Sample records for accidente vascular cerebral

  1. Retinal vascular changes are a marker for cerebral vascular diseases

    PubMed Central

    Moss, Heather E.

    2016-01-01

    The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. PMID:26008809

  2. Cerebral Vascular Injury in Traumatic Brain Injury.

    PubMed

    Kenney, Kimbra; Amyot, Franck; Haber, Margalit; Pronger, Angela; Bogoslovsky, Tanya; Moore, Carol; Diaz-Arrastia, Ramon

    2016-01-01

    Traumatic cerebral vascular injury (TCVI) is a very frequent, if not universal, feature after traumatic brain injury (TBI). It is likely responsible, at least in part, for functional deficits and TBI-related chronic disability. Because there are multiple pharmacologic and non-pharmacologic therapies that promote vascular health, TCVI is an attractive target for therapeutic intervention after TBI. The cerebral microvasculature is a component of the neurovascular unit (NVU) coupling neuronal metabolism with local cerebral blood flow. The NVU participates in the pathogenesis of TBI, either directly from physical trauma or as part of the cascade of secondary injury that occurs after TBI. Pathologically, there is extensive cerebral microvascular injury in humans and experimental animal, identified with either conventional light microscopy or ultrastructural examination. It is seen in acute and chronic TBI, and even described in chronic traumatic encephalopathy (CTE). Non-invasive, physiologic measures of cerebral microvascular function show dysfunction after TBI in humans and experimental animal models of TBI. These include imaging sequences (MRI-ASL), Transcranial Doppler (TCD), and Near InfraRed Spectroscopy (NIRS). Understanding the pathophysiology of TCVI, a relatively under-studied component of TBI, has promise for the development of novel therapies for TBI. Published by Elsevier Inc.

  3. Neural Vascular Mechanism for the Cerebral Blood Flow Autoregulation after Hemorrhagic Stroke.

    PubMed

    Xiao, Ming; Li, Qiang; Feng, Hua; Zhang, Le; Chen, Yujie

    2017-01-01

    During the initial stages of hemorrhagic stroke, including intracerebral hemorrhage and subarachnoid hemorrhage, the reflex mechanisms are activated to protect cerebral perfusion, but secondary dysfunction of cerebral flow autoregulation will eventually reduce global cerebral blood flow and the delivery of metabolic substrates, leading to generalized cerebral ischemia, hypoxia, and ultimately, neuronal cell death. Cerebral blood flow is controlled by various regulatory mechanisms, including prevailing arterial pressure, intracranial pressure, arterial blood gases, neural activity, and metabolic demand. Evoked by the concept of vascular neural network, the unveiled neural vascular mechanism gains more and more attentions. Astrocyte, neuron, pericyte, endothelium, and so forth are formed as a communicate network to regulate with each other as well as the cerebral blood flow. However, the signaling molecules responsible for this communication between these new players and blood vessels are yet to be definitively confirmed. Recent evidence suggested the pivotal role of transcriptional mechanism, including but not limited to miRNA, lncRNA, exosome, and so forth, for the cerebral blood flow autoregulation. In the present review, we sought to summarize the hemodynamic changes and underline neural vascular mechanism for cerebral blood flow autoregulation in stroke-prone state and after hemorrhagic stroke and hopefully provide more systematic and innovative research interests for the pathophysiology and therapeutic strategies of hemorrhagic stroke.

  4. Effects of Mild Blast Traumatic Brain Injury on Cerebral Vascular, Histopathological, and Behavioral Outcomes in Rats

    PubMed Central

    Zeng, Yaping; Deyo, Donald; Parsley, Margaret A.; Hawkins, Bridget E.; Prough, Donald S.; DeWitt, Douglas S.

    2018-01-01

    Abstract To determine the effects of mild blast-induced traumatic brain injury (bTBI), several groups of rats were subjected to blast injury or sham injury in a compressed air-driven shock tube. The effects of bTBI on relative cerebral perfusion (laser Doppler flowmetry [LDF]), and mean arterial blood pressure (MAP) cerebral vascular resistance were measured for 2 h post-bTBI. Dilator responses to reduced intravascular pressure were measured in isolated middle cerebral arterial (MCA) segments, ex vivo, 30 and 60 min post-bTBI. Neuronal injury was assessed (Fluoro-Jade C [FJC]) 24 and 48 h post-bTBI. Neurological outcomes (beam balance and walking tests) and working memory (Morris water maze [MWM]) were assessed 2 weeks post-bTBI. Because impact TBI (i.e., non-blast TBI) is often associated with reduced cerebral perfusion and impaired cerebrovascular function in part because of the generation of reactive oxygen and nitrogen species such as peroxynitrite (ONOO−), the effects of the administration of the ONOO− scavenger, penicillamine methyl ester (PenME), on cerebral perfusion and cerebral vascular resistance were measured for 2 h post-bTBI. Mild bTBI resulted in reduced relative cerebral perfusion and MCA dilator responses to reduced intravascular pressure, increases in cerebral vascular resistance and in the numbers of FJC-positive cells in the brain, and significantly impaired working memory. PenME administration resulted in significant reductions in cerebral vascular resistance and a trend toward increased cerebral perfusion, suggesting that ONOO− may contribute to blast-induced cerebral vascular dysfunction. PMID:29160141

  5. Study of the Dynamics of Transcephalic Cerebral Impedance Data during Cardio-Vascular Surgery

    NASA Astrophysics Data System (ADS)

    Atefi, S. R.; Seoane, F.; Lindecrantz, K.

    2013-04-01

    Postoperative neurological deficits are one of the risks associated with cardio vascular surgery, necessitating development of new techniques for cerebral monitoring. In this study an experimental observation regarding the dynamics of transcephalic Electrical Bioimpedance (EBI) in patients undergoing cardiac surgery with and without extracorporeal circulation (ECC) was conducted to investigate the potential use of electrical Bioimpedance for cerebral monitoring in cardio vascular surgery. Tetrapolar transcephalic EBI measurements at single frequency of 50 kHz were recorded prior to and during cardio vascular surgery. The obtained results show that the transcephalic impedance decreases in both groups of patients as operation starts, however slight differences in these two groups were also observed with the cerebral impedance reduction in patients having no ECC being less common and not as pronounced as in the ECC group. Changes in the cerebral impedance were in agreement with changes of haematocrit and temperature. The origin of EBI changes is still unexplained however these results encourage us to continue investigating the application of electrical bioimpedance cerebral monitoring clinically.

  6. Cerebral vascular reactivity on return from the International Space Station

    NASA Astrophysics Data System (ADS)

    Zuj, Kathryn; Greaves, Danielle; Shoemaker, Kevin; Blaber, Andrew; Hughson, Richard L.

    Returning from spaceflight, astronauts experience a high incidence of orthostatic intolerance and syncope. Longer duration space flight may result in greater adaptations to microgravity which could increase the post-flight incidence of syncope. CCISS (Cardiovascular and Cerebovascular Control on return from the International Space Station) is an ongoing project designed to help determine adaptations that occur during spaceflight which may contribute to orthostatic intolerance. One component of this project involves looking at cerebral vascular responses before and after long duration spaceflight. As a known vasodilator, carbon dioxide (CO2) has been frequently used to assess changes in cerebral vascular reactivity. In this experiment, end tidal PCO2 was manipulated through changes in respired air. Two breaths of a 10% CO2 gas mixture were administered at 1-min intervals resulting in an increase in end tidal PCO2 . Throughout the testing, cerebral blood flow velocity (CBFV) was determined using transcranial Doppler ultrasound. The cerebral resistance index (RI) was calculated from the Doppler wave form using the equation; RI=(CBFVsystolic-CBFVdiastolic)/CBFVsystolic. Changes in this index have been shown to reflect changes in cerebral vascular resistance. Peak responses to the CO2 stimulus were determined and compared to baseline measures taken at the beginning of the testing. Cerebral blood flow velocity increased and RI decreased with the two breaths of CO2. Preliminary data show a 36.0% increase in CBFV and a 9.0% decrease in RI pre-flight. Post flight, the response to CO2 appears to change showing a potentially blunted decrease in resistance (6.8%) and a smaller increase in CBFV (22.8%). Long term spaceflight may result in cerebrovascular changes which could decrease the vasodilatory capacity of cerebral resistance vessels. Further investigations in the CCISS project will reveal the interactive role of CO2 and arterial blood pressure on maintenance of brain

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

    PubMed

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

    2017-08-01

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

  8. Cerebral oximetry in cardiac and major vascular surgery.

    PubMed

    Fischer, G W; Silvay, G

    2010-01-01

    We describe the development and current applications of cerebral oximetry (based on near-infrared reflectance spectroscopy) that can be used during cardiac and major vascular surgery to determined brain tissue oxygen saturation. There are presently three cerebral oximetry devices with FDA approval in the United States to measure and monitor cerebral tissue oxygen saturation. 1. INVOS (Somanetics Corporation, Troy, MI - recently COVIDIEN, Boulder, CO); FORE-SIGHT (CAS Medical Systems, Inc. Branford, CT); EQUANOX (Nonin Medical Inc.Minnesota, MN). All devices are portable, non-invasive and easy to use in operating room and intensive care unit. The data provided in these communication may provided information for improvement of perioperative neuromonitoring techniques, and may be crucial in the design of future clinical trials.

  9. The relationship to age and cerebral vascular accidents of fibrin and fibrinolytic activity

    PubMed Central

    Hume, R.

    1961-01-01

    Three `normal' groups of people—young, middle-aged, and old—have been investigated with regard to the fibrin content and fibrinolytic activity of the blood. The fourth group consisted of middle-aged people who had previously sustained a cerebral vascular accident matched statistically for age with the middle-aged normals. It was concluded that fibrin increases with age but there is an interaction between age and sex, the female having a higher level in the young group and the male a higher level in the middle-aged group. There was no sex difference in the levels of fibrin in the old age group. Fibrinolytic activity increases with age and there is a positive correlation between fibrin and fibrinolytic activity but no age-sex interaction. Those with cerebral vascular accidents tended to have higher fibrin levels and lower fibrinolytic activity but the differences were not statistically significant. There did, however, appear to be an increase in antifibrinolytic activity in the cerebral vascular group. PMID:13716799

  10. [Results of percutaneous transluminal dilatation of cerebral vascular stenoses].

    PubMed

    Kachel, R; Ritter, H; Grossmann, K; Glaser, F H

    1986-03-01

    The present paper is a review of 37 successful catheter dilatations of supra-aortic vascular stenoses. There were sixteen patients with a total of 21 stenoses of the internal carotid, vertebral artery or common carotid artery and sixteen patients with subclavian stenoses. Amongst the patients with stenoses of the cerebral vessels, there were ten with multiple lesions and six with a single stenosis. Three patients had successful dilatations of bilateral stenoses. The indications, technique, and complications of catheter dilatation of lesions of the cerebral vessels are described and discussed.

  11. A failure to communicate: patients with cerebral aneurysms and vascular neurosurgeons.

    PubMed

    King, J T; Yonas, H; Horowitz, M B; Kassam, A B; Roberts, M S

    2005-04-01

    To assess communication between vascular neurosurgeons and their patients with unruptured cerebral aneurysms about treatment options and expected outcomes. Vascular neurosurgeons and their patients with cerebral aneurysms were surveyed immediately following outpatient appointments in a neurosurgery clinic. Data collected included how well the patient understood their aneurysm treatment options, the risks of a poor outcome from various treatments, and the consensus "best" treatment. Patient and neurosurgeon responses were measured using Likert scales, multiple choice questions, and visual analogue scales. Agreement between patient and neurosurgeon was assessed with kappa scores. The Wilcoxon sign rank test was used to compare visual analogue scale responses. Data for 44 patient-neurosurgeon pairs were collected. Only 61% of patient-neurosurgeon pairs agreed on the best treatment plan for the patient's aneurysm (kappa = 0.51, moderate agreement). Among the neurosurgeons, agreement with their patients ranged from 82% (kappa = 0.77, almost perfect agreement) to 52% (kappa = 0.37, fair agreement). Patients estimated much higher risks of stroke or death from surgical clipping, endovascular embolisation, or no intervention compared with the estimates offered by their neurosurgeons (surgical clipping: patient 36% v neurosurgeon 13%, p<0.001; endovascular embolisation: patient 35% v neurosurgeon 19%, p = 0.040; and no patient 63% v neurosurgeon 25%, p<0.001). Following consultation with a vascular neurosurgeon, many patients with cerebral aneurysms have an inaccurate understanding of their aneurysm treatment plan and an exaggerated sense of the risks of aneurysmal disease and treatment.

  12. Selective head cooling during neonatal seizures prevents postictal cerebral vascular dysfunction without reducing epileptiform activity

    PubMed Central

    Harsono, Mimily; Pourcyrous, Massroor; Jolly, Elliott J.; de Jongh Curry, Amy; Fedinec, Alexander L.; Liu, Jianxiong; Basuroy, Shyamali; Zhuang, Daming; Leffler, Charles W.

    2016-01-01

    Epileptic seizures in neonates cause cerebrovascular injury and impairment of cerebral blood flow (CBF) regulation. In the bicuculline model of seizures in newborn pigs, we tested the hypothesis that selective head cooling prevents deleterious effects of seizures on cerebral vascular functions. Preventive or therapeutic ictal head cooling was achieved by placing two head ice packs during the preictal and/or ictal states, respectively, for the ∼2-h period of seizures. Head cooling lowered the brain and core temperatures to 25.6 ± 0.3 and 33.5 ± 0.1°C, respectively. Head cooling had no anticonvulsant effects, as it did not affect the bicuculline-evoked electroencephalogram parameters, including amplitude, duration, spectral power, and spike frequency distribution. Acute and long-term cerebral vascular effects of seizures in the normothermic and head-cooled groups were tested during the immediate (2–4 h) and delayed (48 h) postictal periods. Seizure-induced cerebral vascular injury during the immediate postictal period was detected as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive staining of cerebral arterioles and a surge of brain-derived circulating endothelial cells in peripheral blood in the normothermic group, but not in the head-cooled groups. During the delayed postictal period, endothelium-dependent cerebral vasodilator responses were greatly reduced in the normothermic group, indicating impaired CBF regulation. Preventive or therapeutic ictal head cooling mitigated the endothelial injury and greatly reduced loss of postictal cerebral vasodilator functions. Overall, head cooling during seizures is a clinically relevant approach to protecting the neonatal brain by preventing cerebrovascular injury and the loss of the endothelium-dependent control of CBF without reducing epileptiform activity. PMID:27591217

  13. A failure to communicate: patients with cerebral aneurysms and vascular neurosurgeons

    PubMed Central

    King, J; Yonas, H; Horowitz, M; Kassam, A; Roberts, M

    2005-01-01

    Objective: To assess communication between vascular neurosurgeons and their patients with unruptured cerebral aneurysms about treatment options and expected outcomes. Methods: Vascular neurosurgeons and their patients with cerebral aneurysms were surveyed immediately following outpatient appointments in a neurosurgery clinic. Data collected included how well the patient understood their aneurysm treatment options, the risks of a poor outcome from various treatments, and the consensus "best" treatment. Patient and neurosurgeon responses were measured using Likert scales, multiple choice questions, and visual analogue scales. Agreement between patient and neurosurgeon was assessed with kappa scores. The Wilcoxon sign rank test was used to compare visual analogue scale responses. Results: Data for 44 patient–neurosurgeon pairs were collected. Only 61% of patient–neurosurgeon pairs agreed on the best treatment plan for the patient's aneurysm (κ = 0.51, moderate agreement). Among the neurosurgeons, agreement with their patients ranged from 82% (κ = 0.77, almost perfect agreement) to 52% (κ = 0.37, fair agreement). Patients estimated much higher risks of stroke or death from surgical clipping, endovascular embolisation, or no intervention compared with the estimates offered by their neurosurgeons (surgical clipping: patient 36% v neurosurgeon 13%, p<0.001; endovascular embolisation: patient 35% v neurosurgeon 19%, p = 0.040; and no intervention: patient 63% v neurosurgeon 25%, p<0.001). Conclusions: Following consultation with a vascular neurosurgeon, many patients with cerebral aneurysms have an inaccurate understanding of their aneurysm treatment plan and an exaggerated sense of the risks of aneurysmal disease and treatment. PMID:15774444

  14. Sulforaphane activates the cerebral vascular Nrf2-ARE pathway and suppresses inflammation to attenuate cerebral vasospasm in rat with subarachnoid hemorrhage.

    PubMed

    Zhao, Xudong; Wen, Liting; Dong, Min; Lu, Xiaojie

    2016-12-15

    Nrf2-ARE pathway reportedly plays a protective role in several central nervous system diseases. No study has explored the role of the Nrf2-ARE pathway in cerebral vasospasm(CVS) after subarachnoid hemorrhage(SAH). The purpose of the present study was to investigate the activation of the cerebral vascular Nrf2-ARE pathway and to determine the potential role of this pathway in the development of CVS following SAH. We investigated whether the administration of sulforaphane (SFN, a specific Nrf2 activator) modulated vascular caliber, Nrf2-ARE pathway activity, proinflammatory cytokine expression, and clinical behavior in a rat model of SAH. A two-hemorrhage protocol was used to generate an animal model of SAH in male Sprague-Dawley rats. Administration of SFN to these rats following SAH enhanced the activity of the Nrf2-ARE pathway and suppressed the release of proinflammatory cytokines. Vasospasm was markedly attenuated in the basilar arteries after SFN therapy. Additionally, SFN administration significantly ameliorated two behavioral functions disrupted by SAH. These results suggest that SFN has a therapeutic benefit in post-SAH, and this may be due to elevated Nrf2-ARE pathway activity and inhibition of cerebral vascular proinflammatory cytokine expression. Copyright © 2016. Published by Elsevier B.V.

  15. Simvastatin attenuates the cerebral vascular endothelial inflammatory response in a rat traumatic brain injury.

    PubMed

    Wang, Kuo-Wei; Chen, Han-Jung; Lu, Kang; Liliang, Po-Chou; Liang, Cheng-Loong; Tsai, Yu-Duan; Cho, Chung-Lung

    2014-01-01

    Traumatic brain injury (TBI) leads to important and deleterious inflammation, as evidenced by edema, cytokine production, induction of nitric oxide synthase, and leukocyte infiltration. After TBI, the activation of cerebral vascular endothelial cells plays a crucial role in the pathogenesis of inflammation. In this study, we hypothesized that the activation of cerebral vascular endothelial cells plays a crucial role in the pathogenesis of inflammation and outcome after TBI. It may represent a key cellular target for statin therapy. In our study, cortical contusions were induced, and the effect of continuous treatment of simvastatin on behavior and inflammation in adult rats following experimental TBI was evaluated. The treatment group received 15 mg/kg of simvastatin daily for 3 days. Neurological function was assessed with the grip test. The results showed that the non-treatment control group had a significantly greater increase in ICAM-1 expression from pre-injury to the post-injury 72 h time point as compared to the expression in treatment group. The treatment group had better neurological function as evidenced in a grip test performed from baseline to 72 h. The analysis of a western blot test and pathology also demonstrated reduced ICAM-1 expression and a smaller area of damage and tissue loss. Our findings suggest that simvastatin could attenuate the activation of cerebral vascular endothelial inflammatory response and decrease the loss of neurological function and brain tissue.

  16. Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke

    PubMed Central

    Hu, Xiaoming; De Silva, T. Michael; Chen, Jun; Faraci, Frank M.

    2017-01-01

    The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury following ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood-brain barrier (BBB) is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in BBB integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events. PMID:28154097

  17. Cerebral Vascular Disease and Neurovascular Injury in Ischemic Stroke.

    PubMed

    Hu, Xiaoming; De Silva, T Michael; Chen, Jun; Faraci, Frank M

    2017-02-03

    The consequences of cerebrovascular disease are among the leading health issues worldwide. Large and small cerebral vessel disease can trigger stroke and contribute to the vascular component of other forms of neurological dysfunction and degeneration. Both forms of vascular disease are driven by diverse risk factors, with hypertension as the leading contributor. Despite the importance of neurovascular disease and subsequent injury after ischemic events, fundamental knowledge in these areas lag behind our current understanding of neuroprotection and vascular biology in general. The goal of this review is to address select key structural and functional changes in the vasculature that promote hypoperfusion and ischemia, while also affecting the extent of injury and effectiveness of therapy. In addition, as damage to the blood-brain barrier is one of the major consequences of ischemia, we discuss cellular and molecular mechanisms underlying ischemia-induced changes in blood-brain barrier integrity and function, including alterations in endothelial cells and the contribution of pericytes, immune cells, and matrix metalloproteinases. Identification of cell types, pathways, and molecules that control vascular changes before and after ischemia may result in novel approaches to slow the progression of cerebrovascular disease and lessen both the frequency and impact of ischemic events. © 2017 American Heart Association, Inc.

  18. Effects of acetazolamide on the micro- and macro-vascular cerebral hemodynamics: a diffuse optical and transcranial doppler ultrasound study

    PubMed Central

    Zirak, Peyman; Delgado-Mederos, Raquel; Martí-Fàbregas, Joan; Durduran, Turgut

    2010-01-01

    Acetazolamide (ACZ) was used to stimulate the cerebral vasculature on ten healthy volunteers to assess the cerebral vasomotor reactivity (CVR). We have combined near infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS) and transcranial Doppler (TCD) technologies to non-invasively assess CVR in real-time by measuring oxy- and deoxy-hemoglobin concentrations, using NIRS, local cerebral blood flow (CBF), using DCS, and blood flow velocity (CBFV) in the middle cerebral artery, using TCD. Robust and persistent increases in oxy-hemoglobin concentration, CBF and CBFV were observed. A significant agreement was found between macro-vascular (TCD) and micro-vascular (DCS) hemodynamics, between the NIRS and TCD data, and also within NIRS and DCS results. The relative cerebral metabolic rate of oxygen, rCMRO2, was also determined, and no significant change was observed. Our results showed that the combined diffuse optics-ultrasound technique is viable to follow (CVR) and rCMRO2 changes in adults, continuously, at the bed-side and in real time. PMID:21258561

  19. Effects of acetazolamide on the micro- and macro-vascular cerebral hemodynamics: a diffuse optical and transcranial doppler ultrasound study.

    PubMed

    Zirak, Peyman; Delgado-Mederos, Raquel; Martí-Fàbregas, Joan; Durduran, Turgut

    2010-11-19

    Acetazolamide (ACZ) was used to stimulate the cerebral vasculature on ten healthy volunteers to assess the cerebral vasomotor reactivity (CVR). We have combined near infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS) and transcranial Doppler (TCD) technologies to non-invasively assess CVR in real-time by measuring oxy- and deoxy-hemoglobin concentrations, using NIRS, local cerebral blood flow (CBF), using DCS, and blood flow velocity (CBFV) in the middle cerebral artery, using TCD. Robust and persistent increases in oxy-hemoglobin concentration, CBF and CBFV were observed. A significant agreement was found between macro-vascular (TCD) and micro-vascular (DCS) hemodynamics, between the NIRS and TCD data, and also within NIRS and DCS results. The relative cerebral metabolic rate of oxygen, rCMRO(2), was also determined, and no significant change was observed. Our results showed that the combined diffuse optics-ultrasound technique is viable to follow (CVR) and rCMRO(2) changes in adults, continuously, at the bed-side and in real time.

  20. Disparate cardio-cerebral vascular modulation during standing in multiple system atrophy and Parkinson disease.

    PubMed

    Xu, Wei-Hai; Wang, Han; Wang, Bo; Niu, Fu-Sheng; Gao, Shan; Cui, Li-Ying

    2009-01-15

    The dynamic variance of cerebral blood flow velocity (CBFV), monitored by transcranial doppler (TCD), can reveal the integrated effects of cardio-cerebral vascular autoregulation. We investigated the characteristics of CBFV curve during active standing in multiple system atrophy (MSA), Parkinson's disease (PD) and healthy volunteers. The CBFV curve of middle cerebral arteries was recorded using TCD in 22 patients with probable MSA; 20 PD patients and 20 volunteers matched for age. All individuals started in a supine posture, followed by abrupt standing for 2 min before returning to supine. The features of CBFV curve were compared among the groups. In the healthy volunteers, the CBFV decreased following standing up but quickly rebounded and reached the same or greater level as the supine baseline. Afterwards, the CBFV decreased abruptly to a sustained level, lower than the supine baseline, forming a spike wave that appeared in CBFV curve. This spike wave was present in 5/22 of MSA, significantly less than PD patients (18/20) and volunteers (20/20) (P<0.001). The CBFV decrease after standing showed no significant difference between MSA than PD (9+/-7 vs. 6+/-3 cm/s, P=0.163). The different pattern of CBFV curves during active standing suggests MSA may possess cardio-cerebral vascular modulation different from PD. The clinical value of the CBFV curve in differentiating MSA from PD needs further investigation.

  1. Dual-wavelength hybrid optoacoustic-ultrasound biomicroscopy for functional imaging of large-scale cerebral vascular networks.

    PubMed

    Rebling, Johannes; Estrada, Héctor; Gottschalk, Sven; Sela, Gali; Zwack, Michael; Wissmeyer, Georg; Ntziachristos, Vasilis; Razansky, Daniel

    2018-04-19

    A critical link exists between pathological changes of cerebral vasculature and diseases affecting brain function. Microscopic techniques have played an indispensable role in the study of neurovascular anatomy and functions. Yet, investigations are often hindered by suboptimal trade-offs between the spatiotemporal resolution, field-of-view (FOV) and type of contrast offered by the existing optical microscopy techniques. We present a hybrid dual-wavelength optoacoustic (OA) biomicroscope capable of rapid transcranial visualization of large-scale cerebral vascular networks. The system offers 3-dimensional views of the morphology and oxygenation status of the cerebral vasculature with single capillary resolution and a FOV exceeding 6 × 8 mm 2 , thus covering the entire cortical vasculature in mice. The large-scale OA imaging capacity is complemented by simultaneously acquired pulse-echo ultrasound (US) biomicroscopy scans of the mouse skull. The new approach holds great potential to provide better insights into cerebrovascular function and facilitate efficient studies into neurological and vascular abnormalities of the brain. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Critical role of matrix metalloprotease-9 in chronic high fat diet-induced cerebral vascular remodelling and increase of ischaemic brain injury in mice†

    PubMed Central

    Deng, Jiao; Zhang, Junfeng; Feng, Chenzhuo; Xiong, Lize; Zuo, Zhiyi

    2014-01-01

    Aims About one-third of American adults and 20% of teenagers are obese. Obesity and its associated metabolic disturbances including hyperlipidaemia are risk factors for cardiovascular diseases including stroke. They can worsen neurological outcome after stroke. We determined whether obesity and hyperlipidaemia could induce cerebral vascular remodelling via matrix metalloproteases (MMP) and whether this remodelling affected neurological outcome after brain ischaemia. Methods and results Six-week-old male CD1, C57BL/6J, and MMP-9−/− mice were fed regular diet (RD) or high-fat diet (HFD) for 10 weeks. They were subjected to vascular casting or a 90 min middle cerebral arterial occlusion (MCAO). Mice on HFD were heavier and had higher blood glucose and lipid levels than those on RD. HFD-fed CD1 and C57BL/6J mice had an increased cerebral vascular tortuosity index and decreased inner diameters of the middle cerebral arterial root. HFD increased microvessel density in CD1 mouse cerebral cortex. After MCAO, CD1 and C57BL/6J mice on HFD had a bigger infarct volume, more severe brain oedema and blood–brain barrier damage, higher haemorrhagic transformation rate, greater haemorrhagic volume, and worse neurological function. HFD increased MMP-9 activity in the ischaemic and non-ischaemic brain tissues. Although HFD increased the body weights, blood glucose, and lipid levels in the MMP-9−/− mice on a C57BL/6J genetic background, the HFD-induced cerebral vascular remodelling and worsening of neurological outcome did not occur in these mice. Conclusion HFD induces cerebral vascular remodelling and worsens neurological outcome after transient focal brain ischaemia. MMP-9 activation plays a critical role in these HFD effects. PMID:24935427

  3. Central Pulsatile Pressure and Flow Relationship in the Time and Frequency Domain to Characterise Hydraulic Input to the Brain and Cerebral Vascular Impedance.

    PubMed

    Kim, Mi Ok; O'Rourke, Michael F; Adji, Audrey; Avolio, Alberto P

    2016-01-01

    In the time domain, pulsatile flow and pressure can be characterised as the ratio of the late systolic boost of flow or pressure to the pulse amplitude so as to estimate the hydraulic input to the brain. While vascular impedance has been widely used to represent the load presented to the heart by the systemic circulation, it has not been applied to the cerebral circulation.We set out to study the relationship between the pressure and the flow augmentation index (AIx) in the time domain and to determine cerebral vascular impedance using aortic blood pressure and cerebral blood flow waveforms in the frequency domain. Twenty-four young subjects (aged 21-39 years) were recruited; aortic pressure was derived using SphygmoCor from radial pressure. Flow waveforms were recorded from the middle cerebral artery. In three subjects, we performed the Valsalva manoeuvre to investigate their response to physiological intervention. There was a linear relationship between flow and pressure AIx, and cerebral impedance values were similar to those estimated for low resistance vascular beds. Substantial change in pressure and flow wave contour was observed during the Valsalva manoeuvre; however, the relationship in both the time and the frequency domains were unchanged. This confirms that aortic pressure and cerebral flow waveform can be used to study cerebral impedance.

  4. PPARδ regulation of miR-15a in ischemia-induced cerebral vascular endothelial injury

    PubMed Central

    Yin, K.J.; Deng, Z.; Hamblin, M.; Xiang, Y.; Huang, H.R.; Zhang, J.; Jiang, X. D.; Wang, Y.; Chen, Y. E.

    2010-01-01

    Cerebral endothelial cell (CEC) degeneration significantly contributes to blood-brain barrier (BBB) breakdown and neuronal loss after cerebral ischemia. Recently, emerging data suggest that peroxisome proliferator-activated receptor δ (PPARδ) activation has a potential neuroprotective role in ischemic stroke. Here we report for the first time that PPARδ is significantly reduced in oxygen-glucose deprivation (OGD)-induced mouse CEC death. Interestingly, PPARδ overexpression can suppress OGD-induced caspase-3 activity, Golgi fragmentation, and CEC death through an increase of bcl-2 protein levels without change of bcl-2 mRNA levels. To explore the molecular mechanisms, we have identified that upregulation of PPARδ can alleviate ODG-activated microRNA-15a (miR-15a) expression in CECs. Moreover, we have demonstrated that bcl-2 is a translationally-repressed target of miR-15a. Intriguingly, gain- or loss-of-miR-15a function can significantly reduce or increase OGD-induced CEC death, respectively. Furthermore, we have identified that miR-15a is a transcriptional target of PPARδ. Consistent with the in vitro findings, we found that intracerebroventricular infusion of a specific PPARδ agonist, GW 501516, significantly reduced ischemia-induced miR-15a expression, increased bcl-2 protein levels, and attenuated caspase-3 activity and subsequent DNA fragmentation in isolated cerebral microvessels, leading to decreased BBB disruption and reduced cerebral infarction in mice after transient focal cerebral ischemia. Taken together, these results suggest that PPARδ plays a vascular-protective role in ischemia-like insults via transcriptional repression of miR-15a, resulting in subsequent release of its posttranscriptional inhibition of bcl-2. Thus, regulation of PPARδ-mediated miR-15a inhibition of bcl-2 could provide a novel therapeutic strategy for the treatment of stroke-related vascular dysfunction. PMID:20445066

  5. A theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast MRI.

    PubMed

    Digernes, Ingrid; Bjørnerud, Atle; Vatnehol, Svein Are S; Løvland, Grete; Courivaud, Frédéric; Vik-Mo, Einar; Meling, Torstein R; Emblem, Kyrre E

    2017-06-01

    Mapping the complex heterogeneity of vascular tissue in the brain is important for understanding cerebrovascular disease. In this translational study, we build on previous work using vessel architectural imaging (VAI) and present a theoretical framework for determining cerebral vascular function and heterogeneity from dynamic susceptibility contrast magnetic resonance imaging (MRI). Our tissue model covers realistic structural architectures for vessel branching and orientations, as well as a range of hemodynamic scenarios for blood flow, capillary transit times and oxygenation. In a typical image voxel, our findings show that the apparent MRI relaxation rates are independent of the mean vessel orientation and that the vortex area, a VAI-based parameter, is determined by the relative oxygen saturation level and the vessel branching of the tissue. Finally, in both simulated and patient data, we show that the relative distributions of the vortex area parameter as a function of capillary transit times show unique characteristics in normal-appearing white and gray matter tissue, whereas tumour-voxels in comparison display a heterogeneous distribution. Collectively, our study presents a comprehensive framework that may serve as a roadmap for in vivo and per-voxel determination of vascular status and heterogeneity in cerebral tissue.

  6. Vascular ring complicates accidental button battery ingestion.

    PubMed

    Mercer, Ronald W; Schwartz, Matthew C; Stephany, Joshua; Donnelly, Lane F; Franciosi, James P; Epelman, Monica

    2015-01-01

    Button battery ingestion can lead to dangerous complications, including vasculoesophageal fistula formation. The presence of a vascular ring may complicate battery ingestion if the battery lodges at the level of the ring and its important vascular structures. We report a 4-year-old boy with trisomy 21 who was diagnosed with a vascular ring at the time of button battery ingestion and died 9 days after presentation due to massive upper gastrointestinal bleeding from esophageal erosion and vasculoesophageal fistula formation. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Placental growth factor deficiency is associated with impaired cerebral vascular development in mice.

    PubMed

    Luna, Rayana Leal; Kay, Vanessa R; Rätsep, Matthew T; Khalaj, Kasra; Bidarimath, Mallikarjun; Peterson, Nichole; Carmeliet, Peter; Jin, Albert; Croy, B Anne

    2016-02-01

    Placental growth factor (PGF) is expressed in the developing mouse brain and contributes to vascularization and vessel patterning. PGF is dynamically expressed in fetal mouse brain, particularly forebrain, and is essential for normal cerebrovascular development. PGF rises in maternal plasma over normal human and mouse pregnancy but is low in many women with the acute onset hypertensive syndrome, pre-eclampsia (PE). Little is known about the expression of PGF in the fetus during PE. Pgf  (-/-) mice appear normal but recently cerebral vascular defects were documented in adult Pgf  (-/-) mice. Here, temporal-spatial expression of PGF is mapped in normal fetal mouse brains and cerebral vasculature development is compared between normal and congenic Pgf  (-/-) fetuses to assess the actions of PGF during cerebrovascular development. Pgf/PGF, Vegfa/VEGF, Vegf receptor (Vegfr)1 and Vegfr2 expression were examined in the brains of embryonic day (E)12.5, 14.5, 16.5 and 18.5 C57BL/6 (B6) mice using quantitative PCR and immunohistochemistry. The cerebral vasculature was compared between Pgf  (-/-) and B6 embryonic and adult brains using whole mount techniques. Vulnerability to cerebral ischemia was investigated using a left common carotid ligation assay. Pgf/PGF and Vegfr1 are highly expressed in E12.5-14.5 forebrain relative to VEGF and Vegfr2. Vegfa/VEGF is relatively more abundant in hindbrain (HB). PGF and VEGF expression were similar in midbrain. Delayed HB vascularization was seen at E10.5 and 11.5 in Pgf  (-/-) brains. At E14.5, Pgf  (-/-) circle of Willis showed unilateral hypoplasia and fewer collateral vessels, defects that persisted post-natally. Functionally, adult Pgf  (-/-) mice experienced cerebral ischemia after left common carotid arterial occlusion while B6 mice did not. Since Pgf  (-/-) mice were used, consequences of complete absence of maternal and fetal PGF were defined. Therefore, the effects of maternal versus fetal PGF

  8. Microvasculature of the cerebral cortex: a vascular corrosion cast and immunocytochemical study.

    PubMed

    Scala, Gaetano

    2014-04-01

    In mammals, the cerebral cortex microvasculature (CCM) of the neopallium plays important roles in the physiological and pathological processes of the brain. The aim of the present work is to analyze the CCM by use of the SEM-vascular corrosion cast technique, and to examine the immunocytochemical characteristics of the CCM in adult domestic ruminants (cattle, buffalo, and sheep) by using the SEM-immunogold technique. The CCM originated from the very small, finger-like terminal branches of the macrovasculature of the brain. The superficial cortical arterioles were more numerous than the deep straight arterioles which proceeded toward the white matter. The surface casts of the arterioles and capillaries of the cerebral cortex showed ring-shaped formations in the arterioles and at the origin of the capillaries. All capillaries down-stream from these ring-shaped formations were flaccid. Casts of the capillaries showed wrinkles due to the presence of endothelial folds, which is characteristic of varying blood pressure. Formations having intense anti-GIFAP immunoreactivity were frequently evident along the course of the blood capillaries in the cerebral cortex. These formations were probably astrocytes that might regulate the cerebral microcirculation based on physiological and pathological stimuli, such as neuronal activation. Copyright © 2014 Wiley Periodicals, Inc.

  9. 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.

  10. Cerebral dominance for speech and handwriting of patients with cortical vascular malformations.

    PubMed

    Sass, K J; Buchanan, C P; Westerveld, M; Spencer, D D

    1994-10-01

    Lateralization of speech dominance was established using amobarbital for 22 patients with vascular malformations lateralized to the left cerebral hemisphere. Patients' histories were negative for clinically evident neurological events (e.g., seizures or hemorrhage) prior to adulthood. The vascular lesions were categorized as high flow arteriovenous malformations (AVMs) (n = 4), low flow AVMs (n = 6), cavernous hemangiomas (n = 10), or venous angiomas (n = 2) by reviewing angiographic findings and surgical pathology for those patients whose lesions were excised. Three of the malformations encroached upon primary language areas. The frequency of right hemisphere speech dominance was not significantly elevated in comparison with the normal population, even though the incidence of nonright-handedness was. Ninety-five percent of the patients were left hemisphere dominant for speech: only one patient, with a parietal lobe cavernous hemangioma, was found to be right hemisphere dominant for speech. This malformation did not involve the primary language areas. These findings suggest that vascular malformations do not affect speech dominance as readily as other neurological diseases, but frequently affect manual dominance.

  11. Cortical Cerebral Microinfarcts on 3 Tesla MRI in Patients with Vascular Cognitive Impairment.

    PubMed

    Ferro, Doeschka A; van Veluw, Susanne J; Koek, Huiberdina L; Exalto, Lieza G; Biessels, Geert Jan

    2017-01-01

    Cerebral microinfarcts (CMIs) are small ischemic lesions that are a common neuropathological finding in patients with stroke or dementia. CMIs in the cortex can now be detected in vivo on 3 Tesla MRI. To determine the occurrence of CMIs and associated clinical features in patients with possible vascular cognitive impairment (VCI). 182 memory-clinic patients (mean age 71.4±10.6, 55% male) with vascular injury on brain MRI (i.e., possible VCI) underwent a standardized work-up including 3 Tesla MRI and cognitive assessment. A control group consisted of 70 cognitively normal subjects (mean age 70.6±4.7, 60% male). Cortical CMIs and other neuroimaging markers of vascular brain injury were rated according to established criteria. Occurrence of CMIs was higher (20%) in patients compared to controls (10%). Among patients, the presence of CMIs was associated with male sex, history of stroke, infarcts, and white matter hyperintensities. CMI presence was also associated with a diagnosis of vascular dementia and reduced performance in multiple cognitive domains. CMIs on 3 Tesla MRI are common in patients with possible VCI and co-occur with imaging markers of small and large vessel disease, likely reflecting a heterogeneous etiology. CMIs are associated with worse cognitive performance, independent of other markers of vascular brain injury.

  12. Degos disease: a new simulator of non-accidental injury.

    PubMed

    Moss, Celia; Wassmer, Evangeline; Debelle, Geoff; Hackett, Scott; Goodyear, Helen; Malcomson, Roger; Ryder, Clive; Sgouros, Spyros; Shahidullah, Hossain

    2009-08-01

    Recent high-profile cases have made paediatricians very aware of the serious implications of either missing or wrongly diagnosing non-accidental injury. Subdural fluid collections in non-mobile infants usually represent haemorrhage caused by non-accidental injury. We report a 6-month-old male who presented to the Accident and Emergency Department of Birmingham Heartlands Hospital with bilateral subdural fluid collections and skin ulcers resembling cigarette burns. Non-accidental injury was considered to be the most likely diagnosis. However, while under observation in hospital, the child's neurological condition deteriorated with progressive cerebral infarctions, and serial photographs of the skin lesions showed failure to heal. The revised diagnosis, confirmed histologically, was Degos disease, an extremely rare and often fatal occlusive vasculopathy. The child was treated palliatively and died 8 weeks after presentation. This report informs doctors of a new simulator of non-accidental injury to be considered in infants with otherwise unexplained subdural fluid collections.

  13. Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia.

    PubMed

    Duncombe, Jessica; Kitamura, Akihiro; Hase, Yoshiki; Ihara, Masafumi; Kalaria, Raj N; Horsburgh, Karen

    2017-10-01

    Increasing evidence suggests that vascular risk factors contribute to neurodegeneration, cognitive impairment and dementia. While there is considerable overlap between features of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD), it appears that cerebral hypoperfusion is the common underlying pathophysiological mechanism which is a major contributor to cognitive decline and degenerative processes leading to dementia. Sustained cerebral hypoperfusion is suggested to be the cause of white matter attenuation, a key feature common to both AD and dementia associated with cerebral small vessel disease (SVD). White matter changes increase the risk for stroke, dementia and disability. A major gap has been the lack of mechanistic insights into the evolution and progress of VCID. However, this gap is closing with the recent refinement of rodent models which replicate chronic cerebral hypoperfusion. In this review, we discuss the relevance and advantages of these models in elucidating the pathogenesis of VCID and explore the interplay between hypoperfusion and the deposition of amyloid β (Aβ) protein, as it relates to AD. We use examples of our recent investigations to illustrate the utility of the model in preclinical testing of candidate drugs and lifestyle factors. We propose that the use of such models is necessary for tackling the urgently needed translational gap from preclinical models to clinical treatments. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  14. Cerebral vascular structure in the motor cortex of adult mice is stable and is not altered by voluntary exercise.

    PubMed

    Cudmore, Robert H; Dougherty, Sarah E; Linden, David J

    2017-12-01

    The cerebral vasculature provides blood flow throughout the brain, and local changes in blood flow are regulated to match the metabolic demands of the active brain regions. This neurovascular coupling is mediated by real-time changes in vessel diameter and depends on the underlying vascular network structure. Neurovascular structure is configured during development by genetic and activity-dependent factors. In adulthood, it can be altered by experiences such as prolonged hypoxia, sensory deprivation and seizure. Here, we have sought to determine whether exercise could alter cerebral vascular structure in the adult mouse. We performed repeated in vivo two-photon imaging in the motor cortex of adult transgenic mice expressing membrane-anchored green fluorescent protein in endothelial cells (tyrosine endothelial kinase 2 receptor (Tie2)-Cre:mTmG). This strategy allows for high-resolution imaging of the vessel walls throughout the lifespan. Vascular structure, as measured by capillary branch point number and position, segment diameter and length remained stable over a time scale of months as did pericyte number and position. Furthermore, we compared the vascular structure before, during, and after periods of voluntary wheel running and found no alterations in these same parameters. In both running and control mice, we observed a low rate of capillary segment subtraction. Interestingly, these rare subtraction events preferentially remove short vascular loops.

  15. Improving Cognitive Function in Veterans with Gulf War Illness by Improving Cerebral Vascular Function

    DTIC Science & Technology

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0610 TITLE: Improving Cognitive Function in Veterans with Gulf War Illness by Improving Cerebral Vascular Function...From - To) 15 Sep 2016 - 14 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Improving Cognitive Function in Veterans with Gulf War Illness by...investigate a relationship between cognitive impairment in Veterans with Gulf War Illness (GWI) and reduced vasodilatory function. One of the multiple

  16. Majewski osteodysplastic primordial dwarfism type II (MOPD II) complicated by stroke: clinical report and review of cerebral vascular anomalies.

