRI. In three patients proton MRS revealed elevated concentrations of total N-acetyl compounds (neuronal marker), total creatine (found in all cells) and myo-inositol (astrocytic marker) in cerebral white and gray matter though with regional variation. These alterations were most pronounced in the two patients with abnormal MRI. DTI of these patients revealed mild reductions of fractional anisotropy and mild increase of mean diffusivity in white matter. The present findings indicate an enhanced cellular density in cerebral white matter of MFN2 neuropathy which is primarily due to a reactive gliosis without axonal damage and possibly accompanied by mild demyelination.

Noninvasive, optoacoustic detection and characterization of intra- and extracranial hematomas and cerebral hypoxia

NASA Astrophysics Data System (ADS)

Petrov, Andrey; Prough, Donald S.; Petrov, Yuriy; Petrov, Irene Y.; Robertson, Claudia S.; Asokan, Vasantha; Agbor, Adaeze; Esenaliev, Rinat O.

2015-03-01

Early diagnosis of intracranial hematomas is necessary to improve outcome in patients with traumatic brain injury (TBI). CT and MRI can diagnose intracranial hematomas, but cannot be used until the patient arrives at a major healthcare facility, resulting in delayed diagnosis. Near infrared spectroscopy may suggest the presence of unilateral intracranial hematomas, but provides minimal information on hematoma type and location due to limitations associated with strong light scattering. We have used optoacoustics (which combines high endogenous optical contrast with the resolution of ultrasound) to diagnose hematomas and monitor cerebral oxygenation. We performed animal and clinical studies on detection and characterization of hematomas and on monitoring cerebral hypoxia by probing the superior sagittal sinus (SSS). Recently, we built a medical grade, multi-wavelength, OPO-based optoacoustic system tunable in the near infrared spectral range. We developed new patient interfaces for noninvasive, transcranial measurements in the transmission mode in the presence of dense hair and used it in patients with TBI. The optoacoustic system was capable of detecting and characterizing intra- and extracranial hematomas. SSS blood oxygenation was measured as well with the new interface. The obtained results indicate that the optoacoustic system in the transmission mode provides detection and characterization of hematomas in TBI patients, as well as cerebral venous blood oxygenation monitoring. The transmission mode approach can be used for optoacoustic brain imaging, tomography, and mapping in humans.

Early gray-matter and white-matter concentration in infancy predict later language skills: a whole brain voxel-based morphometry study.

PubMed

Deniz Can, Dilara; Richards, Todd; Kuhl, Patricia K

2013-01-01

Magnetic resonance imaging (MRI) brain scans were obtained from 19 infants at 7 months. Expressive and receptive language performance was assessed at 12 months. Voxel-based morphometry (VBM) identified brain regions where gray-matter and white-matter concentrations at 7 months correlated significantly with children's language scores at 12 months. Early gray-matter concentration in the right cerebellum, early white-matter concentration in the right cerebellum, and early white-matter concentration in the left posterior limb of the internal capsule (PLIC)/cerebral peduncle were positively and strongly associated with infants' receptive language ability at 12 months. Early gray-matter concentration in the right hippocampus was positively and strongly correlated with infants' expressive language ability at 12 months. Our results suggest that the cerebellum, PLIC/cerebral peduncle, and the hippocampus may be associated with early language development. Potential links between these structural predictors and infants' linguistic functions are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

[Insomnia and cerebral hypoperfusion].

PubMed

Káposzta, Zoltán; Rácz, Klára

2007-11-18

Insomnia is defined as difficulty with the initiation, maintenance, duration, or quality of sleep that results in the impairment of daytime functioning, despite adequate opportunity and circumstances for sleep. In most countries approximately every third inhabitant has insomnia. Insomnia can be classified as primary and secondary. The pathogenesis of primary insomnia is unknown, but available evidence suggests a state of hyperarousal. Insomnia secondary to other causes is more common than primary insomnia. Cerebral hypoperfusion can be the cause of insomnia in some cases. In such patients the cerebral blood flow should be improved using parenteral vascular therapy. If insomnia persists despite treatment, then therapy for primary insomnia should be instituted using benzodiazepine-receptor agonists such as Zolpidem, Zopiclone, or Zaleplon. In those cases Midazolam cannot be used for the treatment of insomnia due to its marked negative effect on cerebral blood flow. In Hungary there is a need to organize multidisciplinary Insomnia Clinics because insomnia is more than a disease, it is a public health problem in this century.

Characterization of the rat cerebrospinal fluid proteome following acute cerebral ischemia using an aptamer-based proteomic technology.

PubMed

Simats, Alba; García-Berrocoso, Teresa; Ramiro, Laura; Giralt, Dolors; Gill, Natalia; Penalba, Anna; Bustamante, Alejandro; Rosell, Anna; Montaner, Joan

2018-05-21

The limited accessibility to the brain has turned the cerebrospinal fluid (CSF) into a valuable source that may contribute to the complete understanding of the stroke pathophysiology. Here we have described the CSF proteome in the hyper-acute phase of cerebral ischemia by performing an aptamer-based proteomic assay (SOMAscan) in CSF samples collected before and 30 min after male Wistar rats had undergone a 90 min Middle Cerebral Artery Occlusion (MCAO) or sham-surgery. Proteomic results indicated that cerebral ischemia acutely increased the CSF levels of 716 proteins, mostly overrepresented in leukocyte chemotaxis and neuronal death processes. Seven promising candidates were further evaluated in rat plasma and brain (CKB, CaMK2A, CaMK2B, CaMK2D, PDXP, AREG, CMPK). The 3 CaMK2 family-members and CMPK early decreased in the infarcted brain area and, together with AREG, co-localized with neurons. Conversely, CKB levels remained consistent after the insult and specifically matched with astrocytes. Further exploration of these candidates in human plasma revealed the potential of CKB and CMPK to diagnose stroke, while CaMK2B and CMPK resulted feasible biomarkers of functional stroke outcome. Our findings provided insights into the CSF proteome following cerebral ischemia and identified new outstanding proteins that might be further considered as potential biomarkers of stroke.

Pediatric Cerebral Palsy in Botswana: Etiology, Outcomes, and Comorbidities

PubMed Central

Bearden, David R.; Monokwane, Baphaleng; Khurana, Esha; Baier, James; Baranov, Esther; Westmoreland, Kate; Mazhani, Loeto; Steenhoff, Andrew P.