    PubMed

    Brancati, Francesco; Castori, Marco; Mingarelli, Rita; Dallapiccola, Bruno

    2005-12-15

    We report on a 2 9/12-year-old boy with disproportionate short stature, microcephaly, subtle craniofacial dysmorphisms, and generalized skeletal dysplasia, who developed a left hemiparesis. Brain neuroimaging disclosed a complex cerebral vascular anomaly (CVA) with stenosis of the right anterior cerebral artery and telangiectatic collateral vessels supplying the cerebral cortex, consistent with moyamoya disease. Based on clinical and skeletal features, a diagnosis of Majewski osteodysplastic primordial dwarfism type II (MOPD II) was established. Review of 16 published patients with CVA affected by either Seckel syndrome or MOPD II suggested that CVA is preferentially associated to the latter subtype affecting about 1/4 of the patients. 2005 Wiley-Liss, Inc.

  17. Estradiol modulates post-ischemic cerebral vascular remodeling and improves long-term functional outcome in a rat model of stroke

    PubMed Central

    Ardelt, Agnieszka A.; Carpenter, Randall S.; Lobo, Merryl R.; Zeng, Huadong; Solanki, Rajanikant B.; Zhang, An; Kulesza, Piotr; Pike, Martin M.

    2012-01-01

    We previously observed that 17β-estradiol (E2) augments ischemic borderzone vascular density 10 days after focal cerebral ischemia-reperfusion in rats. We now evaluated the effect of E2 on vascular remodeling, lesional characteristics, and motor recovery up to 30 days after injury. Peri-lesional vascular density in tissue sections from rats treated with 0.72 mg E2 pellets was higher compared to 0.18 mg E2 pellets or placebo (P) pellets: vascular density index, 1.9 ± 0.2 (0.72 mg E2) vs. 1.4 ± 0.2 (0.18 mg E2) vs. 1.5 ± 0.4 (P), p=0.01. This was consistent with perfusion magnetic resonance imaging (MRI) measurements of lesional relative cerebral blood flow (rCBF): 1.89 ± 0.32 (0.72 mg E2) vs. 1.32 ± 0.19 (P), p=0.04. Post-ischemic angiogenesis occurred in P-treated as well as E2-treated rats. There was no treatment-related effect on lesional size, but lesional tissue was better preserved in E2-treated rats: cystic component as a % of total lesion, 30 ± 12 (0.72 mg E2) vs. 29 ± 17 (0.18 mg E2) vs. 61 ± 29 (P), p=0.008. Three weeks after right middle cerebral artery territory injury, rats treated with 0.72 mg E2 pellets used the left forelimb more than P-treated or 0.18 mg E2-treated rats: limb use asymmetry score, 0.09 ± 0.43 (0.72 mg E2) vs. 0.54 ± 0.12 (0.18 mg E2) vs. 0.54 ± 0.40 (P), p=0.05. We conclude that treatment with 0.72 mg E2 pellets beginning one week prior to ischemia/reperfusion and continuing through the one-month recovery period results in augmentation of lesional vascularity and perfusion, as well as improved motor recovery. PMID:22572084

  18. Human apolipoprotein E ɛ4 expression impairs cerebral vascularization and blood–brain barrier function in mice

    PubMed Central

    Alata, Wael; Ye, Yue; St-Amour, Isabelle; Vandal, Milène; Calon, Frédéric

    2015-01-01

    Human apolipoprotein E (APOE) exists in three isoforms ɛ2, ɛ3, and ɛ4, of which APOE4 is the main genetic risk factor of Alzheimer's disease (AD). As cerebrovascular defects are associated with AD, we tested whether APOE genotype has an impact on the integrity and function of the blood–brain barrier (BBB) in human APOE-targeted replacement mice. Using the quantitative in situ brain perfusion technique, we first found lower (13.0% and 17.0%) brain transport coefficient (Clup) of [3H]-diazepam in APOE4 mice at 4 and 12 months, compared with APOE2 and APOE3 mice, reflecting a decrease in cerebral vascularization. Accordingly, results from immunohistofluorescence experiments revealed a structurally reduced cerebral vascularization (26% and 38%) and thinner basement membranes (30% and 35%) in 12-month-old APOE4 mice compared with APOE2 and APOE3 mice, suggesting vascular atrophy. In addition, APOE4 mice displayed a 29% reduction in [3H]-d-glucose transport through the BBB compared with APOE2 mice without significant changes in the expression of its transporter GLUT1 in brain capillaries. However, an increase of 41.3% of receptor for advanced glycation end products (RAGE) was found in brain capillaries of 12-month-old APOE4 mice. In conclusion, profound divergences were observed between APOE genotypes at the cerebrovascular interface, suggesting that APOE4-induced BBB anomalies may contribute to AD development. PMID:25335802

  19. Can vascular risk factors influence number and size of cerebral metastases? A 3D-MRI study in patients with different tumor entities.

    PubMed

    Nagel, Sandra; Berk, Benjamin-Andreas; Kortmann, Rolf-Dieter; Hoffmann, Karl-Titus; Seidel, Clemens

    2018-02-01

    There is increasing evidence that cerebral microangiopathy reduces number of brain metastases. Aim of this study was to analyse if vascular risk factors (arterial hypertension, diabetes mellitus, smoking, and hypercholesterolemia) or the presence of peripheral arterial occlusive disease (PAOD) can have an impact on number or size of brain metastases. 200 patients with pre-therapeutic 3D-brain MRI and available clinical data were analyzed retrospectively. Mean number of metastases (NoM) and mean diameter of metastases (mDM) were compared between patients with/without vascular risk factors (vasRF). No general correlation of vascular risk factors with brain metastases was found in this monocentric analysis of a patient cohort with several tumor types. Arterial hypertension, diabetes mellitus, hypercholesterolemia and smoking did not show an effect in uni- and multivariate analysis. In patients with PAOD the number of BM was lower than without PAOD. This was the case independent from cerebral microangiopathy but did not persist in multivariate analysis. From this first screening approach vascular risk factors do not appear to strongly influence brain metastasation. However, larger prospective multi-centric studies with better characterized severity of vascular risk are needed to more accurately detect effects of individual factors. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Stabilization of VEGFR2 signaling by cerebral cavernous malformation 3 is critical for vascular development.

    PubMed

    He, Yun; Zhang, Haifeng; Yu, Luyang; Gunel, Murat; Boggon, Titus J; Chen, Hong; Min, Wang

    2010-04-06

    Cerebral cavernous malformations (CCMs) are human vascular malformations caused by mutations in three genes of unknown function: CCM1, CCM2, and CCM3. CCM3, also known as PDCD10 (programmed cell death 10), was initially identified as a messenger RNA whose abundance was induced by apoptotic stimuli in vitro. However, the in vivo function of CCM3 has not been determined. Here, we describe mice with a deletion of the CCM3 gene either ubiquitously or specifically in the vascular endothelium, smooth muscle cells, or neurons. Mice with global or endothelial cell-specific deletion of CCM3 exhibited defects in embryonic angiogenesis and died at an early embryonic stage. CCM3 deletion reduced vascular endothelial growth factor receptor 2 (VEGFR2) signaling in embryos and endothelial cells. In response to VEGF stimulation, CCM3 was recruited to and stabilized VEGFR2, and the carboxyl-terminal domain of CCM3 was required for the stabilization of VEGFR2. Indeed, the CCM3 mutants found in human patients lacking the carboxyl-terminal domain were labile and were unable to stabilize and activate VEGFR2. These results demonstrate that CCM3 promotes VEGFR2 signaling during vascular development.

  1. Cerebral vascular amyloid seeds drive amyloid β-protein fibril assembly with a distinct anti-parallel structure

    PubMed Central

    Xu, Feng; Fu, Ziao; Dass, Sharmila; Kotarba, AnnMarie E.; Davis, Judianne; Smith, Steven O.; Van Nostrand, William E.

    2016-01-01

    Cerebrovascular accumulation of amyloid β-protein (Aβ), a condition known as cerebral amyloid angiopathy (CAA), is a common pathological feature of patients with Alzheimer's disease. Familial Aβ mutations, such as Dutch-E22Q and Iowa-D23N, can cause severe cerebrovascular accumulation of amyloid that serves as a potent driver of vascular cognitive impairment and dementia. The distinctive features of vascular amyloid that underlie its unique pathological properties remain unknown. Here, we use transgenic mouse models producing CAA mutants (Tg-SwDI) or overproducing human wild-type Aβ (Tg2576) to demonstrate that CAA-mutant vascular amyloid influences wild-type Aβ deposition in brain. We also show isolated microvascular amyloid seeds from Tg-SwDI mice drive assembly of human wild-type Aβ into distinct anti-parallel β-sheet fibrils. These findings indicate that cerebrovascular amyloid can serve as an effective scaffold to promote rapid assembly and strong deposition of Aβ into a unique structure that likely contributes to its distinctive pathology. PMID:27869115

  2. Vascular Inward Rectifier K+ Channels as External K+ Sensors in the Control of Cerebral Blood Flow

    PubMed Central

    LONGDEN, THOMAS A.; NELSON, MARK T.

    2015-01-01

    For decades it has been known that external potassium (K+) ions are rapid and potent vasodilators that increase cerebral blood flow (CBF). Recent studies have implicated the local release of K+ from astrocytic endfeet—which encase the entirety of the parenchymal vasculature—in the dynamic regulation of local CBF during neurovascular coupling (NVC). It has been proposed that the activation of strong inward rectifier K+ (KIR) channels in the vascular wall by external K+ is a central component of these hyperemic responses; however, a number of significant gaps in our knowledge remain. Here, we explore the concept that vascular KIR channels are the major extracellular K+ sensors in the control of CBF. We propose that K+ is an ideal mediator of NVC, and discuss KIR channels as effectors that produce rapid hyperpolarization and robust vasodilation of cerebral arterioles. We provide evidence that KIR channels, of the KIR2 subtype in particular, are present in both the endothelial and smooth muscle cells of parenchymal arterioles and propose that this dual positioning of KIR2 channels increases the robustness of the vasodilation to external K+, enables the endothelium to be actively engaged in neurovascular coupling, and permits electrical signaling through the endothelial syncytium to promote upstream vasodilation to modulate CBF. PMID:25641345

  3. Structure and vascular function of MEKK3–cerebral cavernous malformations 2 complex

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

    Fisher, Oriana S.; Deng, Hanqiang; Liu, Dou

    Cerebral cavernous malformations 2 (CCM2) loss is associated with the familial form of CCM disease. The protein kinase MEKK3 (MAP3K3) is essential for embryonic angiogenesis in mice and interacts physically with CCM2, but how this interaction is mediated and its relevance to cerebral vasculature are unknown. Here we report that Mekk3 plays an intrinsic role in embryonic vascular development. Inducible endothelial Mekk3 knockout in neonatal mice is lethal due to multiple intracranial haemorrhages and brain blood vessels leakage. We discover direct interaction between CCM2 harmonin homology domain (HHD) and the N terminus of MEKK3, and determine a 2.35 Å cocrystalmore » structure. We find Mekk3 deficiency impairs neurovascular integrity, which is partially dependent on Rho–ROCK signalling, and that disruption of MEKK3:CCM2 interaction leads to similar neurovascular leakage. We conclude that CCM2:MEKK3-mediated regulation of Rho signalling is required for maintenance of neurovascular integrity, unravelling a mechanism by which CCM2 loss leads to disease.« less

  4. Stabiliztin of VEGFR2 Signaling by Cerebral Cavernous Malformation 3 is Critical for Vascular Development

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

    Y He; H Zhang; L Yu

    2011-12-31

    Cerebral cavernous malformations (CCMs) are human vascular malformations caused by mutations in three genes of unknown function: CCM1, CCM2, and CCM3. CCM3, also known as PDCD10 (programmed cell death 10), was initially identified as a messenger RNA whose abundance was induced by apoptotic stimuli in vitro. However, the in vivo function of CCM3 has not been determined. Here, we describe mice with a deletion of the CCM3 gene either ubiquitously or specifically in the vascular endothelium, smooth muscle cells, or neurons. Mice with global or endothelial cell-specific deletion of CCM3 exhibited defects in embryonic angiogenesis and died at an earlymore » embryonic stage. CCM3 deletion reduced vascular endothelial growth factor receptor 2 (VEGFR2) signaling in embryos and endothelial cells. In response to VEGF stimulation, CCM3 was recruited to and stabilized VEGFR2, and the carboxyl-terminal domain of CCM3 was required for the stabilization of VEGFR2. Indeed, the CCM3 mutants found in human patients lacking the carboxyl-terminal domain were labile and were unable to stabilize and activate VEGFR2. These results demonstrate that CCM3 promotes VEGFR2 signaling during vascular development.« less

  5. Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I

    PubMed Central

    2014-01-01

    Background Metabolic stroke is the rapid onset of lasting central neurological deficit associated with decompensation of an underlying metabolic disorder. Glutaric aciduria type I (GA1) is an inherited disorder of lysine and tryptophan metabolism presenting with metabolic stroke in infancy. The clinical presentation includes bilateral striatal necrosis and spontaneous subdural and retinal hemorrhages, which has been frequently misdiagnosed as non-accidental head trauma. The mechanisms underlying metabolic stroke and spontaneous hemorrhage are poorly understood. Results Using a mouse model of GA1, we show that metabolic stroke progresses in the opposite sequence of ischemic stroke, with initial neuronal swelling and vacuole formation leading to cerebral capillary occlusion. Focal regions of cortical followed by striatal capillaries are occluded with shunting to larger non-exchange vessels leading to early filling and dilation of deep cerebral veins. Blood–brain barrier breakdown was associated with displacement of tight-junction protein Occludin. Conclusion Together the current findings illuminate the pathophysiology of metabolic stroke and vascular compromise in GA1, which may translate to other neurometabolic disorders presenting with stroke. PMID:24468193

  6. Mechanism of metabolic stroke and spontaneous cerebral hemorrhage in glutaric aciduria type I.

    PubMed

    Zinnanti, William J; Lazovic, Jelena; Housman, Cathy; Antonetti, David A; Koeller, David M; Connor, James R; Steinman, Lawrence

    2014-01-27

    Metabolic stroke is the rapid onset of lasting central neurological deficit associated with decompensation of an underlying metabolic disorder. Glutaric aciduria type I (GA1) is an inherited disorder of lysine and tryptophan metabolism presenting with metabolic stroke in infancy. The clinical presentation includes bilateral striatal necrosis and spontaneous subdural and retinal hemorrhages, which has been frequently misdiagnosed as non-accidental head trauma. The mechanisms underlying metabolic stroke and spontaneous hemorrhage are poorly understood. Using a mouse model of GA1, we show that metabolic stroke progresses in the opposite sequence of ischemic stroke, with initial neuronal swelling and vacuole formation leading to cerebral capillary occlusion. Focal regions of cortical followed by striatal capillaries are occluded with shunting to larger non-exchange vessels leading to early filling and dilation of deep cerebral veins. Blood-brain barrier breakdown was associated with displacement of tight-junction protein Occludin. Together the current findings illuminate the pathophysiology of metabolic stroke and vascular compromise in GA1, which may translate to other neurometabolic disorders presenting with stroke.

  7. Is Vasomotion in Cerebral Arteries Impaired in Alzheimer's Disease?

    PubMed

    Di Marco, Luigi Yuri; Farkas, Eszter; Martin, Chris; Venneri, Annalena; Frangi, Alejandro F

    2015-01-01

    A substantial body of evidence supports the hypothesis of a vascular component in the pathogenesis of Alzheimer's disease (AD). Cerebral hypoperfusion and blood-brain barrier dysfunction have been indicated as key elements of this pathway. Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder, frequent in AD, characterized by the accumulation of amyloid-β (Aβ) peptide in cerebral blood vessel walls. CAA is associated with loss of vascular integrity, resulting in impaired regulation of cerebral circulation, and increased susceptibility to cerebral ischemia, microhemorrhages, and white matter damage. Vasomotion- the spontaneous rhythmic modulation of arterial diameter, typically observed in arteries/arterioles in various vascular beds including the brain- is thought to participate in tissue perfusion and oxygen delivery regulation. Vasomotion is impaired in adverse conditions such as hypoperfusion and hypoxia. The perivascular and glymphatic pathways of Aβ clearance are thought to be driven by the systolic pulse. Vasomotion produces diameter changes of comparable amplitude, however at lower rates, and could contribute to these mechanisms of Aβ clearance. In spite of potential clinical interest, studies addressing cerebral vasomotion in the context of AD/CAA are limited. This study reviews the current literature on vasomotion, and hypothesizes potential paths implicating impaired cerebral vasomotion in AD/CAA. Aβ and oxidative stress cause vascular tone dysregulation through direct effects on vascular cells, and indirect effects mediated by impaired neurovascular coupling. Vascular tone dysregulation is further aggravated by cholinergic deficit and results in depressed cerebrovascular reactivity and (possibly) impaired vasomotion, aggravating regional hypoperfusion and promoting further Aβ and oxidative stress accumulation.

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

    PubMed

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

    2017-08-01

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

  9. Panax ginseng extract attenuates neuronal injury and cognitive deficits in rats with vascular dementia induced by chronic cerebral hypoperfusion.

    PubMed

    Zhu, Jun-De; Wang, Jun-Jie; Zhang, Xian-Hu; Yu, Yan; Kang, Zhao-Sheng

    2018-04-01

    Panax ginseng is a slow-growing perennial plant. Panax ginseng extract has numerous biological activities, including antitumor, anti-inflammatory and antistress activities. Panax ginseng extract also has a cognition-enhancing effect in rats with alcohol-induced memory impairment. In this study, we partially occluded the bilateral carotid arteries in the rat to induce chronic cerebral hypoperfusion, a well-known model of vascular dementia. The rats were then intragastrically administered 50 or 100 mg/kg Panax ginseng extract. Morris water maze and balance beam tests were used to evaluate memory deficits and motor function, respectively. Protein quantity was used to evaluate cholinergic neurons. Immunofluorescence staining was used to assess the number of glial fibrillary acidic protein-positive cells. Western blot assay was used to evaluate protein levels of vascular endothelial growth factor, basic fibroblast growth factor, Bcl-2 and Bax. Treatment with Panax ginseng extract for 8 weeks significantly improved behavioral function and increased neuronal density and VEGF and bFGF protein expression in the hippocampal CA3 area. Furthermore, Panax ginseng extract reduced the number of glial fibrillary acidic protein-immunoreactive cells, and it decreased apoptosis by upregulating Bcl-2 and downregulating Bax protein expression. The effect of Panax ginseng extract was dose-dependent and similar to that of nimodipine, a commonly used drug for the treatment of vascular dementia. These findings suggest that Panax ginseng extract is neuroprotective against vascular dementia induced by chronic cerebral hypoperfusion, and therefore might have therapeutic potential for preventing and treating the disease.

  10. Nox4 NADPH oxidase mediates oxidative stress and apoptosis caused by TNF-α in cerebral vascular endothelial cells

    PubMed Central

    Basuroy, Shyamali; Bhattacharya, Sujoy; Leffler, Charles W.; Parfenova, Helena

    2009-01-01

    Inflammatory brain disease may damage cerebral vascular endothelium leading to cerebral blood flow dysregulation. The proinflammatory cytokine TNF-α causes oxidative stress and apoptosis in cerebral microvascular endothelial cells (CMVEC) from newborn pigs. We investigated contribution of major cellular sources of reactive oxygen species to endothelial inflammatory response. Nitric oxide synthase and xanthine oxidase inhibitors (Nω-nitro-l-arginine and allopurinol) had no effect, while mitochondrial electron transport inhibitors (CCCP, 2-thenoyltrifluoroacetone, and rotenone) attenuated TNF-α-induced superoxide (O2•−) and apoptosis. NADPH oxidase inhibitors (diphenylene iodonium and apocynin) greatly reduced TNF-α-evoked O2•− generation and apoptosis. TNF-α rapidly increased NADPH oxidase activity in CMVEC. Nox4, the cell-specific catalytic subunit of NADPH oxidase, is highly expressed in CMVEC, contributes to basal O2•− production, and accounts for a burst of oxidative stress in response to TNF-α. Nox4 small interfering RNA, but not Nox2, knockdown prevented oxidative stress and apoptosis caused by TNF-α in CMVEC. Nox4 is colocalized with HO-2, the constitutive isoform of heme oxygenase (HO), which is critical for endothelial protection against TNF-α toxicity. The products of HO activity, bilirubin and carbon monoxide (CO, as a CO-releasing molecule, CORM-A1), inhibited Nox4-generated O2•− and apoptosis caused by TNF-α stimulation. We conclude that Nox4 is the primary source of inflammation- and TNF-α-induced oxidative stress leading to apoptosis in brain endothelial cells. The ability of CO and bilirubin to combat TNF-α-induced oxidative stress by inhibiting Nox4 activity and/or by O2•− scavenging, taken together with close intracellular compartmentalization of HO-2 and Nox4 in cerebral vascular endothelium, may contribute to HO-2 cytoprotection against inflammatory cerebrovascular disease. PMID:19118162

  11. Single Sustained Inflation followed by Ventilation Leads to Rapid Cardiorespiratory Recovery but Causes Cerebral Vascular Leakage in Asphyxiated Near-Term Lambs

    PubMed Central

    Sobotka, Kristina S.; Hooper, Stuart B.; Crossley, Kelly J.; Ong, Tracey; Schmölzer, Georg M.; Barton, Samantha K.; McDougall, Annie R. A.; Miller, Suzie L.; Tolcos, Mary; Klingenberg, Claus; Polglase, Graeme R.

    2016-01-01

    Background A sustained inflation (SI) rapidly restores cardiac function in asphyxic, bradycardic newborns but its effects on cerebral haemodynamics and brain injury are unknown. We determined the effect of different SI strategies on carotid blood flow (CaBF) and cerebral vascular integrity in asphyxiated near-term lambs. Methods Lambs were instrumented and delivered at 139 ± 2 d gestation and asphyxia was induced by delaying ventilation onset. Lambs were randomised to receive 5 consecutive 3 s SI (multiple SI; n = 6), a single 30 s SI (single SI; n = 6) or conventional ventilation (no SI; n = 6). Ventilation continued for 30 min in all lambs while CaBF and respiratory function parameters were recorded. Brains were assessed for gross histopathology and vascular leakage. Results CaBF increased more rapidly and to a greater extent during a single SI (p = 0.01), which then decreased below both other groups by 10 min, due to a higher cerebral oxygen delivery (p = 0.01). Blood brain barrier disruption was increased in single SI lambs as indicated by increased numbers of blood vessel profiles with plasma protein extravasation (p = 0.001) in the cerebral cortex. There were no differences in CaBF or cerebral oxygen delivery between the multiple SI and no SI lambs. Conclusions Ventilation with an initial single 30 s SI improves circulatory recovery, but is associated with greater disruption of blood brain barrier function, which may exacerbate brain injury suffered by asphyxiated newborns. This injury may occur as a direct result of the initial SI or to the higher tidal volumes delivered during subsequent ventilation. PMID:26765258

  12. mTOR drives cerebral blood flow and memory deficits in LDLR-/- mice modeling atherosclerosis and vascular cognitive impairment.

    PubMed

    Jahrling, Jordan B; Lin, Ai-Ling; DeRosa, Nicholas; Hussong, Stacy A; Van Skike, Candice E; Girotti, Milena; Javors, Martin; Zhao, Qingwei; Maslin, Leigh Ann; Asmis, Reto; Galvan, Veronica

    2018-01-01

    We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis. We measured CBF, BVD, cognitive function, markers of inflammation, and parameters of cardiovascular disease in LDLR -/- mice fed maintenance or high-fat diet ± rapamycin. Cardiovascular pathologies were proportional to severity of brain vascular dysfunction. Aortic atheromas were reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated potentially through reduction in systemic and brain inflammation following chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular integrity and function and that mTOR attenuation may restore neurovascular function and cardiovascular health. Together with our previous studies in AD models, our data suggest mTOR-driven vascular damage may be a mechanism shared by age-associated neurological diseases. Therefore, mTOR attenuation may have promise for treatment of cognitive impairment in atherosclerosis.

  13. Is Vasomotion in Cerebral Arteries Impaired in Alzheimer’s Disease?

    PubMed Central

    Di Marco, Luigi Yuri; Farkas, Eszter; Martin, Chris; Venneri, Annalena; Frangi, Alejandro F.

    2015-01-01

    Abstract A substantial body of evidence supports the hypothesis of a vascular component in the pathogenesis of Alzheimer’s disease (AD). Cerebral hypoperfusion and blood-brain barrier dysfunction have been indicated as key elements of this pathway. Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder, frequent in AD, characterized by the accumulation of amyloid-β (Aβ) peptide in cerebral blood vessel walls. CAA is associated with loss of vascular integrity, resulting in impaired regulation of cerebral circulation, and increased susceptibility to cerebral ischemia, microhemorrhages, and white matter damage. Vasomotion— the spontaneous rhythmic modulation of arterial diameter, typically observed in arteries/arterioles in various vascular beds including the brain— is thought to participate in tissue perfusion and oxygen delivery regulation. Vasomotion is impaired in adverse conditions such as hypoperfusion and hypoxia. The perivascular and glymphatic pathways of Aβ clearance are thought to be driven by the systolic pulse. Vasomotion produces diameter changes of comparable amplitude, however at lower rates, and could contribute to these mechanisms of Aβ clearance. In spite of potential clinical interest, studies addressing cerebral vasomotion in the context of AD/CAA are limited. This study reviews the current literature on vasomotion, and hypothesizes potential paths implicating impaired cerebral vasomotion in AD/CAA. Aβ and oxidative stress cause vascular tone dysregulation through direct effects on vascular cells, and indirect effects mediated by impaired neurovascular coupling. Vascular tone dysregulation is further aggravated by cholinergic deficit and results in depressed cerebrovascular reactivity and (possibly) impaired vasomotion, aggravating regional hypoperfusion and promoting further Aβ and oxidative stress accumulation. PMID:25720414

  14. Platelet Factor 4 Mediates Inflammation in Cerebral Malaria

    PubMed Central

    Srivastava, Kalyan; Cockburn, Ian A.; Swaim, AnneMarie; Thompson, Laura E.; Tripathi, Abhai; Fletcher, Craig A.; Shirk, Erin M.; Sun, Henry; Kowalska, M. Anna; Fox-Talbot, Karen; Sullivan, David; Zavala, Fidel; Morrell, Craig N.

    2008-01-01

    Summary Cerebral malaria is a major complication of Plasmodium falciparum infection in children. The pathogenesis of cerebral malaria involves vascular inflammation, immune stimulation and obstruction of cerebral capillaries. Platelets have a prominent role in both immune responses and vascular obstruction. We now demonstrate that the platelet derived chemokine, platelet factor 4 (PF4)/CXCL4, promotes the development of experimental cerebral malaria. Plasmodium infected red blood cells (RBC) activated platelets independent of vascular effects, resulting in increased plasma PF4. PF4 or CXCR3 null mice had less ECM, decreased brain T-cell recruitment, and platelet depletion or aspirin treatment reduced the development of ECM. We conclude that Plasmodium infected RBC can activate platelets and platelet derived PF4 then contributes to immune activation and T-cell trafficking as part of the pathogenesis of ECM. PMID:18692777

  15. Nursing diagnoses in patients with cerebral vascular accident: an integrative review.

    PubMed

    Lima, Ana Carolina Maria Araújo Chagas Costa; Silva, Aurilene Lima da; Guerra, Débora Rodrigues; Barbosa, Islene Victor; Bezerra, Karine de Castro; Oriá, Mônica Oliveira Batista

    2016-01-01

    to verify the nursing diagnoses in patients affected by CVAs. this is an integrative review of the literature. The search was conducted on LILACS, Scielo, Medline, CINAHL, and Scopus databases between February and March 2015, using the following keywords: "Enfermagem", "Acidente Vascular Cerebral", "Diagnóstico de Enfermagem"; and "Nursing", "Stroke", and "Nursing Diagnosis". we found 9 articles published between 2009 and 2015; most of them were Brazilian, cross-sectional, and exploratory, with a level of evidence of 6. The evidence from the publications was classified as: "Evaluation and validation of specific nursing diagnoses for subjects affected by CVAs" and "Application of the nursing process on subjects affected by CVAs". we noticed the publications focused on nursing diagnoses related to motor disorders, such as risk of falls and impaired physical mobility. Domains regarding safety/protection (domain 11) and sleep/resting (domain 4) were present in most evaluated publications.

  16. Neuroprotective Effects of Agomelatine and Vinpocetine Against Chronic Cerebral Hypoperfusion Induced Vascular Dementia.

    PubMed

    Gupta, Surbhi; Singh, Prabhat; Sharma, Brij Mohan; Sharma, Bhupesh

    2015-01-01

    Chronic cerebral hypoperfusion (CCH) has been considered as a critical cause for the development of cognitive decline and dementia of vascular origin. Melatonin receptors have been reported to be beneficial in improving memory deterioration. Phosphodiesterase-1 (PDE1) enzyme offers protection against cognitive impairments and cerebrovascular disorders. Aim of this study is to explore the role of agomelatine (a dual MT1 and MT2 melatonin receptor agonist) and vinpocetine (selective PDE1 inhibitor) in CCH induced vascular dementia (VaD). Two vessel occlusion (2VO) or bilateral common carotid arteries ligation method was performed to initiate a phase of chronic hypoperfusion in mice. 2VO animals have shown significant cognitive deficits (Morris water maze), cholinergic dysfunction (increased acetyl cholinesterase -AChE) activity alongwith increased brain oxidative stress (decreased brain catalase, glutathione, as well as superoxide dismutase with an increase in malondialdehyde levels), and significant increase in brain infarct size (2,3,5- triphenylterazolium chloride-TTC staining). Treatment of agomelatine and vinpocetine reduced CCH induced learning and memory deficits and limited cholinergic dysfunction, oxidative stress, and tissue damage, suggesting that agomelatine and vinpocetine may provide benefits in CCH induced VaD.

  17. Hypertrophy of the vasa vasorum: vascular response to the hungry brain.

    PubMed

    Cho, Hyun-Ji; Roh, Hong Gee; Chun, Young Il; Moon, Chang Taek; Chung, Hyun Woo; Kim, Hahn Young

    2012-05-01

    The vasa vasorum is a network of microvessels that supplies nutrients to the vessel wall itself. In pathologic conditions, the vasa vasorum can develop as potential collateral channels. Previous research documents revascularization through hypertrophy of the vasa vasorum after occlusion of the carotid artery. However, the relationship between the cerebral vascular demands and the hypertrophy of the vasa vasorum has not been well delineated by functional studies. A 66-year-old man presented with left hemiparesis, dysarthria, and hemineglect. Magnetic resonance imaging revealed an acute infarction in the vascular territory of the right middle cerebral artery. Transfemoral cerebral angiography revealed occlusion of the right proximal internal carotid artery (ICA). Single-photon emission computed tomography study showed decreased vascular reserve in the right cerebral hemisphere. Right superficial temporal artery-middle cerebral artery bypass surgery was performed in an attempt to improve hemispheric perfusion. Follow-up angiography 1 year later showed revascularization of the distal ICA by the hypertrophied vasa vasorum. Follow-up single-photon emission computed tomography study showed persistent decreased vascular reserve. In cases of ICA occlusion, a 1-year or less hungry period for the cerebral vascular demand may activate potential collateral channels of the vasa vasorum. In addition to the metabolic demand of the occluded vessel wall itself, the vascular demands of the hypoperfused brain may be a trigger factor that leads to hypertrophy of the vasa vasorum as collateral channels.

  18. Comparison of cerebral vascular reactivity measures obtained using breath-holding and CO2 inhalation

    PubMed Central

    Tancredi, Felipe B; Hoge, Richard D

    2013-01-01

    Stimulation of cerebral vasculature using hypercapnia has been widely used to study cerebral vascular reactivity (CVR), which can be expressed as the quantitative change in cerebral blood flow (CBF) per mm Hg change in end-tidal partial pressure of CO2 (PETCO2). We investigate whether different respiratory manipulations, with arterial spin labeling used to measure CBF, lead to consistent measures of CVR. The approaches included: (1) an automated system delivering variable concentrations of inspired CO2 for prospective targeting of PETCO2, (2) administration of a fixed concentration of CO2 leading to subject-dependent changes in PETCO2, (3) a breath-hold (BH) paradigm with physiologic modeling of CO2 accumulation, and (4) a maneuver combining breath-hold and hyperventilation. When CVR was expressed as the percent change in CBF per mm Hg change in PETCO2, methods 1 to 3 gave consistent results. The CVR values using method 4 were significantly lower. When CVR was expressed in terms of the absolute change in CBF (mL/100 g per minute per mm Hg), greater discrepancies became apparent: methods 2 and 3 gave lower absolute CVR values compared with method 1, and the value obtained with method 4 was dramatically lower. Our findings indicate that care must be taken to ensure that CVR is measured over the linear range of the CBF-CO2 dose–response curve, avoiding hypocapnic conditions. PMID:23571282

  19. Effects of cilazapril on the cerebral circulation in spontaneously hypertensive rats.

    PubMed

    Clozel, J P; Kuhn, H; Hefti, F

    1989-12-01

    Chronic hypertension is associated with a lower cerebral vascular reserve due to thickening of the media of cerebral vessels. The goal of the present study was to determine if long-term inhibition of angiotensin converting enzyme with cilazapril, a new long-acting angiotensin converting enzyme inhibitor, could improve cerebral vascular reserve. For this purpose, two groups of 12 spontaneously hypertensive rats were compared. One group was treated with 10 mg/kg/day cilazapril from 14 weeks to 33 weeks of age and was compared with a group treated with placebo. A third group of 12 Wistar-Kyoto rats treated with placebo was used as reference. At the end of the treatment period, cerebral vascular reserve was evaluated by measuring cerebral blood flow (radioactive microspheres) at rest and during maximal vasodilation induced by seizures provoked by bicuculline. Then, the rats were perfusion-fixed, and morphometry of the cerebral vasculature was performed. Cerebral vascular reserve was severely impaired in the spontaneously hypertensive rats since their maximal cerebral blood flow was decreased by 52% compared with the Wistar-Kyoto rats. Cilazapril normalized cerebral blood flow reserve. This normalization was associated with a decreased thickness of the medial layer in the carotid artery, the middle cerebral artery, and in the pial arteries larger than 100 microns. Further studies are required to determine whether this decreased medial thickness is due to the normalization of blood pressure induced by cilazapril or to the reduction of trophic factors such as angiotensin II.

  20. Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging

    PubMed Central

    Toth, Peter; Tarantini, Stefano; Csiszar, Anna

    2017-01-01

    Increasing evidence from epidemiological, clinical and experimental studies indicate that age-related cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including Alzheimer’s disease. Understanding and targeting the age-related pathophysiological mechanisms that underlie vascular contributions to cognitive impairment and dementia (VCID) are expected to have a major role in preserving brain health in older individuals. Maintenance of cerebral perfusion, protecting the microcirculation from high pressure-induced damage and moment-to-moment adjustment of regional oxygen and nutrient supply to changes in demand are prerequisites for the prevention of cerebral ischemia and neuronal dysfunction. This overview discusses age-related alterations in three main regulatory paradigms involved in the regulation of cerebral blood flow (CBF): cerebral autoregulation/myogenic constriction, endothelium-dependent vasomotor function, and neurovascular coupling responses responsible for functional hyperemia. The pathophysiological consequences of cerebral microvascular dysregulation in aging are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages, microvascular rarefaction, and ischemic neuronal dysfunction and damage. Due to the widespread attention that VCID has captured in recent years, the evidence for the causal role of cerebral microvascular dysregulation in cognitive decline is critically examined. PMID:27793855

  1. [Effect of Electroacupuncture on Expression of Apelin-APJ System of Cerebral Vascular Endothelial Cell in Rats with Cerebral Infarction].

    PubMed

    Yang, Li-Hong; Du, Yuan-Hao; Li, Jing

    2017-02-25

    To observe the regulation of APJ and its ligand Apelin on the angiogenesis pathway after cerebral infarction and the intervention effect of acupuncture. Wistar rats were randomly divided into model group( n =90), electroacupuncture(EA) group( n =90), sham operation group( n =90) and control group( n =10). The first three groups were further divided into 1,3,6,9,12,24 h and 3,7, 12 d subgroups( n =10 in each subgroup). The cerebral infarction model was established by middle cerebral artery occlusion (MCAO). EA(15 Hz, 2 mA) was applied to "Shuigou" (GV 26) for 20 min in the EA group. The 1, 3, 6, 9, 12, 24 h subgroups were treated immediately after modeling, the 3, 7, 9 d subgroups were treated once daily for 3, 7 or 9 days. Real-time fluorescent quantitative (RT-PCR) and Western blot were applied to detect the changes of Apelin and APJ in cerebrovascular endothelial cells, respectively. Compared with the control group, the expression of Apelin-APJ mRNA was decreased in the model group(12 h, 12 d, P <0.05, P <0.01); After EA, the Apelin mRNA expression was increased in the 12 h and 7 d subgroups ( P <0.01), while the APJ mRNA expression was increased in the 6, 9, 12 h subgroups( P <0.05, P <0.01). Compared with the control group, the Apelin(1, 3, 6, 24 h and 3, 7, 12 d) and APJ(1, 3, 6, 9 h and 3 d) protein expressions were decreased in the model group( P <0.01, P <0.05); After EA, the Apelin protein expression was increased in the 6, 24 h and 3, 7, 12 d subgroups ( P <0.05, P <0.01), while the APJ protein expression was increased in the 1, 9, 12, 24 h and 3, 7, 12 d subgroups ( P <0.05, P <0.01). EA can up-regulate the expression of Apelin-APJ mRNA and protein of cerebral vascular endothelial cell in MCAO rats which has an important role in the establishment of blood vessel regeneration and collateral circulation.

  2. Novel vascular endothelial growth factor blocker improves cellular viability and reduces hypobaric hypoxia-induced vascular leakage and oedema in rat brain.

    PubMed

    Saraswat, Deepika; Nehra, Sarita; Chaudhary, Kamal; CVS, Siva Prasad

    2015-05-01

    Vascular endothelial growth factor (VEGF) is an important cerebral angiogenic and permeability factor under hypoxia. There is a need to find effective molecules that may ameliorate hypoxia-induced cerebral oedema. In silico identification of novel candidate molecules that block VEGF-A site were identified and validated with a Ramachandran plot. The active site residues of VEGF-A were detected by Pocketfinder, CASTp, and DogSiteScorer. Based on in silico data, three VEGF-A blocker (VAB) candidate molecules (VAB1, VAB2, and VAB3) were checked for improvement in cellular viability and regulation of VEGF levels in N2a cells under hypoxia (0.5% O2 ). Additionally, the best candidate molecule's efficacy was assessed in male Sprague-Dawley rats for its ameliorative effect on cerebral oedema and vascular leakage under hypobaric hypoxia 7260 m. All experimental results were compared with the commercially available VEGF blocker sunitinib. Vascular endothelial growth factor-A blocker 1 was found most effective in increasing cellular viability and maintaining normal VEGF levels under hypoxia (0.5% oxygen) in N2a cells. Vascular endothelial growth factor-A blocker 1 effectively restored VEGF levels, decreased cerebral oedema, and reduced vascular leakage under hypobaric hypoxia when compared to sunitinib-treated rats. Vascular endothelial growth factor-A blocker 1 may be a promising candidate molecule for ameliorating hypobaric hypoxia-induced vasogenic oedema by regulating VEGF levels. © 2015 Wiley Publishing Asia Pty Ltd.

  3. Hypertonic saline alleviates experimentally induced cerebral oedema through suppression of vascular endothelial growth factor and its receptor VEGFR2 expression in astrocytes.

    PubMed

    Huang, Linqiang; Cao, Wei; Deng, Yiyu; Zhu, Gaofeng; Han, Yongli; Zeng, Hongke

    2016-10-13

    Cerebral oedema is closely related to the permeability of blood-brain barrier, vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) all of which are important blood-brain barrier (BBB) permeability regulatory factors. Zonula occludens 1 (ZO-1) and claudin-5 are also the key components of BBB. Hypertonic saline is widely used to alleviate cerebral oedema. This study aimed to explore the possible mechanisms underlying hypertonic saline that ameliorates cerebral oedema effectively. Middle cerebral artery occlusion (MCAO) model in Sprague-Dawley (SD) rats and of oxygen-glucose deprivation model in primary astrocytes were used in this study. The brain water content (BWC) was used to assess the effect of 10 % HS on cerebral oedema. The assessment of Evans blue (EB) extravasation was performed to evaluate the protective effect of 10 % HS on blood-brain barrier. The quantification of VEGF, VEGFR2, ZO-1 and claudin-5 was used to illustrate the mechanism of 10 % HS ameliorating cerebral oedema. BWC was analysed by wet-to-dry ratios in the ischemic hemisphere of SD rats; it was significantly decreased after 10 % HS treatment (P < 0.05). We also investigated the blood-brain barrier protective effect by 10 % HS which reduced EB extravasation effectively in the peri-ischemic brain tissue. In parallel to the above notably at 24 h following MCAO, mRNA and protein expression of VEGF and VEGFR2 in the peri-ischemic brain tissue was down-regulated after 10 % HS treatment (P < 0.05). Along with this, in vitro studies showed increased VEGF and VEGFR2 mRNA and protein expression in primary astrocytes under hypoxic condition (P < 0.05), but it was suppressed after HS treatment (P < 0.05). In addition, HS inhibited the down-regulation of ZO-1, claudin-5 effectively. The results suggest that 10 % HS could alleviate cerebral oedema possibly through reducing the ischemia induced BBB permeability as a consequence of

  4. Potential of optical microangiography to monitor cerebral blood perfusion and vascular plasticity following traumatic brain injury in mice in vivo

    NASA Astrophysics Data System (ADS)

    Jia, Yali; Alkayed, Nabil; Wang, Ruikang K.

    2009-07-01

    Optical microanglography (OMAG) is a recently developed imaging modality capable of volumetric imaging of dynamic blood perfusion, down to capillary level resolution, with an imaging depth up to 2.00 mm beneath the tissue surface. We report the use of OMAG to monitor the cerebral blood flow (CBF) over the cortex of mouse brain upon traumatic brain injury (TBI), with the cranium left intact, for a period of two weeks on the same animal. We show the ability of OMAG to repeatedly image 3-D cerebral vasculatures during pre- and post-traumatic phases, and to visualize the changes of regulated CBF and the vascular plasticity after TBI. The results indicate the potential of OMAG to explore the mechanism involved in the rehabilitation of TBI.

  5. The vascular neural network—a new paradigm in stroke pathophysiology

    PubMed Central

    Zhang, John H.; Badaut, Jerome; Tang, Jiping; Obenaus, Andre; Hartman, Richard; Pearce, William J.

    2013-01-01

    The concept of the neurovascular unit as the key brain component affected by stroke is controversial, because current definitions of this entity neglect mechanisms that control perfusion and reperfusion of arteries and arterioles upstream of the cerebral microcirculation. Indeed, although definitions vary, many researchers consider the neurovascular unit to be restricted to endothelial cells, neurons and glia within millimetres of the cerebral capillary microcirculation. This Perspectives article highlights the roles of vascular smooth muscle, endothelial cells and perivascular innervation of cerebral arteries in the initiation and progression of, and recovery from, ischaemic stroke. The concept of the vascular neural network—which includes cerebral arteries, arterioles, and downstream neuronal and glial cell types and structures—is introduced as the fundamental component affected by stroke pathophysiology. The authors also propose that the vascular neural network should be considered the main target for future therapeutic intervention after cerebrovascular insult. PMID:23070610

  6. 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

  7. Notch Signaling in Vascular Smooth Muscle Cells

    PubMed Central

    Baeten, J.T.; Lilly, B.

    2018-01-01

    The Notch signaling pathway is a highly conserved pathway involved in cell fate determination in embryonic development and also functions in the regulation of physiological processes in several systems. It plays an especially important role in vascular development and physiology by influencing angiogenesis, vessel patterning, arterial/venous specification, and vascular smooth muscle biology. Aberrant or dysregulated Notch signaling is the cause of or a contributing factor to many vascular disorders, including inherited vascular diseases, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, associated with degeneration of the smooth muscle layer in cerebral arteries. Like most signaling pathways, the Notch signaling axis is influenced by complex interactions with mediators of other signaling pathways. This complexity is also compounded by different members of the Notch family having both overlapping and unique functions. Thus, it is vital to fully understand the roles and interactions of each Notch family member in order to effectively and specifically target their exact contributions to vascular disease. In this chapter, we will review the Notch signaling pathway in vascular smooth muscle cells as it relates to vascular development and human disease. PMID:28212801

  8. Comparing cerebrovascular reactivity measured using BOLD and cerebral blood flow MRI: The effect of basal vascular tension on vasodilatory and vasoconstrictive reactivity

    PubMed Central

    Halani, Sheliza; Kwinta, Jonathan B.; Golestani, Ali M.; Khatamian, Yasha B.; Chen, J. Jean

    2016-01-01

    Cerebrovascular reactivity (CVR) is an important metric of cerebrovascular health. While the BOLD fMRI method in conjunction with carbon-dioxide (CO2) based vascular manipulation has been the most commonly used, the BOLD signal is not a direct measure of vascular changes, and the use of arterial-spin labeling (ASL) cerebral blood flow (CBF) imaging is increasingly advocated. Nonetheless, given the differing dependencies of BOLD and CBF on vascular baseline conditions and the diverse CO2 manipulation types currently used in the literature, knowledge of potential biases introduced by each technique is critical for the interpretation of CVR measurements. In this work, we use simultaneous BOLD-CBF acquisitions during both vasodilatory (hypercapnic) and vasoconstrictive (hypocapnic) stimuli to measure CVR. We further imposed different levels of baseline vascular tension by inducing hypercapnic and hypocapnic baselines, separately from normocapnia by 4 mm Hg. We saw significant and diverse dependencies on vascular stimulus and baseline condition in both BOLD and CBF CVR measurements: (i) BOLD-based CVR is more sensitive to basal vascular tension than CBF-based CVR; (ii) the use of a combination of vasodilatory and vasoconstrictive stimuli maximizes the sensitivity of CBF-based CVR to vascular tension changes; (iii) the BOLD and CBF vascular response delays are both significantly lengthened at predilated baseline. As vascular tension can often be altered by potential pathology, our findings are important considerations when interpreting CVR measurements in health and disease. PMID:25655446

  9. Uric acid promotes oxidative stress and enhances vascular endothelial cell apoptosis in rats with middle cerebral artery occlusion.

    PubMed

    Song, Chengfu; Zhao, Xiangdong

    2018-05-15

    In patients with cerebral infarction (CI), elevated serum uric acid (UA) level may exacerbate the occurrence and development of carotid atherosclerosis (AS). Our study intended to explore the underlying mechanism. We enrolled 86 patients with CI, and divided them into four groups: Non-AS, AS-mild, AS-moderate, and AS-severe groups; the levels of UA and oxidative stress-related factors in serum were detected. The middle cerebral artery occlusion (MCAO) model was used to stimulate CI in rats, and different doses of UA were administrated. The levels of oxidative stress-related factors in serum were detected. Hematoxylin & eosin (H&E) staining was used to observe the morphological alterations, and the apoptotic cell death detection kit was used to detect apoptotic cells. Increased UA concentration and enhanced oxidative stress were found in AS patients. H&E staining results showed that UA treatment exacerbated morphological damage in rats with MCAO, promoted oxidative stress, and enhanced vascular endothelial cell apoptosis in rats with MCAO. © 2017 The Author(s).

  10. The adaptation of the cerebral circulation to pregnancy: mechanisms and consequences

    PubMed Central

    Cipolla, Marilyn J

    2013-01-01

    The adaptation of the cerebral circulation to pregnancy is unique from other vascular beds. Most notably, the growth and vasodilatory response to high levels of circulating growth factors and cytokines that promote substantial hemodynamic changes in other vascular beds is limited in the cerebral circulation. This is accomplished through several mechanisms, including downregulation of key receptors and transcription factors, and production of circulating factors that counteract the vasodilatory effects of vascular endothelial growth factor (VEGF) and placental growth factor. Pregnancy both prevents and reverses hypertensive inward remodeling of cerebral arteries, possibly through downregulation of the angiotensin type 1 receptor. The blood–brain barrier (BBB) importantly adapts to pregnancy by preventing the passage of seizure provoking serum into the brain and limiting the permeability effects of VEGF that is more highly expressed in cerebral vasculature during pregnancy. While the adaptation of the cerebral circulation to pregnancy provides for relatively normal cerebral blood flow and BBB properties in the face of substantial cardiovascular changes and high levels of circulating factors, under pathologic conditions, these adaptations appear to promote greater brain injury, including edema formation during acute hypertension, and greater sensitivity to bacterial endotoxin. PMID:23321787

  11. 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.

  12. Indian-Ink Perfusion Based Method for Reconstructing Continuous Vascular Networks in Whole Mouse Brain

    PubMed Central

    Xue, Songchao; Gong, Hui; Jiang, Tao; Luo, Weihua; Meng, Yuanzheng; Liu, Qian; Chen, Shangbin; Li, Anan

    2014-01-01

    The topology of the cerebral vasculature, which is the energy transport corridor of the brain, can be used to study cerebral circulatory pathways. Limited by the restrictions of the vascular markers and imaging methods, studies on cerebral vascular structure now mainly focus on either observation of the macro vessels in a whole brain or imaging of the micro vessels in a small region. Simultaneous vascular studies of arteries, veins and capillaries have not been achieved in the whole brain of mammals. Here, we have combined the improved gelatin-Indian ink vessel perfusion process with Micro-Optical Sectioning Tomography for imaging the vessel network of an entire mouse brain. With 17 days of work, an integral dataset for the entire cerebral vessels was acquired. The voxel resolution is 0.35×0.4×2.0 µm3 for the whole brain. Besides the observations of fine and complex vascular networks in the reconstructed slices and entire brain views, a representative continuous vascular tracking has been demonstrated in the deep thalamus. This study provided an effective method for studying the entire macro and micro vascular networks of mouse brain simultaneously. PMID:24498247

  13. [Impact of isolated diastolic hypertension on new-onset cardiovascular and cerebro-vascular diseases].

    PubMed

    Xing, Fengmei; Dong, Yan; Tao, Jie; Gao, Xinying; Zhou, Jianhui; Chen, Shuohua; Ji, Chunpeng; Yao, Tao; Wu, Shouling

    2014-08-01

    To explore the impact of isolated diastolic hypertension (IDH) on new-onset cardio-cerebral vascular diseases (CVD). This cohort study involved 101 510 participants who were employees of the Kailuan Group-a state-run coal mining company, in 2006 and 2007. Among them, 6 780 subjects were diagnosed with IDH, 35 448 subjects were diagnosed with high-normal blood pressure and 19 460 subjects were diagnosed with normal tension. However, none of them had the history of either cardio-cerebral vascular disease or malignant cancer. Cardio-cerebral vascular events including cerebral infarction, cerebral hemorrhage, acute myocardial infarction were recorded every 6 months during the follow-up (47.1 ± 4.8) period. Multivariable Cox proportional hazards regression models were used to analyze the risk factors of first-ever CVD events. 1) There were 675 CVD events occurred during the follow-up period. The incidence rates of CVD events (1.7% vs. 0.9%), cerebral infarction (1.0% vs. 0.6%) and cerebral hemorrhage (0.4% vs. 0.1%) were significantly higher in IDH group than that in the normal tension group (all P < 0.05). 2) After adjustment for other established CVD risk factors, the hazards ratios became 1.67 (95% CI: 1.28-2.17) for total CVD events and 1.59 (95% CI: 1.12-2.27) for cerebral infarction and 2.67 (95% CI: 1.54-4.65) for cerebral hemorrhage in the IDH group. 3). In stratified analysis on age, after adjustment for other established CVD risk factors, the hazards ratio was 2.22 (95% CI: 1.41-3.50) for cerebral infarction in lower 60 years old group, while the it was 7.27 (95% CI: 2.58-20.42) for cerebral hemorrhage in groups older than 60 years of age. IDH was the independent risk factor for the total cardio-cerebral vascular events, on both cerebral infarction and cerebral hemorrhage. The predicted values of IDH for different CVD events were diverse on different age groups.

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

    PubMed

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

    2014-08-09

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

  15. 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

  16. Detection of cerebral amyloid angiopathy by 3-T magnetic resonance imaging and amyloid positron emission tomography in a patient with subcortical ischaemic vascular dementia.

    PubMed

    Kida, Hirotaka; Satoh, Masayuki; Ii, Yuichiro; Fukuyama, Hidenao; Maeda, Masayuki; Tomimoto, Hidekazu

    2017-01-01

    The patient was an 81-year-old man who had been treated for hypertension for several decades. In 2012, he developed gait disturbance and mild amnesia. One year later, his gait disturbance worsened, and he developed urinary incontinence. Conventional brain magnetic resonance imaging using T 2 -weighted images and fluid-attenuated inversion recovery showed multiple lacunar infarctions. These findings fulfilled the diagnostic criteria for subcortical ischaemic vascular dementia. However, susceptibility weighted imaging showed multiple lobar microbleeds in the bilateral occipitoparietal lobes, and double inversion recovery and 3-D fluid-attenuated inversion recovery images on 3-T magnetic resonance imaging revealed cortical microinfarctions in the left parietal-temporo-occipito region. Pittsburgh compound B-positron emission tomography revealed diffuse uptake in the cerebral cortex. Therefore, we diagnosed the patient with subcortical ischaemic vascular dementia associated with Alzheimer's disease. The use of the double inversion recovery and susceptibility weighted imaging on 3-T magnetic resonance imaging may be a supplemental strategy for diagnosing cerebral amyloid angiopathy, which is closely associated with Alzheimer's disease. © 2016 The Authors. Psychogeriatrics © 2016 Japanese Psychogeriatric Society.

  17. Effect of electromagnetic pulse exposure on brain micro vascular permeability in rats.

    PubMed

    Ding, Gui-Rong; Li, Kang-Chu; Wang, Xiao-Wu; Zhou, Yong-Chun; Qiu, Lian-Bo; Tan, Juan; Xu, Sheng-Long; Guo, Guo-Zhen

    2009-06-01

    To observe the effect of electromagnetic pulse (EMP) exposure on cerebral micro vascular permeability in rats. The whole-body of male Sprague-Dawley rats were exposed or sham exposed to 200 pulses or 400 pulses (1 Hz) of EMP at 200 kV/m. At 0.5, 1, 3, 6, and 12 h after EMP exposure, the permeability of cerebral micro vascular was detected by transmission electron microscopy and immunohistochemistry using lanthanum nitrate and endogenous albumin as vascular tracers, respectively. The lanthanum nitrate tracer was limited to the micro vascular lumen with no lanthanum nitrate or albumin tracer extravasation in control rat brain. After EMP exposure, the lanthanum nitrate ions reached the tight junction, basal lamina and pericapillary tissue. Similarly, the albumin immunopositive staining was identified in pericapillary tissue. The changes in brain micro vascular permeability were transient, the leakage of micro vascular vessels appeared at 1 h, and reached its peak at 3 h, and nearly recovered at 12 h, after EMP exposure. In addition, the leakage of micro vascular was more obvious after exposure of EMP at 400 pulses than after exposure of EMP at 200 pulses. Exposure to 200 and 400 pulses (1 Hz) of EMP at 200 kV/m can increase cerebral micro vascular permeability in rats, which is recoverable.

  18. Management of Major Vascular Injury: Open.

    PubMed

    Tisherman, Samuel A

    2016-06-01

    Major blood vessels are in proximity to other vital structures in the neck and base of skull. Infections and tumors of the head and neck can invade vascular structures. Vascular injuries can lead to massive hemorrhage, cerebral ischemia, or stroke. Emergency and definitive management can be challenging. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Vascular Variations Associated with Intracranial Aneurysms.

    PubMed

    Orakdogen, Metin; Emon, Selin Tural; Somay, Hakan; Engin, Taner; Is, Merih; Hakan, Tayfun

    2017-01-01

    To investigate the vascular variations in patients with intracranial aneurysm in circle of Willis. We used the data on 128 consecutive intracranial aneurysm cases. Cerebral angiography images were analyzed retrospectively. Arteries were grouped as anterior cerebral arterial system (ACS), posterior cerebral arterial system (PCS) and middle cerebral arterial system (MCS) for grouping vascular variations. Lateralization, being single/multiple, gender; and also any connection with accompanying aneurysms" number, localization, dimension, whether bleeding/incidental aneurysm has been inspected. Variations were demonstrated in 57.8% of the cases. The most common variation was A1 variation (34.4%). The rate of variations was 36.7%, 24.2% and 10.2% respectively in ACS, PCS and MCS. MCS variations were significantly higher in males. Anterior communicating artery (ACoA) aneurysm observance rates were significantly higher and posterior communicating artery (PCoA) aneurysm and middle cerebral artery (MCA) aneurysm observance rates were significantly lower when compared to "no ACS variation detected" cases. In "PCS variation detected" cases, PCoA aneurysm observance rates and coexistence of multiple variations were significantly higher. The rate of vascular variations in patients with aneurysms was 57.8%. Arterial hypoplasia and aplasia were the most common variations. ACS was the most common region that variations were located in; they were mostly detected on the right side. Coexistence of ACoA aneurysm was higher than PCoA and MCA aneurysms. In the PCS variations group, PCoA aneurysms were the most common aneurysms that accompanying the variation and multiple variations were more common than in the other two groups. The variations in MCS were most common in males.

  20. Acute and chronic head-down tail suspension diminishes cerebral perfusion in rats

    NASA Technical Reports Server (NTRS)

    Wilkerson, M. Keith; Colleran, Patrick N.; Delp, Michael D.

    2002-01-01

    The purpose of this study was to test the hypothesis that regional brain blood flow and vascular resistance are altered by acute and chronic head-down tail suspension (HDT). Regional cerebral blood flow, arterial pressure, heart rate, and vascular resistance were measured in a group of control rats during normal standing and following 10 min of HDT and in two other groups of rats after 7 and 28 days of HDT. Heart rate was not different among conditions, whereas mean arterial pressure was elevated at 10 min of HDT relative to the other conditions. Total brain blood flow was reduced from that during standing by 48, 24, and 27% following 10 min and 7 and 28 days of HDT, respectively. Regional blood flows to all cerebral tissues and the eyes were reduced with 10 min of HDT and remained lower in the eye, olfactory bulbs, left and right cerebrum, thalamic region, and the midbrain with 7 and 28 days of HDT. Total brain vascular resistance was 116, 44, and 38% greater following 10 min and 7 and 28 days of HDT, respectively, relative to that during control standing. Vascular resistance was elevated in all cerebral regions with 10 min of HDT and remained higher than control levels in most brain regions. These results demonstrate that HDT results in chronic elevations in total and regional cerebral vascular resistance, and this may be the underlying stimulus for the HDT-induced smooth muscle hypertrophy of cerebral resistance arteries.

  1. Cerebral Small Vessel Disease and Chronic Kidney Disease

    PubMed Central

    2015-01-01

    Chronic kidney disease, defined by a decreased glomerular filtration rate or albuminuria, is recognized as a major global health burden, mainly because it is an established risk factor for cardiovascular and cerebrovascular diseases. The magnitude of the effect of chronic kidney disease on incident stroke seems to be higher in persons of Asian ethnicity. Since the kidney and brain share unique susceptibilities to vascular injury due to similar anatomical and functional features of small artery diseases, kidney impairment can be predictive of the presence and severity of cerebral small vessel diseases. Chronic kidney disease has been reported to be associated with silent brain infarcts, cerebral white matter lesions, and cerebral microbleeds, independently of vascular risk factors. In addition, chronic kidney disease affects cognitive function, partly via the high prevalence of cerebral small vessel diseases. Retinal artery disease also has an independent relationship with chronic kidney disease and cognitive impairment. Stroke experts are no longer allowed to be ignorant of chronic kidney disease. Close liaison between neurologists and nephrologists can improve the management of cerebral small vessel diseases in kidney patients. PMID:25692105

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

    PubMed

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

    2013-02-01

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

  3. Mechanical Injury Induces Brain Endothelial-Derived Microvesicle Release: Implications for Cerebral Vascular Injury during Traumatic Brain Injury.

    PubMed

    Andrews, Allison M; Lutton, Evan M; Merkel, Steven F; Razmpour, Roshanak; Ramirez, Servio H

    2016-01-01

    . These results indicate that following TBI, the cerebral endothelium undergoes vascular remodeling through shedding of eMVs containing TJPs and endothelial markers. The detection of this shedding potentially allows for a novel methodology for real-time monitoring of cerebral vascular health (remodeling), BBB status and neuroinflammation following a TBI event.

  4. [Cerebral hemodynamics in patients with neurosensory hearing loss before and after magnetotherapy].

    PubMed

    Morenko, V M; Enin, I P

    2001-01-01

    Magnetotherapy effects on cerebral hemodynamics were studied using rheoencephalography (REG). When the treatment results and changes in cerebral hemodynamics were compared it was evident that normalization or improvement of vascular status in vertebrobasilar and carotid territories registered at REG results in better hearing. This confirms the role of vascular factor in pathogenesis of neurosensory hypoacusis of different etiology and effectiveness of magnetotherapy in such patients.

  5. VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer

    PubMed Central

    Gerstner, Elizabeth R.; Duda, Dan G.; di Tomaso, Emmanuelle; Ryg, Peter A.; Loeffler, Jay S.; Sorensen, A. Gregory; Ivy, Percy; Jain, Rakesh K.; Batchelor, Tracy T.

    2016-01-01

    Most brain tumors oversecrete vascular endothelial growth factor (VEGF), which leads to an abnormally permeable tumor vasculature. This hyperpermeability allows fluid to leak from the intravascular space into the brain parenchyma, which causes vasogenic cerebral edema and increased interstitial fluid pressure. Increased interstitial fluid pressure has an important role in treatment resistance by contributing to tumor hypoxia and preventing adequate tumor penetration of chemotherapy agents. In addition, edema and the corticosteroids needed to control cerebral edema cause significant morbidity and mortality. Agents that block the VEGF pathway are able to decrease vascular permeability and, thus, cerebral edema, by restoring the abnormal tumor vasculature to a more normal state. Decreasing cerebral edema minimizes the adverse effects of corticosteroids and could improve clinical outcomes. Anti-VEGF agents might also be useful in other cancer-related conditions that increase vascular permeability, such as malignant pleural effusions or ascites. PMID:19333229

  6. Targeted Vascular Drug Delivery in Cerebral Cancer.

    PubMed

    Humle, Nanna; Johnsen, Kasper Bendix; Arendt, Gitte Abildgaard; Nielsen, Rikke Paludan; Moos, Torben; Thomsen, Louiza Bohn

    2016-01-01

    This review presents the present-day literature on the anatomy and physiological mechanisms of the blood-brain barrier and the problematic of cerebral drug delivery in relation to malignant brain tumors. First step in treatment of malignant brain tumors is resection, but there is a high risk of single remnant infiltrative tumor cells in the outer zone of the brain tumor. These infiltrative single-cells will be supplied by capillaries with an intact BBB as opposed to the partly leaky BBB found in the tumor tissue before resection. Even though BBB penetrance of a chemotherapeutic agent is considered irrelevant though the limited success rate for chemotherapeutic treatability of GBM tumors indicate otherwise. Therefore drug delivery strategies to cerebral cancer after resection should be tailored to being able to both penetrate the intact BBB and target the cancer cells. In this review the intact bloodbrain barrier and cerebral cancer with main focus on glioblastoma multiforme (GBM) is introduced. The GBM induced formation of a blood-tumor barrier and the consequences hereof is described and discussed with emphasis on the impact these changes of the BBB has on drug delivery to GBM. The most commonly used drug carriers for drug delivery to GBM is described and the current drug delivery strategies for glioblastoma multiforme including possible routes through the BBB and epitopes, which can be targeted on the GBM cells is outlined. Overall, this review aims to address targeted drug delivery in GBM treatment when taking the differing permeability of the BBB into consideration.

  7. Cerebral malaria in children: using the retina to study the brain

    PubMed Central

    Beare, Nicholas A. V.; Taylor, Terrie E.; Barrera, Valentina; White, Valerie A.; Hiscott, Paul; Molyneux, Malcolm E.; Dhillon, Baljean; Harding, Simon P.

    2014-01-01

    Cerebral malaria is a dangerous complication of Plasmodium falciparum infection, which takes a devastating toll on children in sub-Saharan Africa. Although autopsy studies have improved understanding of cerebral malaria pathology in fatal cases, information about in vivo neurovascular pathogenesis is scarce because brain tissue is inaccessible in life. Surrogate markers may provide insight into pathogenesis and thereby facilitate clinical studies with the ultimate aim of improving the treatment and prognosis of cerebral malaria. The retina is an attractive source of potential surrogate markers for paediatric cerebral malaria because, in this condition, the retina seems to sustain microvascular damage similar to that of the brain. In paediatric cerebral malaria a combination of retinal signs correlates, in fatal cases, with the severity of brain pathology, and has diagnostic and prognostic significance. Unlike the brain, the retina is accessible to high-resolution, non-invasive imaging. We aimed to determine the extent to which paediatric malarial retinopathy reflects cerebrovascular damage by reviewing the literature to compare retinal and cerebral manifestations of retinopathy-positive paediatric cerebral malaria. We then compared retina and brain in terms of anatomical and physiological features that could help to account for similarities and differences in vascular pathology. These comparisons address the question of whether it is biologically plausible to draw conclusions about unseen cerebral vascular pathogenesis from the visible retinal vasculature in retinopathy-positive paediatric cerebral malaria. Our work addresses an important cause of death and neurodisability in sub-Saharan Africa. We critically appraise evidence for associations between retina and brain neurovasculature in health and disease, and in the process we develop new hypotheses about why these vascular beds are susceptible to sequestration of parasitized erythrocytes. PMID:24578549

  8. Transjugular intrahepatic portosystemic shunt with accidental diagnosis of persistence of the left superior vena cava.

    PubMed

    Petridis, Ioannis; Miraglia, Roberto; Marrone, Gianluca; Gruttadauria, Salvatore; Luca, Angelo; Vizzini, Giovanni Battista; Gridelli, Bruno

    2010-03-07

    Transjugular intrahepatic portosystemic shunt (TIPSS) is considered a valid therapeutic option for the treatment of portal hypertension and its complications. The guidelines for this procedure have already been established on the basis of the normal vascular anatomy and of various technical radiological aspects. In some few rare cases, diagnosis of a congenital vascular anomaly can be made accidentally by interventional radiologists, making the procedure of the TIPSS placement extremely difficult or in some cases technically impossible. This report describes a rare vascular malformation characterized by the absence of the right superior vena cava and persistence of the left superior vena cava in a patient with a diagnosis of advanced liver cirrhosis who needed a TIPSS placement in order to control refractory ascites.

  9. Biology of vascular malformations of the brain.

    PubMed

    Leblanc, Gabrielle G; Golanov, Eugene; Awad, Issam A; Young, William L

    2009-12-01

    This review discusses recent research on the genetic, molecular, cellular, and developmental mechanisms underlying the etiology of vascular malformations of the brain (VMBs), including cerebral cavernous malformation, sporadic brain arteriovenous malformation, and the arteriovenous malformations of hereditary hemorrhagic telangiectasia. Summary of Review- The identification of gene mutations and genetic risk factors associated with cerebral cavernous malformation, hereditary hemorrhagic telangiectasia, and sporadic arteriovenous malformation has enabled the development of animal models for these diseases and provided new insights into their etiology. All of the genes associated with VMBs to date have known or plausible roles in angiogenesis and vascular remodeling. Recent work suggests that the angiogenic process most severely disrupted by VMB gene mutation is that of vascular stabilization, the process whereby vascular endothelial cells form capillary tubes, strengthen their intercellular junctions, and recruit smooth muscle cells to the vessel wall. In addition, there is now good evidence that in some cases, cerebral cavernous malformation lesion formation involves a genetic 2-hit mechanism in which a germline mutation in one copy of a cerebral cavernous malformation gene is followed by a somatic mutation in the other copy. There is also increasing evidence that environmental second hits can produce lesions when there is a mutation to a single allele of a VMB gene. Recent findings begin to explain how mutations in VMB genes render vessels vulnerable to rupture when challenged with other inauspicious genetic or environmental factors and have suggested candidate therapeutics. Understanding of the cellular mechanisms of VMB formation and progression in humans has lagged behind that in animal models. New knowledge of lesion biology will spur new translational work. Several well-established clinical and genetic database efforts are already in place, and further

  10. The Association of Type 2 Diabetes Mellitus with Cerebral Gray Matter Volume Is Independent of Retinal Vascular Architecture and Retinopathy.

    PubMed

    Moran, C; Tapp, R J; Hughes, A D; Magnussen, C G; Blizzard, L; Phan, T G; Beare, R; Witt, N; Venn, A; Münch, G; Amaratunge, B C; Srikanth, V

    2016-01-01

    It is uncertain whether small vessel disease underlies the relationship between Type 2 Diabetes Mellitus (T2DM) and brain atrophy. We aimed to study whether retinal vascular architecture, as a proxy for cerebral small vessel disease, may modify or mediate the associations of T2DM with brain volumes. In this cross-sectional study using Magnetic Resonance Imaging (MRI) scans and retinal photographs in 451 people with and without T2DM, we measured brain volumes, geometric measures of retinal vascular architecture, clinical retinopathy, and MRI cerebrovascular lesions. There were 270 people with (mean age 67.3 years) and 181 without T2DM (mean age 72.9 years). T2DM was associated with lower gray matter volume (p = 0.008). T2DM was associated with greater arteriolar diameter (p = 0.03) and optimality ratio (p = 0.04), but these associations were attenuated by adjustments for age and sex. Only optimality ratio was associated with lower gray matter volume (p = 0.03). The inclusion of retinal measures in regression models did not attenuate the association of T2DM with gray matter volume. The association of T2DM with lower gray matter volume was independent of retinal vascular architecture and clinical retinopathy. Retinal vascular measures or retinopathy may not be sufficiently sensitive to confirm a microvascular basis for T2DM-related brain atrophy.

  11. Dynamics of pulsatile flow in fractal models of vascular branching networks.

    PubMed

    Bui, Anh; Sutalo, Ilija D; Manasseh, Richard; Liffman, Kurt

    2009-07-01

    Efficient regulation of blood flow is critically important to the normal function of many organs, especially the brain. To investigate the circulation of blood in complex, multi-branching vascular networks, a computer model consisting of a virtual fractal model of the vasculature and a mathematical model describing the transport of blood has been developed. Although limited by some constraints, in particular, the use of simplistic, uniformly distributed model for cerebral vasculature and the omission of anastomosis, the proposed computer model was found to provide insights into blood circulation in the cerebral vascular branching network plus the physiological and pathological factors which may affect its functionality. The numerical study conducted on a model of the middle cerebral artery region signified the important effects of vessel compliance, blood viscosity variation as a function of the blood hematocrit, and flow velocity profile on the distributions of flow and pressure in the vascular network.

  12. 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.

  13. Cerebral collaterals and collateral therapeutics for acute ischemic stroke.

    PubMed

    Winship, Ian R

    2015-04-01

    Cerebral collaterals are vascular redundancies in the cerebral circulation that can partially maintain blood flow to ischemic tissue when primary conduits are blocked. After occlusion of a cerebral artery, anastomoses connecting the distal segments of the MCA with distal branches of the ACA and PCA (known as leptomeningeal or pial collaterals) allow for partially maintained blood flow in the ischemic penumbra and delay or prevent cell death. However, collateral circulation varies dramatically between individuals, and collateral extent is significant predictor of stroke severity and recanalization rate. Collateral therapeutics attempt to harness these vascular redundancies by enhancing blood flow through pial collaterals to reduce ischemia and brain damage after cerebral arterial occlusion. While therapies to enhance collateral flow remain relatively nascent neuroprotective strategies, experimental therapies including inhaled NO, transient suprarenal aortic occlusion, and electrical stimulation of the parasympathetic sphenopalatine ganglion show promise as collateral therapeutics with the potential to improve treatment of acute ischemic stroke. © 2014 John Wiley & Sons Ltd.

  14. The Third, Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial

    ClinicalTrials.gov

    2018-04-24

    Cerebral Hemorrhage; Stroke; Hypertension; Diabetes; Anticoagulant-induced Bleeding; Cerebral Vascular Disorder; Brain Disorder; Hemorrhage; Intracranial Hemorrhages; Cardiovascular Diseases; Central Nervous System Diseases

  15. Bacterial toxins activation of abbreviated urea cycle in porcine cerebral vascular smooth muscle cells.

    PubMed

    Mishra, Rajesh G; Tseng, Tzu-Ling; Chen, Mei-Fang; Chen, Po-Yi; Lee, Tony J-F

    2016-12-01

    Nitric oxide (NO) overproduction via induction of inducible nitric oxide synthase (iNOS) is implicated in vasodilatory shock in sepsis, leading to septic encephalopathy and accelerating cerebral ischemic injury. An abbreviated urea-cycle (l-citrulline-l-arginine-NO cycle) has been demonstrated in cerebral perivascular nitrergic nerves and endothelial cells but not in normal cerebral vascular smooth muscle cell (CVSMC). This cycle indicates that argininosuccinate synthase (ASS) catalyzes l-citrulline (l-cit) conversion to form argininosuccinate (AS), and subsequent AS cleavage by argininosuccinate lyase (ASL) forms l-arginine (l-arg), the substrate for NO synthesis. The possibility that ASS enzyme in this cycle was induced in the CVSMC in sepsis was examined. Blood-vessel myography technique was used for measuring porcine isolated basilar arterial tone. NO in cultured CVSMC and in condition mediums were estimated by diaminofluorescein (DAF)-induced fluorescence and Griess reaction, respectively. Immunohistochemical and immunoblotting analyses were used to examine iNOS and ASS induction. l-cit and l-arg, which did not relax endothelium-denuded normal basilar arteries precontracted by U-46619, induced significant vasorelaxation with increased NO production in these arteries and the CVSMCs following 6-hour exposure to 20μg/ml lipopolysaccharide (LPS) or lipoteichoic acid (LTA). Pre-treatment with pyrrolidine dithiocarbamate (PDTC) and salicylate (SAL) (NFκB inhibitors), aminoguanidine (AG, an iNOS inhibitor), and nitro-l-arg (NLA, a non-specific NOS inhibitor) blocked NO synthesis in the CVSMC and attenuated l-cit- and l-arg-induced relaxation of LPS- and LTA-treated arteries. Furthermore, immunohistochemical and immunoblotting studies demonstrated that expression of basal iNOS and ASS in the smooth muscle cell of arterial segments denuded of endothelium and the cultured CVSMCs was significantly increased following 6-hour incubation with LPS or LTA. This increased i

  16. Vascular inward rectifier K+ channels as external K+ sensors in the control of cerebral blood flow.

    PubMed

    Longden, Thomas A; Nelson, Mark T

    2015-04-01

    For decades it has been known that external K(+) ions are rapid and potent vasodilators that increase CBF. Recent studies have implicated the local release of K(+) from astrocytic endfeet-which encase the entirety of the parenchymal vasculature-in the dynamic regulation of local CBF during NVC. It has been proposed that the activation of KIR channels in the vascular wall by external K(+) is a central component of these hyperemic responses; however, a number of significant gaps in our knowledge remain. Here, we explore the concept that vascular KIR channels are the major extracellular K(+) sensors in the control of CBF. We propose that K(+) is an ideal mediator of NVC, and discuss KIR channels as effectors that produce rapid hyperpolarization and robust vasodilation of cerebral arterioles. We provide evidence that KIR channels, of the KIR 2 subtype in particular, are present in both the endothelial and SM cells of parenchymal arterioles and propose that this dual positioning of KIR 2 channels increases the robustness of the vasodilation to external K(+), enables the endothelium to be actively engaged in NVC, and permits electrical signaling through the endothelial syncytium to promote upstream vasodilation to modulate CBF. © 2015 John Wiley & Sons Ltd.

  17. Percutaneous Management of Accidentally Retained Foreign Bodies During Image-Guided Non-vascular Procedures: Novel Technique Using a Large-Bore Biopsy System

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

    Cazzato, Roberto Luigi, E-mail: gigicazzato@hotmail.it; Garnon, Julien, E-mail: juleiengarnon@gmail.com; Ramamurthy, Nitin, E-mail: nitin-ramamurthy@hotmail.com

    ObjectiveTo describe a novel percutaneous image-guided technique using a large-bore biopsy system to retrieve foreign bodies (FBs) accidentally retained during non-vascular interventional procedures.Materials and MethodsBetween May 2013 and October 2015, five patients underwent percutaneous retrieval of five iatrogenic FBs, including a biopsy needle tip in the femoral head following osteoblastoma biopsy and radiofrequency ablation (RFA); a co-axial needle shaft within a giant desmoid tumour following cryoablation; and three post-vertebroplasty cement tails within paraspinal muscles. All FBs were retrieved immediately following original procedures under local or general anaesthesia, using combined computed tomography (CT) and fluoroscopic guidance. The basic technique involved positioningmore » a 6G trocar sleeve around the FB long axis and co-axially advancing an 8G biopsy needle to retrieve the FB within the biopsy core. Retrospective chart review facilitated analysis of procedures, FBs, technical success, and complications.ResultsMean FB size was 23 mm (range 8–74 mm). Four FBs were located within 10 mm of non-vascular significant anatomic structures. The basic technique was successful in 3 cases; 2 cases required technical modifications including using a stiff guide-wire to facilitate retrieval in the case of the post-cryoablation FB; and using the central mandrin of the 6G trocar to push a cement tract back into an augmented vertebra when initial retrieval failed. Overall technical success (FB retrieval or removal to non-hazardous location) was 100 %, with no complications.ConclusionPercutaneous image-guided retrieval of iatrogenic FBs using a large-bore biopsy system is a feasible, safe, effective, and versatile technique, with potential advantages over existing methods.« less

  18. The pathobiology of vascular dementia

    PubMed Central

    Iadecola, Costantino

    2013-01-01

    Vascular cognitive impairment defines alterations in cognition, ranging from subtle deficits to full-blown dementia, attributable to cerebrovascular causes. Often coexisting with Alzheimer’s disease, mixed vascular and neurodegenerative dementia has emerged as the leading cause of age-related cognitive impairment. Central to the disease mechanism is the crucial role that cerebral blood vessels play in brain health, not only for the delivery of oxygen and nutrients, but also for the trophic signaling that links inextricably the well being of neurons and glia to that of cerebrovascular cells. This review will examine how vascular damage disrupts these vital homeostatic interactions, focusing on the hemispheric white matter, a region at heightened risk for vascular damage, and on the interplay between vascular factors and Alzheimer’s disease. Finally, preventative and therapeutic prospects will be examined, highlighting the importance of midlife vascular risk factor control in the prevention of late-life dementia. PMID:24267647

  19. Morning Glory Syndrome with Carotid and Middle Cerebral Artery Vasculopathy.

    PubMed

    Nezzar, Hachemi; Mbekeani, Joyce N; Dalens, Helen

    2015-12-01

    To report a case of incidental asymptomatic atypical morning glory syndrome (MGS) with concomitant ipsilateral carotid and middle cerebral dysgenesis. A 6-year-old child was discovered to have incidental findings of MGS, with atypia. All visual functions were normal including vision and stereopsis. Neuroimaging revealed ipsilateral carotid and middle cerebral vascular narrowing without associated collateral vessels or cerebral ischemia commonly seen in Moyamoya disease. Subsequent annual examinations have been stable, without signs of progression. This case demonstrates disparity between structural aberrations and final visual and neurological function and reinforces the association between MGS and intracranial vascular disruption. Full ancillary ophthalmic and neuroimaging studies should be performed in all patients with MGS with interval reassessments, even when the patient is asymptomatic and functionally intact.

  20. Characterization of White Matter Injury in a Rat Model of Chronic Cerebral Hypoperfusion.

    PubMed

    Choi, Bo-Ryoung; Kim, Dong-Hee; Back, Dong Bin; Kang, Chung Hwan; Moon, Won-Jin; Han, Jung-Soo; Choi, Dong-Hee; Kwon, Kyoung Ja; Shin, Chan Young; Kim, Bo-Ram; Lee, Jongmin; Han, Seol-Heui; Kim, Hahn Young

    2016-02-01

    Chronic cerebral hypoperfusion can lead to ischemic white matter injury resulting in vascular dementia. To characterize white matter injury in vascular dementia, we investigated disintegration of diverse white matter components using a rat model of chronic cerebral hypoperfusion. Chronic cerebral hypoperfusion was modeled in Wistar rats by permanent occlusion of the bilateral common carotid arteries. We performed cognitive behavioral tests, including the water maze task, odor discrimination task, and novel object test; histological investigation of neuroinflammation, oligodendrocytes, myelin basic protein, and nodal or paranodal proteins at the nodes of Ranvier; and serial diffusion tensor imaging. Cilostazol was administered to protect against white matter injury. Diverse cognitive impairments were induced by chronic cerebral hypoperfusion. Disintegration of white matter was characterized by neuroinflammation, loss of oligodendrocytes, attenuation of myelin density, structural derangement at the nodes of Ranvier, and disintegration of white matter tracts. Cilostazol protected against cognitive impairments and white matter disintegration. White matter injury induced by chronic cerebral hypoperfusion can be characterized by disintegration of diverse white matter components. Cilostazol might be a therapeutic strategy against white matter disintegration in patients with vascular dementia. © 2015 American Heart Association, Inc.

  1. Multichannel optical brain imaging to separate cerebral vascular, tissue metabolic, and neuronal effects of cocaine

    NASA Astrophysics Data System (ADS)

    Ren, Hugang; Luo, Zhongchi; Yuan, Zhijia; Pan, Yingtian; Du, Congwu

    2012-02-01

    Characterization of cerebral hemodynamic and oxygenation metabolic changes, as well neuronal function is of great importance to study of brain functions and the relevant brain disorders such as drug addiction. Compared with other neuroimaging modalities, optical imaging techniques have the potential for high spatiotemporal resolution and dissection of the changes in cerebral blood flow (CBF), blood volume (CBV), and hemoglobing oxygenation and intracellular Ca ([Ca2+]i), which serves as markers of vascular function, tissue metabolism and neuronal activity, respectively. Recently, we developed a multiwavelength imaging system and integrated it into a surgical microscope. Three LEDs of λ1=530nm, λ2=570nm and λ3=630nm were used for exciting [Ca2+]i fluorescence labeled by Rhod2 (AM) and sensitizing total hemoglobin (i.e., CBV), and deoxygenated-hemoglobin, whereas one LD of λ1=830nm was used for laser speckle imaging to form a CBF mapping of the brain. These light sources were time-sharing for illumination on the brain and synchronized with the exposure of CCD camera for multichannel images of the brain. Our animal studies indicated that this optical approach enabled simultaneous mapping of cocaine-induced changes in CBF, CBV and oxygenated- and deoxygenated hemoglobin as well as [Ca2+]i in the cortical brain. Its high spatiotemporal resolution (30μm, 10Hz) and large field of view (4x5 mm2) are advanced as a neuroimaging tool for brain functional study.

  2. Axon-glial disruption: the link between vascular disease and Alzheimer's disease?

    PubMed

    Horsburgh, Karen; Reimer, Michell M; Holland, Philip; Chen, Guiquan; Scullion, Gillian; Fowler, Jill H

    2011-08-01

    Vascular risk factors play a critical role in the development of cognitive decline and AD (Alzheimer's disease), during aging, and often result in chronic cerebral hypoperfusion. The neurobiological link between hypoperfusion and cognitive decline is not yet defined, but is proposed to involve damage to the brain's white matter. In a newly developed mouse model, hypoperfusion, in isolation, produces a slowly developing and diffuse damage to myelinated axons, which is widespread in the brain, and is associated with a selective impairment in working memory. Cerebral hypoperfusion, an early event in AD, has also been shown to be associated with white matter damage and notably an accumulation of amyloid. The present review highlights some of the published data linking white matter disruption to aging and AD as a result of vascular dysfunction. A model is proposed by which chronic cerebral hypoperfusion, as a result of vascular factors, results in both the generation and accumulation of amyloid and injury to white matter integrity, resulting in cognitive impairment. The generation of amyloid and accumulation in the vasculature may act to perpetuate further vascular dysfunction and accelerate white matter pathology, and as a consequence grey matter pathology and cognitive decline.

  3. Protective or pathogenic effects of vascular endothelial growth factor (VEGF) as potential biomarker in cerebral malaria.

    PubMed

    Canavese, Miriam; Spaccapelo, Roberta

    2014-03-01

    Cerebral malaria (CM) is the major lethal complication of Plasmodium falciparum infection. It is characterized by persistent coma along with symmetrical motor signs. Several clinical, histopathological, and laboratory studies have suggested that cytoadherence of parasitized erythrocytes, neural injury by malarial toxin, and excessive inflammatory cytokine production are possible pathogenic mechanisms. Although the detailed pathophysiology of CM remains unsolved, it is thought that the binding of parasitized erythrocytes to the cerebral endothelia of microvessels, leading to their occlusion and the consequent angiogenic dysregulation play a key role in the disease pathogenesis. Recent evidences showed that vascular endothelial growth factor (VEGF) and its receptor-related molecules are over-expressed in the brain tissues of CM patients, as well as increased levels of VEGF are detectable in biologic samples from malaria patients. Whether the modulation of VEGF is causative agent of CM mortality or a specific phenotype of patients with susceptibility to fatal CM needs further evaluation. Currently, there is no biological test available to confirm the diagnosis of CM and its complications. It is hoped that development of biomarkers to identify patients and potential risk for adverse outcomes would greatly enhance better intervention and clinical management to improve the outcomes. We review and discuss here what it is currently known in regard to the role of VEGF in CM as well as VEGF as a potential biomarker.

  4. Social evaluation of intentional, truly accidental, and negligently accidental helpers and harmers by 10-month-old infants.

    PubMed

    Woo, Brandon M; Steckler, Conor M; Le, Doan T; Hamlin, J Kiley

    2017-11-01

    Whereas adults largely base their evaluations of others' actions on others' intentions, a host of research in developmental psychology suggests that younger children privilege outcome over intention, leading them to condemn accidental harm. To date, this question has been examined only with children capable of language production. In the current studies, we utilized a non-linguistic puppet show paradigm to examine the evaluation of intentional and accidental acts of helping or harming in 10-month-old infants. In Experiment 1 (n=64), infants preferred intentional over accidental helpers but accidental over intentional harmers, suggestive that by this age infants incorporate information about others' intentions into their social evaluations. In Experiment 2 (n=64), infants did not distinguish "negligently" accidental from intentional helpers or harmers, suggestive that infants may find negligent accidents somewhat intentional. In Experiment 3 (n=64), we found that infants preferred truly accidental over negligently accidental harmers, but did not reliably distinguish negligently accidental from truly accidental helpers, consistent with past work with adults and children suggestive that humans are particularly sensitive to negligently accidental harm. Together, these results imply that infants engage in intention-based social evaluation of those who help and harm accidentally, so long as those accidents do not stem from negligence. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Evoked Electrical and Cerebral Vascular Responses Following Sleep Deprivation

    PubMed Central

    Schei, Jennifer L.; Rector, David M.