2016-01-01

BACKGROUND Cerebral palsy is the most common cause of motor dysfunction in children worldwide and is often accompanied by multiple comorbidities. Although cerebral palsy has been studied extensively in high-resource settings, there are few published studies on cerebral palsy etiology, outcomes and comorbidities in low-resource settings. METHODS Children with cerebral palsy were prospectively enrolled from inpatient and outpatient settings at a referral center in Gaborone, Botswana, in a cross-sectional study conducted from 2013 to 2014. Cerebral palsy etiology, outcomes, and comorbidities were determined through caregiver interviews, review of medical records, and direct physical examination. RESULTS Sixty-eight children with cerebral palsy were enrolled. Subjects were 41% male, with a median age of 4 years (interquartile range = 2 to 7). The most common etiologies for cerebral palsy in our cohort were intrapartum hypoxic events (18%), postnatal infections (15%), prematurity (15%), focal ischemic strokes (10%), and prenatal infections (10%). Severe motor impairment was common, with the most severe category present in 41%. The predominant comorbidities were cognitive impairment (84%), epilepsy (77%), and visual impairment (46%). CONCLUSIONS Cerebral palsy in Botswana has different etiologies and is associated with poorer outcomes and higher prevalence of comorbidities than what has been reported in high-resource settings. Further studies are necessary to determine optimal preventative and treatment strategies in this population. PMID:27114082

Early rehabilitation outcome in patients with middle cerebral artery stroke.

PubMed

Balaban, Birol; Tok, Fatih; Yavuz, Ferdi; Yaşar, Evren; Alaca, Rıdvan

2011-07-12

Although important data on the prognosis and rehabilitation outcome in stroke patients have been reported, data on functional recovery according to stroke subtypes are limited. This retrospective study aimed to evaluate functional outcome in patients with middle cerebral artery (MCA) stroke-the most common subtype of ischemic stroke. The records of stroke patients that underwent the rehabilitation program at our brain injury rehabilitation service between January 2007 and December 2008 were reviewed, and those with MCA stroke were included in the study. Patient demographic and clinical data, and Barthel Index (BI) and Functional Independence Measure (FIM) scores at admission and discharge were collected. The study included 80 MCA stroke patients with a mean age of 63.54 years. FIM and BI scores improved significantly post rehabilitation (P<0.05). Age was negatively correlated with both BI and FIM scores at admission and discharge. Length of stay was not correlated with improvement in BI or FIM scores during hospitalization. The patients that had ≤1 month of inpatient rehabilitation had similar outcomes as those that had >1 month of inpatient rehabilitation (P>0.05). Length of time after stroke onset was not correlated with BI or FIM scores at admission. Regardless of initial functional status, prediction of discharge functional status was misleading. Physiatrists should keep in mind that functional improvement does not always increase with duration of inpatient therapy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Early life linguistic ability, late life cognitive function, and neuropathology: findings from the Nun Study.

PubMed

Riley, Kathryn P; Snowdon, David A; Desrosiers, Mark F; Markesbery, William R

2005-03-01

The relationships between early life variables, cognitive function, and neuropathology were examined in participants in the Nun Study who were between the ages of 75 and 95. Our early life variable was idea density, which is a measure of linguistic ability, derived from autobiographies written at a mean age of 22 years. Six discrete categories of cognitive function, including mild cognitive impairments, were evaluated, using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. Neuropathologic data included Braak staging, neurofibrillary tangle and senile plaque counts, brain weight, degree of cerebral atrophy, severity of atherosclerosis, and the presence of brain infarcts. Early-life idea density was significantly related to the categories of late-life cognitive function, including mild cognitive impairments: low idea density was associated with greater impairment. Low idea density also was significantly associated with lower brain weight, higher degree of cerebral atrophy, more severe neurofibrillary pathology, and the likelihood of meeting neuropathologic criteria for Alzheimer's disease.

Loss of Intralipid®- but Not Sevoflurane-Mediated Cardioprotection in Early Type-2 Diabetic Hearts of Fructose-Fed Rats: Importance of ROS Signaling

PubMed Central

Zhang, Liyan; Affolter, Andreas; Gandhi, Manoj; Hersberger, Martin; Warren, Blair E.; Lemieux, Hélène; Sobhi, Hany F.; Clanachan, Alexander S.; Zaugg, Michael

2014-01-01

Background Insulin resistance and early type-2 diabetes are highly prevalent. However, it is unknown whether Intralipid® and sevoflurane protect the early diabetic heart against ischemia-reperfusion injury. Methods Early type-2 diabetic hearts from Sprague-Dawley rats fed for 6 weeks with fructose were exposed to 15 min of ischemia and 30 min of reperfusion. Intralipid® (1%) was administered at the onset of reperfusion. Peri-ischemic sevoflurane (2 vol.-%) served as alternative protection strategy. Recovery of left ventricular function was recorded and the activation of Akt and ERK 1/2 was monitored. Mitochondrial function was assessed by high-resolution respirometry and mitochondrial ROS production was measured by Amplex Red and aconitase activity assays. Acylcarnitine tissue content was measured and concentration-response curves of complex IV inhibition by palmitoylcarnitine were obtained. Results Intralipid® did not exert protection in early diabetic hearts, while sevoflurane improved functional recovery. Sevoflurane protection was abolished by concomitant administration of the ROS scavenger N-2-mercaptopropionyl glycine. Sevoflurane, but not Intralipid® produced protective ROS during reperfusion, which activated Akt. Intralipid® failed to inhibit respiratory complex IV, while sevoflurane inhibited complex I. Early diabetic hearts exhibited reduced carnitine-palmitoyl-transferase-1 activity, but palmitoylcarnitine could not rescue protection and enhance postischemic functional recovery. Cardiac mitochondria from early diabetic rats exhibited an increased content of subunit IV-2 of respiratory complex IV and of uncoupling protein-3. Conclusions Early type-2 diabetic hearts lose complex IV-mediated protection by Intralipid® potentially due to a switch in complex IV subunit expression and increased mitochondrial uncoupling, but are amenable to complex I-mediated sevoflurane protection. PMID:25127027

A Virtual Environment to Improve the Detection of Oral-Facial Malfunction in Children with Cerebral Palsy

PubMed Central

Martín-Ruiz, María-Luisa; Máximo-Bocanegra, Nuria; Luna-Oliva, Laura

2016-01-01

The importance of an early rehabilitation process in children with cerebral palsy (CP) is widely recognized. On the one hand, new and useful treatment tools such as rehabilitation systems based on interactive technologies have appeared for rehabilitation of gross motor movements. On the other hand, from the therapeutic point of view, performing rehabilitation exercises with the facial muscles can improve the swallowing process, the facial expression through the management of muscles in the face, and even the speech of children with cerebral palsy. However, it is difficult to find interactive games to improve the detection and evaluation of oral-facial musculature dysfunctions in children with CP. This paper describes a framework based on strategies developed for interactive serious games that is created both for typically developed children and children with disabilities. Four interactive games are the core of a Virtual Environment called SONRIE. This paper demonstrates the benefits of SONRIE to monitor children’s oral-facial difficulties. The next steps will focus on the validation of SONRIE to carry out the rehabilitation process of oral-facial musculature in children with cerebral palsy. PMID:27023561

Noninvasive optoacoustic monitoring of cerebral venous blood oxygenation in newborns

NASA Astrophysics Data System (ADS)

Petrov, Irene Y.; Wynne, Karon E.; Petrov, Yuriy; Esenaliev, Rinat O.; Richardson, C. Joan; Prough, Donald S.