    2011-01-01

    Neuronal activity elicits vascular dilation, delivering additional blood and metabolites to the activated region. With increasing neural activity, vessels stretch and may become less compliant. Most functional imaging studies assume that limits to vascular expansion are not normally reached except under pathological conditions, with the possibility that metabolism could outpace supply. However, we previously demonstrated that evoked hemodynamic responses were larger during quiet sleep when compared to both waking and REM sleep, suggesting that high basal activity during wake may elicit blunted evoked hemodynamic responses due to vascular expansion limits. We hypothesized that extended brain activity through sleep deprivation will further dilate blood vessels, and exacerbate the blunted evoked hemodynamic responses observed during wake, and dampen responses in subsequent sleep. We measured evoked electrical and hemodynamic responses from rats using auditory clicks (0.5 s, 10 Hz, 2–13 s random ISIs) for one hour following 2, 4, or 6 hours of sleep deprivation. Time-of-day matched controls were recorded continuously for 7 hours. Within quiet sleep periods following deprivation, ERP amplitude did not differ; however, the evoked vascular response was smaller with longer sleep deprivation periods. These results suggest that prolonged neural activity periods through sleep deprivation may diminish vascular compliance as indicated by the blunted vascular response. Subsequent sleep may allow vessels to relax, restoring their ability to deliver blood. These results also suggest that severe sleep deprivation or chronic sleep disturbances could push the vasculature to critical limits, leading to metabolic deficit and the potential for tissue trauma. PMID:21854966

  6. 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.

  7. Endothelial Mineralocorticoid Receptor Mediates Parenchymal Arteriole and Posterior Cerebral Artery Remodeling During Angiotensin II-Induced Hypertension.

    PubMed

    Diaz-Otero, Janice M; Fisher, Courtney; Downs, Kelsey; Moss, M Elizabeth; Jaffe, Iris Z; Jackson, William F; Dorrance, Anne M

    2017-12-01

    The brain is highly susceptible to injury caused by hypertension because the increased blood pressure causes artery remodeling that can limit cerebral perfusion. Mineralocorticoid receptor (MR) antagonism prevents hypertensive cerebral artery remodeling, but the vascular cell types involved have not been defined. In the periphery, the endothelial MR mediates hypertension-induced vascular injury, but cerebral and peripheral arteries are anatomically distinct; thus, these findings cannot be extrapolated to the brain. The parenchymal arterioles determine cerebrovascular resistance. Determining the effects of hypertension and MR signaling on these arterioles could lead to a better understanding of cerebral small vessel disease. We hypothesized that endothelial MR signaling mediates inward cerebral artery remodeling and reduced cerebral perfusion during angiotensin II (AngII) hypertension. The biomechanics of the parenchymal arterioles and posterior cerebral arteries were studied in male C57Bl/6 and endothelial cell-specific MR knockout mice and their appropriate controls using pressure myography. AngII increased plasma aldosterone and decreased cerebral perfusion in C57Bl/6 and MR-intact littermates. Endothelial cell MR deletion improved cerebral perfusion in AngII-treated mice. AngII hypertension resulted in inward hypotrophic remodeling; this was prevented by MR antagonism and endothelial MR deletion. Our studies suggest that endothelial cell MR mediates hypertensive remodeling in the cerebral microcirculation and large pial arteries. AngII-induced inward remodeling of cerebral arteries and arterioles was associated with a reduction in cerebral perfusion that could worsen the outcome of stroke or contribute to vascular dementia. © 2017 American Heart Association, Inc.

  8. AltitudeOmics: effect of ascent and acclimatization to 5260 m on regional cerebral oxygen delivery.

    PubMed

    Subudhi, Andrew W; Fan, Jui-Lin; Evero, Oghenero; Bourdillon, Nicolas; Kayser, Bengt; Julian, Colleen G; Lovering, Andrew T; Roach, Robert C

    2014-05-01

    Cerebral hypoxaemia associated with rapid ascent to high altitude can be life threatening; yet, with proper acclimatization, cerebral function can be maintained well enough for humans to thrive. We investigated adjustments in global and regional cerebral oxygen delivery (DO2) as 21 healthy volunteers rapidly ascended and acclimatized to 5260 m. Ultrasound indices of cerebral blood flow in internal carotid and vertebral arteries were measured at sea level, upon arrival at 5260 m (ALT1; atmospheric pressure 409 mmHg) and after 16 days of acclimatization (ALT16). Cerebral DO2 was calculated as the product of arterial oxygen content and flow in each respective artery and summed to estimate global cerebral blood flow. Vascular resistances were calculated as the quotient of mean arterial pressure and respective flows. Global cerebral blood flow increased by ∼70% upon arrival at ALT1 (P < 0.001) and returned to sea-level values at ALT16 as a result of changes in cerebral vascular resistance. A reciprocal pattern in arterial oxygen content maintained global cerebral DO2 throughout acclimatization, although DO2 to the posterior cerebral circulation was increased by ∼25% at ALT1 (P = 0.032). We conclude that cerebral DO2 is well maintained upon acute exposure and acclimatization to hypoxia, particularly in the posterior and inferior regions of the brain associated with vital homeostatic functions. This tight regulation of cerebral DO2 was achieved through integrated adjustments in local vascular resistances to alter cerebral perfusion during both acute and chronic exposure to hypoxia. © 2013 The Authors. Experimental Physiology © 2013 The Physiological Society.

  9. Unusual Association: Cerebral Arteriovenous Malformation and Chiari Type I Malformation.

    PubMed

    Ogul, Hayri; Kantarci, Mecit

    2017-06-01

    Cerebral arteriovenous malformation (AVM) is a common type of cerebral vascular malformation. The imaging findings are enlarged vessels, thrombosed sinuses, and hemorrhage or gliosis on adjacent brain parenchyma. Magnetic resonance (MR) imaging can be used safely for diagnosis. Chiari type I malformation is characterized by a caudal descent of the cerebellar tonsil. Coincidence of cerebral AVM and Chiari type I malformation is very rare. In this paper, the authors report MR imaging findings of a patient with coincidence of cerebral AVM and Chiari type I malformation.

  10. Local estrogenic/androgenic balance in the cerebral vasculature

    PubMed Central

    Krause, Diana N.; Duckles, Sue P.; Gonzales, Rayna J.

    2011-01-01

    Reproductive effects of sex steroids are well-known, however it is increasingly apparent that these hormones have important actions on non-reproductive tissues such as the vasculature. The latter effects can be relevant throughout the lifespan, not just limited to reproductive years, and are not necessarily restricted to one sex or the other. Our work has established that cerebral blood vessels are a non-reproductive target tissue for sex steroids. We have found that estrogen and androgens alter vascular tone, endothelial function, oxidative stress and inflammatory responses in cerebral vessels. Often the actions of estrogen and androgens oppose each other. Moreover, it is clear that cerebral vessels are directly targeted by sex steroids as they express specific receptors for these hormones. Interestingly, cerebral blood vessels also express enzymes that metabolize sex steroids. These findings suggest that local synthesis of 17β-estradiol and dihydrotestosterone can occur within the vessel wall. One of the enzymes present, aromatase, converts testosterone to 17β-estradiol, which would alter the local balance of androgenic and estrogenic influences. Thus cerebral vessels are affected by circulating sex hormones as well as locally synthesized sex steroids. The presence of vascular endocrine effector mechanisms has important implications for male-female differences in cerebrovascular function and disease. Moreover, the cerebral circulation is a target for gonadal hormones as well as anabolic steroids and therapeutic drugs used to manipulate sex steroid actions. The long-term consequences of these influences have yet to be determined. PMID:21535417

  11. The Effect of Vascular Neuropathology on Late-life Cognition: Results from the SMART Project.

    PubMed

    Kryscio, R J; Abner, E L; Nelson, P T; Bennett, D; Schneider, J; Yu, L; Hemmy, L S; Lim, K O; Masaki, K; Cairns, N; Xiong, C; Woltjer, R; Dodge, H H; Tyas, S; Fardo, D W; Lou, W; Wan, L; Schmitt, F A

    2016-06-01

    Cerebral vascular pathology may contribute to cognitive decline experienced by some elderly near death. Given evidence for mixed neuropathologies in advanced age, preventing or reducing cerebrovascular burden in late life may be beneficial. To correlate measures of cerebral vascular pathology with cognitive trajectories. Observational study. A cohort of 2,274 individuals who came to autopsy at a mean age of 89.3 years and 82 percent of whom had at least two cognitive assessments within the last six years of life was compiled from six centers conducting longitudinal studies. For each cognitive domain: immediate and delayed memory, language, and naming, three trajectories were examined: good, intermediate, and poor cognition. The probability of a participant belonging to each trajectory was associated with measures of cerebral vascular pathology after adjustment for demographics, APOE, and Alzheimer neuropathology. A large proportion of the cohort (72-94%) experienced good or intermediate cognition in the four domains examined. The presence of arteriolosclerosis and the presence of lacunar infarcts doubled the odds of belonging to the poor cognitive trajectory for language when compared to the good trajectory. The presence of lacunar infarcts increased the odds of an intermediate or poor trajectory for immediate and delayed recall while the presence of large artery infarcts increased the odds of poor trajectories for all four cognitive domains examined. Microinfarcts and cerebral amyloid angiopathy had little effect on the trajectories. Indicators of cerebral vascular pathology act differently on late life cognition.

  12. Cervical spine injuries in young children: pattern and outcomes in accidental versus inflicted trauma.

    PubMed

    Baerg, Joanne; Thirumoorthi, Arul; Hazboun, Rajaie; Vannix, Rosemary; Krafft, Paul; Zouros, Alexander

    2017-11-01

    The aim of the study was to compare the cervical spine (c-spine) pattern of injury and outcomes in children below 3 y with a head injury from confirmed inflicted versus accidental trauma. After Institutional Review Board approval, data were prospectively collected between July 2011 and January 2016. Inclusion criteria were age below 3 y, a loss of consciousness, and any one of the following initial head computed tomography (CT) findings (subdural hematoma, intraventricular, intraparenchymal, subarachnoid hemorrhage, or cerebral edema). A protocol of brain and neck magnetic resonance imaging and magnetic resonance angiography was instituted. Brain and neck imaging results, clinical variables, and outcomes were recorded. Data were compared by t-test for continuous and Fisher exact test for categorical variables. 73 children were identified, 52 (71%) with inflicted and 21 (29%) with accidental trauma. The median age was 11 mo; (range: 1-35 mo). Ten (14%) had c-spine injuries, 7/52 (13%) inflicted, and 3/21 (14%) accidental. The mechanism was shaking for all inflicted and motor vehicle accident or pedestrian struck for accidental c-spine injuries. The inflicted group were significantly younger (P = 0.03), had higher Injury Severity Scores (P = 0.02), subdural hematomas (P = 0.03), fractures (P = 0.03), retinal hemorrhages (P = 0.02), brain infarcts (P = 0.01), and required cardiopulmonary resuscitation (P = 0.01). Seven with inflicted trauma died from brain injury (9.5%), one had atlanto-occipital dissociation. Six mortalities (86%) had no c-spine injury. Six with inflicted c-spine injuries survived with neurologic impairment, whereas three with accidental survived without disability, including one atlanto-occipital dissociation. Compared to accidental trauma, young children with inflicted c-spine injuries have more multisystem trauma, long-term disability from brain injury, and an injury pattern consistent with shaking. Copyright © 2017 Elsevier Inc

  13. Cerebro vascular reactivity (CVR) of middle cerebral artery in response to CO2 5% inhalation in preeclamptic women.

    PubMed

    Sariri, Elaheh; Vahdat, Mansoureh; Behbahani, Afsaneh Shariati; Rohani, Mohammad; Kashanian, Maryam

    2013-07-01

    To compare the cerebro vascular reactivity (CVR) of middle cerebral artery (MCA) in response to CO2 5% inhalation between preeclamptic and normotensive pregnant women, also, between mild and severe preeclampsia. A comparative study was performed on 61 women with preeclampsia and 65 normotensive pregnant women who were in the third trimester of gestation. MCA transcranial Doppler ultrasound was used to measure CVR in response to CO2 5% inhalation. Pulsatility index (PI), resistance index (RI), blood pressure, maternal age, gestational age and gravidity were also recorded. Baseline PI and RI were lower in the preeclamptic group (p < 0.05). Inhalation of CO2 5% caused significant increase in CVR among normotensive pregnant women in comparison with preeclamptic group (1.006 ± 0.229 versus 0.503 ± 0.209, p = 0.0001). Significantly, more cerebral vasodilatation was found among mild preeclamptic women in comparison with severe preeclamptic women (0.583 ± 0.193 versus 0.383 ± 0.173, p = 0.0001). The receiver operating characteristics curve analysis revealed acceptable difference between CO2 stimulation test of preeclamptic and normotensive women (Area under curve = 0.973, p = 0.0001). CVR in response to CO2 5% is less in preeclamptic pregnant women than normotensives, also, in severe preeclampsia, it is less than mild preeclampsia.

  14. 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.

  15. Experimental and clinical study of EHF treatment of vascular-vestibular dysfunction

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

    Mal`tsev, A.E.; Abakarov, A.T.; Istomin, V.S.

    1994-07-01

    The authors present the results of a study of the effectiveness of EHF radiation on the cerebral hemodynamics, bioelectrical activity of the cerebral cortex, and functional state of the vestibular analyzer in chronic studies of cats using a model of vascular-vestibular dysfunction. The clinical part of the work reflects the results of studies of the functional state of cerebral blood circulation and the vestibular analyzer during the EHF treatment of angiovertebrogenic vestibular dysfunction in a background of initial manifestations of cerebral blood supply deficiency (angiodistonic variant).

  16. Extracellular matrix inflammation in vascular cognitive impairment and dementia.

    PubMed

    Rosenberg, Gary A

    2017-03-01

    Vascular cognitive impairment and dementia (VCID) include a wide spectrum of chronic manifestations of vascular disease related to large vessel strokes and small vessel disease (SVD). Lacunar strokes and white matter (WM) injury are consequences of SVD. The main vascular risk factor for SVD is brain hypoperfusion from cerebral blood vessel narrowing due to chronic hypertension. The hypoperfusion leads to activation and degeneration of astrocytes with the resulting fibrosis of the extracellular matrix (ECM). Elasticity is lost in fibrotic cerebral vessels, reducing the response of stiffened blood vessels in times of increased metabolic need. Intermittent hypoxia/ischaemia activates a molecular injury cascade, producing an incomplete infarction that is most damaging to the deep WM, which is a watershed region for cerebral blood flow. Neuroinflammation caused by hypoxia activates microglia/macrophages to release proteases and free radicals that perpetuate the damage over time to molecules in the ECM and the neurovascular unit (NVU). Matrix metalloproteinases (MMPs) secreted in an attempt to remodel the blood vessel wall have the undesired consequences of opening the blood-brain barrier (BBB) and attacking myelinated fibres. This dual effect of the MMPs causes vasogenic oedema in WM and vascular demyelination, which are the hallmarks of the subcortical ischaemic vascular disease (SIVD), which is the SVD form of VCID also called Binswanger's disease (BD). Unravelling the complex pathophysiology of the WM injury-related inflammation in the small vessel form of VCID could lead to novel therapeutic strategies to reduce damage to the ECM, preventing the progressive damage to the WM. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  17. 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.

  18. A quantitative brain map of experimental cerebral malaria pathology.

    PubMed

    Strangward, Patrick; Haley, Michael J; Shaw, Tovah N; Schwartz, Jean-Marc; Greig, Rachel; Mironov, Aleksandr; de Souza, J Brian; Cruickshank, Sheena M; Craig, Alister G; Milner, Danny A; Allan, Stuart M; Couper, Kevin N

    2017-03-01

    The murine model of experimental cerebral malaria (ECM) has been utilised extensively in recent years to study the pathogenesis of human cerebral malaria (HCM). However, it has been proposed that the aetiologies of ECM and HCM are distinct, and, consequently, no useful mechanistic insights into the pathogenesis of HCM can be obtained from studying the ECM model. Therefore, in order to determine the similarities and differences in the pathology of ECM and HCM, we have performed the first spatial and quantitative histopathological assessment of the ECM syndrome. We demonstrate that the accumulation of parasitised red blood cells (pRBCs) in brain capillaries is a specific feature of ECM that is not observed during mild murine malaria infections. Critically, we show that individual pRBCs appear to occlude murine brain capillaries during ECM. As pRBC-mediated congestion of brain microvessels is a hallmark of HCM, this suggests that the impact of parasite accumulation on cerebral blood flow may ultimately be similar in mice and humans during ECM and HCM, respectively. Additionally, we demonstrate that cerebrovascular CD8+ T-cells appear to co-localise with accumulated pRBCs, an event that corresponds with development of widespread vascular leakage. As in HCM, we show that vascular leakage is not dependent on extensive vascular destruction. Instead, we show that vascular leakage is associated with alterations in transcellular and paracellular transport mechanisms. Finally, as in HCM, we observed axonal injury and demyelination in ECM adjacent to diverse vasculopathies. Collectively, our data therefore shows that, despite very different presentation, and apparently distinct mechanisms, of parasite accumulation, there appear to be a number of comparable features of cerebral pathology in mice and in humans during ECM and HCM, respectively. Thus, when used appropriately, the ECM model may be useful for studying specific pathological features of HCM.

  19. A quantitative brain map of experimental cerebral malaria pathology

    PubMed Central

    Schwartz, Jean-Marc; Greig, Rachel; Mironov, Aleksandr; de Souza, J. Brian; Cruickshank, Sheena M.; Craig, Alister G.; Milner, Danny A.; Allan, Stuart M.

    2017-01-01

    The murine model of experimental cerebral malaria (ECM) has been utilised extensively in recent years to study the pathogenesis of human cerebral malaria (HCM). However, it has been proposed that the aetiologies of ECM and HCM are distinct, and, consequently, no useful mechanistic insights into the pathogenesis of HCM can be obtained from studying the ECM model. Therefore, in order to determine the similarities and differences in the pathology of ECM and HCM, we have performed the first spatial and quantitative histopathological assessment of the ECM syndrome. We demonstrate that the accumulation of parasitised red blood cells (pRBCs) in brain capillaries is a specific feature of ECM that is not observed during mild murine malaria infections. Critically, we show that individual pRBCs appear to occlude murine brain capillaries during ECM. As pRBC-mediated congestion of brain microvessels is a hallmark of HCM, this suggests that the impact of parasite accumulation on cerebral blood flow may ultimately be similar in mice and humans during ECM and HCM, respectively. Additionally, we demonstrate that cerebrovascular CD8+ T-cells appear to co-localise with accumulated pRBCs, an event that corresponds with development of widespread vascular leakage. As in HCM, we show that vascular leakage is not dependent on extensive vascular destruction. Instead, we show that vascular leakage is associated with alterations in transcellular and paracellular transport mechanisms. Finally, as in HCM, we observed axonal injury and demyelination in ECM adjacent to diverse vasculopathies. Collectively, our data therefore shows that, despite very different presentation, and apparently distinct mechanisms, of parasite accumulation, there appear to be a number of comparable features of cerebral pathology in mice and in humans during ECM and HCM, respectively. Thus, when used appropriately, the ECM model may be useful for studying specific pathological features of HCM. PMID:28273147

  20. Functional stability of cerebral circulatory system

    NASA Technical Reports Server (NTRS)

    Moskalenko, Y. Y.

    1980-01-01

    The functional stability of the cerebral circulation system seems to be based on the active mechanisms and on those stemming from specific of the biophysical structure of the system under study. This latter parameter has some relevant criteria for its quantitative estimation. The data obtained suggest that the essential part of the mechanism for active responses of cerebral vessels which maintains the functional stability of this portion of the vascular system, consists of a neurogenic component involving central nervous structures localized, for instance, in the medulla oblongata.

  1. The Effect of Vascular Neuropathology on Late-life Cognition: Results from the SMART Project

    PubMed Central

    Kryscio, R.J.; Abner, E.L.; Nelson, P.T.; Bennett, D.; Schneider, J.; Yu, L.; Hemmy, L.S.; Lim, K.O.; Masaki, K.; Cairns, N.; Xiong, C.; Woltjer, R.; Dodge, H.H.; Tyas, S.; Fardo, D.W.; Lou, W.; Wan, L.; Schmitt, F.A.

    2016-01-01

    Background Cerebral vascular pathology may contribute to cognitive decline experienced by some elderly near death. Given evidence for mixed neuropathologies in advanced age, preventing or reducing cerebrovascular burden in late life may be beneficial. Objective To correlate measures of cerebral vascular pathology with cognitive trajectories. Setting Observational study. Participants A cohort of 2,274 individuals who came to autopsy at a mean age of 89.3 years and 82 percent of whom had at least two cognitive assessments within the last six years of life was compiled from six centers conducting longitudinal studies. Measurements For each cognitive domain: immediate and delayed memory, language, and naming, three trajectories were examined: good, intermediate, and poor cognition. The probability of a participant belonging to each trajectory was associated with measures of cerebral vascular pathology after adjustment for demographics, APOE, and Alzheimer neuropathology. Results A large proportion of the cohort (72-94%) experienced good or intermediate cognition in the four domains examined. The presence of arteriolosclerosis and the presence of lacunar infarcts doubled the odds of belonging to the poor cognitive trajectory for language when compared to the good trajectory. The presence of lacunar infarcts increased the odds of an intermediate or poor trajectory for immediate and delayed recall while the presence of large artery infarcts increased the odds of poor trajectories for all four cognitive domains examined. Microinfarcts and cerebral amyloid angiopathy had little effect on the trajectories. Conclusion Indicators of cerebral vascular pathology act differently on late life cognition. PMID:27709107

  2. P14.21 Can vascular risk factors influence number of brain metastases?

    PubMed Central

    Berk, B.; Nagel, S.; Kortmann, R.; Hoffmann, K.; Gaudino, C.; Seidel, C.

    2017-01-01

    Abstract BACKGROUND: Up to 30-40% of patients with solid tumors develop cerebral metastases. Number of cerebral metastases is relevant for treatment and prognosis. However, factors that determine number of metastases are not well defined. Distribution of metastases is influenced by blood vessels and cerebral small vessel disease can reduce number of metastases. Aim of this pilot study was to analyze the influence of vascular risk factors (arterial hypertension, diabetes mellitus, smoking, hypercholesterolemia) and of peripheral arterial occlusive disease (PAOD) on number of brain metastases. METHODS: 200 patients with pre-therapeutic 3D-brain MRI and available clinical data were analyzed retrospectively. Number of metastases (NoM) was compared between patients with/without vascular risk factors (vasRF). Results: Patients with PAOD had significant less brain metastases than patients without PAOD (NoM=4.43 vs. 6.02, p=0.043), no other single vasRF conferred a significant effect on NoM. NoM differed significantly between different tumor entities. CONCLUSION: Presence of PAOD showed some effect on number of brain metastases implying that tumor-independent vascular factors can influence brain metastasation.

  3. Effects of forskolin on cerebral blood flow: implications for a role of adenylate cyclase

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

    Wysham, D.G.; Brotherton, A.F.; Heistad, D.D.

    1986-11-01

    We have studied cerebral vascular effects of forskolin, a drug which stimulates adenylate cyclase and potentiates dilator effects of adenosine in other vascular beds. Our goals were to determine whether forskolin is a cerebral vasodilator and whether it potentiates cerebral vasodilator responses to adenosine. We measured cerebral blood flow with microspheres in anesthetized rabbits. Forskolin (10 micrograms/kg per min) increased blood flow (ml/min per 100 gm) from 39 +/- 5 (mean +/- S.E.) to 56 +/- 9 (p less than 0.05) in cerebrum, and increased flow to myocardium and kidney despite a decrease in mean arterial pressure. Forskolin did notmore » alter cerebral oxygen consumption, which indicates that the increase in cerebral blood flow is a direct vasodilator effect and is not secondary to increased metabolism. We also examined effects of forskolin on the response to infusion of adenosine. Cerebral blood flow was measured during infusion of 1-5 microM/min adenosine into one internal carotid artery, under control conditions and during infusion of forskolin at 3 micrograms/kg per min i.v. Adenosine alone increased ipsilateral cerebral blood flow from 32 +/- 3 to 45 +/- 5 (p less than 0.05). Responses to adenosine were not augmented during infusion of forskolin. We conclude that forskolin is a direct cerebral vasodilator and forskolin does not potentiate cerebral vasodilator responses to adenosine.« less

  4. Vascular determinants of cholinergic deficits in Alzheimer disease and vascular dementia.

    PubMed

    Román, Gustavo C; Kalaria, Raj N

    2006-12-01

    Alzheimer's disease (AD) and vascular dementia (VaD) are widely accepted as the most common forms of dementia. Cerebrovascular lesions frequently coexist with AD, creating an overlap in the clinical and pathological features of VaD and AD. This review assembles evidence for a role for cholinergic mechanisms in the pathogenesis of VaD, as has been established for AD. We first consider the anatomy and vascularization of the basal forebrain cholinergic neuronal system, emphasizing its susceptibility to the effects of arterial hypertension, sustained hypoperfusion, and ischemic cerebrovascular disease. The impact of aging and consequences of disruption of the cholinergic system in cognition and in control of cerebral blood flow are further discussed. We also summarize preclinical and clinical evidence supporting cholinergic deficits and the use of cholinesterase inhibitors in patients with VaD. We postulate that vascular pathology likely plays a common role in initiating cholinergic neuronal abnormalities in VaD and AD.

  5. The pathology and pathophysiology of vascular dementia.

    PubMed

    Kalaria, Raj N

    2017-12-19

    Vascular dementia (VaD) is widely recognised as the second most common type of dementia. Consensus and accurate diagnosis of clinically suspected VaD relies on wide-ranging clinical, neuropsychological and neuroimaging measures in life but more importantly pathological confirmation. Factors defining subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes as well as time after the initial vascular event. Atherosclerotic and cardioembolic diseases combined appear the most common subtypes of vascular brain injury. In recent years, cerebral small vessel disease (SVD) has gained prominence worldwide as an important substrate of cognitive impairment. SVD is characterised by arteriolosclerosis, lacunar infarcts and cortical and subcortical microinfarcts and diffuse white matter changes, which involve myelin loss and axonal abnormalities. Global brain atrophy and focal degeneration of the cerebrum including medial temporal lobe atrophy are also features of VaD similar to Alzheimer's disease. Hereditary arteriopathies have provided insights into the mechanisms of dementia particularly how arteriolosclerosis, a major contributor of SVD promotes cognitive impairment. Recently developed and validated neuropathology guidelines indicated that the best predictors of vascular cognitive impairment were small or lacunar infarcts, microinfarcts, perivascular space dilation, myelin loss, arteriolosclerosis and leptomeningeal cerebral amyloid angiopathy. While these substrates do not suggest high specificity, VaD is likely defined by key neuronal and dendro-synaptic changes resulting in executive dysfunction and related cognitive deficits. Greater understanding of the molecular pathology is needed to clearly define microvascular disease and vascular substrates of dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Cigarette smoking impairs nitric oxide-mediated cerebral blood flow increase: Implications for Alzheimer's disease.

    PubMed

    Toda, Noboru; Okamura, Tomio

    2016-08-01

    Cerebral blood flow is mainly regulated by nitrergic (parasympathetic, postganglionic) nerves and nitric oxide (NO) liberated from endothelial cells in response to shear stress and stretch of vasculature, whereas sympathetic vasoconstrictor control is quite weak. On the other hand, peripheral vascular resistance and blood flow are mainly controlled by adrenergic vasoconstrictor nerves; endothelium-derived NO and nitrergic nerves play some roles as vasodilator factors. Cigarette smoking impairs NO synthesis in cerebral vascular endothelial cells and nitrergic nerves leading to interference with cerebral blood flow and glucose metabolism in the brain. Smoking-induced cerebral hypoperfusion is induced by impairment of synthesis and actions of NO via endothelial nitric oxide synthase (eNOS)/neuronal NOS (nNOS) inhibition and by increased production of oxygen radicals, resulting in decreased actions of NO on vascular smooth muscle. Nicotine acutely and chronically impairs the action of endothelial NO and also inhibits nitrergic nerve function in chronic use. Impaired cerebral blood supply promotes the synthesis of amyloid β that accelerates blood flow decrease. This vicious cycle is thought to be one of the important factors involving in Alzheimer's disease (AD). Quitting smoking is undoubtedly one of the important ways to prevent and delay the genesis or slow the progress of impaired cognitive function and AD. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  7. Effects of Cerebral Ischemia in Mice Deficient in Neuronal Nitric Oxide Synthase

    NASA Astrophysics Data System (ADS)

    Huang, Zhihong; Huang, Paul L.; Panahian, Nariman; Dalkara, Turgay; Fishman, Mark C.; Moskowitz, Michael A.

    1994-09-01

    The proposal that nitric oxide (NO) or its reactant products mediate toxicity in brain remains controversial in part because of the use of nonselective agents that block NO formation in neuronal, glial, and vascular compartments. In mutant mice deficient in neuronal NO synthase (NOS) activity, infarct volumes decreased significantly 24 and 72 hours after middle cerebral artery occlusion, and the neurological deficits were less than those in normal mice. This result could not be accounted for by differences in blood flow or vascular anatomy. However, infarct size in the mutant became larger after endothelial NOS inhibition by nitro-L-arginine administration. Hence, neuronal NO production appears to exacerbate acute ischemic injury, whereas vascular NO protects after middle cerebral artery occlusion. The data emphasize the importance of developing selective inhibitors of the neuronal isoform.

  8. Cerebral versus systemic hemodynamics during graded orthostatic stress in humans

    NASA Technical Reports Server (NTRS)

    Levine, B. D.; Giller, C. A.; Lane, L. D.; Buckey, J. C.; Blomqvist, C. G.

    1994-01-01

    BACKGROUND: Orthostatic syncope is usually attributed to cerebral hypoperfusion secondary to systemic hemodynamic collapse. Recent research in patients with neurocardiogenic syncope has suggested that cerebral vasoconstriction may occur during orthostatic hypotension, compromising cerebral autoregulation and possibly contributing to the loss of consciousness. However, the regulation of cerebral blood flow (CBF) in such patients may be quite different from that of healthy individuals, particularly when assessed during the rapidly changing hemodynamic conditions associated with neurocardiogenic syncope. To be able to interpret the pathophysiological significance of these observations, a clear understanding of the normal responses of the cerebral circulation to orthostatic stress must be obtained, particularly in the context of the known changes in systemic and regional distributions of blood flow and vascular resistance during orthostasis. Therefore, the specific aim of this study was to examine the changes that occur in the cerebral circulation during graded reductions in central blood volume in the absence of systemic hypotension in healthy humans. We hypothesized that cerebral vasoconstriction would occur and CBF would decrease due to activation of the sympathetic nervous system. We further hypothesized, however, that the magnitude of this change would be small compared with changes in systemic or skeletal muscle vascular resistance in healthy subjects with intact autoregulation and would be unlikely to cause syncope without concomitant hypotension. METHODS AND RESULTS: To test this hypothesis, we studied 13 healthy men (age, 27 +/- 7 years) during progressive lower body negative pressure (LBNP). We measured systemic flow (Qc is cardiac output; C2H2 rebreathing), regional forearm flow (FBF; venous occlusion plethysmography), and blood pressure (BP; Finapres) and calculated systemic (SVR) and forearm (FVR) vascular resistances. Changes in brain blood flow were

  9. Systematization, distribution and territory of the middle cerebral artery on the brain surface in chinchilla (Chinchilla lanigera).

    PubMed

    De Araujo, A C P; Campos, R

    2009-02-01

    The aim of the present study was to analyse thirty chinchilla (Chinchilla lanigera) brains, injected with latex, and to systematize and describe the distribution and the vascularization territories of the middle cerebral artery. This long vessel, after it has originated from the terminal branch of the basilar artery, formed the following collateral branches: rostral, caudal and striated (perforating) central branches. After crossing the lateral rhinal sulcus, the middle cerebral artery emitted a sequence of rostral and caudal convex hemispheric cortical collateral branches on the convex surface of the cerebral hemisphere to the frontal, parietal, temporal and occipital lobes. Among the rostral convex hemispheric branches, a trunk was observed, which reached the frontal and parietal lobes and, in a few cases, the occipital lobe. The vascular territory of the chinchilla's middle cerebral artery included, in the cerebral hemisphere basis, the lateral cerebral fossa, the caudal third of the olfactory trigone, the rostral two-thirds of the piriform lobe, the lateral olfactory tract, and most of the convex surface of the cerebral hemisphere, except for a strip between the cerebral longitudinal fissure and the vallecula, which extended from the rostral to the caudal poles bordering the cerebral transverse fissure.

  10. Review: Cerebral microvascular pathology in aging and neurodegeneration

    PubMed Central

    Brown, William R.; Thore, Clara R.

    2010-01-01

    This review of age-related brain microvascular pathologies focuses on topics studied by this laboratory, including anatomy of the blood supply, tortuous vessels, venous collagenosis, capillary remnants, vascular density, and microembolic brain injury. Our studies feature thick sections, large blocks embedded in celloidin, and vascular staining by alkaline phosphatase (AP). This permits study of the vascular network in three dimensions, and the differentiation of afferent from efferent vessels. Current evidence suggests that there is decreased vascular density in aging, Alzheimer’s disease (AD), and leukoaraiosis (LA), and cerebrovascular dysfunction precedes and accompanies cognitive dysfunction and neurodegeneration. A decline in cerebrovascular angiogenesis may inhibit recovery from hypoxia-induced capillary loss. Cerebral blood flow (CBF) is inhibited by tortuous arterioles and deposition of excessive collagen in veins and venules. Misery perfusion due to capillary loss appears to occur before cell loss in LA, and CBF is also reduced in the normal-appearing white matter. Hypoperfusion occurs early in AD, inducing white matter lesions and correlating with dementia. In vascular dementia, cholinergic reductions are correlated with cognitive impairment, and cholinesterase inhibitors have some benefit. Most lipid microemboli from cardiac surgery pass through the brain in a few days, but some remain for weeks. They can cause what appears to be a type of vascular dementia years after surgery. Donepezil has shown some benefit. Emboli, such as clots, cholesterol crystals, and microspheres can be extruded through the walls of cerebral vessels, but there is no evidence yet that lipid emboli undergo such extravasation. PMID:20946471

  11. Composite accidental axions

    NASA Astrophysics Data System (ADS)

    Redi, Michele; Sato, Ryosuke

    2016-05-01

    We present several models where the QCD axion arises accidentally. Confining gauge theories can generate axion candidates whose properties are uniquely determined by the quantum numbers of the new fermions under the Standard Model. The Peccei-Quinn symmetry can emerge accidentally if the gauge theory is chiral. We generalise previous constructions in a unified framework. In some cases these models can be understood as the deconstruction of 5-dimensional gauge theories where the Peccei-Quinn symmetry is protected by locality but more general constructions are possible.

  12. Epidemiology of accidental radiation exposures.

    PubMed Central

    Cardis, E

    1996-01-01

    Much of the information on the health effects of radiation exposure available to date comes from long-term studies of the atomic bombings in Hiroshima and Nagasaki. Accidental exposures, such as those resulting from the Chernobyl and Kyshtym accidents, have as yet provided little information concerning health effects of ionizing radiation. This paper will present the current state of our knowledge concerning radiation effects, review major large-scale accidental radiation exposures, and discuss information that could be obtained from studies of accidental exposures and the types of studies that are needed. PMID:8781398

  13. Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle.

    PubMed

    Simakova, Maria N; Bisen, Shivantika; Dopico, Alex M; Bukiya, Anna N

    2017-12-01

    Statins constitute the most commonly prescribed drugs to decrease cholesterol (CLR). CLR is an important modulator of alcohol-induced cerebral artery constriction (AICAC). Using rats on a high CLR diet (2% CLR) we set to determine whether atorvastatin administration (10mg/kg daily for 18-23weeks) modified AICAC. Middle cerebral arteries were pressurized in vitro at 60mmHg and AICAC was evoked by 50mM ethanol, that is within the range of blood alcohol detected in humans following moderate-to-heavy drinking. AICAC was evident in high CLR+atorvastatin group but not in high CLR diet+placebo. Statin exacerbation of AICAC persisted in de-endothelialized arteries, and was blunted by CLR enrichment in vitro. Fluorescence imaging of filipin-stained arteries showed that atorvastatin decreased vascular smooth muscle (VSM) CLR when compared to placebo, this difference being reduced by CLR enrichment in vitro. Voltage- and calcium-gated potassium channels of large conductance (BK) are known VSM targets of ethanol, with their beta1 subunit being necessary for ethanol-induced channel inhibition and resulting AICAC. Ethanol-induced BK inhibition in excised membrane patches from freshly isolated myocytes was exacerbated in the high CLR diet+atorvastatin group when compared to high CLR diet+placebo. Unexpectedly, atorvastatin decreased the amount and function of BK beta1 subunit as documented by immunofluorescence imaging and functional patch-clamp studies. Atorvastatin exacerbation of ethanol-induced BK inhibition disappeared upon artery CLR enrichment in vitro. Our study demonstrates for the first time statin's ability to exacerbate the vascular effect of a widely consumed drug of abuse, this exacerbation being driven by statin modulation of ethanol-induced BK channel inhibition in the VSM via CLR-mediated mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. A Comparative Investigation on the Performance of Different Micro Mixers: Toward Cerebral Microvascular Analysis

    NASA Astrophysics Data System (ADS)

    Abdi, Mohsen; Pishbin, Esmail; Karimi, Alireza; Navidbakhsh, Mahdi

    In this study, a novel fluidic concept was presented to resemble the cerebral microvascular in four types to assess its complexity by using centrifugal platform. The setup consisted of a microstructured disk with a round mixing chamber rotating on a macroscopic drive unit. The left and right internal carotid arteries (L.ICA and R.ICA) and basilar artery (BA) are two isolated vascular system supplying circle of Willis (CoW). The left and right middle cerebral arteries (L.MCA and R.MCA), left and right anterior cerebral arteries (L.ACA and R.ACA), and finally left and right posterior cerebral arteries (L.PCA and R.PCA) constitute efferent arteries of CoW. In this study, cerebral microvascular was investigated by microfluidics approach. The results revealed that a more complex mixing chamber provides normal pixel percentage distribution with respect to the other ones. The outcomes of this study may have implications not only for perception of the intracranial vascular hemodynamic in healthy circumstance, but also for diagnosing the diseases in the blood circulatory system of the human body.

  15. 5 CFR 870.206 - Accidental death and dismemberment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Accidental death and dismemberment. 870....206 Accidental death and dismemberment. (a) (1) Accidental death and dismemberment coverage is an automatic part of Basic and Option A insurance for employees. (2) There is no accidental death and...

  16. 5 CFR 870.206 - Accidental death and dismemberment.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Accidental death and dismemberment. 870....206 Accidental death and dismemberment. (a)(1) Accidental death and dismemberment coverage is an automatic part of Basic and Option A insurance for employees. (2) There is no accidental death and...

  17. 5 CFR 870.206 - Accidental death and dismemberment.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Accidental death and dismemberment. 870....206 Accidental death and dismemberment. (a)(1) Accidental death and dismemberment coverage is an automatic part of Basic and Option A insurance for employees. (2) There is no accidental death and...

  18. 5 CFR 870.206 - Accidental death and dismemberment.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Accidental death and dismemberment. 870....206 Accidental death and dismemberment. (a)(1) Accidental death and dismemberment coverage is an automatic part of Basic and Option A insurance for employees. (2) There is no accidental death and...

  19. 5 CFR 870.206 - Accidental death and dismemberment.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Accidental death and dismemberment. 870....206 Accidental death and dismemberment. (a)(1) Accidental death and dismemberment coverage is an automatic part of Basic and Option A insurance for employees. (2) There is no accidental death and...

  20. Attenuated flow‐induced dilatation of middle cerebral arteries is related to increased vascular oxidative stress in rats on a short‐term high salt diet

    PubMed Central

    Cosic, Anita; Jukic, Ivana; Stupin, Ana; Mihalj, Martina; Mihaljevic, Zrinka; Novak, Sanja; Vukovic, Rosemary

    2016-01-01

    Key points Recent studies have shown that high salt (HS) intake leads to endothelial dysfunction and impaired vascular reactivity in different vascular beds in both animal and human models, due to increased oxidative stress.The objective of this study was to assess vascular response to flow‐induced dilatation (FID) and to elucidate the role of vascular oxidative stress/antioxidative capacity in middle cerebral arteries (MCAs) of HS‐fed rats in vitro.The novelty of this study is in demonstrating impaired flow‐induced dilatation of MCAs and down‐regulation of vascular antioxidant genes with HS intake, leading to increased levels of oxidative stress in blood vessels and peripheral lymph organs, which together contribute to impaired FID.In addition, results show increased oxidative stress in leukocytes of peripheral lymph organs, suggesting the occurrence of inflammatory processes due to HS intake.Recirculation of leukocytes might additionally increase vascular oxidative stress in vivo. Abstract The aim of this study was to determine flow‐induced dilatation (FID) and the role of oxidative stress/antioxidative capacity in isolated, pressurized middle cerebral arteries (MCAs) of high salt (HS)‐fed rats. Healthy male Sprague‐Dawley rats (11 weeks old) were fed low salt (0.4% NaCl; LS group) or high salt (4% NaCl; HS group) diets for 1 week. Reactivity of MCAs in response to stepwise increases in pressure gradient (Δ10–Δ100 mmHg) was determined in the absence or presence of the superoxide dismutase (SOD) mimetic TEMPOL and/or the nitric oxide synthases (NOS) inhibitor N ω‐nitro‐l‐arginine methyl ester (l‐name). mRNA levels of antioxidative enzymes, NAPDH‐oxidase components, inducible (iNOS) and endothelial nitric oxide synthases (eNOS) were determined by quantitative real‐time PCR. Blood pressure (BP), antioxidant enzymes activity, oxidative stress in peripheral leukocytes, lipid peroxidation products and the antioxidant capacity of plasma

  1. Attenuated flow-induced dilatation of middle cerebral arteries is related to increased vascular oxidative stress in rats on a short-term high salt diet.