2012-02-01

Cerebral ischemia after birth and during labor is a major cause of death and severe complications such as cerebral palsy. In the USA alone, cerebral palsy results in permanent disability of 10,000 newborns per year and approximately 500,000 of the total population. Currently, no technology is capable of direct monitoring of cerebral oxygenation in newborns. This study proposes the use of an optoacoustic technique for noninvasive cerebral ischemia monitoring by probing the superior sagittal sinus (SSS), a large central cerebral vein. We developed and built a multi-wavelength, near-infrared optoacoustic system suitable for noninvasive monitoring of cerebral ischemia in newborns with normal weight (NBW), low birth-weight (LBW, 1500 - 2499 g) and very low birth-weight (VLBW, < 1500 g). The system was capable of detecting SSS signals through the open anterior and posterior fontanelles as well as through the skull. We tested the system in NBW, LBW, and VLBW newborns (weight range: from 675 g to 3,000 g) admitted to the neonatal intensive care unit. We performed single and continuous measurements of the SSS blood oxygenation. The data acquisition, processing and analysis software developed by our group provided real-time, absolute SSS blood oxygenation measurements. The SSS blood oxygenation ranged from 60% to 80%. Optoacoustic monitoring of the SSS blood oxygenation provides valuable information because adequate cerebral oxygenation would suggest that no therapy was necessary; conversely, evidence of cerebral ischemia would prompt therapy to increase cerebral blood flow.

Neuroprotective effect of antioxidants on ischaemia and reperfusion-induced cerebral injury.

PubMed

Gupta, Ram; Singh, Manjeet; Sharma, Ajay

2003-08-01

The present study is designed to investigate the effect of dietary flavanoid rutin, micronutrient selenium and garlic oil on ischaemia and reperfusion-induced cerebral injury. Global cerebral ischaemia was induced by occluding right and left common carotid arteries for 10min followed by reperfusion for 24h. Cerebral infarct size was estimated using triphenyltetrazolium chloride staining. Elevated plus maze was employed to estimate short-term memory. Degree of motor incoordination was evaluated using inclined beam-walking test and lateral push test. Mitochondrial thiobarbituric acid reactive substances (TBARS) assay was employed as an index of oxidative stress. Global cerebral ischaemia followed by reperfusion produced a significant impairment in short-term memory and motor coordination and produced a notable increase in mitochondrial TBARS. Administration of rutin and garlic oil before global cerebral ischaemia markedly reduced cerebral infarct size and attenuated impairment in short-term memory and motor coordination. Administration of sodium selenite either before or after global cerebral ischaemia markedly reduced cerebral infarct size and attenuated impairment in short-term memory and motor coordination. The protective effect of rutin, sodium selenite and garlic oil was accompanied by a marked decrease in mitochondrial TBARS. On the basis of these results, it may be suggested that rutin and garlic oil administrated before cerebral ischaemia may scavenge reactive oxygen species and consequently attenuate global cerebral ischaemia and reperfusion-induced cerebral injury. Sodium selenite administrated before and after cerebral ischaemia may be neuroprotective due to its antioxidant effect.

Comparison between antegrade and retrograde cerebral perfusion or profound hypothermia as brain protection strategies during repair of type A aortic dissection

PubMed Central

Rausch, Laura A.; Kouchoukos, Nicholas T.; Lobdell, Kevin W.; Khabbaz, Kamal; Murphy, Edward; Hagberg, Robert C.

2016-01-01

Background The goal of this study was to compare early postoperative outcomes and actuarial-free survival between patients who underwent repair of acute type A aortic dissection by the method of cerebral perfusion used. Methods A total of 324 patients from five academic medical centers underwent repair of acute type A aortic dissection between January 2000 and December 2010. Of those, antegrade cerebral perfusion (ACP) was used for 84 patients, retrograde cerebral perfusion (RCP) was used for 55 patients, and deep hypothermic circulatory arrest (DHCA) was used for 184 patients during repair. Major morbidity, operative mortality, and 5-year actuarial survival were compared between groups. Multivariate logistic regression was used to determine predictors of operative mortality and Cox Regression hazard ratios were calculated to determine the predictors of long term mortality. Results Operative mortality was not influenced by the type of cerebral protection (19% for ACP, 14.5% for RCP and 19.1% for DHCA, P=0.729). In multivariable logistic regression analysis, hemodynamic instability [odds ratio (OR) =19.6, 95% confidence intervals (CI), 0.102–0.414, P<0.001] and CPB time >200 min(OR =4.7, 95% CI, 1.962–1.072, P=0.029) emerged as independent predictors of operative mortality. Actuarial 5-year survival was unchanged by cerebral protection modality (48.8% for ACP, 61.8% for RCP and 66.8% for no cerebral protection, log-rank P=0.844). Conclusions During surgical repair of type A aortic dissection, ACP, RCP or DHCA are safe strategies for cerebral protection in selected patients with type A aortic dissection. PMID:27563545

Association of Lead Levels and Cerebral Palsy

PubMed Central

Bansal, Neha; Aggarwal, Anju; Faridi, M. M. A.; Sharma, Tusha; Baneerjee, B. D.

2017-01-01

Background: Cerebral palsy is a common motor disability in childhood. Raised lead levels affect cognition. Children with cerebral palsy may have raised lead levels, further impairing their residual cognitive motor and behavioral abilities. Environmental exposure and abnormal eating habits may lead to increased lead levels. Aims and Objectives: To measure blood lead levels in children with cerebral palsy and compare them with healthy neurologically normal children. To correlate blood lead levels with environmental factors. Material and Methods: Design: Prospective case-control study. Setting: Tertiary care hospital. Participants: Cases comprised 34 children with cerebral palsy, and controls comprised 34 neurologically normal, age- and sex-matched children. Methods: Clinical and demographic details were recorded as per proforma. Detailed environmental history was recorded to know the source of exposure to lead. These children were investigated and treated as per protocol. Venous blood was collected in ethylenediaminetetraacetic acid vials for analysis of blood lead levels. Lead levels were estimated by Schimadzu Flame AA-6800 (atomic absorption spectrophotometer). Data were analyzed using SPSS version 17. P < .05 was taken as significant. Results: Mean blood lead levels were 9.20 ± 8.31 µg/dL in cerebral palsy cases and 2.89 ± 3.04 µg/dL in their controls (P < .001). Among children with cerebral palsy, 19 (55.88%) children had blood lead levels ≥5 µg/dL. Lead levels in children with pica were 12.33 ± 10.02 µg/dL in comparison to children with no history of pica, 6.70 ± 4.60 µg/dL (P = .029). No correlation was found between hemoglobin and blood lead levels in cases and controls. Conclusion: In our study, blood lead levels are raised in children with cerebral palsy. However, further studies are required to show effects of raised levels in these children. PMID:28491920

The importance of bilateral monitoring of cerebral oxygenation (NIRS): Clinical case of asymmetry during cardiopulmonary bypass secondary to previous cerebral infarction.