    PubMed

    Cosic, Anita; Jukic, Ivana; Stupin, Ana; Mihalj, Martina; Mihaljevic, Zrinka; Novak, Sanja; Vukovic, Rosemary; Drenjancevic, Ines

    2016-09-01

    Recent studies have shown that high salt (HS) intake leads to endothelial dysfunction and impaired vascular reactivity in different vascular beds in both animal and human models, due to increased oxidative stress. The objective of this study was to assess vascular response to flow-induced dilatation (FID) and to elucidate the role of vascular oxidative stress/antioxidative capacity in middle cerebral arteries (MCAs) of HS-fed rats in vitro. The novelty of this study is in demonstrating impaired flow-induced dilatation of MCAs and down-regulation of vascular antioxidant genes with HS intake, leading to increased levels of oxidative stress in blood vessels and peripheral lymph organs, which together contribute to impaired FID. In addition, results show increased oxidative stress in leukocytes of peripheral lymph organs, suggesting the occurrence of inflammatory processes due to HS intake. Recirculation of leukocytes might additionally increase vascular oxidative stress in vivo. The aim of this study was to determine flow-induced dilatation (FID) and the role of oxidative stress/antioxidative capacity in isolated, pressurized middle cerebral arteries (MCAs) of high salt (HS)-fed rats. Healthy male Sprague-Dawley rats (11 weeks old) were fed low salt (0.4% NaCl; LS group) or high salt (4% NaCl; HS group) diets for 1 week. Reactivity of MCAs in response to stepwise increases in pressure gradient (Δ10-Δ100 mmHg) was determined in the absence or presence of the superoxide dismutase (SOD) mimetic TEMPOL and/or the nitric oxide synthases (NOS) inhibitor N(ω) -nitro-l-arginine methyl ester (l-NAME). mRNA levels of antioxidative enzymes, NAPDH-oxidase components, inducible (iNOS) and endothelial nitric oxide synthases (eNOS) were determined by quantitative real-time PCR. Blood pressure (BP), antioxidant enzymes activity, oxidative stress in peripheral leukocytes, lipid peroxidation products and the antioxidant capacity of plasma were measured for both groups. FID was

  2. Blast-induced phenotypic switching in cerebral vasospasm

    PubMed Central

    Alford, Patrick W.; Dabiri, Borna E.; Goss, Josue A.; Hemphill, Matthew A.; Brigham, Mark D.; Parker, Kevin Kit

    2011-01-01

    Vasospasm of the cerebrovasculature is a common manifestation of blast-induced traumatic brain injury (bTBI) reported among combat casualties in the conflicts in Afghanistan and Iraq. Cerebral vasospasm occurs more frequently, and with earlier onset, in bTBI patients than in patients with other TBI injury modes, such as blunt force trauma. Though vasospasm is usually associated with the presence of subarachnoid hemorrhage (SAH), SAH is not required for vasospasm in bTBI, which suggests that the unique mechanics of blast injury could potentiate vasospasm onset, accounting for the increased incidence. Here, using theoretical and in vitro models, we show that a single rapid mechanical insult can induce vascular hypercontractility and remodeling, indicative of vasospasm initiation. We employed high-velocity stretching of engineered arterial lamellae to simulate the mechanical forces of a blast pulse on the vasculature. An hour after a simulated blast, injured tissues displayed altered intracellular calcium dynamics leading to hypersensitivity to contractile stimulus with endothelin-1. One day after simulated blast, tissues exhibited blast force dependent prolonged hypercontraction and vascular smooth muscle phenotype switching, indicative of remodeling. These results suggest that an acute, blast-like injury is sufficient to induce a hypercontraction-induced genetic switch that potentiates vascular remodeling, and cerebral vasospasm, in bTBI patients. PMID:21765001

  3. An intelligent support system for automatic detection of cerebral vascular accidents from brain CT images.

    PubMed

    Hajimani, Elmira; Ruano, M G; Ruano, A E

    2017-07-01

    This paper presents a Radial Basis Functions Neural Network (RBFNN) based detection system, for automatic identification of Cerebral Vascular Accidents (CVA) through analysis of Computed Tomographic (CT) images. For the design of a neural network classifier, a Multi Objective Genetic Algorithm (MOGA) framework is used to determine the architecture of the classifier, its corresponding parameters and input features by maximizing the classification precision, while ensuring generalization. This approach considers a large number of input features, comprising first and second order pixel intensity statistics, as well as symmetry/asymmetry information with respect to the ideal mid-sagittal line. Values of specificity of 98% and sensitivity of 98% were obtained, at pixel level, by an ensemble of non-dominated models generated by MOGA, in a set of 150 CT slices (1,867,602pixels), marked by a NeuroRadiologist. This approach also compares favorably at a lesion level with three other published solutions, in terms of specificity (86% compared with 84%), degree of coincidence of marked lesions (89% compared with 77%) and classification accuracy rate (96% compared with 88%). Copyright © 2017. Published by Elsevier B.V.

  4. Cerebral Proliferative Angiopathy (CPA): Imaging Findings and Response to Therapy.

    PubMed

    Lopci, Egesta; Olivari, Laura; Bello, Lorenzo; Navarria, Pierina; Chiti, Arturo

    2016-12-01

    We report the case of a 55-year-old woman with cerebral proliferative angiopathy (CPA). Her medical history included brain surgery for small vascular lesions and suspicion of cerebral malignancy. C methionine PET (C-METH PET) demonstrated a diffusely increased uptake on the right hemisphere. Contrast-enhanced MRI documented a massive lesion with a diffuse "nidus" appearance, involving the right cerebral hemisphere (sparing the inferior frontal gyrus and the anterior frontal lobe), the brainstem, and the middle cerebellar peduncle. Pathology confirmed the diagnosis of CPA and, after radiation treatment, the patient presented with clinical and radiological response.

  5. Systematization and distribution of the middle cerebral artery on the brain surface in pampas fox (Pseudalopex gymnocercus).

    PubMed

    Depedrini, J S; Campos, R

    2007-12-01

    The present study has analysed 30 pampas fox brains (Pseudalopex gymnocercus), injected with latex, aiming to systematize and describe the distribution and vascularization territories of the middle cerebral artery. After being originated from the rostral branch of the internal carotid artery this vessel formed the following collateral branches: rostral choroidal artery, rostral and caudal central branches and cortical branches. Before crossing the lateral rhinal sulcus, the common trunk of the middle cerebral artery frequently bifurcated in a rostral and a caudal branch. In a smaller amount, the common trunk did not show any bifurcation, ramifying in arborescence. The vascular territory of the pampas fox middle cerebral artery included the lateral cerebral fossa, the lateral third of the olfactory trigone, the two rostral thirds of the piriform lobe, the lateral olfactory tract and most of the convex surface of the cerebral hemisphere, except for the more rostromedial areas of the frontal lobe bordering the endomarginal sulcus in the parietal and occipital lobes as well as the transverse fissure at the caudal pole of the cerebral hemisphere.

  6. Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

    PubMed

    Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

    2016-01-01

    Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions

  7. 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

  8. Coma in fatal adult human malaria is not caused by cerebral oedema

    PubMed Central

    2011-01-01

    Background The role of brain oedema in the pathophysiology of cerebral malaria is controversial. Coma associated with severe Plasmodium falciparum malaria is multifactorial, but associated with histological evidence of parasitized erythrocyte sequestration and resultant microvascular congestion in cerebral vessels. To determine whether these changes cause breakdown of the blood-brain barrier and resultant perivascular or parenchymal cerebral oedema, histology, immunohistochemistry and image analysis were used to define the prevalence of histological patterns of oedema and the expression of specific molecular pathways involved in water balance in the brain in adults with fatal falciparum malaria. Methods The brains of 20 adult Vietnamese patients who died of severe malaria were examined for evidence of disrupted vascular integrity. Immunohistochemistry and image analysis was performed on brainstem sections for activation of the vascular endothelial growth factor (VEGF) receptor 2 and expression of the aquaporin 4 (AQP4) water channel protein. Fibrinogen immunostaining was assessed as evidence of blood-brain barrier leakage and perivascular oedema formation. Correlations were performed with clinical, biochemical and neuropathological parameters of severe malaria infection. Results The presence of oedema, plasma protein leakage and evidence of VEGF signalling were heterogeneous in fatal falciparum malaria and did not correlate with pre-mortem coma. Differences in vascular integrity were observed between brain regions with the greatest prevalence of disruption in the brainstem, compared to the cortex or midbrain. There was a statistically non-significant trend towards higher AQP4 staining in the brainstem of cases that presented with coma (P = .02). Conclusions Histological evidence of cerebral oedema or immunohistochemical evidence of localised loss of vascular integrity did not correlate with the occurrence of pre-mortem coma in adults with fatal falciparum malaria

  9. Coma in fatal adult human malaria is not caused by cerebral oedema.

    PubMed

    Medana, Isabelle M; Day, Nicholas P J; Sachanonta, Navakanit; Mai, Nguyen T H; Dondorp, Arjen M; Pongponratn, Emsri; Hien, Tran T; White, Nicholas J; Turner, Gareth D H

    2011-09-17

    The role of brain oedema in the pathophysiology of cerebral malaria is controversial. Coma associated with severe Plasmodium falciparum malaria is multifactorial, but associated with histological evidence of parasitized erythrocyte sequestration and resultant microvascular congestion in cerebral vessels. To determine whether these changes cause breakdown of the blood-brain barrier and resultant perivascular or parenchymal cerebral oedema, histology, immunohistochemistry and image analysis were used to define the prevalence of histological patterns of oedema and the expression of specific molecular pathways involved in water balance in the brain in adults with fatal falciparum malaria. The brains of 20 adult Vietnamese patients who died of severe malaria were examined for evidence of disrupted vascular integrity. Immunohistochemistry and image analysis was performed on brainstem sections for activation of the vascular endothelial growth factor (VEGF) receptor 2 and expression of the aquaporin 4 (AQP4) water channel protein. Fibrinogen immunostaining was assessed as evidence of blood-brain barrier leakage and perivascular oedema formation. Correlations were performed with clinical, biochemical and neuropathological parameters of severe malaria infection. The presence of oedema, plasma protein leakage and evidence of VEGF signalling were heterogeneous in fatal falciparum malaria and did not correlate with pre-mortem coma. Differences in vascular integrity were observed between brain regions with the greatest prevalence of disruption in the brainstem, compared to the cortex or midbrain. There was a statistically non-significant trend towards higher AQP4 staining in the brainstem of cases that presented with coma (P = .02). Histological evidence of cerebral oedema or immunohistochemical evidence of localised loss of vascular integrity did not correlate with the occurrence of pre-mortem coma in adults with fatal falciparum malaria. Enhanced expression of AQP4 water

  10. [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.

  11. Cerebral Arterial Gas Embolism During Upper Endoscopy.

    PubMed

    Eoh, Eun J; Derrick, Bruce; Moon, Richard

    2015-09-15

    Arterial gas embolism can be caused by direct entry of gas into systemic arteries or indirectly by venous-to-arterial shunting. Although arterial gas embolism is rare, most documented cases are iatrogenic, resulting from the entry of gas during procedures that involve direct vascular cannulation or intracavitary air insufflation. Of the 18 identified case reports of air embolism during endoscopy, 11 cases describe findings of cerebral arterial gas embolism during upper endoscopy. Only 1 of these occurred during endoscopic balloon dilation of an esophageal stricture. We report a rare case of cerebral arterial gas embolism in a 64-year-old woman, which occurred during endoscopic dilation of an esophageal stricture and was subsequently treated with hyperbaric oxygen therapy. In this case report, we explore the possible etiologies, clinical workup, and therapeutic management of cerebral artery gas embolisms. Hyperbaric oxygen therapy is the treatment of choice for cerebral arterial gas embolism, with earlier treatments resulting in better outcomes.

  12. Cerebral blood velocity and other cardiovascular responses to 2 days of head-down tilt

    NASA Technical Reports Server (NTRS)

    Frey, Mary A. B.; Mader, Thomas H.; Bagian, James P.; Charles, John B.; Meehan, Richard T.

    1993-01-01

    Spaceflight induces a cephalad redistribution of fluid volume and blood flow within the human body, and space motion sickness, which is a problem during the first few days of space flight, could be related to these changes in fluid status and in blood flow of the cerebrum and vestibular system. To evaluate possible changes in cerebral blood flow during simulated weightlessness, we measured blood velocity in the middle cerebral artery (MCA) along with retinal vascular diameters, intraocular pressure, impedance cardiography, and sphygmomanometry on nine men (26.2 +/- 6.6 yr) morning and evening for 2 days during continuous 10 deg head-down tilt (HDT). When subjects went from seated to head-down bed rest, their heart rate and retinal diameters decreased, and intraocular pressures increased. After 48 h of HDT, blood flow velocity in the MCA was decreased and thoracic impedance was increased, indicating less fluid in the thorax. Percent changes in blood flow velocities in the MCA after 48 h of HDT were inversely correlated with percent changes in retinal vascular diameters. Blood flow velocities in the MCA were inversely correlated (intersubject) with arterial pressures and retinal vascular diameters. Heart rate, stroke volume, cardiac output, systolic arterial pressure, and at times pulse pressure and blood flow velocities in the MCA were greater in the evening. Total peripheral resistance was higher in the morning. Although cerebral blood velocity is reduced after subjects are head down for 2 days, the inverse relationship with retinal vessel diameters, which have control analogous to that of cerebral vessels, indicates cerebral blood flow is not reduced.

  13. Response of local vascular volumes to lower body negative pressure stress

    NASA Technical Reports Server (NTRS)

    Wolthuis, R. A.; Leblanc, A.; Carpentier, W. A.; Bergman, S. A., Jr.

    1975-01-01

    The present study involved an intravenous injection of radioactive iodinated serum albumin, equilibration of this isotope within the vascular space, and the continuous measurement of isotope activity over selected anatomical areas before, during and following multiple human LBNP tests. Both rate and magnitude of vascular pooling were distinctly different within each of five selected lower body anatomical areas. In the upper body, all areas except the abdomen showed depletions from their resting vascular volumes during LBNP. The presence of uniquely different pooling patterns in the lower body, the apparent stability of abdominal vascular volumes, and a possible decrease in cerebral blood volume during LBNP represent the major findings of this study.

  14. Non-accidental carbon monoxide poisoning from burning charcoal in attempted combined homicide-suicide.

    PubMed

    Lee, A C W; Ou, Y; Lam, S Y; So, K T; Kam, C W

    2002-10-01

    To describe an emerging form of serious child abuse in combined homicide-suicide in Hong Kong. This is a retrospective hospital chart review in a regional hospital in Hong Kong from January to December 2000. Eight children, with a mean age of 7.8 years (range 0.5-11 years), from four families were admitted to hospital because of non-accidental exposure to carbon monoxide when their parents attempted suicide by burning charcoal. A 7-year-old boy died on arrival. His 5.6-year-old sister and another 6-month-old boy had cerebral hypoxia on admission. Hyperbaric oxygen therapy was used in both cases, with rapid improvement, although there were persistent neurological deficits in the girl. The other children in the present study were asymptomatic and none had delayed neurological sequelae. Concomitant use of sedatives was also detected in three of the surviving patients. Non-accidental poisoning with carbon monoxide appears to be a new means of child abuse with potentially serious consequences. Concomitant intoxication with psychotropic drugs is common in such cases. The reason for parents killing their own children under such circumstances was unclear, but a desire to exact revenge on an estranged partner was suggested.

  15. Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1

    PubMed Central

    Morland, Cecilie; Andersson, Krister A.; Haugen, Øyvind P.; Hadzic, Alena; Kleppa, Liv; Gille, Andreas; Rinholm, Johanne E.; Palibrk, Vuk; Diget, Elisabeth H.; Kennedy, Lauritz H.; Stølen, Tomas; Hennestad, Eivind; Moldestad, Olve; Cai, Yiqing; Puchades, Maja; Offermanns, Stefan; Vervaeke, Koen; Bjørås, Magnar; Wisløff, Ulrik; Storm-Mathisen, Jon; Bergersen, Linda H.

    2017-01-01

    Physical exercise can improve brain function and delay neurodegeneration; however, the initial signal from muscle to brain is unknown. Here we show that the lactate receptor (HCAR1) is highly enriched in pial fibroblast-like cells that line the vessels supplying blood to the brain, and in pericyte-like cells along intracerebral microvessels. Activation of HCAR1 enhances cerebral vascular endothelial growth factor A (VEGFA) and cerebral angiogenesis. High-intensity interval exercise (5 days weekly for 7 weeks), as well as L-lactate subcutaneous injection that leads to an increase in blood lactate levels similar to exercise, increases brain VEGFA protein and capillary density in wild-type mice, but not in knockout mice lacking HCAR1. In contrast, skeletal muscle shows no vascular HCAR1 expression and no HCAR1-dependent change in vascularization induced by exercise or lactate. Thus, we demonstrate that a substance released by exercising skeletal muscle induces supportive effects in brain through an identified receptor. PMID:28534495

  16. Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1.

    PubMed

    Morland, Cecilie; Andersson, Krister A; Haugen, Øyvind P; Hadzic, Alena; Kleppa, Liv; Gille, Andreas; Rinholm, Johanne E; Palibrk, Vuk; Diget, Elisabeth H; Kennedy, Lauritz H; Stølen, Tomas; Hennestad, Eivind; Moldestad, Olve; Cai, Yiqing; Puchades, Maja; Offermanns, Stefan; Vervaeke, Koen; Bjørås, Magnar; Wisløff, Ulrik; Storm-Mathisen, Jon; Bergersen, Linda H

    2017-05-23

    Physical exercise can improve brain function and delay neurodegeneration; however, the initial signal from muscle to brain is unknown. Here we show that the lactate receptor (HCAR1) is highly enriched in pial fibroblast-like cells that line the vessels supplying blood to the brain, and in pericyte-like cells along intracerebral microvessels. Activation of HCAR1 enhances cerebral vascular endothelial growth factor A (VEGFA) and cerebral angiogenesis. High-intensity interval exercise (5 days weekly for 7 weeks), as well as L-lactate subcutaneous injection that leads to an increase in blood lactate levels similar to exercise, increases brain VEGFA protein and capillary density in wild-type mice, but not in knockout mice lacking HCAR1. In contrast, skeletal muscle shows no vascular HCAR1 expression and no HCAR1-dependent change in vascularization induced by exercise or lactate. Thus, we demonstrate that a substance released by exercising skeletal muscle induces supportive effects in brain through an identified receptor.

  17. [Accidental hanging during auto-erotic practices].

    PubMed

    Vieira, D N; da Silva, A G

    1989-01-01

    An unusual case of accidental hanging during autoerotic practices in a 25-year-old male student is described and the autoerotic asphyxia syndrome briefly discussed. The authors stressed the importance of a correct diagnostic of accidental death in these cases.

  18. Vitamin D status and vascular dementia due to cerebral small vessel disease in the elderly Asian Indian population.

    PubMed

    Prabhakar, Puttachandra; Chandra, Sadanandavalli Retnaswami; Supriya, Manjunath; Issac, Thomas Gregor; Prasad, Chandrajit; Christopher, Rita

    2015-12-15

    Vitamin D plays vital roles in human health and recent studies have shown its beneficial effect on brain functioning. The present study was designed to evaluate the association of vitamin D with vascular dementia (VaD) due to cerebral small vessel disease (SVD) in Asian Indian population. 140 VaD patients aged ≥ 60 years with neuroimaging evidence of SVD, and 132 age and gender-matched controls, were investigated. Vitamin D status was estimated by measuring serum 25-hydroxy vitamin D. Logistic regression model revealed that deficient levels of vitamin D (<12 ng/ml) were associated with 2.2-fold increase in odds of VaD after adjustment with covariates. Hypertension was independently associated with 11.3-fold increased odds of VaD. In hypertensives with vitamin D deficiency and insufficiency (12-20 ng/ml), the odds were increased to 31.6-fold and 14.4-fold, respectively. However, in hypertensives with vitamin D sufficiency (>20 ng/ml), the odds of VaD were increased by 3.8-fold only. Pearson correlation showed that serum vitamin D was inversely associated with systolic and diastolic blood pressure (r=-0.401 and -0.411, p<0.01, respectively) in vitamin D-deficient subjects. Since the combined presence of hypertension and vitamin D deficiency increases the probability of developing VaD, screening for vitamin D status in addition to regular monitoring of blood pressure, could reduce the risk of VaD associated with cerebral SVD in the elderly Asian Indian subjects. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. [Intraoperative monitoring of oxygen tissue pressure: Applications in vascular neurosurgery].

    PubMed

    Arikan, Fuat; Vilalta, Jordi; Torne, Ramon; Chocron, Ivette; Rodriguez-Tesouro, Ana; Sahuquillo, Juan

    2014-01-01

    Ischemic lesions related to surgical procedures are a major cause of postoperative morbidity in patients with cerebral vascular disease. There are different systems of neuromonitoring to detect intraoperative ischemic events, including intraoperative monitoring of oxygen tissue pressure (PtiO2). The aim of this article was to describe, through the discussion of 4 cases, the usefulness of intraoperative PtiO2 monitoring during vascular neurosurgery. In presenting these cases, we demonstrate that monitoring PtiO2 is a reliable way to detect early ischemic events during surgical procedures. Continuous monitoring of PtiO2 in an area at risk allows the surgeon to resolve the cause of the ischemic event before it evolves to an established cerebral infarction. Copyright © 2014 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  20. Multiple Spontaneous Cerebral Microbleeds and Leukoencephalopathy in PSEN1-Associated Familial Alzheimer's Disease: Mirror of Cerebral Amyloid Angiopathy?

    PubMed

    Floris, Gianluca; Di Stefano, Francesca; Cherchi, Maria Valeria; Costa, Gianna; Marrosu, Francesco; Marrosu, Maria Giovanna

    2015-01-01

    Cerebral microbleeds (CMB) might reflect specific underlying vascular pathologies like cerebral amyloid angiopathy (CAA). In the present study we report the gradient-echo MRI pattern of two siblings with P284S PSEN1 mutation. T2* gradient-echo images of the two subjects demonstrated multiple microbleeds in lobar regions. The role and causes of CMB in sporadic Alzheimer's disease (AD) patients have not been clearly established and useful contributions could derive from familial AD studies. Furthermore, since CAA is a potential risk factor for developing adverse events in AD immunization trials, the identification in vivo of CAA through non-invasive MRI methods could be useful to monitoring side effects.

  1. Heterogeneity in Kv7 channel function in the Cerebral and Coronary Circulation

    PubMed Central

    Tanner, Miles A.; Li, Min; Hill, Michael A.

    2014-01-01

    Kv7 channels are considered important regulators of vascular smooth muscle contractility. The present study examined the hypotheses that 1. Kv7 channels are present in mouse cerebral and coronary arteries and regulate vascular reactivity, and 2. regional differences exist in the activity of these channels. PCR confirmed that basilar, Circle of Willis and left anterior descending (LAD) arteries express predominantly Kv7.1 and 7.4. Western blot analysis, however, showed greater Kv7.4 protein levels in the cerebral vessels. Relaxation to the Kv7 channel activator, retigabine (1-50μM) was significantly greater in basilar compared to LAD. Similarly, the Kv7 channel inhibitor, linopirdine (10μM) caused stronger contraction of the basilar artery. Furthermore, pre-incubation with linopirdine reduced forskolin (cAMP activator)-induced vasorelaxation in basilar while not altering forskolin-induced vasorelaxation of the LAD, suggesting that Kv7 channels play a more prominent role in the cerebral than coronary circulation. Consistent with the vessel data, whole cell Kv7 currents in cerebral VSMCs were potentiated by retigabine and inhibited by linopirdine, while these responses were blunted in coronary VSMCs. This study provides evidence that mouse Kv7 channels may contribute differently to regulating the functional properties of cerebral and coronary arteries. Such heterogeneity has important implications for developing novel therapeutics for cardiovascular dysfunction. PMID:25476662

  2. Cobalt chloride attenuates hypobaric hypoxia induced vascular leakage in rat brain: Molecular mechanisms of action of cobalt chloride

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

    Kalpana, S.; Dhananjay, S.; Anju, B.

    2008-09-15

    This study reports the efficacy of cobalt preconditioning in preventing hypobaric hypoxia induced vascular leakage (an indicator of cerebral edema) using male Sprague-Dawley rats as model system. Exposure of animals to hypobaric hypoxia led to a significant increase in vascular leakage, reactive oxygen species (ROS), nitric oxide (NO), and vascular endothelial growth factor (VEGF) levels. There was a marked increase in Nuclear Factor {kappa}B (NF{kappa}B) DNA binding activity and levels of pro-inflammatory cytokines such as Monocyte chemoattractant protein (MCP-1), Interferon-{gamma} (IFN-{gamma}), Interleukin-1 (IL-1), and Tumor Necrosis Factor-{alpha} (TNF-{alpha}) and cell adhesion molecules such as Vascular Cell Adhesion Molecule-1 (VCAM-1), andmore » P-selectin. Chemical preconditioning by cobalt for 7 days (12.5 mg Co/kg b.w., oral) significantly attenuated cerebral vascular leakage and the expression of inflammatory mediators induced by hypoxia. Administration of NF{kappa}B inhibitor, curcumin (50 mg/kg b.w.; i.p.) appreciably inhibited hypoxia induced vascular leakage indicating the involvement of NF{kappa}B in causing vascular leakage. Interestingly, cobalt when administered at 12.5 mg Co/kg b.w. (i.p.), 1 h before hypoxia could not prevent the vascular leakage indicating that cobalt per se did not have an effect on NF{kappa}B. The lower levels of NF{kappa}B observed in the brains of cobalt administered animals might be due to higher levels of antioxidant and anti-inflammatory proteins (hemeoxygenase-1 and metallothionein). To conclude cobalt preconditioning inhibited hypobaric hypoxia induced cerebral vascular leakage by lowering NF{kappa}B DNA binding activity and its regulated pro-inflammatory mediators. This is contemplated to be mediated by cobalt induced reduction in ROS/NO and increase in HO-1 and MT.« less

  3. A model of the instantaneous pressure-velocity relationships of the neonatal cerebral circulation.

    PubMed

    Panerai, R B; Coughtrey, H; Rennie, J M; Evans, D H

    1993-11-01

    The instantaneous relationship between arterial blood pressure (BP) and cerebral blood flow velocity (CBFV), measured with Doppler ultrasound in the anterior cerebral artery, is represented by a vascular waterfall model comprising vascular resistance, compliance, and critical closing pressure. One min recordings obtained from 61 low birth weight newborns were fitted to the model using a least-squares procedures with correction for the time delay between the BP and CBFV signals. A sensitivity analysis was performed to study the effects of low-pass filtering (LPF), cutoff frequency, and noise on the estimated parameters of the model. Results indicate excellent fitting of the model (F-test, p < 0.0001) when the BP and CBFV signals are LPF at 7.5 Hz. Reconstructed CBFV waveforms using the BP signal and the model parameters have a mean correlation coefficient of 0.94 with the measured flow velocity tracing (N = 232 epochs). The model developed can be useful for interpreting clinical findings and as a framework for research into cerebral autoregulation.

  4. [Effects of xenon anesthesia on cerebral blood flow in neurosurgical patients without intracranial hypertension].

    PubMed

    Rylova, A V; Beliaev, A Iu; Lubnin, A Iu

    2013-01-01

    Among anesthetic agents used in neurosurgery xenon appears to be the most advantageous. It preserves arterial blood pressure, assures rapid recovery and neuroprotection. But the data is lacking on xenon effect upon cerebral blood flow under anesthetic conditions. We measured flow velocity in middle cerebral artery in neurosurgical patients without intracranial hypertension during closed circuit xenon anesthesia comparing propofol and xenon effect in the same patients. In our study xenon didn't seem to induce clinically relevant changes in cerebral blood flow and preserved cerebral vascular reactivity thus proving its safety in patients without intracranial hypertension.

  5. Cerebral Perfusion Enhancing Interventions: A New Strategy for the Prevention of Alzheimer Dementia.

    PubMed

    de la Torre, Jack C

    2016-09-01

    Cardiovascular and cerebrovascular diseases are major risk factors in the development of cognitive impairment and Alzheimer's disease (AD). These cardio-cerebral disorders promote a variety of vascular risk factors which in the presence of advancing age are prone to markedly reduce cerebral perfusion and create a neuronal energy crisis. Long-term hypoperfusion of the brain evolves mainly from cardiac structural pathology and brain vascular insufficiency. Brain hypoperfusion in the elderly is strongly associated with the development of mild cognitive impairment (MCI) and both conditions are presumed to be precursors of Alzheimer dementia. A therapeutic target to prevent or treat MCI and consequently reduce the incidence of AD aims to elevate cerebral perfusion using novel pharmacological agents. As reviewed here, the experimental pharmaca include the use of Rho kinase inhibitors, neurometabolic energy boosters, sirtuins and vascular growth factors. In addition, a compelling new technique in laser medicine called photobiomodulation is reviewed. Photobiomodulation is based on the use of low level laser therapy to stimulate mitochondrial energy production non-invasively in nerve cells. The use of novel pharmaca and photobiomodulation may become important tools in the treatment or prevention of cognitive decline that can lead to dementia. © 2016 International Society of Neuropathology.

  6. Anatomic vascular phantom for the verification of MRA and XRA visualization and fusion

    NASA Astrophysics Data System (ADS)

    Mankovich, Nicholas J.; Lambert, Timothy; Zrimec, Tatjana; Hiller, John B.

    1995-05-01

    A project is underway to develop automated methods of fusing cerebral magnetic resonance angiography (MRA) and x-ray angiography (XRA) for creating accurate visualizations used in planning treatment of vascular disease. We have developed a vascular phantom suitable for testing segmentation and fusion algorithms with either derived images (psuedo-MRA/psuedo-XRA) or actual MRA or XRA image sequences. The initial unilateral arterial phantom design, based on normal human anatomy, contains 48 tapering vascular segments with lumen diameters from 2.5 millimeter to 0.25 millimeter. The initial phantom used rapid prototyping technology (stereolithography) with a 0.9 millimeter vessel wall fabricated in an ultraviolet-cured plastic. The model fabrication resulted in a hollow vessel model comprising the internal carotid artery, the ophthalmic artery, and the proximal segments of the anterior, middle, and posterior cerebral arteries. The complete model was fabricated but the model's lumen could not be cleared for vessels with less than 1 millimeter diameter. Measurements of selected vascular outer diameters as judged against the CAD specification showed an accuracy of 0.14 mm and precision (standard deviation) of 0.15 mm. The plastic vascular model produced provides a fixed geometric framework for the evaluation of imaging protocols and the development of algorithms for both segmentation and fusion.

  7. [Oral contraception and the vascular risk].

    PubMed

    Garnier, L F; Gruel, Y

    1989-01-01

    Vascular risk, mainly thromboembolitic risk, attributed to oral contraceptives (OCs) since 1962, has been primarily linked to ethinyl estradiol (EE). OCs which combine estrogen and have been associated with cerebral vascular accidents. A 1977 study showed a 40% increase of mortality due to cardiovascular complications in women taking OCs. There were of both an arterial and a venous character. The risk of myocardial infarction was 3 times more frequent among OC users. Deep venous thrombosis and pulmonary embolism were more numerous. Some other risk factors include smoking, hypertension, diabetes, and age 35. The risk of heart attack vanishes a few years after stopping OC use. The reduction of EE (and similarly progesterone) dosage from 100-50 mcg also lower the risk of hypertension, cerebral vascular accidents, and venous thrombosis. Prolonged use of OCs causes disorders of hemostasis affecting the walls of blood vessels, modifying the viscosity of blood flow (increase of hematocrits, reduction of venous tonus), modifying plasmatic coagulation (increase of platelets, increase of factors VII and X and plasma fibrinogen, and decrease of antithrombin III activity), and increased fibrinolysis. These anomalies are exclusively associated with high doses of estrogens. 5% of women using OCs develop moderate hypertension of 5-10 mm Hg of systolic pressure 5 years later, but after cessation it is reversed. OCs stimulate the renin-angiotensin-aldosterone system causing accelerated production of angiotensin II with the resultant forceful vasotension. 3 months after quitting OC use, high blood pressure returns to normal. EE can provoke diabetes; it increases very low density lipoprotein (VLDL) and high density lipoprotein (HDL) production, but total cholesterol is hardly affected. The androgenic property of progestogens reduces HDL. Combined OCs are contraindicated for women with hypertension, hyperlipidemia, diabetes, and a family history of vascular accidents.

  8. [THREE CASES OF ACCIDENTAL AUTO-INJECTION OF ADRENALINE].

    PubMed

    Yanagida, Noriyuki; Iikura, Katsuhito; Ogura, Kiyotake; Wang, Ling-jen; Asaumi, Tomoyuki; Sato, Sakura; Ebisawa, Motohiro

    2015-12-01

    Reports on accidental auto-injection of adrenaline are few. We encountered three cases of accidental injection of adrenaline. In this study, we have examined and reported the clinical courses and symptoms of our cases. CASE 1 involved a female physician in her 50s who had attended an explanatory meeting on auto-injection of adrenaline. She mistook EpiPen® to be the EpiPen trainer and accidentally injected herself with 0.3 mg EpiPen®. Her systolic/diastolic pressure peaked at 7 min to reach 144/78 mmHg and decreased to 120/77 mmHg at 14 min. Except for palpitation after 7 min, the only subjective symptom was local pain at the injection site. CASE 2 was noted in a 6-year-old boy. He accidentally pierced his right forefinger with 0.15 mg EpiPen®, and after 20 min, his right forefinger was swollen. The swelling improved 80 min after the accidental injection. CASE 3 was noted in a 4-year-old girl. She accidentally injected herself with 0.15 mg EpiPen®. Her systolic/diastolic pressure peaked at 23 min to reach 123/70 mmHg and decreased to 96/86 mmHg at 28 min. Severe adverse effects of accidental auto-injection of adrenaline were not observed in these three cases. Our findings suggest that while handling adrenaline auto-injectors, we should keep in mind the possibility of accidental injection.

  9. Comprehensive Overview of Contemporary Management Strategies for Cerebral Aneurysms.

    PubMed

    Manhas, Amitoz; Nimjee, Shahid M; Agrawal, Abhishek; Zhang, Jonathan; Diaz, Orlando; Zomorodi, Ali R; Smith, Tony; Powers, Ciarán J; Sauvageau, Eric; Klucznik, Richard P; Ferrell, Andrew; Golshani, Kiarash; Stieg, Philip E; Britz, Gavin W

    2015-10-01

    Aneurysmal subarachnoid hemorrhage (SAH) remains an important health issue in the United States. Despite recent improvements in the diagnosis and treatment of cerebral aneurysms, the mortality rate following aneurysm rupture. In those patients who survive, up to 50% are left severely disabled. The goal of preventing the hemorrhage or re-hemorrhage can only be achieved by successfully excluding the aneurysm from the circulation. This article is a comprehensive review by contemporary vascular neurosurgeons and interventional neuroradiolgists on the modern management of cerebral aneurysms. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Vascular signaling abnormalities in Alzheimer disease.

    PubMed

    Grammas, Paula; Sanchez, Alma; Tripathy, Debjani; Luo, Ester; Martinez, Joseph

    2011-08-01

    Our laboratory has documented that brain microvessels derived from patients with Alzheimer disease (AD) express or release a myriad of factors that have been implicated in vascular activation and angiogenesis. In addition, we have documented that signaling cascades associated with vascular activation and angiogenesis are upregulated in AD-derived brain microvessels. These results are consistent with emerging data suggesting that factors and processes characteristic of vascular activation and angiogenesis are found in the AD brain. Despite increases in proangiogenic factors and signals in the AD brain, however, evidence for increased vascularity in AD is lacking. Cerebral hypoperfusion/hypoxia, a potent stimulus for vascular activation and angiogenesis, triggers hypometabolic, cognitive, and degenerative changes in the brain. In our working model, hypoxia stimulates the angiogenic process; yet, there is no new vessel growth. Therefore, there are no feedback signals to shut off vascular activation, and endothelial cells become irreversibly activated. This activation results in release of a large number of proteases, inflammatory proteins, and other gene products with biologic activity that can injure or kill neurons. Pathologic activation of brain vasculature may contribute noxious mediators that lead to neuronal injury and disease processes in AD brains. This concept is supported by preliminary experiments in our laboratory, which show that pharmacologic blockade of vascular activation improves cognitive function in an animal model of AD. Thus, "vascular activation" could be a novel, unexplored therapeutic target in AD.

  11. Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke

    PubMed Central

    Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

    2016-01-01

    Purpose Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Methods Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3–7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Results Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Conclusions Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process

  12. Development of functional in vivo imaging of cerebral lenticulostriate artery using novel synchrotron radiation angiography

    NASA Astrophysics Data System (ADS)

    Lin, Xiaojie; Miao, Peng; Mu, Zhihao; Jiang, Zhen; Lu, Yifan; Guan, Yongjing; Chen, Xiaoyan; Xiao, Tiqiao; Wang, Yongting; Yang, Guo-Yuan

    2015-02-01

    The lenticulostriate artery plays a vital role in the onset and development of cerebral ischemia. However, current imaging techniques cannot assess the in vivo functioning of small arteries such as the lenticulostriate artery in the brain of rats. Here, we report a novel method to achieve a high resolution multi-functional imaging of the cerebrovascular system using synchrotron radiation angiography, which is based on spatio-temporal analysis of contrast density in the arterial cross section. This method provides a unique tool for studying the sub-cortical vascular elasticity after cerebral ischemia in rats. Using this technique, we demonstrated that the vascular elasticity of the lenticulostriate artery decreased from day 1 to day 7 after transient middle cerebral artery occlusion in rats and recovered from day 7 to day 28 compared to the controls (p < 0.001), which paralleled with brain edema formation and inversely correlated with blood flow velocity (p < 0.05). Our results demonstrated that the change of vascular elasticity was related to the levels of brain edema and the velocity of focal blood flow, suggesting that reducing brain edema is important for the improvement of the function of the lenticulostriate artery in the ischemic brain.

  13. MTHFR and ACE Gene Polymorphisms and Risk of Vascular and Degenerative Dementias in the Elderly

    ERIC Educational Resources Information Center

    Pandey, Pratima; Pradhan, Sunil; Modi, Dinesh Raj; Mittal, Balraj

    2009-01-01

    Focal lacunar infarctions due to cerebral small vessel atherosclerosis or single/multiple large cortical infarcts lead to vascular dementia, and different genes and environmental factors have been implicated in causation or aggravation of the disease. Previous reports suggest that some of the risk factors may be common to both vascular as well as…

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

    PubMed

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

    2018-06-01

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

  15. [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)

  16. Neuroimmunological Blood Brain Barrier Opening in Experimental Cerebral Malaria

    PubMed Central

    Baer, Kerstin; Mikolajczak, Sebastian A.; Kappe, Stefan H. I.; Frevert, Ute

    2012-01-01

    Plasmodium falciparum malaria is responsible for nearly one million annual deaths worldwide. Because of the difficulty in monitoring the pathogenesis of cerebral malaria in humans, we conducted a study in various mouse models to better understand disease progression in experimental cerebral malaria (ECM). We compared the effect on the integrity of the blood brain barrier (BBB) and the histopathology of the brain of P. berghei ANKA, a known ECM model, P. berghei NK65, generally thought not to induce ECM, P. yoelii 17XL, originally reported to induce human cerebral malaria-like histopathology, and P. yoelii YM. As expected, P. berghei ANKA infection caused neurological signs, cerebral hemorrhages, and BBB dysfunction in CBA/CaJ and Swiss Webster mice, while Balb/c and A/J mice were resistant. Surprisingly, PbNK induced ECM in CBA/CaJ mice, while all other mice were resistant. P. yoelii 17XL and P. yoelii YM caused lethal hyperparasitemia in all mouse strains; histopathological alterations, BBB dysfunction, or neurological signs were not observed. Intravital imaging revealed that infected erythrocytes containing mature parasites passed slowly through capillaries making intimate contact with the endothelium, but did not arrest. Except for relatively rare microhemorrhages, mice with ECM presented no obvious histopathological alterations that would explain the widespread disruption of the BBB. Intravital imaging did reveal, however, that postcapillary venules, but not capillaries or arterioles, from mice with ECM, but not hyperparasitemia, exhibit platelet marginalization, extravascular fibrin deposition, CD14 expression, and extensive vascular leakage. Blockage of LFA-1 mediated cellular interactions prevented leukocyte adhesion, vascular leakage, neurological signs, and death from ECM. The endothelial barrier-stabilizing mediators imatinib and FTY720 inhibited vascular leakage and neurological signs and prolonged survival to ECM. Thus, it appears that neurological

  17. Shunting effects in patients with idiopathic normal pressure hydrocephalus; correlation with cerebral and leptomeningeal biopsy findings.

    PubMed

    Bech, R A; Waldemar, G; Gjerris, F; Klinken, L; Juhler, M

    1999-01-01

    Normal Pressure Hydrocephalus (NPH) is a potentially treatable syndrome with abnormal cerebrospinal fluid dynamics. Meningeal fibrosis and/or obliteration of the subarachnoid space have been suggested as one of the patho-anatomical substrates. However, other types of adult onset dementia, predominantly Alzheimer's disease and Vascular Dementia, may mimic the clinical NPH characteristics. The purpose of the present study was to correlate cerebral parenchymal and leptomeningeal biopsy findings to the clinical outcome after CSF shunting in a prospective group of idiopathic NPH (INPH) patients. The study comprises 27 patients with INPH, diagnosed and shunted according to generally accepted clinical, imaging and hydrodynamic criteria. In all patients a frontal leptomeningeal and brain biopsy was obtained prior to the shunt insertion. Degenerative cerebral changes, most often Alzheimer (6 cases) or vascular changes (7 cases) were described in 14 out of 27 biopsies. Arachnoid fibrosis was found in 9 of the 18 biopsies containing arachnoid tissue. Overall, nine patients (33%) improved, of whom 6 presented Alzheimer or vascular changes in their biopsies. No correlation was found between clinical outcome and the presence or absence of degenerative cerebral changes and/or arachnoid fibrosis. However, a tendency towards higher improvement rates was noted in the subgroups presenting degenerative cerebral changes or arachnoid fibrosis. The results suggest that no constant morphological element exists in the syndrome of INPH. Various aetiologies may be involved in the pathogenesis and possibly in some cases co-existing: Patients may also improve by shunting despite the presence of degenerative cerebral parenchymal changes.

  18. Heterogeneity in Kv7 channel function in the cerebral and coronary circulation.

    PubMed

    Lee, Sewon; Yang, Yan; Tanner, Miles A; Li, Min; Hill, Michael A

    2015-02-01

    Kv7 channels are considered important regulators of vascular smooth muscle contractility. The present study aimed to examine the hypotheses that (i) Kv7 channels are present in mouse cerebral and coronary arteries and regulate vascular reactivity and (ii) regional differences exist in the activity of these channels. PCR confirmed that basilar, Circle of Willis and LAD arteries express predominantly Kv7.1 and 7.4. Western blot analysis, however, showed greater Kv7.4 protein levels in the cerebral vessels. Relaxation to the Kv7 channel activator, retigabine (1-50 μM) was significantly greater in the basilar artery compared to the LAD artery. Similarly, the Kv7 channel inhibitor, linopirdine (10 μM) caused a stronger contraction of the basilar artery. Furthermore, pre-incubation with linopirdine reduced forskolin (cAMP activator)-induced vasorelaxation in basilar while not altering forskolin-induced vasorelaxation of the LAD, suggesting that Kv7 channels play a more prominent role in the cerebral than in the coronary circulation. Consistent with the vessel data, whole cell Kv7 currents in cerebral VSMCs were potentiated by retigabine and inhibited by linopirdine, while these responses were blunted in coronary VSMCs. This study provides evidence that mouse Kv7 channels may contribute differently to regulating the functional properties of cerebral and coronary arteries. Such heterogeneity has important implications for developing novel therapeutics for cardiovascular dysfunction. © 2014 John Wiley & Sons Ltd.

  19. The characterization and evaluation of accidental explosions

    NASA Technical Reports Server (NTRS)

    Strehlow, R. A.; Baker, W. E.

    1975-01-01

    Accidental explosions are discussed from a number of viewpoints. First, all accidental explosions, intentional explosions and natural explosions are characterized by type. Second, the nature of the blast wave produced by an ideal (point source or HE) explosion is discussed to form a basis for describing how other explosion processes yield deviations from ideal blast wave behavior. The current status blast damage mechanism evaluation is also discussed. Third, the current status of our understanding of each different category of accidental explosions is discussed in some detail.

  20. 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

  1. 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.

  2. 21 CFR 1002.20 - Reporting of accidental radiation occurrences.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Reporting of accidental radiation occurrences... SERVICES (CONTINUED) RADIOLOGICAL HEALTH RECORDS AND REPORTS Manufacturers' Reports on Accidental Radiation Occurrences § 1002.20 Reporting of accidental radiation occurrences. (a) Manufacturers of electronic products...

  3. 21 CFR 1002.20 - Reporting of accidental radiation occurrences.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Reporting of accidental radiation occurrences... SERVICES (CONTINUED) RADIOLOGICAL HEALTH RECORDS AND REPORTS Manufacturers' Reports on Accidental Radiation Occurrences § 1002.20 Reporting of accidental radiation occurrences. (a) Manufacturers of electronic products...

  4. 21 CFR 1002.20 - Reporting of accidental radiation occurrences.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Reporting of accidental radiation occurrences... SERVICES (CONTINUED) RADIOLOGICAL HEALTH RECORDS AND REPORTS Manufacturers' Reports on Accidental Radiation Occurrences § 1002.20 Reporting of accidental radiation occurrences. (a) Manufacturers of electronic products...