PubMed

Matcan, S; Sanabria Carretero, P; Gómez Rojo, M; Castro Parga, L; Reinoso-Barbero, F

2018-03-01

Cerebral oximetry based on near infrared spectroscopy (NIRS) technology is used to determine cerebral tissue oxygenation. We hereby present the clinical case of a 12-month old child with right hemiparesis secondary to prior left middle cerebral artery stroke 8 months ago. The child underwent surgical enlargement of the right ventricular outflow tract (RVOT) with cardiopulmonary bypass. During cardiopulmonary bypass, asymmetric NIRS results were detected between both hemispheres. The utilization of multimodal neuromonitoring (NIRS-BIS) allowed acting on both perfusion pressure and anesthetic depth to balance out the supply and demand of cerebral oxygen consumption. No new neurological sequelae were observed postoperatively. We consider bilateral NIRS monitoring necessary in order to detect asymmetries between cerebral hemispheres. Although asymmetries were not present at baseline, they can arise intraoperatively and its monitoring thus allows the detection and treatment of cerebral ischemia-hypoxia in the healthy hemisphere, which if undetected and untreated would lead to additional neurological damage. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Fludrocortisone therapy in cerebral salt wasting.

PubMed

Taplin, Craig E; Cowell, Christopher T; Silink, Martin; Ambler, Geoffrey R

2006-12-01

Cerebral salt wasting is an increasingly recognized condition in pediatrics and is characterized by inappropriate natriuresis and volume contraction in the presence of cerebral pathology. Diagnosis can be difficult and therapy challenging. A few single case reports of the successful use of fludrocortisone exist. We report 4 patients with cerebral salt wasting, all of whom presented with hyponatremia in the presence of known intracerebral pathology. All had clinically significant hyponatremia, and 3 had hyponatremic seizures. Two of the patients also satisfied clinical criteria for diabetes insipidus. They all were treated with regimens using increased sodium and fluid administration but experienced ongoing salt wasting. Fludrocortisone was instituted in all 4 patients and in 3 resulted in rapid improvement in net sodium balance, enabling the weaning of hypertonic fluids and stabilization of serum electrolytes. In 3 patients, fludrocortisone treatment was complicated by hypokalemia, and in 1 patient by hypertension, which necessitated a dose reduction or brief cessation of therapy. Duration of therapy was 4 to 125 days. Cerebral salt wasting presents considerable management challenges; however, fludrocortisone therapy can be an effective adjunct to treatment.

[The optimization of an early rehabilitation program for cerebral stroke patients: the use of different methods of magneto- and laser therapy].

PubMed

Kochetkov, A V; Gorbunov, F E; Minenkov, A A; Strel'tsova, E N; Filina, T F; Krupennikov, A I

2000-01-01

Magnetotherapy and laser therapy were used in complex and complex-combined regimens in 75 patients after cerebral ischemic or hemorrhagic stroke starting on the poststroke week 4-5. Clinico-neurologic, neurophysiological and cerebrohemodynamic findings evidence for the highest effectiveness of neurorehabilitation including complex magneto-laser therapy in hemispheric ischemic and hemorrhagic stroke of subcortical location in the absence of marked clinico-tomographic signs of dyscirculatory encephalopathy. Complex-combined magneto-laser therapy is more effective for correction of spastic dystonia. Mutual potentiation of magnetotherapy and laser therapy results in maximal development of collateral circulation and cerebral hemodynamic reserve (84% of the patients). Complex effects manifest in arteriodilating and venotonic effects. Complex magneto-laser therapy is accompanied by reduction of hyperthrombocythemia and hyperfibrinogenemia.

Somatosensory discrimination deficits following pediatric cerebral malaria.

PubMed

Dugbartey, A T; Spellacy, F J; Dugbartey, M T

1998-09-01

Pathologic studies of central nervous system damage in human falciparum malaria indicate primary localization in the cerebral white matter. We report a sensory-perceptual investigation of 20 Ghanaian children with a recent history of cerebral malaria who were age-, gender-, and education-matched with 20 healthy control subjects. Somatosensory examinations failed to show any evidence of hemianesthesia, pseudohemianesthesia, or extinction to double simultaneous tactile stimulation. While unilateral upper limb testing revealed intact unimanual tactile roughness discrimination, bimanual tactile discrimination, however, was significantly impaired in the cerebral malaria group. A strong negative correlation (r = -0.72) between coma duration and the bimanual tactile roughness discrimination test was also found. An inefficiency in the integrity of callosal fibers appear to account for our findings, although alternative subcortical mechanisms known to be involved in information transfer across the cerebral hemispheres may be compromised as well.

Bedside diagnosis of mitochondrial dysfunction after malignant middle cerebral artery infarction.

PubMed

Nielsen, T H; Schalén, W; Ståhl, N; Toft, P; Reinstrup, P; Nordström, C H

2014-08-01

The study explores whether the cerebral biochemical pattern in patients treated with hemicraniectomy after large middle cerebral artery infarcts reflects ongoing ischemia or non-ischemic mitochondrial dysfunction. The study includes 44 patients treated with decompressive hemicraniectomy (DCH) due to malignant middle cerebral artery infarctions. Chemical variables related to energy metabolism obtained by microdialysis were analyzed in the infarcted tissue and in the contralateral hemisphere from the time of DCH until 96 h after DCH. Reperfusion of the infarcted tissue was documented in a previous report. Cerebral lactate/pyruvate ratio (L/P) and lactate were significantly elevated in the infarcted tissue compared to the non-infarcted hemisphere (p < 0.05). From 12 to 96 h after DCH the pyruvate level was significantly higher in the infarcted tissue than in the non-infarcted hemisphere (p < 0.05). After a prolonged period of ischemia and subsequent reperfusion, cerebral tissue shows signs of protracted mitochondrial dysfunction, characterized by a marked increase in cerebral lactate level with a normal or increased cerebral pyruvate level resulting in an increased LP-ratio. This biochemical pattern contrasts to cerebral ischemia, which is characterized by a marked decrease in cerebral pyruvate. The study supports the hypothesis that it is possible to diagnose cerebral mitochondrial dysfunction and to separate it from cerebral ischemia by microdialysis and bed-side biochemical analysis.

Elevated cerebral glutamate and myo-inositol levels in cognitively normal middle-aged adults with metabolic syndrome.

PubMed

Haley, Andreana P; Gonzales, Mitzi M; Tarumi, Takashi; Miles, Steven C; Goudarzi, Katayoon; Tanaka, Hirofumi

2010-12-01

Metabolic syndrome (MetS) is a cluster of risk factors associated with significant cardiovascular morbidity and mortality and diminished cognitive function. Given that the cerebral mechanisms mediating the relationship between peripheral metabolic dysfunction and cognitive impairment are unknown, we set out to examine the relationship between diagnosis of metabolic syndrome and cerebral metabolism. Thirteen participants with MetS (aged 48 ± 6 years) and 25 healthy adults (aged 51 ± 6 years) underwent neuropsychological assessment, health screen and proton magnetic resonance spectroscopy ((1)H MRS) examining N-acetyl-aspartate (NAA), myo-inositol (mI), creatine (Cr), choline (Cho), and glutamate (Glu) concentrations in occipitoparietal grey matter. Cerebral metabolite ratios (NAA/Cr, Cho/Cr, mI/Cr, and Glu/Cr) of participants with MetS, defined by the International Diabetes Federation criteria, were compared with controls matched for age, education, cognition, and emotional function. There were no significant differences in global cognitive function, memory, language, and psychomotor performance between the groups. Diagnosis of MetS was associated with significantly higher mI/Cr (F(1,36) = 5.02, p = 0.031) and Glu/Cr ratio (F(1,36) = 4.81, p = 0.035). Even in cognitively normal adults, MetS is related to cerebral metabolic disturbances, a possible indication of early brain vulnerability. Longitudinal studies that begin in mid-life can help validate the use of (1)H MRS markers as indicators of long-term cognitive outcomes.