  5. Hypertension-Induced Cerebral Small Vessel Disease Leading to Cognitive Impairment.

    PubMed

    Liu, Yang; Dong, Yan-Hong; Lyu, Pei-Yuan; Chen, Wei-Hong; Li, Rui

    2018-03-05

    Alzheimer's disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease (CSVD) is strongly associated with both hypertension and cognitive impairment. In this review, we identify the pathophysiological changes in CSVD that are caused by hypertension and further explore the relationship between CSVD and cognitive impairment. We searched and scanned the PubMed database for recently published literatures up to December 2017. We used the keywords of "hypertension", "cerebral small vessel disease", "white matter lesions", "enlarged perivascular spaces", "lacunar infarcts", "cerebral microbleeds", and "cognitive impairment" in the database of PubMed. Articles were obtained and reviewed to analyze the hypertension-induced pathophysiological changes that occur in CSVD and the correlation between CSVD and cognitive impairment. In recent years, studies have demonstrated that hypertension-related changes (e.g., small vascular lesions, inflammatory reactions, hypoperfusion, oxidative stress, damage to autoregulatory processes and the blood-brain barrier, and cerebral amyloid angiopathy) can occur over time in cerebral small vessels, potentially leading to lower cognitive function when blood pressure (BP) control is poor or lacking. Both isolated and co-occurrent CSVD can lead to cognitive deterioration, and this effect may be attributable to a dysfunction in either the cholinergic system or the functionality of cortical and subcortical tracts. We explore the currently available evidence about the hypertensive vasculopathy and inflammatory changes that occur in CSVD. Both are vital prognostic indicators of the development of cognitive impairment. Future studies should be performed to validate the relationship between BP levels and CSVD progression and between the numbers, volumes, and anatomical locations of CSVD and cognitive impairment.

  6. Reduced global brain metabolism but maintained vascular function in amnestic mild cognitive impairment.

    PubMed

    Thomas, Binu P; Sheng, Min; Tseng, Benjamin Y; Tarumi, Takashi; Martin-Cook, Kristen; Womack, Kyle B; Cullum, Munro C; Levine, Benjamin D; Zhang, Rong; Lu, Hanzhang

    2017-04-01

    Amnestic mild cognitive impairment represents an early stage of Alzheimer's disease, and characterization of physiological alterations in mild cognitive impairment is an important step toward accurate diagnosis and intervention of this condition. To investigate the extent of neurodegeneration in patients with mild cognitive impairment, whole-brain cerebral metabolic rate of oxygen in absolute units of µmol O 2 /min/100 g was quantified in 44 amnestic mild cognitive impairment and 28 elderly controls using a novel, non-invasive magnetic resonance imaging method. We found a 12.9% reduction ( p = 0.004) in cerebral metabolic rate of oxygen in mild cognitive impairment, which was primarily attributed to a reduction in the oxygen extraction fraction, by 10% ( p = 0.016). Global cerebral blood flow was not found to be different between groups. Another aspect of vascular function, cerebrovascular reactivity, was measured by CO 2 -inhalation magnetic resonance imaging and was found to be equivalent between groups. Therefore, there seems to be a global, diffuse diminishment in neural function in mild cognitive impairment, while their vascular function did not show a significant reduction.

  7. Retinal Vascular Fractal Dimension, Childhood IQ, and Cognitive Ability in Old Age: The Lothian Birth Cohort Study 1936

    PubMed Central

    Taylor, Adele M.; MacGillivray, Thomas J.; Henderson, Ross D.; Ilzina, Lasma; Dhillon, Baljean; Starr, John M.; Deary, Ian J.

    2015-01-01

    Purpose Cerebral microvascular disease is associated with dementia. Differences in the topography of the retinal vascular network may be a marker for cerebrovascular disease. The association between cerebral microvascular state and non-pathological cognitive ageing is less clear, particularly because studies are rarely able to adjust for pre-morbid cognitive ability level. We measured retinal vascular fractal dimension (D f) as a potential marker of cerebral microvascular disease. We examined the extent to which it contributes to differences in non-pathological cognitive ability in old age, after adjusting for childhood mental ability. Methods Participants from the Lothian Birth Cohort 1936 Study (LBC1936) had cognitive ability assessments and retinal photographs taken of both eyes aged around 73 years (n = 648). IQ scores were available from childhood. Retinal vascular D f was calculated with monofractal and multifractal analysis, performed on custom-written software. Multiple regression models were applied to determine associations between retinal vascular D f and general cognitive ability (g), processing speed, and memory. Results Only three out of 24 comparisons (two eyes × four D f parameters × three cognitive measures) were found to be significant. This is little more than would be expected by chance. No single association was verified by an equivalent association in the contralateral eye. Conclusions The results show little evidence that fractal measures of retinal vascular differences are associated with non-pathological cognitive ageing. PMID:25816017

  8. 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

  9. Fabrication of cerebral aneurysm simulator with a desktop 3D printer

    PubMed Central

    Liu, Yu; Gao, Qing; Du, Song; Chen, ZiChen; Fu, JianZhong; Chen, Bing; Liu, ZhenJie; He, Yong

    2017-01-01

    Now, more and more patients are suffering cerebral aneurysm. However, long training time limits the rapid growth of cerebrovascular neurosurgeons. Here we developed a novel cerebral aneurysm simulator which can be better represented the dynamic bulging process of cerebral aneurysm The proposed simulator features the integration of a hollow elastic vascular model, a skull model and a brain model, which can be affordably fabricated at the clinic (Fab@Clinic), under $25.00 each with the help of a low-cost desktop 3D printer. Moreover, the clinical blood flow and pulsation pressure similar to the human can be well simulated, which can be used to train the neurosurgical residents how to clip aneurysms more effectively. PMID:28513626

  10. Fabrication of cerebral aneurysm simulator with a desktop 3D printer

    NASA Astrophysics Data System (ADS)

    Liu, Yu; Gao, Qing; Du, Song; Chen, Zichen; Fu, Jianzhong; Chen, Bing; Liu, Zhenjie; He, Yong

    2017-05-01

    Now, more and more patients are suffering cerebral aneurysm. However, long training time limits the rapid growth of cerebrovascular neurosurgeons. Here we developed a novel cerebral aneurysm simulator which can be better represented the dynamic bulging process of cerebral aneurysm The proposed simulator features the integration of a hollow elastic vascular model, a skull model and a brain model, which can be affordably fabricated at the clinic (Fab@Clinic), under $25.00 each with the help of a low-cost desktop 3D printer. Moreover, the clinical blood flow and pulsation pressure similar to the human can be well simulated, which can be used to train the neurosurgical residents how to clip aneurysms more effectively.

  11. Behçet syndrome: the vascular cluster.

    PubMed

    Yazıcı, Hasan; Seyahi, Emire

    2016-11-17

    Although skin-mucosa lesions are common in almost all patients with Behçet syndrome (BS), clinical properties may differ from one patient to another. Within BS, there are subsets with different organ involvement and hence probably different pathological pathways. These subsets can be described as a) solo skin-mucosa disease with no major organ involvement, b) eye disease, c) seronegative spondyloarthropathy-like disease (arthritis, enthesopathy, and folliculitis), d) Crohn-like disease, and finally the topic of this chapter: e) vascular disease. In the vascular disease subset, not surprisingly, several types of vascular involvement may be observed in the same individual. These subsets may make up the total clinical picture all at the same time or step by step with each relapse. Significant correlations exist between cerebral vascular thrombosis and pulmonary artery involvement, intracardiac thrombi and pulmonary artery involvement, Budd-Chiari syndrome, and inferior vena cava syndrome. Lower extremity vein thrombosis is often present in these associations and even precedes them. The recognition of these clusters is not only important in diagnosis and management but also in basic science, including genetic studies.

  12. Large-scale subject-specific cerebral arterial tree modeling using automated parametric mesh generation for blood flow simulation.

    PubMed

    Ghaffari, Mahsa; Tangen, Kevin; Alaraj, Ali; Du, Xinjian; Charbel, Fady T; Linninger, Andreas A

    2017-12-01

    In this paper, we present a novel technique for automatic parametric mesh generation of subject-specific cerebral arterial trees. This technique generates high-quality and anatomically accurate computational meshes for fast blood flow simulations extending the scope of 3D vascular modeling to a large portion of cerebral arterial trees. For this purpose, a parametric meshing procedure was developed to automatically decompose the vascular skeleton, extract geometric features and generate hexahedral meshes using a body-fitted coordinate system that optimally follows the vascular network topology. To validate the anatomical accuracy of the reconstructed vasculature, we performed statistical analysis to quantify the alignment between parametric meshes and raw vascular images using receiver operating characteristic curve. Geometric accuracy evaluation showed an agreement with area under the curves value of 0.87 between the constructed mesh and raw MRA data sets. Parametric meshing yielded on-average, 36.6% and 21.7% orthogonal and equiangular skew quality improvement over the unstructured tetrahedral meshes. The parametric meshing and processing pipeline constitutes an automated technique to reconstruct and simulate blood flow throughout a large portion of the cerebral arterial tree down to the level of pial vessels. This study is the first step towards fast large-scale subject-specific hemodynamic analysis for clinical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Chronic Supplementation of Paeonol Combined with Danshensu for the Improvement of Vascular Reactivity in the Cerebral Basilar Artery of Diabetic Rats

    PubMed Central

    Hu, Jing; Li, Ya-Ling; Li, Zi-Lin; Li, Hua; Zhou, Xuan-Xuan; Qiu, Peng-Cheng; Yang, Qian; Wang, Si-Wang

    2012-01-01

    One of the leading causes of death in the world is cerebrovascular disease. Numerous Chinese traditional medicines, such as Cortex Moutan (root bark of Paeonia suffruticosa Andrew) and Radix Salviae miltiorrhizae (root and rhizome of Salvia miltiorrhiza Bunge), protect against cerebrovascular diseases and exhibit anti-atherosclerotic effects. Traditional medicines have been routinely used for a long time in China. In addition, these two herbs are prescribed together in clinical practice. Therefore, the pharmacodynamic interactions between the active constituents of these two herbs, which are paeonol (Pae) and danshensu (DSS), should be particularly studied. The study of Pae and DSS can provide substantial foundations in understanding their mechanisms and empirical evidence to support clinical practice. This study investigated the effects and possible mechanisms of the pharmacodynamic interaction between Pae and DSS on cerebrovascular malfunctioning in diabetes. Experimental diabetes was induced in rats, which was then treated with Pae, DSS, and Pae + DSS for eight weeks. Afterward, cerebral arteries from all groups were isolated and equilibrated in an organ bath with Krebs buffer and ring tension. Effects of Pae, DSS, and Pae + DSS were observed on vessel relaxation with or without endothelium as well as on the basal tonus of vessels from normal and diabetic rats. Indexes about oxidative stress were also determined. We report that the cerebral arteries from diabetic rats show decreased vascular reactivity to acetylcholine (ACh) which was corrected in Pae, DSS, and Pae + DSS treated groups. Furthermore, phenylephrine (PE)-induced contraction response decreased in the treated groups. Phenylephrine and CaCl2-induced vasoconstrictions are partially inhibited in the three treated groups under Ca2+-free medium. Pre-incubated with tetraethylammonium, a non-selective K+ channel blocker, the antagonized relaxation responses increased in DSS and Pae + DSS treated diabetic

  14. Cerebral ischaemia: A neuroradiological study

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

    Bories, J.

    1985-01-01

    After a brief clinical and pathophysiological approach, the papers presented in this book are devoted to CT and angiography. Concerning CT, a particular study has been made of cerebral arterial territories on cuts parallel to the orbito-meatal line: these are very important in making the differential diagnosis from some tumors. Also concerning CT, a paper has been devoted to cerebral ''lacunae.'' The term ''lacuna'' as far as CT imaging is concerned, should be reserved only for those hypodense areas corresponding to small cavities containing fluid, which are sequelae of infarcts in the territory of penetrating arteries. Before this sequellar statemore » come all the evolutive states of a small deep infarct. The angiographic study specifies the indications of angiography in the study of cerebral ischemia, and the techniques to be used. It shows the main etiologic aspects. Because of the important place of vascular surgery today, it seemed necessary to show also the main post operative angiographic aspects. After CT and angiography, some pages are reserved to more modern techniques. Finally, some pages are devoted to certain particular associations and etiologies: childhood, cardiopathies, migraine, oral contraception and end with venous infarction.« less

  15. EPIDEMIOLOGY OF ACCIDENTAL POISONING

    PubMed Central

    Bissell, D. M.; McInnes, Robert S.

    1960-01-01

    In San Jose, California, studies of cases of accidental poisoning showed that the greatest hazard was to children 1 through 3 years of age. Drugs accounted for half the cases, household products for another third, and insecticides and rodenticides and others for the remainder. Most often poison material was within easy reach of the children. An analysis of families in which an accident occurred indicated that accidental poisoning might happen to any family. Since there was little after-effect of poisoning in cases in which treatment was obtained promptly, education directed toward getting prompt treatment seems most advisable. Community agencies interested in poison control need to focus their attention on parents of pre-school children. PMID:13801023

  16. Effects of Sustained Low-Level Elevations of Carbon Dioxide on Cerebral Blood Flow and Autoregulation of the Intracerebral Arteries in Humans

    NASA Technical Reports Server (NTRS)

    Sliwka, U.; Krasney, J. A.; Simon, S. G.; Schmidt, P.

    1996-01-01

    Cerebral blood flow velocity (CBFv) was measured by insonating the middle cerebral arteries of 4 subjects using a 2 Mhz transcranial Doppler. Ambient CO2 was elevated to 0.7% for 23 days in the first study and to 1.2% for 23 days in the same subjects in the second study. By non-parametric testing CBFv was elevated significantly by +35% above pre-exposure levels during the first 1-3 days at both exposure levels after which CBFv progressively readjusted to pre-exposure levels. Despite similar CBFv responses, headache was only reported during the initial phase of exposure to 1.2% CO2. Vascular reactivity to CO2 assessed by rebreathing showed a similar pattern with the CBFv increases early in the exposures being greater than those elicited later. An increase in metabolic rate of the visual cortex was evoked by having the subjects open and close their eyes during a visual stimulus. Evoked CBFv responses measured in the posterior cerebral artery were also elevated in the first 1-3 days of both studies returning to pre-exposure levels as hypercapnia continued. Cerebral vascular autoregulation assessed by raising head pressure during 10 deg head-down tilt both during the low-level exposures and during rebreathing was unaltered. There were no changes in the retinal microcirculation during serial fundoscopy studies. The time-dependent changes in CO2 vascular reactivity might be due either to retention of bicarbonate in brain extracellular fluid or to progressive increases in ventilation, or both. Cerebral vascular autoregulation appears preserved during chronic exposure to these levels of ambient CO2.

  17. Accidental death in autoerotic maneuvers.

    PubMed

    Focardi, Martina; Gualco, Barbara; Norelli, GianAristide

    2008-03-01

    The authors from the Florence Forensic Department present a case that demonstrates the paradigms attached to accidental deaths while performing autoerotic maneuvers. The incidents of such practices are underestimated and are only the tip of the iceberg since they do not represent the cases that are never reported due to successful practice. After analyzing the statistic data, the authors describe the case and discuss about the element that prove the accidental nature of the death and the importance of the correct application of forensic methodology at the scene and in the mortuary.

  18. Protective effects of D-Limonene against transient cerebral ischemia in stroke-prone spontaneously hypertensive rats.

    PubMed

    Wang, Xifeng; Li, Gang; Shen, Wei

    2018-01-01

    Stroke is a leading cause of disability and death world-wide and there is currently a lack of effective treatments for acute stroke. D-Limonene is a common natural monocyclic monoterpene possessing various activities. The present study aimed to evaluate the therapeutic efficacy of D-limonene against ischemia-associated cerebral injury in hypertensive SHRsp rats. Although systolic blood pressure was not altered by ischemia, D-Limonene decreased the systolic blood pressure of SHRsp rats following stroke. Induction of stroke resulted in increased escape latency time, decreased time spent in the target quadrant in the probe trial, decreased capacity to distinguish between familiar objects and novel objects, and increased sensory neglect in the SHRsp rat, however these symptoms were significantly inhibited by D-limonene. D-limonene also decreased the cerebral infarct size in the SHRsp rats following stroke. D-Limonene markedly decreased the mRNA expression of interleukin-1β, monocyte chemoattractant protein-1 and cyclooxygenase-2 in SHRsp rats following stroke. The mRNA expression of vascular endothelial growth factor in the brain of SHRsp rats following stroke was significantly increased by D-Limonene. D-Limonene increased the activities of superoxide dismutase and catalase, decreased the malondialdehyde level, increased glutathione content and reduced the DHE-staining in SHRsp rats following stroke. Overall, inhibition of cerebral inflammation, vascular remodeling and antioxidant activities of D-Limonene may be involved in the protective effects against ischemia-induced damage in SHRsp rats. The present study identified D-Limonene as a potential therapeutic candidate for treatment of stroke-associated cerebral and vascular damage under conditions of hypertension.

  19. Investigation of the cerebral hemodynamic response function in single blood vessels by functional photoacoustic microscopy

    PubMed Central

    Liao, Lun-De; Lin, Chin-Teng; Shih, Yen-Yu I.; Lai, Hsin-Yi; Zhao, Wan-Ting; Duong, Timothy Q.; Chang, Jyh-Yeong; Chen, You-Yin

    2012-01-01

    Abstract. The specificity of the hemodynamic response function (HRF) is determined spatially by the vascular architecture and temporally by the evolution of hemodynamic changes. Here, we used functional photoacoustic microscopy (fPAM) to investigate single cerebral blood vessels of rats after left forepaw stimulation. In this system, we analyzed the spatiotemporal evolution of the HRFs of the total hemoglobin concentration (HbT), cerebral blood volume (CBV), and hemoglobin oxygen saturation (SO2). Changes in specific cerebral vessels corresponding to various electrical stimulation intensities and durations were bilaterally imaged with 36×65-μm2 spatial resolution. Stimulation intensities of 1, 2, 6, and 10 mA were applied for periods of 5 or 15 s. Our results show that the relative functional changes in HbT, CBV, and SO2 are highly dependent not only on the intensity of the stimulation, but also on its duration. Additionally, the duration of the stimulation has a strong influence on the spatiotemporal characteristics of the HRF as shorter stimuli elicit responses only in the local vasculature (smaller arterioles), whereas longer stimuli lead to greater vascular supply and drainage. This study suggests that the current fPAM system is reliable for studying relative cerebral hemodynamic changes, as well as for offering new insights into the dynamics of functional cerebral hemodynamic changes in small animals. PMID:22734740

  20. Molecular mechanisms and cell signaling of 20-hydroxyeicosatetraenoic acid in vascular pathophysiology

    PubMed Central

    Fan, Fan; Ge, Ying; Lv, Wenshan; Elliott, Matthew R.; Muroya, Yoshikazu; Hirata, Takashi; Booz, George W.; Roman, Richard J.

    2016-01-01

    Cytochrome P450s enzymes catalyze the metabolism of arachidonic acid to epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid and hydroxyeicosatetraeonic acid (HETEs). 20-HETE is a vasoconstrictor that depolarizes vascular smooth muscle cells by blocking K+ channels. EETs serve as endothelial derived hyperpolarizing factors. Inhibition of the formation of 20-HETE impairs the myogenic response and autoregulation of renal and cerebral blood flow. Changes in the formation of EETs and 20-HETE have been reported in hypertension and drugs that target these pathways alter blood pressure in animal models. Sequence variants in CYP4A11 and CYP4F2 that produce 20-HETE, UDP-glucuronosyl transferase involved in the biotransformation of 20-HETE and soluble epoxide hydrolase that inactivates EETs are associated with hypertension in human studies. 20-HETE contributes to the regulation of vascular hypertrophy, restenosis, angiogenesis and inflammation. It also promotes endothelial dysfunction and contributes to cerebral vasospasm and ischemia-reperfusion injury in the brain, kidney and heart. This review will focus on the role of 20-HETE in vascular dysfunction, inflammation, ischemic and hemorrhagic stroke and cardiac and renal ischemia reperfusion injury. PMID:27100515

  1. The Effects of Obesity on the Cerebral Vasculature

    PubMed Central

    Dorrance, Anne M; Matin, Nusrat; Pires, Paulo W

    2016-01-01

    The incidence of obesity in the population is increasing at an alarming rate, with this comes an increased risk of insulin resistance (IR). Obesity and IR increase an individual’s risk of having a stroke and they have been linked to several forms of dementia. Stroke and dementia are associated with, or exacerbated by, reduced cerebral blood flow, which has recently been described in obese patients. In this review we will discuss the effects of obesity on cerebral artery function and structure. Regarding their function, we will focus on the endothelium and nitric oxide (NO) dependent dilation. NO dependent dilation is impaired in cerebral arteries from obese rats, and the majority of evidence suggests this is a result of increased oxidative stress. We will also describe the limited studies showing that inward cerebral artery remodeling occurs in models of obesity, and that the remodeling is associated with an increase in the damage caused by cerebral ischemia. We will also discuss some of the more paradoxical findings associated with stroke and obesity, including the evidence that obesity is a positive factor for stroke survival. Finally we will discuss the evidence that links these changes in vascular structure and function to cognitive decline and dementia. PMID:24846235

  2. Upregulation of Fibronectin and the α5β1 and αvβ3 Integrins on Blood Vessels within the Cerebral Ischemic Penumbra

    PubMed Central

    Li, Longxuan; Liu, Fudong; Welser-Alves, Jennifer V.; McCullough, Louise D.; Milner, Richard

    2012-01-01

    Following focal cerebral ischemia, blood vessels in the ischemic border, or penumbra, launch an angiogenic response. In light of the critical role for fibronectin in angiogenesis, and the observation that fibronectin and its integrin receptors are strongly upregulated on angiogenic vessels in the hypoxic CNS, the aim of this study was to establish whether angiogenic vessels in the ischemic CNS also show this response. Focal cerebral ischemia was established in C57/Bl6 mice by middle cerebral artery occlusion (MCA:O), and brain tissue analyzed seven days following re-perfusion, a time at which angiogenesis is ongoing. Within the ischemic core, immunofluorescent (IF) studies demonstrated vascular expression of MECA-32, a marker of leaky cerebral vessels, and vascular breakdown, defined by loss of staining for the endothelial marker, CD31, and the vascular adhesion molecules, laminin, dystroglycan and α6 integrin. Within the ischemic penumbra, dual-IF with CD31 and Ki67 revealed the presence of proliferating endothelial cells, indicating ongoing angiogenesis. Significantly, vessels in the ischemic penumbra showed strong upregulation of fibronectin and the fibronectin receptors, α5β1 and αvβ3 integrins. Taken together with our recent finding that the α5β1 integrin plays an important role in promoting cerebral angiogenesis in response to hypoxia, these results suggest that stimulation of the fibronectin-α5β1 integrin signalling pathway may provide a novel approach to amplifying the intrinsic angiogenic response to cerebral ischemia. PMID:22056225

  3. [Hyperbaric oxygen therapy and inert gases in cerebral ischemia and traumatic brain injury].

    PubMed

    Chhor, V; Canini, F; De Rudnicki, S; Dahmani, S; Gressens, P; Constantin, P

    2013-12-01

    Cerebral ischemia is a common thread of acute cerebral lesions, whether vascular or traumatic origin. Hyperbaric oxygen (HBO) improves tissue oxygenation and may prevent impairment of reversible lesions. In experimental models of cerebral ischemia or traumatic brain injury, HBO has neuroprotective effects which are related to various mechanisms such as modulation of oxidative stress, neuro-inflammation or cerebral and mitochondrial metabolism. However, results of clinical trials failed to prove any neuroprotective effects for cerebral ischemia and remained to be confirmed for traumatic brain injury despite preliminary encouraging results. The addition of inert gases to HBO sessions, especially argon or xenon which show neuroprotective experimental effects, may provide an additional improvement of cerebral lesions. Further multicentric studies with a strict methodology and a better targeted definition are required before drawing definitive conclusions about the efficiency of combined therapy with HBO and inert gases in acute cerebral lesions. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

  4. Vascular Contributions to Cognitive Impairment and Dementia

    PubMed Central

    Gorelick, Philip B.; Scuteri, Angelo; Black, Sandra E.; DeCarli, Charles; Greenberg, Steven M.; Iadecola, Costantino; Launer, Lenore J.; Laurent, Stephane; Lopez, Oscar L.; Nyenhuis, David; Petersen, Ronald C.; Schneider, Julie A.; Tzourio, Christophe; Arnett, Donna K.; Bennett, David A.; Chui, Helena C.; Higashida, Randall T.; Lindquist, Ruth; Nilsson, Peter M.; Roman, Gustavo C.; Sellke, Frank W.; Seshadri, Sudha

    2013-01-01

    Background and Purpose This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment and dementia of later life are common. Definitions of vascular cognitive impairment (VCI), neuropathology, basic science and pathophysiological aspects, role of neuroimaging and vascular and other associated risk factors, and potential opportunities for prevention and treatment are reviewed. This statement serves as an overall guide for practitioners to gain a better understanding of VCI and dementia, prevention, and treatment. Methods Writing group members were nominated by the writing group co-chairs on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council Scientific Statement Oversight Committee, the Council on Epidemiology and Prevention, and the Manuscript Oversight Committee. The writing group used systematic literature reviews (primarily covering publications from 1990 to May 1, 2010), previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, formulate recommendations using standard American Heart Association criteria. All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. After peer review by the American Heart Association, as well as review by the Stroke Council leadership, Council on Epidemiology and Prevention Council, and Scientific Statements Oversight Committee, the statement was approved by the American Heart Association Science Advisory and Coordinating Committee. Results The construct of VCI has been introduced to capture the entire spectrum of cognitive disorders associated with all forms of cerebral vascular brain injury—not solely stroke—ranging from mild cognitive impairment through fully developed

  5. Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) with multiple vascular complications misdiagnosed as Dubowitz syndrome.

    PubMed

    Dieks, Jana-Katharina; Baumer, Alessandra; Wilichowski, Ekkehard; Rauch, Anita; Sigler, Matthias

    2014-09-01

    To date, the genetic basis of Dubowitz syndrome (short stature, microcephaly, facial abnormalities, eczema) is unknown and vascular complications are not known to be associated with this syndrome. In microcephalic osteodysplastic primordial dwarfism type II (MOPD II; disproportionate short statue, microcephaly, facial abnormalities), however, cerebral aneurysms and other vascular abnormalities are frequent complications. MOPD II is a genetic disorder caused by mutations in the pericentrin (PCNT) gene (21q22). We report on a patient who came to our attention as a 22-year-old with subarachnoid bleeding due to a ruptured cranial aneurysm. Until then, the patient was thought and published to have Dubowitz syndrome; previously, he was treated with coronary bypass surgery for extensive coronary angiopathy. Consecutive genetic testing revealed MOPD II. After clinical stabilization, the patient was discharged to a specialized rehabilitation center where he died due to re-rupture of a cranial aneurysm. In patients with short stature-especially when clinical features are accompanied by vascular complications-MOPD II should be considered as a differential diagnosis leading to consecutive genetic testing. After detection of mutations in the PCNT gene, a full vascular status including cerebral imaging and cardiac evaluation needs to be determined in order to analyze vascular abnormalities and initiate prophylactic treatment.

  6. The development of cerebral amyloid angiopathy in cerebral vessels. A review with illustrations based upon own investigated post mortem cases.

    PubMed

    Mendel, T A; Wierzba-Bobrowicz, T; Lewandowska, E; Stępień, T; Szpak, G M

    2013-12-01

    The process of β-amyloid accumulation in cerebral vessels is presented. Cerebral amyloid angiopathy (CAA) was confirmed during an autopsy. It was diagnosed according to the Boston criteria. Cerebral amyloid angiopathy can involve all kinds of cerebral vessels (cortical and leptomeningeal arterioles, capillaries and veins). The development of CAA is a progressive process. β-amyloid appears first in the tunica media, surrounding smooth muscle cells, and in the adventitia. β-amyloid is progressively accumulated, causing a gradual loss of smooth muscle cells in the vessel wall and finally replacing them. Then, the detachment and delamination of the outer part of the tunica media results in the "double barrel" appearance, fibrinoid necrosis, and microaneurysm formation. Microbleeding with perivascular deposition of erythrocytes and blood breakdown products can also occur. β-amyloid can also be deposited in the surrounding of the affected vessels of the brain parenchyma, known as "dysphoric CAA". Ultrastructurally, when deposits of amyloid fibers were localized in or outside the arteriolar wall, the degenerating vascular smooth muscle cells were observed. In the Institute of Psychiatry and Neurology the study was carried out in a group of 48 patients who died due to intracerebral hemorrhage caused by sporadic CAA.

  7. About Assessment Criteria of Driver's Accidental Abilities

    ERIC Educational Resources Information Center

    Lobanova, Yuliya I.; Glushko, Kirill V.

    2016-01-01

    The article points at the importance of studying the human factor as a cause of accidents of drivers, especially in loosely structured traffic situations. The description of the experiment on the measurement of driver's accidental abilities is given. Under accidental ability is meant the capability to ensure the security of driving as a behavior…

  8. Accidental awareness during general anaesthesia - a narrative review.

    PubMed

    Tasbihgou, S R; Vogels, M F; Absalom, A R

    2018-01-01

    Unintended accidental awareness during general anaesthesia represents failure of successful anaesthesia, and so has been the subject of numerous studies during the past decades. As return to consciousness is both difficult to describe and identify, the reported incidence rates vary widely. Similarly, a wide range of techniques have been employed to identify cases of accidental awareness. Studies which have used the isolated forearm technique to identify responsiveness to command during intended anaesthesia have shown remarkably high incidences of awareness. For example, the ConsCIOUS-1 study showed an incidence of responsiveness around the time of laryngoscopy of 1:25. On the other hand, the 5th Royal College of Anaesthetists National Audit Project, which reported the largest ever cohort of patients who had experienced accidental awareness, used a system to identify patients who spontaneously self-reported accidental awareness. In this latter study, the incidence of accidental awareness was 1:19,600. In the recently published SNAP-1 observational study, in which structured postoperative interviews were performed, the incidence was 1:800. In almost all reported cases of intra-operative responsiveness, there was no subsequent explicit recall of intra-operative events. To date, there is no evidence that this occurrence has any psychological consequences. Among patients who experience accidental awareness and can later remember details of their experience, the consequences are better known. In particular, when awareness occurs in a patient who has been given neuromuscular blocking agents, it may result in serious sequelae such as symptoms of post-traumatic stress disorder and a permanent aversion to surgery and anaesthesia, and is feared by patients and anaesthetists. In this article, the published literature on the incidence, consequences and management of accidental awareness under general anaesthesia with subsequent recall will be reviewed. © 2017 The Association

  9. Modelling Cerebral Blood Flow and Temperature Using a Vascular Porous Model

    NASA Astrophysics Data System (ADS)

    Blowers, Stephen; Thrippleton, Michael; Marshall, Ian; Harris, Bridget; Andrews, Peter; Valluri, Prashant

    2016-11-01

    Macro-modelling of cerebral blood flow can assist in determining the impact of temperature intervention to reduce permanent tissue damage during instances of brain trauma. Here we present a 3D two phase fluid-porous model for simulating blood flow through the capillary region linked to intersecting 1D arterial and venous vessel trees. This combined vasculature porous (VaPor) model simulates both flow and energy balances, including heat from metabolism, using a vasculature extracted from MRI data which are expanded upon using a tree generation algorithm. Validation of temperature balance has been achieved using rodent brain data. Direct flow validation is not as straight forward due to the method used in determining regional cerebral blood flow (rCBF). In-vivo measurements are achieved using a tracer, which disagree with direct measurements of simulated flow. However, by modelling a virtual tracer, rCBF values are obtained that agree with those found in literature. Temperature profiles generated with the VaPor model show a reduction in core brain temperature after cooling the scalp not seen previously in other models.

  10. 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.

  11. 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.

  12. l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease: A systematic review.

    PubMed

    Karlsson, William K; Sørensen, Caspar G; Kruuse, Christina

    2017-01-01

    Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and N G -monomethyl-l-arginine (l-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible according to inclusion and exclusion criteria. Studies investigated the effect of age (n=2), type 2 diabetes mellitus (DM) (n=1), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (n=1), leukoaraiosis (n=1), and prior ischaemic stroke or transient ischaemic attack (TIA) (n=2) on cerebral ED. Most studies applied transcranial Doppler to quantify cerebral ED. Endothelium-dependent vasodilatation (EDV) induced by l-arginine was impaired in elderly and subjects with leukoaraiosis, but enhanced in CADASIL patients. Studies including subjects with prior ischaemic stroke or TIA reported both enhanced and impaired EDV to l-arginine. Responses to l-NMMA deviated between subjects with type 2 DM and the elderly. We found only few studies investigating cerebral endothelial responses to l-arginine and l-NMMA in subjects with vascular risk factors or ischaemic cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease. © 2016 John Wiley & Sons Australia, Ltd.

  13. Scaling and Multifractality in Road Accidental Distances

    NASA Astrophysics Data System (ADS)

    Qiu, Tian; Wan, Chi; Zou, Xiang-Xiang; Wang, Xiao-Fan

    Accidental distance dynamics is investigated, based on the road accidental data of the Great Britain. The distance distribution of all the districts as an ensemble presents a power law tail, which is different from that of the individual district. A universal distribution is found for different districts, by rescaling the distribution functions of individual districts, which can be well fitted by the Weibull distribution. The male and female drivers behave similarly in the distance distribution. The multifractal characteristic is further studied for the individual district and all the districts as an ensemble, and different behaviors are also revealed between them. The accidental distances of the individual district show a weak multifractality, whereas of all the districts present a strong multifractality when taking them as an ensemble.

  14. The effects of adaptive servo ventilation on cerebral vascular reactivity in patients with congestive heart failure and sleep-disordered breathing.

    PubMed

    Morrell, Mary J; Meadows, Guy E; Hastings, Peter; Vazir, Ali; Kostikas, Konstantinos; Simonds, Anita K; Corfield, Douglas R

    2007-05-01

    Hypercapnic cerebral vascular reactivity (HCVR) is reduced in patients with congestive heart failure (CHF) and sleep-disordered breathing (SDB); this may be associated with an increased risk of stroke. We tested the hypothesis that reversal of SDB in CHF patients using adaptive servo ventilation (ASV) would increase morning HCVR. Interventional, cross-over clinical study. Research sleep laboratory. Ten CHF patients with SDB, predominantly obstructive sleep apnea. The HCVR was measured from the change in middle cerebral artery velocity, using pulsed Doppler ultrasound. HCVR was determined during the evening (before) and morning (after) 1 night of sleep on ASV and 1 night of spontaneous sleep (control). Compared with the control situation, ASV decreased the apnea-hypopnea index (group mean +/- SEM, control: 48 +/- 12, ASV: 4 +/- 1 events per hour). HCVR was 23% lower in the morning, compared with the evening, on the control night (evening: 1.3 +/- 0.2, morning: 1.0 +/- 0.2 cm/sec per mm Hg, P < 0.05) and 27% lower following the ASV night (evening: 1.5 +/- 0.2, morning: 1.1 +/- 0.2 cm/sec per mm Hg, P < 0.05). The effect of ASV on the evening-to-morning reduction in HCVR was not significant, compared with the control night (0.02 cm/sec per mm Hg, 95% confidence interval: -0.28, 0.32 P = 0.89). In CHF patients with SDB, HCVR was reduced in the morning compared with the evening. However, removal of SDB for 1 night did not reverse the reduced HCVR. The relatively low morning HCVR could be linked with an increased risk of stroke.

  15. Course Management Systems for Learning: Beyond Accidental Pedagogy

    ERIC Educational Resources Information Center

    McGee, Patricia; Carmean, Colleen; Jafari, Ali

    2005-01-01

    "Course Management Systems for Learning: Beyond Accidental Pedagogy" is a comprehensive overview of standards, practices and possibilities of course management systems in higher education. "Course Management Systems for Learning: Beyond Accidental Pedagogy" focuses on what the current knowledge is (in best practices, research, standards and…

  16. Summary of Research Adaptions of Visceral and Cerebral Resistance Arteries to Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Delp, Michael

    2003-01-01

    The proposed studies were designed address the effects of simulated microgravity on vascular smooth muscle and endothelial cell function in resistance arteries isolated from visceral tissues (spleen, mesentery and kidneys) and cerebrum. Alterations in vascular function induced by microgravity are particularly relevant to the problems of orthostatic intolerance and reduced exercise capacity experienced by astronauts upon re-entry into the earth's gravitational field. Decrements in contractile function or enhanced vasodilatory responsiveness of peripheral resistance arteries could lead to decreased peripheral resistance and orthostatic hypotension. Alternatively, augmentation of contractile function in cerebral resistance arteries could lead to increased cerebral vascular resistance and diminished perfusion of the brain. The Specific Aims and hypotheses were proposed in this grant. Following each of the Specific Aims, progress toward addressing that specific aim is presented. With the exception of Specific Aim VI (see aim for details), all aims have been experimentally addressed as proposed. The final six months of the granting period will be used for manuscript preparation; manuscripts in preparation will contain results from Specific Aims I-IV. Results from Specific Aims V and VI have been published.

  17. 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.

  18. [The magneto-, photo- and laser therapy of headaches in patients with vascular brain lesions].

    PubMed

    Troshin, V D; Miasnikov, I G; Belousova, T E

    1994-01-01

    To manage vascular cephalalgia, a combined approach is proposed: segmentally oriented magnetic, photo- and photomagnetic therapy plus intravenous laser treatment. The effect was directly correlated with cerebral hemodynamic condition, damage to vegetative innervation segmental-peripheral link and physiotherapeutic factors.

  19. Reversible cerebral vasoconstriction syndrome with involvement of external carotid artery branches.

    PubMed

    Shaik, S; Chhetri, S K; Roberts, G; Wuppalapati, S; Emsley, H C A

    2014-07-01

    A 44-year-old woman presented with recurrent episodes of thunderclap headache. Neurological examination and computed tomography brain imaging were unremarkable. Cerebrospinal fluid findings were consistent with subarachnoid hemorrhage. Computed tomography angiography of the circle of Willis showed multiple areas of segmental vasoconstriction. This finding was confirmed on cerebral catheter angiography, with segmental vasoconstriction involving bilateral internal carotid, posterior cerebral, and external carotid branches. No aneurysm or other vascular abnormality was identified. She received treatment with nimodipine. A selective serotonin reuptake inhibitor, started 4 weeks earlier, was discontinued. Follow-up angiography after 3 months demonstrated complete resolution of the segmental vasoconstriction, confirming the diagnosis of reversible cerebral vasoconstriction syndrome (RCVS). She remained headache free at follow-up. To our knowledge, external carotid artery branch involvement in RCVS has been described only in one previous occasion.

  20. Cigarette Smoke and Inflammation: Role in Cerebral Aneurysm Formation and Rupture

    PubMed Central

    Chalouhi, Nohra; Ali, Muhammad S.; Starke, Robert M.; Jabbour, Pascal M.; Tjoumakaris, Stavropoula I.; Gonzalez, L. Fernando; Rosenwasser, Robert H.; Koch, Walter J.; Dumont, Aaron S.

    2012-01-01

    Smoking is an established risk factor for subarachnoid hemorrhage yet the underlying mechanisms are largely unknown. Recent data has implicated a role of inflammation in the development of cerebral aneurysms. Inflammation accompanying cigarette smoke exposure may thus be a critical pathway underlying the development, progression, and rupture of cerebral aneurysms. Various constituents of the inflammatory response appear to be involved including adhesion molecules, cytokines, reactive oxygen species, leukocytes, matrix metalloproteinases, and vascular smooth muscle cells. Characterization of the molecular basis of the inflammatory response accompanying cigarette smoke exposure will provide a rational approach for future targeted therapy. In this paper, we review the current body of knowledge implicating cigarette smoke-induced inflammation in cerebral aneurysm formation/rupture and attempt to highlight important avenues for future investigation. PMID:23316103

  1. The Accidental Transgressor: Morally Relevant Theory of Mind

    PubMed Central

    Killen, Melanie; Mulvey, Kelly Lynn; Richardson, Cameron; Jampol, Noah

    2014-01-01

    To test young children’s false belief theory of mind in a morally relevant context, two experiments were conducted. In Experiment 1, children (N = 162) at 3.5, 5.5, and 7.5 years of age were administered 3 tasks: prototypic moral transgression task, false belief theory of mind task (ToM), and an “accidental transgressor” task, which measured a morally relevant false belief theory of mind (MoToM). Children who did not pass false belief ToM were more likely to attribute negative intentions to an accidental transgressor than children who passed false belief ToM, and to use moral reasons when blaming the accidental transgressor. In Experiment 2, children (N = 46) who did not pass false belief ToM viewed it as more acceptable to punish the accidental transgressor than did participants who passed false belief ToM. Findings are discussed in light of research on the emergence of moral judgment and theory of mind. PMID:21377148

  2. On the history of lacunes, etat criblé, and the white matter lesions of vascular dementia.

    PubMed

    Román, Gustavo C

    2002-01-01

    The history of lesions associated with vascular dementia (17th to 19th century) is reviewed. Recognition of ischemic and hemorrhagic stroke types dates back to the 17th century; however, at that time a third type ('cerebral congestion') emerged as the most common form of apoplexy. This entity vanished as arterial hypertension became established with the introduction of the sphygmomanometer (1905). Before the 19th century, apoplexy was considered a uniformly fatal disease, although Willis first recognized post-stroke dementia in 1672. Dechambre (1838) first reported 'lacunes' in stroke survivors with small cerebral softenings. Durand-Fardel (1842) described interstitial atrophy of the brain (leukoaraiosis) and état criblé (cribriform state) reflecting chronic cerebral congestion. In 1894, Alzheimer and Binswanger identified 'arteriosclerotic brain atrophy,' a form of vascular dementia characterized by 'miliary apoplexies' (lacunes). Also in 1894, Binswanger described the disease that now bears his name. In 1901, Pierre Marie coined the name état lacunaire (lacunar state) for the clinical syndrome of elderly patients with multiple lacunes. Copyright 2002 S. Karger AG, Basel

  3. Intraoperative indocyanine green videoangiography for spinal vascular lesions: case report.

    PubMed

    Murakami, Tomohiro; Koyanagi, Izumi; Kaneko, Takahisa; Iihoshi, Satoshi; Houkin, Kiyohiro

    2011-03-01

    In surgery of spinal vascular lesions such as spinal arteriovenous fistula or vascular tumors, assessment of feeding arteries and draining veins is important. Intraoperative digital subtraction angiography is useful but is invasive and sometimes technically demanding. Near-infrared indocyanine green (ICG) videoangiography is less invasive and has been reported as an intraoperative diagnosis of arterial patency during clipping surgery of cerebral aneurysms or bypass surgeries. We present our experience with intraoperative ICG videoangiography in 3 cases of spinal vascular lesions. Two patients had spinal arteriovenous fistula (perimedullary, n = 1; dural, n = 1), and 1 patient had spinal cord hemangioblastoma at the thoracic or thoracolumbar level. The surgical microscope was an OPMI Pentero (Carl Zeiss, Oberkochen, Germany). After laminectomy and opening of the dura, ICG (5 mg) was injected intravenously. The ICG angiography clearly demonstrated feeding and draining vessels. The ICG findings greatly helped successful interruption of arteriovenous fistula and total removal of the tumor. Intraoperative ICG videoangiography for spinal vascular lesions was useful by providing information on vascular dynamics directly. However, the diagnostic area is limited to the field of the surgical microscope. Although intraoperative digital subtraction angiography is still needed in cases of complex spinal vascular lesions, ICG videoangiography will be an important diagnostic modality in the field of spinal vascular surgeries.