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.

Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia

PubMed Central

Jones, Phill B.; Shin, Hwa Kyoung; Boas, David A.; Hyman, Bradley T.; Moskowitz, Michael A.; Ayata, Cenk; Dunn, Andrew K.

2009-01-01

Real-time investigation of cerebral blood flow (CBF), and oxy- and deoxyhemoglobin concentration (HbO, HbR) dynamics has been difficult until recently due to limited spatial and temporal resolution of techniques like laser Doppler flowmetry and magnetic resonance imaging (MRI). The combination of laser speckle flowmetry (LSF) and multispectral reflectance imaging (MSRI) yields high-resolution spatiotemporal maps of hemodynamic and metabolic changes in response to functional cortical activation. During acute focal cerebral ischemia, changes in HbO and HbR are much larger than in functional activation, resulting in the failure of the Beer-Lambert approximation to yield accurate results. We describe the use of simultaneous LSF and MSRI, using a nonlinear Monte Carlo fitting technique, to record rapid changes in CBF, HbO, HbR, and cerebral metabolic rate of oxygen (CMRO2) during acute focal cerebral ischemia induced by distal middle cerebral artery occlusion (dMCAO) and reperfusion. This technique captures CBF and CMRO2 changes during hemodynamic and metabolic events with high temporal and spatial resolution through the intact skull and demonstrates the utility of simultaneous LSF and MSRI in mouse models of cerebrovascular disease. PMID:19021335

Low HDL and High LDL Serum Cholesterol Are Associated With Cerebral Amyloidosis

PubMed Central

Reed, Bruce; Villeneuve, Sylvia; Mack, Wendy; DeCarli, Charles; Chui, Helena C.; Jagust, William

2014-01-01

Importance Because deposition of cerebral beta amyloid (Aβ) appears to be a key initiating event in Alzheimer’s disease, factors associated with increased deposition are of great interest. Whether or not elevated serum cholesterol acts as such a factor is unknown. Objective To investigate the relationship between serum cholesterol levels and cerebral Aβ during life, early in the AD process. Design Cross sectional analysis of potential associations between contemporaneously measured total serum cholesterol, HDL cholesterol, LDL cholesterol and cerebral Aβ, measured using PIB PET. Setting Multi-site, university medical center based study of vascular contributions to dementia. Participants 74 persons, mean age 78, recruited via direct outreach in stroke clinics and community senior facilities following a protocol designed to obtain a cohort enriched for cerebrovascular disease and elevated vascular risk. Three cases had mild dementia. All others were clinically normal (33 cases) or had mild cognitive impairment (38 cases). Results Cerebral Aβ was quantified using a global PIB index, which averages PIB retention in cortical areas prone to amyloidosis. Statistical models that controlled for age and the apoE ε4 allele showed independent associations between LDL cholesterol, HDL cholesterol and PIB index. Higher LDL and lower HDL were both associated with higher PIB index. No association was found between total cholesterol and PIB index. No association was found between statin use and PIB index, nor did controlling for cholesterol treatment in the statistical models alter the basic findings. Conclusions and Relevance Elevated cerebral Aβ was associated with cholesterol fractions in a pattern analogous to that found in coronary artery disease. This finding, in living, non-demented humans, is consistent with prior autopsy reports, with epidemiological findings, and with both animal and in vitro work suggesting an important role for cholesterol in Aβ processing

Hydrogen sulfide triggers late-phase preconditioning in postischemic small intestine by an NO- and p38 MAPK-dependent mechanism

PubMed Central

Yusof, Mozow; Kamada, Kazuhiro; Kalogeris, Theodore; Gaskin, F. Spencer; Korthuis, Ronald J.

2009-01-01

Hydrogen sulfide (H2S) is one of three endogenous gases, along with carbon monoxide (CO) and nitric oxide (NO), that exert a variety of important vascular actions in vivo. Although it has been demonstrated that CO or NO can trigger the development of a preconditioned phenotype in postischemic tissues, it is unclear whether H2S may also induce protection in organs subsequently exposed to ischemia-reperfusion (I/R). In light of these observations, we postulated that preconditioning with the exogenous H2S donor sodium hydrosulfide (NaHS-PC) would inhibit leukocyte rolling (LR) and adhesion (LA) induced by I/R. We used intravital microscopic techniques to demonstrate that NaHS-PC 24 h, but not 1 h, before I/R causes postcapillary venules to shift to an anti-inflammatory phenotype in wild-type (WT) mice such that these vessels fail to support LR and LA during reperfusion. The protective effect of NaHS-PC on LR was largely abolished by coincident pharmacological inhibition of NO synthase (NOS) in WT animals and was absent in endothelial NOS-deficient (eNOS−/−) mice. A similar pattern of response was noted in WT mice treated concomitantly with NaHS plus p38 mitogen-activated protein kinase (MAPK) inhibitors (SB 203580 or SK-86002). Whereas the reduction in LA induced by antecedent NaHS was attenuated by pharmacological inhibition of NOS or p38 MAPK in WT mice, the antiadhesive effect of NaHS was still evident in eNOS−/− mice. Thus NaHS-PC prevents LR and LA by triggering the activation of an eNOS- and p38 MAPK-dependent mechanism. However, the role of eNOS in the antiadhesive effect of NaHS-PC was less prominent than its effect to reduce LR. PMID:19168723

Cerebral vasculopathy in children with sickle cell anemia.

PubMed

Fasano, Ross M; Meier, Emily R; Hulbert, Monica L

2015-01-01

Sickle cell anemia (SCA)-associated cerebral vasculopathy and moyamoya is a unique entity reflecting the abnormal interactions between sickled red blood cells (RBCs) and the cerebral arterial endothelium. Endothelial injury, coagulation activation, and the inflammatory response generated by sickled RBCs are implicated in the development of cerebral vasculopathy, but the pathophysiology remains incompletely understood. SCA-specific screening and treatment guidelines have successfully reduced the incidence of overt strokes in this high-risk population. However, despite aggressive hematological management, many children with cerebral vasculopathy due to SCA have progressive vasculopathy and recurrent strokes; therefore, more effective therapies, such as revascularization surgery and curative hematopoietic stem cell transplant, are urgently needed. Copyright © 2014 Elsevier Inc. All rights reserved.

Cerebral Palsy: General Information. Fact Sheet Number 2 = La Paralisis Cerebral: Informacion General. Fact Sheet Number 18.

ERIC Educational Resources Information Center

Interstate Research Associates, McLean, VA.

This fact sheet on cerebral palsy is offered in both English and Spanish. First, it provides a definition and considers various causes (e.g., an insufficient amount of oxygen reaching the fetal or newborn brain). The fact sheet then offers incidence figures and explains characteristics of the three main types of cerebral palsy: spastic, athetoid,…

Multivariate Analysis and Machine Learning in Cerebral Palsy Research.

PubMed

Zhang, Jing

2017-01-01

Cerebral palsy (CP), a common pediatric movement disorder, causes the most severe physical disability in children. Early diagnosis in high-risk infants is critical for early intervention and possible early recovery. In recent years, multivariate analytic and machine learning (ML) approaches have been increasingly used in CP research. This paper aims to identify such multivariate studies and provide an overview of this relatively young field. Studies reviewed in this paper have demonstrated that multivariate analytic methods are useful in identification of risk factors, detection of CP, movement assessment for CP prediction, and outcome assessment, and ML approaches have made it possible to automatically identify movement impairments in high-risk infants. In addition, outcome predictors for surgical treatments have been identified by multivariate outcome studies. To make the multivariate and ML approaches useful in clinical settings, further research with large samples is needed to verify and improve these multivariate methods in risk factor identification, CP detection, movement assessment, and outcome evaluation or prediction. As multivariate analysis, ML and data processing technologies advance in the era of Big Data of this century, it is expected that multivariate analysis and ML will play a bigger role in improving the diagnosis and treatment of CP to reduce mortality and morbidity rates, and enhance patient care for children with CP.

Prevalence of cerebral palsy in Uganda: a population-based study.

PubMed

Kakooza-Mwesige, Angelina; Andrews, Carin; Peterson, Stefan; Wabwire Mangen, Fred; Eliasson, Ann Christin; Forssberg, Hans

2017-12-01

Few population-based studies of cerebral palsy have been done in low-income and middle-income countries. We aimed to examine cerebral palsy prevalence and subtypes, functional impairments, and presumed time of injury in children in Uganda. In this population-based study, we used a nested, three-stage, cross-sectional method (Iganga-Mayuge Health and Demographic Surveillance System [HDSS]) to screen for cerebral palsy in children aged 2-17 years in a rural eastern Uganda district. A specialist team confirmed the diagnosis and determined the subtype, motor function (according to the Gross Motor Function Classification System [GMFCS]), and possible time of brain injury for each child. Triangulation and interviews with key village informants were used to identify additional cases of suspected cerebral palsy. We estimated crude and adjusted cerebral palsy prevalence. We did χ 2 analyses to examine differences between the group screened at stage 1 and the entire population and regression analyses to investigate associations between the number of cases and age, GMFCS level, subtype, and time of injury. We used data from the March 1, 2015, to June 30, 2015, surveillance round of the Iganga-Mayuge HDSS. 31 756 children were screened for cerebral palsy, which was confirmed in 86 (19%) of 442 children who screened positive in the first screening stage. The crude cerebral palsy prevalence was 2·7 (95% CI 2·2-3·3) per 1000 children, and prevalence increased to 2·9 (2·4-3·6) per 1000 children after adjustment for attrition. The prevalence was lower in older (8-17 years) than in younger (<8 years) children. Triangulation added 11 children to the cohort. Spastic unilateral cerebral palsy was the most common subtype (45 [46%] of 97 children) followed by bilateral cerebral palsy (39 [40%] of 97 children). 14 (27%) of 51 children aged 2-7 years had severe cerebral palsy (GMFCS levels 4-5) compared with only five (12%) of 42 children aged 8-17 years. Few children (two [2%] of

Cerebral aneurysms: Formation, progression and developmental chronology

PubMed Central

Etminan, Nima; Buchholz, Bruce A.; Dreier, Rita; Bruckner, Peter; Torner, James C.; Steiger, Hans-Jakob; Hänggi, Daniel; Macdonald, R. Loch

2015-01-01

The prevalence of unruptured intracranial aneurysms (UAIs) in the general population is up to 3%. Existing epidemiological data suggests that only a small fraction of UIAs progress towards rupture over the lifetime of an individual, but the surrogates for subsequent rupture and the natural history of UIAs are discussed very controversially at present. In case of rupture of an UIA, the case-fatality is up to 50%, which therefore continues to stimulate interest in the pathogenesis of cerebral aneurysm formation and progression. Actual data on the chronological development of cerebral aneurysm has been especially difficult to obtain and, until recently, the existing knowledge in this respect is mainly derived from animal or mathematical models or short-term observational studies. Here, we highlight the current data on cerebral aneurysm formation and progression as well as a novel approach to investigate the developmental chronology of cerebral aneurysms. PMID:24323717

The inhibitor of 20-HETE synthesis, TS-011, improves cerebral microcirculatory autoregulation impaired by middle cerebral artery occlusion in mice.

PubMed

Marumo, Toshiyuki; Eto, Kei; Wake, Hiroaki; Omura, Tomohiro; Nabekura, Junichi

2010-11-01

20-Hydroxyeicosatetraenoic acid is a potent vasoconstrictor that contributes to cerebral ischaemia. An inhibitor of 20-Hydroxyeicosatetraenoic acid synthesis, TS-011, reduces infarct volume and improves neurological deficits in animal stroke models. However, little is known about how TS-011 affects the microvessels in ischaemic brain. Here, we investigated the effect of TS-011 on microvessels after cerebral ischaemia. TS-011 (0.3 mg·kg(-1) ) or a vehicle was infused intravenously for 1 h every 6 h in a mouse model of stroke, induced by transient occlusion of the middle cerebral artery occlusion following photothrombosis. The cerebral blood flow velocity and the vascular perfusion area of the peri-infarct microvessels were measured using in vivo two-photon imaging. The cerebral blood flow velocities in the peri-infarct microvessels decreased at 1 and 7 h after reperfusion, followed by an increase at 24 h after reperfusion in the vehicle-treated mice. We found that TS-011 significantly inhibited both the decrease and the increase in the blood flow velocities in the peri-infarct microvessels seen in the vehicle-treated mice after reperfusion. In addition, TS-011 significantly inhibited the reduction in the microvascular perfusion area after reperfusion, compared with the vehicle-treated group. Moreover, TS-011 significantly reduced the infarct volume by 40% at 72 h after middle cerebral artery occlusion. These findings demonstrated that infusion of TS-011 improved defects in the autoregulation of peri-infarct microcirculation and reduced the infarct volume. Our results could be relevant to the treatment of cerebral ischaemia. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

Investigating cerebral oedema using poroelasticity.