  4. Effects of hyper +Gz acceleration on cardiovascular function, visual evoked potentials and cerebral blood flow in anesthetized rats.

    PubMed

    Matsunami, K; Satake, H; Konishi, T

    1998-07-01

    Sustained hyper-gravity acceleration, particularly along the long axis of the body of animals or man (Gz), produces significant mal-effects on subjects, and hence it has been well studied, The most common syndromes of Gz application were cardio-vascular de-conditioning, and black-out, red-out, and loss of consciousness, which finally lead subjects into death. However, in most previous studies, the duration of applied Gz was rather short. In the present experiments, we can use longer duration of 1000 seconds. In addition, recent technological innovation make it possible to record directly local cerebral blood flow at a target cortical area with a Laser Doppler flow meter. We used this innovated method to measure local cerebral blood flow of rats in relation to visual evoked potentials (VEPs) under hyper-Gz acceleration. Also we recorded cardio-vascular parameters like heart rate from ECG, systolic and diastolic blood pressure and correlated them with cerebral blood flow and VEPs.

  5. Vinpocetine suppresses pathological vascular remodeling by inhibiting vascular smooth muscle cell proliferation and migration.

    PubMed

    Cai, Yujun; Knight, Walter E; Guo, Shujie; Li, Jian-Dong; Knight, Peter A; Yan, Chen

    2012-11-01

    Abnormal vascular smooth muscle cell (SMC) activation is associated with various vascular disorders such as atherosclerosis, in-stent restenosis, vein graft disease, and transplantation-associated vasculopathy. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. However, its role in pathological vascular remodeling remains unexplored. Herein, we show that systemic administration of vinpocetine significantly reduced neointimal formation in carotid arteries after ligation injury. Vinpocetine also markedly decreased spontaneous remodeling of human saphenous vein explants in ex vivo culture. In cultured SMCs, vinpocetine dose-dependently suppressed cell proliferation and caused G1-phase cell cycle arrest, which is associated with a decrease in cyclin D1 and an increase in p27Kip1 levels. In addition, vinpocetine dose-dependently inhibited platelet-derived growth factor (PDGF)-stimulated SMC migration as determined by the two-dimensional migration assays and three-dimensional aortic medial explant invasive assay. Moreover, vinpocetine significantly reduced PDGF-induced type I collagen and fibronectin expression. It is noteworthy that PDGF-stimulated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), but not protein kinase B, was specifically inhibited by vinpocetine. Vinpocetine powerfully attenuated intracellular reactive oxidative species (ROS) production, which largely mediates the inhibitory effects of vinpocetine on ERK1/2 activation and SMC growth. Taken together, our results reveal a novel function of vinpocetine in attenuating neointimal hyperplasia and pathological vascular remodeling, at least partially through suppressing ROS production and ERK1/2 activation in SMCs. Given the safety profile of vinpocetine, this study provides insight into the therapeutic potential of vinpocetine in proliferative vascular disorders.

  6. Vinpocetine Suppresses Pathological Vascular Remodeling by Inhibiting Vascular Smooth Muscle Cell Proliferation and Migration

    PubMed Central

    Cai, Yujun; Knight, Walter E.; Guo, Shujie; Li, Jian-Dong; Knight, Peter A.

    2012-01-01

    Abnormal vascular smooth muscle cell (SMC) activation is associated with various vascular disorders such as atherosclerosis, in-stent restenosis, vein graft disease, and transplantation-associated vasculopathy. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. However, its role in pathological vascular remodeling remains unexplored. Herein, we show that systemic administration of vinpocetine significantly reduced neointimal formation in carotid arteries after ligation injury. Vinpocetine also markedly decreased spontaneous remodeling of human saphenous vein explants in ex vivo culture. In cultured SMCs, vinpocetine dose-dependently suppressed cell proliferation and caused G1-phase cell cycle arrest, which is associated with a decrease in cyclin D1 and an increase in p27Kip1 levels. In addition, vinpocetine dose-dependently inhibited platelet-derived growth factor (PDGF)-stimulated SMC migration as determined by the two-dimensional migration assays and three-dimensional aortic medial explant invasive assay. Moreover, vinpocetine significantly reduced PDGF-induced type I collagen and fibronectin expression. It is noteworthy that PDGF-stimulated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), but not protein kinase B, was specifically inhibited by vinpocetine. Vinpocetine powerfully attenuated intracellular reactive oxidative species (ROS) production, which largely mediates the inhibitory effects of vinpocetine on ERK1/2 activation and SMC growth. Taken together, our results reveal a novel function of vinpocetine in attenuating neointimal hyperplasia and pathological vascular remodeling, at least partially through suppressing ROS production and ERK1/2 activation in SMCs. Given the safety profile of vinpocetine, this study provides insight into the therapeutic potential of vinpocetine in proliferative vascular disorders. PMID:22915768

  7. [Neuroradiological pattern of peripartum cerebro vascular disease medicating transfer to determine care unit].

    PubMed

    Lakhdar, Rim; Baffoun, Nader; Hammami, Nadia; Nagi, Sonia; Baccar, Kamel; Drissi, Syrine; Kaddour, Chokri

    2012-03-01

    Pregnancy and puerperium are considered a period of a high risk of stroke responsible in a part of the morbidity and mortality in women. Imaging is the pivotal tool to diagnostics and care. To investigate the clinical and imaging features cerebrovascular complications during pregnancy and in post partum period. We report a retrospective analysis of forty four patients (November 2002 - October 2010) admitted in the intensive car department of the national institute of neurology for cerebro-vascular complications during pregnancy and in post partum period. Cerebro-vascular imaging modalities included cerebral computed tomography (CCT) with and without contrast in 94% of cases, magnetic resonance imaging (MRI) in 30.6% of cases completed by venous angiography MRI in 27.2% of cases and angiography MRI of Willis polygon in 11.3% of cases and by cerebral angiography in 13.6% of cases. Posterior reversible encephalopathy syndrome (PRES) is diagnosed in 61.4 % of cases followed by meningo-cerebral haemorrhage (MCH) in 29.5% and finally cerebral venous thrombosis (CVT) and arterial ischemia in 4.5% of cases each one. The cerebro-vascular complications are revelled in 86.3 % of the cases during the postpartum and were associated with the eclampsia or preeclampsia in 90.9 % of the cases (n=40). CCT showed typical lesions of PRES in 23 patients. It confirms the presence of hematoma in the 13 patients with MCH and find hypodense lesion in one case with ischemic stroke. CCT show direct (delta sign) and indirect signs of CVT. MRI confirms the diagnostic of PRES, when done (11 of 12 cases) and show cortical sub cortical hyper signal on T2 and FLAIR and hypo signal on T1 sequences. MRI was normal in one case. It shows hemorrhagic lesion in the 2 cases of MCH, thrombosis in the cases of CVT and ischemic lesion in the cases of ischemic stroke. CCT and MRI done within 48 hours from admission were decisive for early diagnostic and for fast and adequate care. Early recognition of stroke

  8. "Float first and kick for your life": Psychophysiological basis for safety behaviour on accidental short-term cold water immersion.

    PubMed

    Barwood, Martin J; Burrows, Holly; Cessford, Jess; Goodall, Stuart

    2016-02-01

    Accidental cold-water immersion (CWI) evokes the life threatening cold shock response (CSR) which increases the risk of drowning. Consequently, the safety behaviour selected is critical in determining survival; the present advice is to 'float first' and remain stationary (i.e. rest). We examined whether leg only exercise (i.e., treading water; 'CWI-Kick') immediately on CWI could reduce the symptoms of the CSR, offset the reduction in cerebral blood flow that is known to occur and reduce the CSR's symptoms of breathlessness. We also examined whether perceptual responses instinctive to accidental CWI were exacerbated by this alternative behaviour. We contrasted CWI-Kick to a 'CWI-Rest' condition and a thermoneutral control (35°C); 'TN-Rest'. Seventeen participants were tested (9 males, 8 females). All immersions were standardised; water temperature in cold conditions (i.e., 12°C) was matched ±/0.5°C within participant. Middle cerebral artery blood flow velocity (MCAv) and cardiorespiratory responses were measured along with thermal perception (sensation and comfort) and dyspnoea. Data were analysed using repeated measures ANOVA (alpha level of 0.05). MCAv was significantly reduced in CWI-Rest (-6 (9)%; 1st minute of immersion) but was offset by leg only exercise immediately on cold water entry; CWI-Kick MCAv was never different to TN-Rest (-3 (16)% cf. 5 (4)%). All CWI cardiorespiratory and perceptual responses were different to TN-Rest but were not exacerbated by leg only exercise. Treading water may aid survival by offsetting the reduction in brain blood flow velocity without changing the instinctive behavioural response (i.e. perceptions). "Float first - and kick for your life" would be a suitable amendment to the water safety advice. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Egas Moniz: 90 Years (1927-2017) from Cerebral Angiography.

    PubMed

    Artico, Marco; Spoletini, Marialuisa; Fumagalli, Lorenzo; Biagioni, Francesca; Ryskalin, Larisa; Fornai, Francesco; Salvati, Maurizio; Frati, Alessandro; Pastore, Francesco Saverio; Taurone, Samanta

    2017-01-01

    In June 2017 we celebrate the 90th anniversary of the pioneer discovery of cerebral angiography, the seminal imaging technique used for visualizing cerebral blood vessels and vascular alterations as well as other intracranial disorders. Egas Moniz (1874-1955) was the first to describe the use of this revolutionary technique which, until 1975 (when computed tomography, CT, scan was introduced in the clinical practice), was the sole diagnostic tool to provide an imaging of cerebral vessels and therefore alterations due to intracranial pathology. Moniz introduced in the clinical practice this fundamental and important diagnostic tool. The present contribution wishes to pay a tribute to the Portuguese neurosurgeon, who was also a distinguished neurologist and statesman. Despite his tremendous contribution in modern brain imaging, Egas Moniz was awarded the Nobel Prize in Physiology or Medicine in 1949 for prefrontal leucotomy, the neurosurgical intervention nowadays unacceptable, but should rather be remembered for his key contribution to modern brain imaging.

  10. Placental Ischemia Impairs Middle Cerebral Artery Myogenic Responses in the Pregnant Rat

    PubMed Central

    Ryan, Michael J.; Gilbert, Emily L.; Glover, Porter H.; George, Eric M.; Masterson, C. Warren; McLemore, Gerald R.; LaMarca, Babbette; Granger, Joey P.; Drummond, Heather A.

    2011-01-01

    One potential mechanism contributing to the increased risk for encephalopathies in women with preeclampsia is altered cerebral vascular autoregulation resulting from impaired myogenic tone. Whether placental ischemia, a commonly proposed initiator of preeclampsia, alters cerebral vascular function is unknown. This study tested the hypothesis that placental ischemia in pregnant rats (induced by reducing uterine perfusion pressure, RUPP) leads to impaired myogenic responses in middle cerebral arteries (MCA). Mean arterial pressure (in mmHg) was increased by RUPP (135±3) compared with normal pregnant rats (NP, 103±2) and non-pregnant controls (Ctrl, 116±1). MCA from rats sacrificed on gestation day 19 were assessed in a pressure ateriograph under active (+ Ca2+) and passive (0 Ca2+) conditions while luminal pressure was varied between 25 and 150 mmHg. The slope of the relationship between tone and pressure in the MCA was 0.08±0.01 in CTRL rats and was similar in NP rats (0.05±0.01). In the RUPP model of placental ischemia, this relationship was markedly reduced (slope = 0.01±0.00, p<0.05). Endothelial dependent and independent dilation was not different between groups nor was there evidence of vascular remodeling assessed by the wall:lumen ratio and calculated wall stress. The impaired myogenic response associated with brain edema measured by % water content (RUPP p<0.05 vs. CTRL and NP). This study demonstrates that placental ischemia in pregnant rats leads to impaired myogenic tone in the MCA and that the RUPP model is a potentially important tool to examine mechanisms leading to encephalopathy during preeclamptic pregnancies. PMID:22068864

  11. Increased Notch3 Activity Mediates pathological Changes in Structure of Cerebral arteries

    PubMed Central

    Baron-Menguy, Celine; Domenga-Denier, Valérie; Ghezali, Lamia; Faraci, Frank; Joutel, Anne

    2016-01-01

    CADASIL, the most frequent genetic cause of stroke and vascular dementia, is caused by highly stereotyped mutations in the NOTCH3 receptor, which is predominantly expressed in vascular smooth muscle. The well-established TgNotch3R169C mouse model develops characteristic features of the human disease, with deposition of NOTCH3 and other proteins, including TIMP3 (tissue inhibitor of metalloproteinase 3), on brain vessels as well as reduced maximal dilation, and attenuated myogenic tone of cerebral arteries, but without elevated blood pressure. Increased TIMP3 levels were recently shown to be a major determinant of altered myogenic tone. In this study, we investigated the contribution of TIMP3 and Notch3 signaling to the impairment of maximal vasodilator capacity caused by the archetypal R169C mutation. Maximally dilated cerebral arteries in TgNotch3R169C mice exhibited a decrease in lumen diameter over a range of physiological pressures that occurred prior to myogenic tone deficits. This defect was not prevented by genetic reduction of TIMP3 in TgNotch3R169C mice and was not observed in mice overexpressing TIMP3. Knock-in mice with the R169C mutation (Notch3R170C/R170C) exhibited similar reductions in arterial lumen, and both TgNotch3R169C and Notch3R170C/R170C mice showed increased cerebral artery expression of Notch3 target genes. Reduced maximal vasodilation was prevented by conditional reduction of Notch activity in smooth muscle of TgNotch3R169C mice and mimicked by conditional activation of Notch3 in smooth muscle, an effect that was blood pressure-independent. We conclude that increased Notch3 activity mediates reduction in maximal dilator capacity of cerebral arteries in CADASIL and may contribute to reductions in cerebral blood flow. PMID:27821617

  12. Correlation between dynamic contrast-enhanced perfusion MRI relative cerebral blood volume and vascular endothelial growth factor expression in meningiomas.

    PubMed

    Ginat, Daniel T; Mangla, Rajiv; Yeaney, Gabrielle; Schaefer, Pamela W; Wang, Henry

    2012-08-01

    To determine whether there is a correlation between vascular endothelial growth factor (VEGF) expression and cerebral blood flow (CBV) measurements in dynamic contrast-enhanced susceptibility perfusion magnetic resonance imaging (MRI) and to correlate the perfusion characteristics in high- versus low-grade meningiomas. A total of 48 (24 high-grade and 24 low-grade) meningiomas with available dynamic susceptibility-weighted MRI were retrospectively reviewed for maximum CBV and semiquantitative VEGF immunoreactivity. Correlation between normalized CBV and VEGF was made using the Spearman rank test and comparison between CBV in high- versus low-grade meningiomas was made using the Wilcoxon test. There was a significant (P = .01) correlation between normalized maximum CBV and VEGF scores with a Spearman correlation coefficient of 0.37. In addition, there was a significant (P < .01) difference in normalized maximum CBV ratios between high-grade meningiomas (mean 12.6; standard deviation 5.2) and low-grade meningiomas (mean 8.2; standard deviation 5.2). The data suggest that CBV accurately reflects VEGF expression and tumor grade in meningiomas. Perfusion-weighted MRI can potentially serve as a useful biomarker for meningiomas, pending prospective studies. Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.

  13. Increased Notch3 Activity Mediates Pathological Changes in Structure of Cerebral Arteries.

    PubMed

    Baron-Menguy, Celine; Domenga-Denier, Valérie; Ghezali, Lamia; Faraci, Frank M; Joutel, Anne

    2017-01-01

    CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy), the most frequent genetic cause of stroke and vascular dementia, is caused by highly stereotyped mutations in the NOTCH3 receptor, which is predominantly expressed in vascular smooth muscle. The well-established TgNotch3 R169C mouse model develops characteristic features of the human disease, with deposition of NOTCH3 and other proteins, including TIMP3 (tissue inhibitor of metalloproteinase 3), on brain vessels, as well as reduced maximal dilation, and attenuated myogenic tone of cerebral arteries, but without elevated blood pressure. Increased TIMP3 levels were recently shown to be a major determinant of altered myogenic tone. In this study, we investigated the contribution of TIMP3 and Notch3 signaling to the impairment of maximal vasodilator capacity caused by the archetypal R169C mutation. Maximally dilated cerebral arteries in TgNotch3 R169C mice exhibited a decrease in lumen diameter over a range of physiological pressures that occurred before myogenic tone deficits. This defect was not prevented by genetic reduction of TIMP3 in TgNotch3 R169C mice and was not observed in mice overexpressing TIMP3. Knock-in mice with the R169C mutation (Notch3 R170C/R170C ) exhibited similar reductions in arterial lumen, and both TgNotch3 R169C and Notch3 R170C/R170C mice showed increased cerebral artery expression of Notch3 target genes. Reduced maximal vasodilation was prevented by conditional reduction of Notch activity in smooth muscle of TgNotch3 R169C mice and mimicked by conditional activation of Notch3 in smooth muscle, an effect that was blood pressure-independent. We conclude that increased Notch3 activity mediates reduction in maximal dilator capacity of cerebral arteries in CADASIL and may contribute to reductions in cerebral blood flow. © 2016 American Heart Association, Inc.

  14. Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia

    USDA-ARS?s Scientific Manuscript database

    Cerebral ischemia is caused by an interruption of blood flow to the brain which generally leads to irreversible brain damage. Ischemic injury is associated with vascular leakage, inflammation, tissue injury, and cell death. Cellular changes associated with ischemia include impairment of metabolism, ...

  15. Orthostatic hypotension, cerebral hypoperfusion, and visuospatial deficits in Lewy body disorders.

    PubMed

    Robertson, Andrew D; Messner, Michelle A; Shirzadi, Zahra; Kleiner-Fisman, Galit; Lee, Joyce; Hopyan, Julia; Lang, Anthony E; Black, Sandra E; MacIntosh, Bradley J; Masellis, Mario

    2016-01-01

    Orthostatic hypotension and cognitive impairment are two non-motor attributes of Lewy body spectrum disorders that impact independence. This proof-of-concept study examined cerebral blood flow (perfusion) as a mediator of orthostatic hypotension and cognition. In fifteen patients with Lewy body disorders, we estimated regional perfusion using pseudo-continuous arterial spin labeling MRI, and quantified orthostatic hypotension from the change in systolic blood pressure between supine and standing positions. Executive, visuospatial, attention, memory, and language domains were characterized by neuropsychological tests. A matching sample of non-demented adults with cerebral small vessel disease was obtained to contrast perfusion patterns associated with comorbid vascular pathology. Compared to the vascular group, patients with Lewy body disorders exhibited lower perfusion to temporal and occipital lobes than to frontal and parietal lobes (q < 0.05). A greater orthostatic drop in systolic pressure was associated with lower occipito-parietal perfusion in these patients (uncorrected p < 0.005; cluster size ≥ 20 voxels). Although orthostatic hypotension and supine hypertension were strongly correlated (r = -0.79, p < 0.001), the patterns of association for each with perfusion were distinct. Specifically, supine hypertension was associated with high perfusion to anterior and middle cerebral arterial territories, as well as with low perfusion to posterior regions. Perfusion within orthostatic hypotension-defined regions was directly related to performance on visuospatial and attention tasks, independent of dementia severity (p < 0.05). These findings provide new insight that regional cerebral hypoperfusion is related to orthostatic hypotension, and may be involved in domain-specific cognitive deficits in Lewy body disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Pathophysiology of the vascular wall and its relevance for cerebrovascular disorders in aged rodents.

    PubMed

    Popa-Wagner, A; Pirici, D; Petcu, E B; Mogoanta, L; Buga, A-M; Rosen, C L; Leon, R; Huber, J

    2010-08-01

    Chronic hypertension and cerebral amyloid angiopathy (CAA) are the main pathologies which can induce the rupture of cerebral vessels and intracerebral hemorrhages, as a result of degenerative changes in the vascular wall. A lot of progress has been made in this direction since the successful creation of the first mouse model for the study of Alzheimer's disease (AD), as the spectrum of AD pathology includes a plethora of changes found in pure cerebrovascular diseases. We describe here some of these mouse models having important vascular changes that parallel human AD pathology, and more importantly, we show how these models have helped us understand more about the mechanisms that lead to CAA formation. An important cellular event associated with reduced structural and functional recovery after stroke in aged animals is the early formation of a scar in the infarcted region that impairs subsequent neural recovery and repair. We review recent evidence showing that the rapid formation of the glial scar following stroke in aged rats is associated with premature cellular proliferation that originates primarily from the walls of capillaries in the corpus callosum adjacent to the infarcted region. After stroke several vascular mechanisms are turned-on immediately to protect the brain from further damage and help subsequent neuroregeneration and functional recovery. Although does occur after stroke, vasculogenesis is overshadowed in its protective/restorative role by the angiogenesis and arteriogenesis. Understanding the basic mechanisms underlying functional recovery after cerebral stroke in aging subjects is likely to yield new insights into the treatment of brain injury in the clinic.

  17. Lactate transport and receptor actions in cerebral malaria

    PubMed Central

    Mariga, Shelton T.; Kolko, Miriam; Gjedde, Albert; Bergersen, Linda H.

    2014-01-01

    Cerebral malaria (CM), caused by Plasmodium falciparum infection, is a prevalent neurological disorder in the tropics. Most of the patients are children, typically with intractable seizures and high mortality. Current treatment is unsatisfactory. Understanding the pathogenesis of CM is required in order to identify therapeutic targets. Here, we argue that cerebral energy metabolic defects are probable etiological factors in CM pathogenesis, because malaria parasites consume large amounts of glucose metabolized mostly to lactate. Monocarboxylate transporters (MCTs) mediate facilitated transfer, which serves to equalize lactate concentrations across cell membranes in the direction of the concentration gradient. The equalizing action of MCTs is the basis for lactate’s role as a volume transmitter of metabolic signals in the brain. Lactate binds to the lactate receptor GPR81, recently discovered on brain cells and cerebral blood vessels, causing inhibition of adenylyl cyclase. High levels of lactate delivered by the parasite at the vascular endothelium may damage the blood–brain barrier, disrupt lactate homeostasis in the brain, and imply MCTs and the lactate receptor as novel therapeutic targets in CM. PMID:24904266

  18. [Etiologies of cerebral palsy and classical treatment possibilities].

    PubMed

    Maurer, Ute

    2002-01-01

    Cerebral palsy is a non-progressive disorder of the developing brain with different etiologies in the pre-, peri- or postnatal period. The most important of these diseases is cystic periventricular leukomalacia (PVL), followed by intra- and periventricular hemorrhage, hypoxic-ischemic encephalopathy, vascular disorders, infections or brain malformations. The underlying cause is always a damage of the first motor neuron. Prevalence of cerebral palsy in Europe is 2-3 per 1000 live births with a broad spectrum in different birth weight groups. Our own data concerning only pre-term infants in the NICU with birth weight below 1500 g (VLBW) are between 10%-20%. Established classical treatment methods include physiotherapy (Bobath, Vojta, Hippotherapy), methods of speech and occupational therapists (Castillo-Morales, Sensory Integration) and other therapeutical concepts (Petö, Affolter, Frostig).

  19. 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.

  20. Accidental poisoning with "Chinese chalk".

    PubMed

    Martínez-Navarrete, Juan; Loria-Castellanos, Jorge; Nava-Ocampo, Alejandro A

    2008-04-01

    We present a 1.5-year old, 11 kg, female infant with a history of bronchial hyper-responsiveness who accidentally ingested half of a "Chinese chalk". A day later, the infant showed vomiting, cough, fever, drowsiness, and irritability and her clinical conditions progressively worsened. She was admitted to the emergency department with cough, respiratory distress, and hepatomegaly. It has been reported that the chalk may contain deltamethrin and cypermethrin. The patient was successfully treated with supportive therapy. This report identifies "Chinese chalk" as a potential source of accidental poisoning in children and should be considered as part of the differential diagnoses in the emergency rooms since poisoning with these compounds may be misdiagnosed as organophosphate poisoning due to the presentation of similar symptoms.

  1. A Pilot Study Evaluating Cerebral Vasculitis in Kawasaki's Disease.

    PubMed

    Yeom, Jung Sook; Cho, Young Hye; Koo, Chung Mo; Jun, Jin Su; Park, Ji Sook; Park, Eun Sil; Seo, Ji-Hyun; Lim, Jae-Young; Woo, Hyang-Ok; Youn, Hee-Shang

    2018-06-18

    Cerebral vasculitis is thought to be a possible underlying mechanism of severe neurological complications of Kawasaki's disease (KD), such as cerebral infarct or aneurysm rupture. To evaluate the intracranial inflammatory response in patients with acute-stage KD, we measured the levels of cytokines (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) and pentraxin-3 (PTX3) in the cerebrospinal fluid of patients with KD ( n  = 7) and compared the levels to those of the age- and sex-matched febrile control patients (bacterial meningitis [ n  = 5], enteroviral meningitis [ n  = 10], nonspecific viral illness without central nervous system involvement [ n  = 10]). PTX3 and TNF-α were rarely detected and only in trace concentration in KD, and the levels of IL-6 were not different from those of nonspecific viral illnesses. These mediators are not established biomarkers for cerebral vasculitis but might reflect vascular inflammation in various diseases including KD. Therefore, intracranial inflammation including vasculitis seems to be insignificant in our patients with KD. However, our results might be attributed to the fact that these patients lacked any clinical signs of cerebral or coronary vessel involvement. None of them underwent brain imaging. To clarify this issue, further studies involving patients with neurologic symptoms and proven involvement of cerebral vessels are needed. Georg Thieme Verlag KG Stuttgart · New York.

  2. Accidental Nuclear War: The Growing Peril. Part I [and] Part II.

    ERIC Educational Resources Information Center

    Newcombe, Alan, Ed.

    1984-01-01

    Two volumes designed to increase awareness of accidental nuclear war dangers are presented. The first of 5 sections in volume I proposes that although accidental war is preventable, the current arms race and secrecy about accidents and false alarms increase the possibility of an accidental war. Section 2 posits that decreased decision-making time…

  3. Advancement Is Seldom Accidental.

    ERIC Educational Resources Information Center

    Frantzreb, Arthur C.

    1981-01-01

    Success in college goals and programs for institutional advancement is seldom accidental: success in philanthropic support is seen as 90 percent planning and 10 percent implementation. Trustee membership, long-range plans, the motivational case, experienced staff, adequate budgets, prospect research, supportive communication all meld into a plan…

  4. CD8+ T Cells Induce Fatal Brainstem Pathology during Cerebral Malaria via Luminal Antigen-Specific Engagement of Brain Vasculature

    PubMed Central

    Swanson, Phillip A.; Hart, Geoffrey T.; Russo, Matthew V.; Nayak, Debasis; Yazew, Takele; Peña, Mirna; Khan, Shahid M.; Pierce, Susan K.; McGavern, Dorian B.

    2016-01-01

    Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection that results in thousands of deaths each year, mostly in African children. The in vivo mechanisms underlying this fatal condition are not entirely understood. Using the animal model of experimental cerebral malaria (ECM), we sought mechanistic insights into the pathogenesis of CM. Fatal disease was associated with alterations in tight junction proteins, vascular breakdown in the meninges / parenchyma, edema, and ultimately neuronal cell death in the brainstem, which is consistent with cerebral herniation as a cause of death. At the peak of ECM, we revealed using intravital two-photon microscopy that myelomonocytic cells and parasite-specific CD8+ T cells associated primarily with the luminal surface of CNS blood vessels. Myelomonocytic cells participated in the removal of parasitized red blood cells (pRBCs) from cerebral blood vessels, but were not required for the disease. Interestingly, the majority of disease-inducing parasite-specific CD8+ T cells interacted with the lumen of brain vascular endothelial cells (ECs), where they were observed surveying, dividing, and arresting in a cognate peptide-MHC I dependent manner. These activities were critically dependent on IFN-γ, which was responsible for activating cerebrovascular ECs to upregulate adhesion and antigen-presenting molecules. Importantly, parasite-specific CD8+ T cell interactions with cerebral vessels were impaired in chimeric mice rendered unable to present EC antigens on MHC I, and these mice were in turn resistant to fatal brainstem pathology. Moreover, anti-adhesion molecule (LFA-1 / VLA-4) therapy prevented fatal disease by rapidly displacing luminal CD8+ T cells from cerebrovascular ECs without affecting extravascular T cells. These in vivo data demonstrate that parasite-specific CD8+ T cell-induced fatal vascular breakdown and subsequent neuronal death during ECM is associated with luminal, antigen

  5. In vivo imaging of spontaneous low-frequency oscillations in cerebral hemodynamics with a digital red-green-blue camera

    NASA Astrophysics Data System (ADS)

    Mustari, Afrina; Nakamura, Naoki; Nishidate, Izumi; Kawauchi, Satoko; Sato, Shunichi; Sato, Manabu; Kokobo, Yasuaki

    2017-04-01

    Nervous system relies on a continuous and adequate supply of blood flow, bringing the nutrients that it needs and removing the waste products of metabolism. Failure of these mechanisms is found in a number of devastating cerebral diseases, including stroke, vascular dementia, brain injury and trauma. Vasomotion which is the spontaneous low-frequency oscillation derived by the contraction and relaxation of arterioles and appears to be an intrinsic property of the cerebral vasculature, is important for monitoring the cerebral flow, tissue metabolism and health status of brain tissue. In the present study, we investigated a method to visualize the spontaneous low-frequency oscillation of cerebral blood volume based on the sequential RGB images of exposed brain.

  6. Longitudinal decrease in blood oxygenation level dependent response in cerebral amyloid angiopathy.

    PubMed

    Switzer, Aaron R; McCreary, Cheryl; Batool, Saima; Stafford, Randall B; Frayne, Richard; Goodyear, Bradley G; Smith, Eric E

    2016-01-01

    Lower blood oxygenation level dependent (BOLD) signal changes in response to a visual stimulus in functional magnetic resonance imaging (fMRI) have been observed in cross-sectional studies of cerebral amyloid angiopathy (CAA), and are presumed to reflect impaired vascular reactivity. We used fMRI to detect a longitudinal change in BOLD responses to a visual stimulus in CAA, and to determine any correlations between these changes and other established biomarkers of CAA progression. Data were acquired from 22 patients diagnosed with probable CAA (using the Boston Criteria) and 16 healthy controls at baseline and one year. BOLD data were generated from the 200 most active voxels of the primary visual cortex during the fMRI visual stimulus (passively viewing an alternating checkerboard pattern). In general, BOLD amplitudes were lower at one year compared to baseline in patients with CAA (p = 0.01) but were unchanged in controls (p = 0.18). The longitudinal difference in BOLD amplitudes was significantly lower in CAA compared to controls (p < 0.001). White matter hyperintensity (WMH) volumes and number of cerebral microbleeds, both presumed to reflect CAA-mediated vascular injury, increased over time in CAA (p = 0.007 and p = 0.001, respectively). Longitudinal increases in WMH (rs = 0.04, p = 0.86) or cerebral microbleeds (rs = -0.18, p = 0.45) were not associated with the longitudinal decrease in BOLD amplitudes.

  7. Cranial Nerve Palsy after Onyx Embolization as a Treatment for Cerebral Vascular Malformation

    PubMed Central

    Lee, Jong Min; Whang, Kum; Cho, Sung Min; Kim, Jong Yeon; Oh, Ji Woong; Koo, Youn Moo; Hu, Chul; Pyen, Jinsoo

    2017-01-01

    The Onyx liquid embolic system is a relatively safe and commonly used treatment for vascular malformations, such as arteriovenous fistulas and arteriovenous malformations. However, studies on possible complications after Onyx embolization in patients with vascular malformations are limited, and the occurrence of cranial nerve palsy is occasionally reported. Here we report the progress of two different types of cranial nerve palsy that can occur after embolization. In both cases, Onyx embolization was performed to treat vascular malformations and ipsilateral oculomotor and facial nerve palsies were observed. Both patients were treated with steroids and exhibited symptom improvement after several months. The most common types of neuropathy that can occur after Onyx embolization are facial nerve palsy and trigeminal neuralgia. Although the mechanisms underlying these neuropathies are not clear, they may involve traction injuries sustained while extracting the microcatheter, mass effects resulting from thrombi and edema, or Onyx reflux into the vasa nervorum. In most cases, the neuropathy spontaneously resolves several months following the procedure. PMID:29159152

  8. Cranial Nerve Palsy after Onyx Embolization as a Treatment for Cerebral Vascular Malformation.

    PubMed

    Lee, Jong Min; Whang, Kum; Cho, Sung Min; Kim, Jong Yeon; Oh, Ji Woong; Koo, Youn Moo; Hu, Chul; Pyen, Jinsoo; Choi, Jong Wook

    2017-09-01

    The Onyx liquid embolic system is a relatively safe and commonly used treatment for vascular malformations, such as arteriovenous fistulas and arteriovenous malformations. However, studies on possible complications after Onyx embolization in patients with vascular malformations are limited, and the occurrence of cranial nerve palsy is occasionally reported. Here we report the progress of two different types of cranial nerve palsy that can occur after embolization. In both cases, Onyx embolization was performed to treat vascular malformations and ipsilateral oculomotor and facial nerve palsies were observed. Both patients were treated with steroids and exhibited symptom improvement after several months. The most common types of neuropathy that can occur after Onyx embolization are facial nerve palsy and trigeminal neuralgia. Although the mechanisms underlying these neuropathies are not clear, they may involve traction injuries sustained while extracting the microcatheter, mass effects resulting from thrombi and edema, or Onyx reflux into the vasa nervorum. In most cases, the neuropathy spontaneously resolves several months following the procedure.

  9. Egas Moniz: 90 Years (1927–2017) from Cerebral Angiography

    PubMed Central

    Artico, Marco; Spoletini, Marialuisa; Fumagalli, Lorenzo; Biagioni, Francesca; Ryskalin, Larisa; Fornai, Francesco; Salvati, Maurizio; Frati, Alessandro; Pastore, Francesco Saverio; Taurone, Samanta

    2017-01-01

    In June 2017 we celebrate the 90th anniversary of the pioneer discovery of cerebral angiography, the seminal imaging technique used for visualizing cerebral blood vessels and vascular alterations as well as other intracranial disorders. Egas Moniz (1874–1955) was the first to describe the use of this revolutionary technique which, until 1975 (when computed tomography, CT, scan was introduced in the clinical practice), was the sole diagnostic tool to provide an imaging of cerebral vessels and therefore alterations due to intracranial pathology. Moniz introduced in the clinical practice this fundamental and important diagnostic tool. The present contribution wishes to pay a tribute to the Portuguese neurosurgeon, who was also a distinguished neurologist and statesman. Despite his tremendous contribution in modern brain imaging, Egas Moniz was awarded the Nobel Prize in Physiology or Medicine in 1949 for prefrontal leucotomy, the neurosurgical intervention nowadays unacceptable, but should rather be remembered for his key contribution to modern brain imaging. PMID:28974927

  10. Protective effects of sulphonated formononetin in a rat model of cerebral ischemia and reperfusion injury.

    PubMed

    Zhu, Haibo; Zou, Libo; Tian, Jingwei; Lin, Fei; He, Jie; Hou, Jian

    2014-03-01

    Sodium formononetin-3'-sulphonate is a derivative of the plant isoflavone formononetin. The present study aimed to investigate the neuroprotective and angiogenesis effects of sodium formononetin-3'-sulphonate in vivo and in vitro. Treatment with sodium formononetin-3'-sulphonate (3, 7.5, 15, and 30 mg/kg, intravenous injection) could protect the brain from ischemia and reperfusion injury by improving neurological function, suppressing cell apoptosis, and increasing expression levels of vascular endothelial growth factor and platelet endothelial cell adhesion molecule 1 by middle cerebral artery occlusion. Treatment with sodium formononetin-3'-sulphonate (10 and 20 µg/mL) significantly increased cell migration, tube formation, and vascular endothelial growth factor and platelet endothelial cell adhesion molecule levels in human umbilical vein endothelial cells. Our results suggest that sodium formononetin-3'-sulphonate provides significant neuroprotective effects against cerebral ischemia and reperfusion injury in rats, and improves cerebrovascular angiogenesis in human umbilical vein endothelial cells. The protective mechanisms of sodium formononetin-3'-sulphonate may be attributed to the suppression of cell apoptosis and improved cerebrovascular angiogenesis by promoting vascular endothelial growth factor and platelet endothelial cell adhesion molecule expression. Georg Thieme Verlag KG Stuttgart · New York.

  11. Experimental Cerebral Malaria Pathogenesis—Hemodynamics at the Blood Brain Barrier

    PubMed Central

    Nacer, Adéla; Movila, Alexandru; Sohet, Fabien; Girgis, Natasha M.; Gundra, Uma Mahesh; Loke, P'ng; Daneman, Richard; Frevert, Ute

    2014-01-01

    Cerebral malaria claims the lives of over 600,000 African children every year. To better understand the pathogenesis of this devastating disease, we compared the cellular dynamics in the cortical microvasculature between two infection models, Plasmodium berghei ANKA (PbA) infected CBA/CaJ mice, which develop experimental cerebral malaria (ECM), and P. yoelii 17XL (PyXL) infected mice, which succumb to malarial hyperparasitemia without neurological impairment. Using a combination of intravital imaging and flow cytometry, we show that significantly more CD8+ T cells, neutrophils, and macrophages are recruited to postcapillary venules during ECM compared to hyperparasitemia. ECM correlated with ICAM-1 upregulation on macrophages, while vascular endothelia upregulated ICAM-1 during ECM and hyperparasitemia. The arrest of large numbers of leukocytes in postcapillary and larger venules caused microrheological alterations that significantly restricted the venous blood flow. Treatment with FTY720, which inhibits vascular leakage, neurological signs, and death from ECM, prevented the recruitment of a subpopulation of CD45hi CD8+ T cells, ICAM-1+ macrophages, and neutrophils to postcapillary venules. FTY720 had no effect on the ECM-associated expression of the pattern recognition receptor CD14 in postcapillary venules suggesting that endothelial activation is insufficient to cause vascular pathology. Expression of the endothelial tight junction proteins claudin-5, occludin, and ZO-1 in the cerebral cortex and cerebellum of PbA-infected mice with ECM was unaltered compared to FTY720-treated PbA-infected mice or PyXL-infected mice with hyperparasitemia. Thus, blood brain barrier opening does not involve endothelial injury and is likely reversible, consistent with the rapid recovery of many patients with CM. We conclude that the ECM-associated recruitment of large numbers of activated leukocytes, in particular CD8+ T cells and ICAM+ macrophages, causes a severe restriction in

  12. Vascular depression consensus report - a critical update.

    PubMed

    Aizenstein, Howard J; Baskys, Andrius; Boldrini, Maura; Butters, Meryl A; Diniz, Breno S; Jaiswal, Manoj Kumar; Jellinger, Kurt A; Kruglov, Lev S; Meshandin, Ivan A; Mijajlovic, Milija D; Niklewski, Guenter; Pospos, Sarah; Raju, Keerthy; Richter, Kneginja; Steffens, David C; Taylor, Warren D; Tene, Oren

    2016-11-03

    Vascular depression is regarded as a subtype of late-life depression characterized by a distinct clinical presentation and an association with cerebrovascular damage. Although the term is commonly used in research settings, widely accepted diagnostic criteria are lacking and vascular depression is absent from formal psychiatric manuals such as the Diagnostic and Statistical Manual of Mental Disorders, 5 th edition - a fact that limits its use in clinical settings. Magnetic resonance imaging (MRI) techniques, showing a variety of cerebrovascular lesions, including extensive white matter hyperintensities, subcortical microvascular lesions, lacunes, and microinfarcts, in patients with late life depression, led to the introduction of the term "MRI-defined vascular depression". This diagnosis, based on clinical and MRI findings, suggests that vascular lesions lead to depression by disruption of frontal-subcortical-limbic networks involved in mood regulation. However, despite multiple MRI approaches to shed light on the spatiotemporal structural changes associated with late life depression, the causal relationship between brain changes, related lesions, and late life depression remains controversial. While postmortem studies of elderly persons who died from suicide revealed lacunes, small vessel, and Alzheimer-related pathologies, recent autopsy data challenged the role of these lesions in the pathogenesis of vascular depression. Current data propose that the vascular depression connotation should be reserved for depressed older patients with vascular pathology and evident cerebral involvement. Based on current knowledge, the correlations between intra vitam neuroimaging findings and their postmortem validity as well as the role of peripheral markers of vascular disease in late life depression are discussed. The multifold pathogenesis of vascular depression as a possible subtype of late life depression needs further elucidation. There is a need for correlative clinical

  13. Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria

    PubMed Central

    Freeman, Brandi D.; Martins, Yuri C.; Akide-Ndunge, Oscar B.; Bruno, Fernando P.; Wang, Hua; Tanowitz, Herbert B.; Spray, David C.; Desruisseaux, Mahalia S.

    2016-01-01

    Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA) antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria. PMID:27031954

  14. Occipital Artery to Middle Cerebral Artery Bypass: Operative Nuances.

    PubMed

    Kimura, Toshikazu; Morita, Akio

    2017-12-01

    Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is a common procedure for vascular neurosurgeons, and it is used in a variety of diseases. However, there are cases in which the STA is absent or is too hypoplastic to be used as a donor for revascularization. Occipital artery (OA)-MCA bypass may be a treatment option in these cases. We encountered 4 cases of symptomatic cerebral ischemia in which the STA was absent or unavailable. These cases were treated by revascularization from the OA to the periphery of the MCA. By meticulous dissection of the OA to the level of the superior temporal line, the OA could reach the periphery of the angular artery and be anastomosed to it in the usual fashion. The patency of the donor artery was confirmed by magnetic resonance angiography soon after the operation and 3 years later. OA-MCA bypass may be a surgical option for cerebral revascularization when the STA is not available. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. De novo development of a cerebral arteriovenous malformation following radiation therapy: Case report and an update to classical arteriovenous malformation nomenclature.

    PubMed

    Koch, Matthew J; Agarwalla, Pankaj K; Stapleton, Christopher J; Ogilvy, Christopher S; Loeffler, Jay S

    2016-06-01

    Cerebral arteriovenous malformations (AVM) are traditionally considered primary congenital lesions that result from embryological aberrations in vasculogenesis. Recent insights, however, suggest that these lesions may be secondary to a vascular insult such as ischemia or trauma. Herein, the authors present a rare case of a secondary cerebral AVM, occurring in a young girl who received prior cranial radiation therapy. At age 3years, she underwent surgical resection, chemotherapy, and photon radiation therapy for treatment of a fourth ventricular ependymoma. At age 19years, she developed new onset seizures and was found to have a left medial temporal lobe AVM. Her seizures were managed successfully with anti-epileptic medications and the AVM was treated with proton radiation therapy. This case highlights a rare but possible vascular sequela of radiation therapy and adds to the growing body of evidence that cerebral AVM may arise as secondary lesions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer's disease

    PubMed Central

    Lin, Ai-Ling; Zheng, Wei; Halloran, Jonathan J; Burbank, Raquel R; Hussong, Stacy A; Hart, Matthew J; Javors, Martin; Shih, Yen-Yu Ian; Muir, Eric; Solano Fonseca, Rene; Strong, Randy; Richardson, Arlan G; Lechleiter, James D; Fox, Peter T; Galvan, Veronica

    2013-01-01

    Vascular pathology is a major feature of Alzheimer's disease (AD) and other dementias. We recently showed that chronic administration of the target-of-rapamycin (TOR) inhibitor rapamycin, which extends lifespan and delays aging, halts the progression of AD-like disease in transgenic human (h)APP mice modeling AD when administered before disease onset. Here we demonstrate that chronic reduction of TOR activity by rapamycin treatment started after disease onset restored cerebral blood flow (CBF) and brain vascular density, reduced cerebral amyloid angiopathy and microhemorrhages, decreased amyloid burden, and improved cognitive function in symptomatic hAPP (AD) mice. Like acetylcholine (ACh), a potent vasodilator, acute rapamycin treatment induced the phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) and NO release in brain endothelium. Administration of the NOS inhibitor L-NG-Nitroarginine methyl ester reversed vasodilation as well as the protective effects of rapamycin on CBF and vasculature integrity, indicating that rapamycin preserves vascular density and CBF in AD mouse brains through NOS activation. Taken together, our data suggest that chronic reduction of TOR activity by rapamycin blocked the progression of AD-like cognitive and histopathological deficits by preserving brain vascular integrity and function. Drugs that inhibit the TOR pathway may have promise as a therapy for AD and possibly for vascular dementias. PMID:23801246

  17. Vascular cognitive impairment, a cardiovascular complication.

    PubMed

    Frances, Adiukwu; Sandra, Ofori; Lucy, Ugbomah

    2016-06-22

    Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension.