PubMed

Vardakis, John C; Chou, Dean; Tully, Brett J; Hung, Chang C; Lee, Tsong H; Tsui, Po-Hsiang; Ventikos, Yiannis

2016-01-01

Cerebral oedema can be classified as the tangible swelling produced by expansion of the interstitial fluid volume. Hydrocephalus can be succinctly described as the abnormal accumulation of cerebrospinal fluid (CSF) within the brain which ultimately leads to oedema within specific sites of parenchymal tissue. Using hydrocephalus as a test bed, one is able to account for the necessary mechanisms involved in the interaction between oedema formation and cerebral fluid production, transport and drainage. The current state of knowledge about integrative cerebral dynamics and transport phenomena indicates that poroelastic theory may provide a suitable framework to better understand various diseases. In this work, Multiple-Network Poroelastic Theory (MPET) is used to develop a novel spatio-temporal model of fluid regulation and tissue displacement within the various scales of the cerebral environment. The model is applied through two formats, a one-dimensional finite difference - Computational Fluid Dynamics (CFD) coupling framework, as well as a two-dimensional Finite Element Method (FEM) formulation. These are used to investigate the role of endoscopic fourth ventriculostomy in alleviating oedema formation due to fourth ventricle outlet obstruction (1D coupled model) in addition to observing the capability of the FEM template in capturing important characteristics allied to oedema formation, like for instance in the periventricular region (2D model). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Microsurgery Simulator of Cerebral Aneurysm Clipping with Interactive Cerebral Deformation Featuring a Virtual Arachnoid.

PubMed

Shono, Naoyuki; Kin, Taichi; Nomura, Seiji; Miyawaki, Satoru; Saito, Toki; Imai, Hideaki; Nakatomi, Hirofumi; Oyama, Hiroshi; Saito, Nobuhito

2018-05-01

A virtual reality simulator for aneurysmal clipping surgery is an attractive research target for neurosurgeons. Brain deformation is one of the most important functionalities necessary for an accurate clipping simulator and is vastly affected by the status of the supporting tissue, such as the arachnoid membrane. However, no virtual reality simulator implementing the supporting tissue of the brain has yet been developed. To develop a virtual reality clipping simulator possessing interactive brain deforming capability closely dependent on arachnoid dissection and apply it to clinical cases. Three-dimensional computer graphics models of cerebral tissue and surrounding structures were extracted from medical images. We developed a new method for modifiable cerebral tissue complex deformation by incorporating a nonmedical image-derived virtual arachnoid/trabecula in a process called multitissue integrated interactive deformation (MTIID). MTIID made it possible for cerebral tissue complexes to selectively deform at the site of dissection. Simulations for 8 cases of actual clipping surgery were performed before surgery and evaluated for their usefulness in surgical approach planning. Preoperatively, each operative field was precisely reproduced and visualized with the virtual brain retraction defined by users. The clear visualization of the optimal approach to treating the aneurysm via an appropriate arachnoid incision was possible with MTIID. A virtual clipping simulator mainly focusing on supporting tissues and less on physical properties seemed to be useful in the surgical simulation of cerebral aneurysm clipping. To our knowledge, this article is the first to report brain deformation based on supporting tissues.

Cerebral Small Vessel Disease: Targeting Oxidative Stress as a Novel Therapeutic Strategy?

PubMed Central

De Silva, T. Michael; Miller, Alyson A.

2016-01-01

Cerebral small vessel disease (SVD) is a major contributor to stroke, and a leading cause of cognitive impairment and dementia. Despite the devastating effects of cerebral SVD, the pathogenesis of cerebral SVD is still not completely understood. Moreover, there are no specific pharmacological strategies for its prevention or treatment. Cerebral SVD is characterized by marked functional and structural abnormalities of the cerebral microcirculation. The clinical manifestations of these pathological changes include lacunar infarcts, white matter hyperintensities, and cerebral microbleeds. The main purpose of this review is to discuss evidence implicating oxidative stress in the arteriopathy of both non-amyloid and amyloid (cerebral amyloid angiopathy) forms of cerebral SVD and its most important risk factors (hypertension and aging), as well as its contribution to cerebral SVD-related brain injury and cognitive impairment. We also highlight current evidence of the involvement of the NADPH oxidases in the development of oxidative stress, enzymes that are a major source of reactive oxygen species in the cerebral vasculature. Lastly, we discuss potential pharmacological strategies for oxidative stress in cerebral SVD, including some of the historical and emerging NADPH oxidase inhibitors. PMID:27014073

Cerebral blood flow regulation during cognitive tasks

PubMed Central

Sorond, Farzaneh A.; Schnyer, D.M.; Serrador, J.M.; Milberg, W.P.; Lipsitz, L.A.

2008-01-01

Aging is associated with frontal subcortical microangiopathy and executive cognitive dysfunction, suggesting that elderly individuals may have impaired metabolic activation of cerebral blood flow to the frontal lobes. We used transcranial Doppler (TCD) ultrasound to examine the cerebral blood flow response to executive control and visual tasks in the anterior and posterior cerebral circulations and to determine the effects of healthy aging on cerebral blood flow regulation during cognitive tasks. Continuous simultaneous anterior cerebral artery (ACA) and posterior cerebral artery (PCA) blood flow velocities (BFVs) and mean arterial pressure (MAP) were measured in response to word stem completion (WSC) and a visual search (VS) task in 29 healthy subjects (14 young, 30 ± 1.5 years; 15 old, 74 ± 1.4 years). We found that: (1) ACA and PCA blood flow velocities are both significantly increased during WSC and VS cognitive tasks, (2) ACA and PCA activations were task specific in our young volunteers, with ACA > PCA BFV during the WSC task and PCA > ACA BFV during the VS task, (3) while healthy elderly subjects also had PCA > ACA BFV during the VS task, they did not have ACA > PCA activation during the WSC task, and (4) healthy elderly subjects tend to have overall greater increases in BFV during both cognitive tasks. We conclude that TCD can be used to monitor cerebrovascular hemodynamics during the performance of cognitive tasks. Our data suggest that there is differential blood flow increase in the ACA and PCA in young versus elderly subjects during cognitive tasks. PMID:18387547

Crossed aphasia following cerebral infarction in a right-handed patient with atypical cerebral language dominance.

PubMed

Tan, Xiaoping; Guo, Yang; Dun, Saihong; Sun, Hongzan

2018-05-18

Crossed aphasia (CA), usually referred to as an acquired language disturbance, is caused by a lesion in the cerebral hemisphere ipsilateral to the dominant hand, and the exact mechanism is not clear. The development of handedness is influenced by education and training and the impact of habitualization, while language is more susceptible to the impact of speech habits, and it is not absolutely accurate to judge cerebral language dominance by the degree of hand preference. We describe a case of CA after right hemispheric stroke in a right-handed patient with atypical language dominance and attempt to analyze the mechanism of CA based on functional imaging methods, including arterial spin labeling (ASL) and positron emission tomography/magnetic resonance imaging (PET-MRI). Brain MRI at 24 h after admission showed a large cerebral infarction in the right cerebral hemisphere, including the posteroinferior part of Broca's area in the right frontal lobe, the right temporal lobe, and the right occipital lobe. The patient exhibited a non-fluent aphasia on a standard language test (the Aphasia Battery of Chinese [ABC]) performed on the 7th day after onset. Thus, atypical language dominance was suspected. One week after admission, ASL imaging showed high perfusion in the infarct core zone and low perfusion in the left cerebellar hemisphere. Two months later, PET/MRI demonstrated low metabolism in the posterior frontal lobe, temporal lobe, temporal occipital junction area, and the right basal ganglia. The findings suggest that the patient has right-sided cerebral language dominance, or that both hemispheres have linguistic functions. Not all patients show linguistic capabilities on the side opposite hand preference. The language dominance should be predicted by a combination of clinical manifestations and functional imaging techniques.

Multiple Transmitter Receptors in Regions and Layers of the Human Cerebral Cortex

PubMed Central

Zilles, Karl; Palomero-Gallagher, Nicola

2017-01-01

We measured the densities (fmol/mg protein) of 15 different receptors of various transmitter systems in the supragranular, granular and infragranular strata of 44 areas of visual, somatosensory, auditory and multimodal association systems of the human cerebral cortex. Receptor densities were obtained after labeling of the receptors using quantitative in vitro receptor autoradiography in human postmortem brains. The mean density of each receptor type over all cortical layers and of each of the three major strata varies between cortical regions. In a single cortical area, the multi-receptor fingerprints of its strata (i.e., polar plots, each visualizing the densities of multiple different receptor types in supragranular, granular or infragranular layers of the same cortical area) differ in shape and size indicating regional and laminar specific balances between the receptors. Furthermore, the three strata are clearly segregated into well definable clusters by their receptor fingerprints. Fingerprints of different cortical areas systematically vary between functional networks, and with the hierarchical levels within sensory systems. Primary sensory areas are clearly separated from all other cortical areas particularly by their very high muscarinic M2 and nicotinic α4β2 receptor densities, and to a lesser degree also by noradrenergic α2 and serotonergic 5-HT2 receptors. Early visual areas of the dorsal and ventral streams are segregated by their multi-receptor fingerprints. The results are discussed on the background of functional segregation, cortical hierarchies, microstructural types, and the horizontal (layers) and vertical (columns) organization in the cerebral cortex. We conclude that a cortical column is composed of segments, which can be assigned to the cortical strata. The segments differ by their patterns of multi-receptor balances, indicating different layer-specific signal processing mechanisms. Additionally, the differences between the strata-and area

Chronic kidney disease and poor outcomes in ischemic stroke: is impaired cerebral autoregulation the missing link?

PubMed

Castro, Pedro; Azevedo, Elsa; Rocha, Isabel; Sorond, Farzaneh; Serrador, Jorge M

2018-03-02

Chronic kidney disease increases stroke incidence and severity but the mechanisms behind this cerebro-renal interaction are mostly unexplored. Since both vascular beds share similar features, microvascular dysfunction could be the possible missing link. Therefore, we examined the relationship between renal function and cerebral autoregulation in the early hours post ischemia and its impact on outcome. We enrolled 46 ischemic strokes (middle cerebral artery). Dynamic cerebral autoregulation was assessed by transfer function (coherence, phase and gain) of spontaneous blood pressure oscillations to blood flow velocity within 6 h from symptom-onset. Estimated glomerular filtration rate (eGFR) was calculated. Hemorrhagic transformation (HT) and white matter lesions (WML) were collected from computed tomography performed at presentation and 24 h. Outcome was evaluated with modified Rankin Scale at 3 months. High gain (less effective autoregulation) was correlated with lower eGFR irrespective of infarct side (p < 0.05). Both lower eGFR and higher gain correlated with WML grade (p < 0.05). Lower eGFR and increased gain, alone and in combination, progressively reduced the odds of a good functional outcome [ipsilateral OR = 4.39 (CI95% 3.15-25.6), p = 0.019; contralateral OR = 8.15 (CI95% 4.15-15.6), p = 0.002] and increased risk of HT [ipsilateral OR = 3.48 (CI95% 0.60-24.0), p = 0.132; contralateral OR = 6.43 (CI95% 1.40-32.1), p = 0.034]. Lower renal function correlates with less effective dynamic cerebral autoregulation in acute ischemic stroke, both predicting a bad outcome. The evaluation of serum biomarkers of renal dysfunction could have interest in the future for assessing cerebral microvascular risk and relationship with stroke complications.

Cerebral oxygenation during intermittent hypoxemia and bradycardia in preterm infants.

PubMed

Schmid, Manuel B; Hopfner, Reinhard J; Lenhof, Susanne; Hummler, Helmut D; Fuchs, Hans

2015-01-01

Episodes of hypoxemia and bradycardia frequently occur with apnea of prematurity in preterm infants. Little is known about the impact of different event types on the brain. To describe the influence of hypoxemia and bradycardia, either isolated or in combination, on cerebral oxygenation. In 16 preterm infants with intermittent hypoxemia and/or bradycardia, cerebral tissue oxygen saturation (StO2, as measured by near-infrared spectroscopy), heart rate and pulse oximetric saturation (SpO2) were recorded simultaneously for 16 h. Events were classified as isolated bradycardia (type 1), isolated hypoxemia (type 2) or combined (simultaneous, type 3; bradycardia first, type 4; hypoxemia first, type 5). Primary outcome was a score representing the area below baseline for cerebral StO2 desaturation during an event. Secondary outcomes were duration and depth of cerebral desaturation. Patients had a median (range) gestational age of 25.9 (22.6-30.4) weeks and a postnatal age of 32.5 (7-58) days. The median (quartiles) number of events was 49 (34-58). Isolated hypoxemias were the most frequent events (24; 9-36) and isolated bradycardias the least common (0; 0-1). Cerebral StO2 baseline was not different between event types. Cerebral desaturation score, duration of event and depth of cerebral desaturation were smallest for isolated bradycardias and largest for combined events, especially for those starting with hypoxemia followed by bradycardia. Regardless of event type, 12/16 infants maintained cerebral StO2 >60% despite severe SpO2 desaturations. Isolated bradycardias had the lowest impact on cerebral desaturation, and combined events had the highest. Most infants preserved cerebral oxygenation >60% during events. © 2014 S. Karger AG, Basel.

Mechanisms of Acupuncture Therapy for Cerebral Ischemia: an Evidence-Based Review of Clinical and Animal Studies on Cerebral Ischemia.

PubMed

Zhu, Wen; Ye, Yang; Liu, Yi; Wang, Xue-Rui; Shi, Guang-Xia; Zhang, Shuai; Liu, Cun-Zhi

2017-12-01

Ischemic stroke is a major cause of mortality and disability worldwide. As a part of Traditional Chinese Medicine (TCM), acupuncture has been shown to be effective in promoting recovery after stroke. In this article, we review the clinical and experimental studies that demonstrated the mechanisms of acupuncture treatment for cerebral ischemia. Clinical studies indicated that acupuncture activated relevant brain regions, modulated cerebral blood flow and related molecules in stroke patients. Evidence from laboratory indicated that acupuncture regulates cerebral blood flow and metabolism after the interrupt of blood supply. Acupuncture regulates multiple molecules and signaling pathways that lead to excitoxicity, oxidative stress, inflammation, neurons death and survival. Acupuncture also promotes neurogenesis, angiogenesis as well as neuroplasticity after ischemic damage. The evidence provided from clinical and laboratory suggests that acupuncture induces multi-level regulation via complex mechanisms and a single factor may not be enough to explain the beneficial effects against cerebral ischemia.

Cerebral metabolic intermediate response following severe canine intrauterine growth retardation.