  18. Vascular cognitive impairment, a cardiovascular complication

    PubMed Central

    Frances, Adiukwu; Sandra, Ofori; Lucy, Ugbomah

    2016-01-01

    Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension. PMID:27354961

  19. Vascular space occupancy (VASO) cerebral blood volume-weighted MRI identifies hemodynamic impairment in patients with carotid artery disease.

    PubMed

    Donahue, Manus J; van Laar, Peter Jan; van Zijl, Peter C M; Stevens, Robert D; Hendrikse, Jeroen

    2009-03-01

    To assess the role of vascular space occupancy (VASO) magnetic resonance imaging (MRI), a noninvasive cerebral blood volume (CBV)-weighted technique, for evaluating CBV reactivity in patients with internal carotid artery (ICA) stenosis. VASO reactivity, defined as a signal change in response to hypercapnic stimulus (4-second exhale, 14-second breath-hold), was measured in the left and right ICA flow territories in patients (n=10) with varying degrees of unilateral and bilateral ICA stenosis and in healthy volunteers (n=10). Percent VASO reactivity was more negative (P<0.01) bilaterally in patients (ipsilateral: -3.6+/-1.5%; contralateral: -3.4+/-1.2%) compared with age-matched controls (left: -1.9+/-0.6%; right: -1.9+/-0.8%). Owing to the nature of the VASO contrast mechanism, this more negative VASO reactivity was attributed to autoregulatory CBV effects in patients. A postbreath-hold overshoot, which was absent in healthy volunteers, was observed unilaterally in a subset of patients. More negative VASO reactivity was observed in patients with ICA stenosis and may be a marker of autoregulatory effects. Furthermore, the postbreath-hold overshoot observed in patients is consistent with compensatory microvascular vasoconstriction and may be a marker of hemodynamic impairment. Based on the results of this feasibility study, VASO should be useful for identifying CBV adjustments in patients with steno-occlusive disease of the ICA. Copyright (c) 2009 Wiley-Liss, Inc.

  20. The effects of hypertension on the cerebral circulation

    PubMed Central

    Pires, Paulo W.; Dams Ramos, Carla M.; Matin, Nusrat

    2013-01-01

    Maintenance of brain function depends on a constant blood supply. Deficits in cerebral blood flow are linked to cognitive decline, and they have detrimental effects on the outcome of ischemia. Hypertension causes alterations in cerebral artery structure and function that can impair blood flow, particularly during an ischemic insult or during periods of low arterial pressure. This review will focus on the historical discoveries, novel developments, and knowledge gaps in 1) hypertensive cerebral artery remodeling, 2) vascular function with emphasis on myogenic reactivity and endothelium-dependent dilation, and 3) blood-brain barrier function. Hypertensive artery remodeling results in reduction in the lumen diameter and an increase in the wall-to-lumen ratio in most cerebral arteries; this is linked to reduced blood flow postischemia and increased ischemic damage. Many factors that are increased in hypertension stimulate remodeling; these include the renin-angiotensin-aldosterone system and reactive oxygen species levels. Endothelial function, vital for endothelium-mediated dilation and regulation of myogenic reactivity, is impaired in hypertension. This is a consequence of alterations in vasodilator mechanisms involving nitric oxide, epoxyeicosatrienoic acids, and ion channels, including calcium-activated potassium channels and transient receptor potential vanilloid channel 4. Hypertension causes blood-brain barrier breakdown by mechanisms involving inflammation, oxidative stress, and vasoactive circulating molecules. This exposes neurons to cytotoxic molecules, leading to neuronal loss, cognitive decline, and impaired recovery from ischemia. As the population ages and the incidence of hypertension, stroke, and dementia increases, it is imperative that we gain a better understanding of the control of cerebral artery function in health and disease. PMID:23585139

  1. 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

  2. Diabetic microangiopathy: impact of impaired cerebral vasoreactivity and delayed angiogenesis after permanent middle cerebral artery occlusion on stroke damage and cerebral repair in mice.

    PubMed

    Poittevin, Marine; Bonnin, Philippe; Pimpie, Cynthia; Rivière, Léa; Sebrié, Catherine; Dohan, Anthony; Pocard, Marc; Charriaut-Marlangue, Christiane; Kubis, Nathalie

    2015-03-01

    Diabetes increases the risk of stroke by three, increases related mortality, and delays recovery. We aimed to characterize functional and structural alterations in cerebral microvasculature before and after experimental cerebral ischemia in a mouse model of type 1 diabetes. We hypothesized that preexisting brain microvascular disease in patients with diabetes might partly explain increased stroke severity and impact on outcome. Diabetes was induced in 4-week-old C57Bl/6J mice by intraperitoneal injections of streptozotocin (60 mg/kg). After 8 weeks of diabetes, the vasoreactivity of the neurovascular network to CO2 was abolished and was not reversed by nitric oxide (NO) donor administration; endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) mRNA, phospho-eNOS protein, nNOS, and phospho-nNOS protein were significantly decreased; angiogenic and vessel maturation factors (vascular endothelial growth factor a [VEGFa], angiopoietin 1 (Ang1), Ang2, transforming growth factor-β [TGF-β], and platelet-derived growth factor-β [PDGF-β]) and blood-brain barrier (BBB) occludin and zona occludens 1 (ZO-1) expression were significantly decreased; and microvessel density was increased without changes in ultrastructural imaging. After permanent focal cerebral ischemia induction, infarct volume and neurological deficit were significantly increased at D1 and D7, and neuronal death (TUNEL+ / NeuN+ cells) and BBB permeability (extravasation of Evans blue) at D1. At D7, CD31+ / Ki67+ double-immunolabeled cells and VEGFa and Ang2 expression were significantly increased, indicating delayed angiogenesis. We show that cerebral microangiopathy thus partly explains stroke severity in diabetes. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  3. Hazards of Improper Dispensary: Literature Review and Report of an Accidental Chloroform Injection.

    PubMed

    Verma, Prashant; Tordik, Patricia; Nosrat, Ali

    2018-06-01

    Several clear, transparent solutions are used in endodontics. Inappropriate dispensing methods can lead to accidental injection or accidental irrigation. These accidents can cause permanent tissue damage including damage to the bone, periodontium, nerves, and vasculature. This article reports on the consequences of an accidental chloroform injection. Nonsurgical retreatment of tooth #8 was planned as part of a restorative treatment plan in a 69-year-old woman. The dentist accidentally injected chloroform instead of local anesthesia because chloroform was loaded into the anesthetic syringe. The patient experienced severe pain and swelling and soft tissue necrosis and suffered permanent sensory and motor nerve damage. A review of the literature was performed on accidents caused by improper dispensary, namely accidental injections and accidental irrigations. The data were extracted and summarized. Sodium hypochlorite, chlorhexidine, formalin, formocresol, 1:1000 adrenaline, benzalkonium chloride, and lighter fuel were accidentally injected as an intraoral nerve block or as infiltration injections. Bone and soft tissue necrosis, tooth loss, and sensory nerve damage (anesthesia and paresthesia) were the most common consequences reported. Such disastrous events can be prevented by appropriate labeling and separate dispensing methods for each solution. There is a need for disseminating information on toxicity and biocompatibility of materials/solutions used in endodontics. The authors recommend training dental students and endodontic residents on immediate and long-term therapeutic management of patients when an accidental injection or accidental irrigation occurs. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  4. Mistakes in diagnosing non-accidental injury: 10 years' experience

    PubMed Central

    Wheeler, David M; Hobbs, Christopher J

    1988-01-01

    Fifty children who were referred to the child abuse team in Leeds over the 10 years 1976-86 with suspected non-accidental injury were found to have conditions which mimicked non-accidental injury. These included impetigo (nine children) and blue spots (five children). Five children who presented with multiple bruising had haemostatic disorders. Eight children had disorders of the bone. Five children had been previously abused physically. Four showed evidence of neglect. One had evidence of non-accidental injury as well as the condition mimicking abuse. It is emphasised that when child abuse is suspected a sensitive and thorough assessment should be carried out by a paediatrician who is experienced in this. ImagesFIG 1 PMID:3133026

  5. 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.

  6. Doctor Ward's Accidental Terrarium.

    ERIC Educational Resources Information Center

    Hershey, David R.

    1996-01-01

    Presents the story of the accidental invention of the Wardian case, or terrarium, by Nathaniel Bagshaw Ward. Advocates the use of this story in teaching precollege biology as an illustration of how a chance event can lead to a major scientific advancement and as an example of the common occurrence of multiple discovery in botany. Contains 34…

  7. Effects of Prostacyclin, Indomethacin, and Heparin on Cerebral Blood Flow and Platelet Adhesion After Multifocal Ischemia of Canine Brain

    DTIC Science & Technology

    1988-06-01

    Hoff IT: Sodium 5-(3’-pyridinyl- methyl)benzoilzran-2-carboxylate (U-63557A) potentiates pro- tective effect of intravenrous eicosapentaenoic acid on...PAF.3- Hydroxy acids and PAP are pro- on the vascular endothelium.2 Although we were unable duced by platelets during aggregation and are potent to...Pickard JD: Role of prostaglandins and arachidonic acid derivatives in the coupling of cerebral blood flow to cerebral metabolism. J Cereb Blood Flow

  8. Hypertonic Lactate to Improve Cerebral Perfusion and Glucose Availability After Acute Brain Injury.

    PubMed

    Carteron, Laurent; Solari, Daria; Patet, Camille; Quintard, Hervé; Miroz, John-Paul; Bloch, Jocelyne; Daniel, Roy T; Hirt, Lorenz; Eckert, Philippe; Magistretti, Pierre J; Oddo, Mauro

    2018-06-19

    Lactate promotes cerebral blood flow and is an efficient substrate for the brain, particularly at times of glucose shortage. Hypertonic lactate is neuroprotective after experimental brain injury; however, human data are limited. Prospective study (clinicaltrials.gov NCT01573507). Academic ICU. Twenty-three brain-injured subjects (13 traumatic brain injury/10 subarachnoid hemorrhage; median age, 59 yr [41-65 yr]; median Glasgow Coma Scale, 6 [3-7]). Three-hour IV infusion of hypertonic lactate (sodium lactate, 1,000 mmol/L; concentration, 30 µmol/kg/min) administered 39 hours (26-49 hr) from injury. We examined the effect of hypertonic lactate on cerebral perfusion (using transcranial Doppler) and brain energy metabolism (using cerebral microdialysis). The majority of subjects (13/23 = 57%) had reduced brain glucose availability (baseline pretreatment cerebral microdialysis glucose, < 1 mmol/L) despite normal baseline intracranial pressure (10 [7-15] mm Hg). Hypertonic lactate was associated with increased cerebral microdialysis lactate (+55% [31-80%]) that was paralleled by an increase in middle cerebral artery mean cerebral blood flow velocities (+36% [21-66%]) and a decrease in pulsatility index (-21% [13-26%]; all p < 0.001). Cerebral microdialysis glucose increased above normal range during hypertonic lactate (+42% [30-78%]; p < 0.05); reduced brain glucose availability correlated with a greater improvement of cerebral microdialysis glucose (Spearman r = -0.53; p = 0.009). No significant changes in cerebral perfusion pressure, mean arterial pressure, systemic carbon dioxide, and blood glucose were observed during hypertonic lactate (all p > 0.1). This is the first clinical demonstration that hypertonic lactate resuscitation improves both cerebral perfusion and brain glucose availability after brain injury. These cerebral vascular and metabolic effects appeared related to brain lactate supplementation rather than to systemic effects.

  9. H2S Regulates Hypobaric Hypoxia-Induced Early Glio-Vascular Dysfunction and Neuro-Pathophysiological Effects

    PubMed Central

    Kumar, Gaurav; Chhabra, Aastha; Mishra, Shalini; Kalam, Haroon; Kumar, Dhiraj; Meena, Ramniwas; Ahmad, Yasmin; Bhargava, Kalpana; Prasad, Dipti N.; Sharma, Manish

    2016-01-01

    Hypobaric Hypoxia (HH) is an established risk factor for various neuro-physiological perturbations including cognitive impairment. The origin and mechanistic basis of such responses however remain elusive. We here combined systems level analysis with classical neuro-physiological approaches, in a rat model system, to understand pathological responses of brain to HH. Unbiased ‘statistical co-expression networks’ generated utilizing temporal, differential transcriptome signatures of hippocampus—centrally involved in regulating cognition—implicated perturbation of Glio-Vascular homeostasis during early responses to HH, with concurrent modulation of vasomodulatory, hemostatic and proteolytic processes. Further, multiple lines of experimental evidence from ultra-structural, immuno-histological, substrate-zymography and barrier function studies unambiguously supported this proposition. Interestingly, we show a significant lowering of H2S levels in the brain, under chronic HH conditions. This phenomenon functionally impacted hypoxia-induced modulation of cerebral blood flow (hypoxic autoregulation) besides perturbing the strength of functional hyperemia responses. The augmentation of H2S levels, during HH conditions, remarkably preserved Glio-Vascular homeostasis and key neuro-physiological functions (cerebral blood flow, functional hyperemia and spatial memory) besides curtailing HH-induced neuronal apoptosis in hippocampus. Our data thus revealed causal role of H2S during HH-induced early Glio-Vascular dysfunction and consequent cognitive impairment. PMID:27211559

  10. Genetic enhancement of microsomal epoxide hydrolase improves metabolic detoxification but impairs cerebral blood flow regulation.

    PubMed

    Marowsky, Anne; Haenel, Karen; Bockamp, Ernesto; Heck, Rosario; Rutishauser, Sibylle; Mule, Nandkishor; Kindler, Diana; Rudin, Markus; Arand, Michael

    2016-12-01

    Microsomal epoxide hydrolase (mEH) is a detoxifying enzyme for xenobiotic compounds. Enzymatic activity of mEH can be greatly increased by a point mutation, leading to an E404D amino acid exchange in its catalytic triad. Surprisingly, this variant is not found in any vertebrate species, despite the obvious advantage of accelerated detoxification. We hypothesized that this evolutionary avoidance is due to the fact that the mEH plays a dualistic role in detoxification and control of endogenous vascular signaling molecules. To test this, we generated mEH E404D mice and assessed them for detoxification capacity and vascular dynamics. In liver microsomes from these mice, turnover of the xenobiotic compound phenanthrene-9,10-oxide was four times faster compared to WT liver microsomes, confirming accelerated detoxification. mEH E404D animals also showed faster metabolization of a specific class of endogenous eicosanoids, arachidonic acid-derived epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs). Significantly higher DHETs/EETs ratios were found in mEH E404D liver, urine, plasma, brain and cerebral endothelial cells compared to WT controls, suggesting a broad impact of the mEH mutant on endogenous EETs metabolism. Because EETs are strong vasodilators in cerebral vasculature, hemodynamics were assessed in mEH E404D and WT cerebral cortex and hippocampus using cerebral blood volume (CBV)-based functional magnetic resonance imaging (fMRI). Basal CBV 0 levels were similar between mEH E404D and control mice in both brain areas. But vascular reactivity and vasodilation in response to the vasodilatory drug acetazolamide were reduced in mEH E404D forebrain compared to WT controls by factor 3 and 2.6, respectively. These results demonstrate a critical role for mEH E404D in vasodynamics and suggest that deregulation of endogenous signaling pathways is the undesirable gain of function associated with the E404D variant.

  11. Impaired cerebral development in fetuses with congenital cardiovascular malformations: Is it the result of inadequate glucose supply?

    PubMed

    Rudolph, Abraham M

    2016-08-01

    Cerebral development may be impaired in fetuses with congenital cardiovascular malformations, particularly hypoplastic left heart syndrome (HLHS) and aortopulmonary transposition (APT). The decreased cerebral arterial pusatility index observed in some of these fetuses led to the belief that cerebral vascular resistance was reduced as a result of arterial hypoxemia and cerebral hypoxia is thought to be responsible for impaired cerebral growth. However, other hemodynamic factors could affect pulsatility index. I propose that cerebral blood flow is reduced in fetuses with HLHS and that reduced glucose, rather than oxygen, delivery interferes with cerebral development. This is based on the fact that most of these fetuses do not have lactate accumulation in the brain.In fetuses with APT, umbilical venous blood, containing oxygen and glucose derived across the placenta, is distributed to the lungs and lower body; venous blood, with low oxygen and glucose content, is delivered to the ascending aorta and brain. Oxygen and glucose delivery may further be reduced by decreased cerebral blood flow resulting from run-off of aortic blood through the ductus arteriosus to the pulmonary circulation during diastole. In APT fetuses, lack of lactate in the brain also supports my proposal that glucose deficiency interferes with cerebral development.

  12. Are pre-hospital deaths from accidental injury preventable?

    PubMed Central

    Hussain, L. M.; Redmond, A. D.

    1994-01-01

    OBJECTIVE--To determine what proportion of pre-hospital deaths from accidental injury--deaths at the scene of the accident and those that occur before the person has reached hospital--are preventable. DESIGN--Retrospective study of all deaths from accidental injury that occurred between 1 January 1987 and 31 December 1990 and were reported to the coroner. SETTING--North Staffordshire. MAIN OUTCOME MEASURES--Injury severity score, probability of survival (probit analysis), and airway obstruction. RESULTS--There were 152 pre-hospital deaths from accidental injury (110 males and 42 females). In the same period there were 257 deaths in hospital from accidental injury (136 males and 121 females). The average age at death was 41.9 years for those who died before reaching hospital, and their average injury severity score was 29.3. In contrast, those who died in hospital were older and equally likely to be males or females. Important neurological injury occurred in 113 pre-hospital deaths, and evidence of airway obstruction in 59. Eighty six pre-hospital deaths were due to road traffic accidents, and 37 of these were occupants in cars. On the basis of the injury severity score and age, death was found to have been inevitable or highly likely in 92 cases. In the remaining 60 cases death had not been inevitable and airway obstruction was present in up to 51 patients with injuries that they might have survived. CONCLUSION--Death was potentially preventable in at least 39% of those who died from accidental injury before they reached hospital. Training in first aid should be available more widely, and particularly to motorists as many pre-hospital deaths that could be prevented are due to road accidents. PMID:8173428

  13. White matter hyperintensities and vascular risk factors in monozygotic twins.

    PubMed

    Ten Kate, Mara; Sudre, Carole H; den Braber, Anouk; Konijnenberg, Elles; Nivard, Michel G; Cardoso, M Jorge; Scheltens, Philip; Ourselin, Sébastien; Boomsma, Dorret I; Barkhof, Frederik; Visser, Pieter Jelle

    2018-06-01

    Cerebral white matter hyperintensities (WMHs) have been associated with vascular risk factors, both of which are under genetic influence. We examined in a monozygotic twin sample whether the association between vascular risk and WMHs is influenced by overlapping genetic factors. We included 195 cognitively normal monozygotic twins (age = 70 ± 7 years), including 94 complete pairs. Regional WMH load was estimated using an automated algorithm. Vascular risk was summarized with the Framingham score. The within-twin pair correlation for total WMHs was 0.76 and for Framingham score was 0.77. Within participants, Framingham score was associated with total and periventricular WMHs (r = 0.32). Framingham score in 1 twin was also associated with total WMHs in the co-twin (r = 0.26). Up to 83% of the relation between both traits could be explained by shared genetic effects. In conclusion, monozygotic twins have highly similar vascular risk and WMH burden, confirming a genetic background for these traits. The association between both traits is largely driven by overlapping genetic factors. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Cerebral Embolic Activity in a Patient during Acute Crisis of Takayasu's Arteritis

    PubMed Central

    Nogueira, Ricardo de Carvalho; Bor-Seng-Shu, Edson; Marchiori, Paulo Eurípedes; Teixeira, Manoel Jacobsen

    2012-01-01

    Takayasu's arteritis is a disease that affects large vessels and may cause neurological symptoms either by stenoses/occlusions or embolisms from vessels with an inflammatory process. Transcranial Doppler (TCD) ultrasound can provide useful information for diagnosis and monitoring during the active phase of the disease. Cerebral embolic signals can be detected by TCD and have been considered a risk factor for vascular events. We report a patient in whom TCD ultrasound was used to monitor cerebral embolic signals during the active phase of the disease. This case report suggests that embolic activity in Takayasu's arteritis may represent disease activity, and its monitoring may be useful for evaluating the response to therapy. PMID:22379479

  15. Role of Hydrogen Sulfide in Early Blood-Brain Barrier Disruption following Transient Focal Cerebral Ischemia

    PubMed Central

    Jiang, Zheng; Li, Chun; Manuel, Morganne L.; Yuan, Shuai; Kevil, Christopher G.; McCarter, Kimberly D.; Lu, Wei; Sun, Hong

    2015-01-01

    We determined the role of endogenous hydrogen sulfide (H₂S) in cerebral vasodilation/hyperemia and early BBB disruption following ischemic stroke. A cranial window was prepared over the left frontal, parietal and temporal cortex in mice. Transient focal cerebral Ischemia was induced by directly ligating the middle cerebral artery (MCA) for two hours. Regional vascular response and cerebral blood flow (CBF) during ischemia and reperfusion were measured in real time. Early BBB disruption was assessed by Evans Blue (EB) and sodium fluorescein (Na-F) extravasation at 3 hours of reperfusion. Topical treatment with DL-propargylglycine (PAG, an inhibitor for cystathionine γ-lyase (CSE)) and aspartate (ASP, inhibitor for cysteine aminotransferase/3-mercaptopyruvate sulfurtransferase (CAT/3-MST)), but not O-(Carboxymethyl)hydroxylamine hemihydrochloride (CHH, an inhibitor for cystathionine β-synthase (CBS)), abolished postischemic cerebral vasodilation/hyperemia and prevented EB and Na-F extravasation. CSE knockout (CSE-/-) reduced postischemic cerebral vasodilation/hyperemia but only inhibited Na-F extravasation. An upregulated CBS was found in cerebral cortex of CSE-/- mice. Topical treatment with CHH didn’t further alter postischemic cerebral vasodilation/hyperemia, but prevented EB extravasation in CSE-/- mice. In addition, L-cysteine-induced hydrogen sulfide (H2S) production similarly increased in ischemic side cerebral cortex of control and CSE-/- mice. Our findings suggest that endogenous production of H2S by CSE and CAT/3-MST during reperfusion may be involved in postischemic cerebral vasodilation/hyperemia and play an important role in early BBB disruption following transient focal cerebral ischemia. PMID:25695633

  16. Accidental introductions are an important source of invasive plants in the continental United States.

    PubMed

    Lehan, Nora E; Murphy, Julia R; Thorburn, Lukas P; Bradley, Bethany A

    2013-07-01

    Preventing new plant invasions is critical for reducing large-scale ecological change. Most studies have focused on the deliberate introduction of nonnatives via the ornamental plant trade. However, accidental introduction may be an important source of nonnative, invasive plants. Using Web and literature searches, we compiled pathways of introduction to the United States for 1112 nonnative plants identified as invasive in the continental United States. We assessed how the proportion of accidentally and deliberately introduced invasive plants varies over time and space and by growth habit across the lower 48 states. Deliberate introductions of ornamentals are the primary source of invasive plants in the United States, but accidental introductions through seed contaminants are an important secondary source. Invasive forbs and grasses are the most likely to have arrived accidentally through seed contaminants, while almost all nonnative, invasive trees were introduced deliberately. Nonnative plants invading eastern states primarily arrived deliberately as ornamentals, while a high proportion of invasive plants in western states arrived accidentally as seed contaminants. Accidental introductions may be increasing in importance through time. Before 1850, 10 of 89 (11%) of invasive plants arrived accidentally. After 1900, 20 of 65 (31%) arrived accidentally. Recently enacted screening protocols and weed risk assessments aim to reduce the number of potentially invasive species arriving to the United States via deliberate introduction pathways. Increasing proportions of accidentally introduced invasive plants, particularly associated with contaminated seed imports across the western states, suggest that accidental introduction pathways also need to be considered in future regulatory decisions.

  17. Sleep Apnea, Sleep Duration and Brain MRI Markers of Cerebral Vascular Disease and Alzheimer's Disease: The Atherosclerosis Risk in Communities Study (ARIC).

    PubMed

    Lutsey, Pamela L; Norby, Faye L; Gottesman, Rebecca F; Mosley, Thomas; MacLehose, Richard F; Punjabi, Naresh M; Shahar, Eyal; Jack, Clifford R; Alonso, Alvaro

    2016-01-01

    A growing body of literature has suggested that obstructive sleep apnea (OSA) and habitual short sleep duration are linked to poor cognitive function. Neuroimaging studies may provide insight into this relation. We tested the hypotheses that OSA and habitual short sleep duration, measured at ages 54-73 years, would be associated with adverse brain morphology at ages 67-89 years. Included in this analysis are 312 ARIC study participants who underwent in-home overnight polysomnography in 1996-1998 and brain MRI scans about 15 years later (2012-2013). Sleep apnea was quantified by the apnea-hypopnea index and categorized as moderate/severe (≥15.0 events/hour), mild (5.0-14.9 events/hour), or normal (<5.0 events/hour). Habitual sleep duration was categorized, in hours, as <7, 7 to <8, ≥8. MRI outcomes included number of infarcts (total, subcortical, and cortical) and white matter hyperintensity (WMH) and Alzheimer's disease signature region volumes. Multivariable adjusted logistic and linear regression models were used. All models incorporated inverse probability weighting, to adjust for potential selection bias. At the time of the sleep study participants were 61.7 (SD: 5.0) years old and 54% female; 19% had moderate/severe sleep apnea. MRI imaging took place 14.8 (SD: 1.0) years later, when participants were 76.5 (SD: 5.2) years old. In multivariable models which accounted for body mass index, neither OSA nor abnormal sleep duration were statistically significantly associated with odds of cerebral infarcts, WMH brain volumes or regional brain volumes. In this community-based sample, mid-life OSA and habitually short sleep duration were not associated with later-life cerebral markers of vascular dementia and Alzheimer's disease. However, selection bias may have influenced our results and the modest sample size led to relatively imprecise associations.

  18. Imitation of Intentional and Accidental Actions by Children with Autism

    ERIC Educational Resources Information Center

    D'Entremont, Barbara; Yazbek, Aimee

    2007-01-01

    To determine whether children with autism (CWA) would selectively imitate intentional, as opposed to accidental actions, an experimenter demonstrated either an "intentional" and an "accidental" action or two "intentional" actions on the same toy [Carpenter, Akhtar, & Tomasello ("1998a") "Infant Behavior and Development, 21," 315-330]. CWA tended…

  19. 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

  20. Evaluation of spontaneous low-frequency oscillations in cerebral hemodynamics with time-series red-green-blue images

    NASA Astrophysics Data System (ADS)

    Nishidate, Izumi; Mustari, Afrina; Nakamura, Naoki; Kawauchi, Satoko; Sato, Shunichi; Sato, Manabu; Kokubo, Yasuaki

    2017-02-01

    The brain relies on a continuous and adequate supply of blood flow, bringing the nutrients that it needs and removing the waste products of metabolism. It is thus one of the most tightly regulated systems in the body, whereby a whole range of mechanisms act to maintain this supply, despite changes in blood pressure etc. Failure of these mechanisms is found in a number of devastating cerebral diseases, including stroke, vascular dementia and brain injury and trauma. Spontaneous contraction and relaxation of arterioles (and in some instances venules) termed vasomotion has been observed in an extensive variety of tissues and species. Vasomotion has a beneficial effect on tissue oxygenation and enhance blood flow. Although vasomotion is strictly a local phenomenon, the regulation of contractile activity of vascular smooth muscle cells is dependent on the complex interplay between vasodilator and vasoconstrictor stimuli from circulating hormones, neurotransmitters, endothelial derived factors, and blood pressure. Therefore, evaluation of the spontaneous oscillations in cerebral vasculatures might be a useful tool for assessing risk and investigating different treatment strategies in neurological disorders, such as traumatic brain injury, seizure, ischemia, and stroke. In the present study, we newly propose a method to visualize the spontaneous low-frequency oscillation of cerebral blood volume based on the sequential RGB images of exposed brain.

  1. Association factor analysis between osteoporosis with cerebral artery disease: The STROBE study.

    PubMed

    Jin, Eun-Sun; Jeong, Je Hoon; Lee, Bora; Im, Soo Bin

    2017-03-01

    The purpose of this study was to determine the clinical association factors between osteoporosis and cerebral artery disease in Korean population. Two hundred nineteen postmenopausal women and men undergoing cerebral computed tomography angiography were enrolled in this study to evaluate the cerebral artery disease by cross-sectional study. Cerebral artery disease was diagnosed if there was narrowing of 50% higher diameter in one or more cerebral vessel artery or presence of vascular calcification. History of osteoporotic fracture was assessed using medical record, and radiographic data such as simple radiography, MRI, and bone scan. Bone mineral density was checked by dual-energy x-ray absorptiometry. We reviewed clinical characteristics in all patients and also performed subgroup analysis for total or extracranial/ intracranial cerebral artery disease group retrospectively. We performed statistical analysis by means of chi-square test or Fisher's exact test for categorical variables and Student's t-test or Wilcoxon's rank sum test for continuous variables. We also used univariate and multivariate logistic regression analyses were conducted to assess the factors associated with the prevalence of cerebral artery disease. A two-tailed p-value of less than 0.05 was considered as statistically significant. All statistical analyses were performed using R (version 3.1.3; The R Foundation for Statistical Computing, Vienna, Austria) and SPSS (version 14.0; SPSS, Inc, Chicago, Ill, USA). Of the 219 patients, 142 had cerebral artery disease. All vertebral fracture was observed in 29 (13.24%) patients. There was significant difference in hip fracture according to the presence or absence of cerebral artery disease. In logistic regression analysis, osteoporotic hip fracture was significantly associated with extracranial cerebral artery disease after adjusting for multiple risk factors. Females with osteoporotic hip fracture were associated with total calcified cerebral artery

  2. Experiences of Causing an Accidental Death: An Interpretative Phenomenological Analysis

    ERIC Educational Resources Information Center

    Rassool, Sara B.; Nel, Pieter W.

    2012-01-01

    Accidentally killing or feeling responsible for another person's death constitutes an event that is different from many typical traumatic stressors in that the responsibility for causing the trauma is located in the person themselves, rather than another person or persons. Research exploring the perspective of those who have accidentally caused a…

  3. Diffuse correlation spectroscopy for non-invasive, micro-vascular cerebral blood flow measurement

    PubMed Central

    Durduran, Turgut; Yodh, Arjun G.

    2013-01-01

    Diffuse correlation spectroscopy (DCS) uses the temporal fluctuations of near-infrared (NIR) light to measure cerebral blood flow (CBF) non-invasively. Here, we provide a brief history of DCS applications in brain with an emphasis on the underlying physical ideas, common instrumentation and validation. Then we describe recent clinical research that employs DCS-measured CBF as a biomarker of patient well-being, and as an indicator of hemodynamic and metabolic response to functional stimuli. PMID:23770408

  4. [Progress of researches on mechanism of acupuncture therapy underlying improvement of acute cerebral hemorrhage].

    PubMed

    Wang, Fan; Wang, Hai-qiao; Dong, Gui-rong

    2011-04-01

    In the present paper, the authors review the progress of researches on the mechanism of acupuncture therapy underlying improvement of acute cerebral hemorrhage from experimental studies and research methods. The effects of acupuncture intervention mainly involve (1) lessening inflammatory reactions, (2) reducing impairment of free radicals and excitatory amino acids on cerebral neurons, (3) balancing release of vascular bioactive substances to increase regional cerebral blood flow, and (4) promoting repair and regeneration of the neural tissue, etc. In regard to the research methods, many new biological techniques such as biological molecular approaches, neuro-cellular chemical methods, reverse transcription-polymerase chain reaction (RT-PCR) or quantitative real time-PCR, situ hybridization, western blotting, electron microscope, etc., have been extensively applied to researches on the underlying mechanism of acupuncture therapy for cerebral infarction. In addition, the authors also pointed out that in spite of achieving some bigger progresses in experimental studies, most of the results basically reflect static, isolated and regional changes rather than dynamic and whole body changes. For this reason, more vivo research techniques and noninvasive research methods are highly recommended to be used in the future research on the underlying mechanisms of acupuncture therapy for acute cerebral ischemia.

  5. Accidental degeneracies in nonlinear quantum deformed systems

    NASA Astrophysics Data System (ADS)

    Aleixo, A. N. F.; Balantekin, A. B.

    2011-09-01

    We construct a multi-parameter nonlinear deformed algebra for quantum confined systems that includes many other deformed models as particular cases. We demonstrate that such systems exhibit the property of accidental pairwise energy level degeneracies. We also study, as a special case of our multi-parameter deformation formalism, the extension of the Tamm-Dancoff cutoff deformed oscillator and the occurrence of accidental pairwise degeneracy in the energy levels of the deformed system. As an application, we discuss the case of a trigonometric Rosen-Morse potential, which is successfully used in models for quantum confined systems, ranging from electrons in quantum dots to quarks in hadrons.

  6. Donepezil attenuates hippocampal neuronal damage and cognitive deficits after global cerebral ischemia in gerbils.

    PubMed

    Min, Dongyu; Mao, Xiaoyuan; Wu, Kuncan; Cao, Yonggang; Guo, Feng; Zhu, Shu; Xie, Ni; Wang, Lei; Chen, Tianbao; Shaw, Chris; Cai, Jiqun

    2012-02-21

    Decreased cerebral blood flow causes cognitive impairments and neuronal injury in vascular dementia. In the present study, we reported that donepezil, a cholinesterase inhibitor, improved transient global cerebral ischemia-induced spatial memory impairment in gerbils. Treatment with 5mg/kg of donepezil for 21 consecutive days following a 10-min period of ischemia significantly inhibited delayed neuronal death in the hippocampal CA1 region. In Morris water maze test, memory impairment was significantly improved by donepezil treatment. Western blot analysis showed that donepezil treatment prevented reductions in p-CaMKII and p-CREB protein levels in the hippocampus. These results suggest that donepezil attenuates the memory deficit induced by transient global cerebral ischemia and this neuroprotection may be associated with the phosphorylation of CaMKII and CERB in the hippocampus. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. Age and Vascular Burden Determinants of Cortical Hemodynamics Underlying Verbal Fluency.

    PubMed

    Heinzel, Sebastian; Metzger, Florian G; Ehlis, Ann-Christine; Korell, Robert; Alboji, Ahmed; Haeussinger, Florian B; Wurster, Isabel; Brockmann, Kathrin; Suenkel, Ulrike; Eschweiler, Gerhard W; Maetzler, Walter; Berg, Daniela; Fallgatter, Andreas J

    2015-01-01

    Aging processes and several vascular burden factors have been shown to increase the risk of dementia including Alzheimer's disease. While pathological alterations in dementia precede diagnosis by many years, reorganization of brain processing might temporarily delay cognitive decline. We hypothesized that in healthy elderly individuals both age-related neural and vascular factors known to be related to the development of dementia impact functional cortical hemodynamics during increased cognitive demands. Vascular burden factors and cortical functional hemodynamics during verbal fluency were assessed in 1052 non-demented elderly individuals (51 to 83 years; cross-sectional data of the longitudinal TREND study) using functional near-infrared spectroscopy (fNIRS). The prediction of functional hemodynamic responses by age in multiple regressions and the impact of single and cumulative vascular burden factors including hypertension, diabetes, obesity, smoking and atherosclerosis were investigated. Replicating and extending previous findings we could show that increasing age predicted functional hemodynamics to be increased in right prefrontal and bilateral parietal cortex, and decreased in bilateral inferior frontal junction during phonological fluency. Cumulative vascular burden factors, with hypertension in particular, decreased left inferior frontal junction hemodynamic responses during phonological fluency. However, age and vascular burden factors showed no statistical interaction on functional hemodynamics. Based on these findings, one might hypothesize that increased fronto-parietal processing may represent age-related compensatory reorganization during increased cognitive demands. Vascular burden factors, such as hypertension, may contribute to regional cerebral hypoperfusion. These neural and vascular hemodynamic determinants should be investigated longitudinally and combined with other markers to advance the prediction of future cognitive decline and dementia.

  8. Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemia.

    PubMed

    Dong, Beibei; Cai, Min; Fang, Zongping; Wei, Haidong; Zhu, Fangyun; Li, Guochao; Dong, Hailong; Xiong, Lize

    2013-06-10

    The plasma protein hemopexin (HPX) exhibits the highest binding affinity to free heme. In vitro experiments and gene-knock out technique have suggested that HPX may have a neuroprotective effect. However, the expression of HPX in the brain was not well elucidated and its expression after cerebral ischemia-reperfusion injury was also poorly studied. Furthermore, no in vivo data were available on the effect of HPX given centrally on the prognosis of focal cerebral ischemia. In the present study, we systematically investigated expression of HPX in normal rat brain by immunofluorescent staining. The results showed that HPX was mainly expressed in vascular system and neurons, as well as in a small portion of astrocytes adjacent to the vessels in normal rat brain. Further, we determined the role of HPX in the process of focal cerebral ischemic injury and explored the effects of HPX treatment in a rat model of transient focal cerebral ischemia. After 2 h' middle cerebral artery occlusion (MCAO) followed by 24 h' reperfusion, the expression of HPX was increased in the neurons and astrocytes in the penumbra area, as demonstrated by immunohistochemistry and Western blot techniques. Intracerebroventricular injection of HPX at the onset of reperfusion dose-dependently reduced the infarct volumes and improved measurements of neurological function of the rat subjected to transient focal cerebral ischemia. The neuroprotective effects of HPX sustained for up to 7 days after experiments. Our study provides a new insight into the potential neuroprotective role of HPX as a contributing factor of endogenous protective mechanisms against focal cerebral ischemia injury, and HPX might be developed as a potential agent for treatment of ischemic stroke.

  9. [Clinical and electroencephalographic characteristic of noopept in patients with mild cognitive impairment of posttraumatic and vascular origin].

    PubMed

    Bochkarev, V K; Teleshova, E S; Siuniakov, S A; Davydova, D V; Neznamov, G G

    2008-01-01

    An effect of a new nootropic drug noopept on the dynamics of main EEG rhythms and narrow-band spectral EEG characteristics in patients with cerebral asthenic and cognitive disturbances caused by traumas or vascular brain diseases has been studied. Noopept caused the EEG changes characteristic of the action of nootropics: the increase of alpha- and beta-rhythms power and reduction of delta-rhythms power. The reaction of alpha-rhythm was provided mostly by the dynamics of its low and medium frequencies (6,7-10,2 Hz), the changes of beta-rhythm were augmented in frontal and attenuated in occipital areas. The analysis of frequency and spatial structure of EEG changes reveals that noopept exerts a nonspecific activation and anxyolytic effect. The differences in EEG changes depending on the brain pathology were found. The EEG indices of nootropic effect of the drug were most obvious in cerebral vascular diseases. The EEG changes in posttraumatic brain lesion were less typical.

  10. Spaceflight on the Bion-M1 biosatellite alters cerebral artery vasomotor and mechanical properties in mice

    PubMed Central

    Sofronova, Svetlana I.; Tarasova, Olga S.; Gaynullina, Dina; Borzykh, Anna A.; Behnke, Bradley J.; Stabley, John N.; McCullough, Danielle J.; Maraj, Joshua J.; Hanna, Mina; Muller-Delp, Judy M.; Vinogradova, Olga L.

    2015-01-01

    Conditions during spaceflight, such as the loss of the head-to-foot gravity vector, are thought to potentially alter cerebral blood flow and vascular resistance. The purpose of the present study was to determine the effects of long-term spaceflight on the functional, mechanical, and structural properties of cerebral arteries. Male C57BL/6N mice were flown 30 days in a Bion-M1 biosatellite. Basilar arteries isolated from spaceflight (SF) (n = 6), habitat control (HC) (n = 6), and vivarium control (VC) (n = 16) mice were used for in vitro functional and mechanical testing and histological structural analysis. The results demonstrate that vasoconstriction elicited through a voltage-gated Ca2+ mechanism (30–80 mM KCl) and thromboxane A2 receptors (10−8 − 3 × 10−5 M U46619) are lower in cerebral arteries from SF mice. Inhibition of Rho-kinase activity (1 μM Y27632) abolished group differences in U46619-evoked contractions. Endothelium-dependent vasodilation elicited by acetylcholine (10 μM, 2 μM U46619 preconstriction) was virtually absent in cerebral arteries from SF mice. The pressure-diameter relation was lower in arteries from SF mice relative to that in HC mice, which was not related to differences in the extracellular matrix protein elastin or collagen content or the elastin/collagen ratio in the basilar arteries. Diameter, medial wall thickness, and medial cross-sectional area of unpressurized basilar arteries were not different among groups. These results suggest that the microgravity-induced attenuation of both vasoconstrictor and vasodilator properties may limit the range of vascular control of cerebral perfusion or impair the distribution of brain blood flow during periods of stress. PMID:25593287

  11. Effect of the α(2)-adrenoceptor antagonist yohimbine on vascular regulation of the middle cerebral artery and the ophthalmic artery in healthy subjects.

    PubMed

    Kaya, S; Kolodjaschna, J; Berisha, F; Polska, E; Pemp, B; Garhöfer, G; Schmetterer, L

    2011-01-01

    There is evidence that vascular beds distal to the ophthalmic artery (OA) show vasoconstriction in response to a step decrease in systemic blood pressure (BP). The mediators of this response are mostly unidentified. The aim of the current study was to test the hypothesis that α2-adrenoreceptors may contribute to the regulatory process in response to a decrease in BP. In this randomized, double-masked, placebo-controlled study 14 healthy male volunteers received either 22mg yohimbine hydrochloride or placebo. Beat-to-beat BP was measured by analysis of arterial pressure waveform; blood flow velocities in the middle cerebral artery (MCA) and the OA were measured with Doppler ultrasound. Measurements were done before, during and after a step decrease in BP. The step decrease in BP was induced by bilateral thigh cuffs at a suprasystolic pressure followed by a rapid cuff deflation. After cuff deflation, BP returned to baseline after 7-8 pulse cycles (PC). Blood velocities in the MCA returned to baseline earlier (4 PC) than BP indicating peripheral vasodilatation. Blood velocities in the OA returned to baseline later (15-20 PC) indicating peripheral vasoconstriction. Yohimbine did not affect the blood velocity response in the MCA, but significantly shortened the time of OA blood velocities to return to baseline values (6-7 PC, p<0.05). In conclusion, our results indicate that yohimbine did not alter the regulatory response in the MCA, but modified the response of vascular beds distal to the OA. This suggests that α2-adrenoceptors play a role in the vasoconstrictor response of the vasculatures distal to the OA. 2010 Elsevier Inc. All rights reserved.

  12. Expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in brain tissue of diabetic rats with ischemia reperfusion.

    PubMed

    Liang, Yu-Zhi; Zeng, Zhi-Lei; Hua, Lin-Lin; Li, Jin-Feng; Wang, Yun-Liang; Bi, Xi-Zhuang

    2016-06-01

    To discuss the expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in the brain tissue of diabetic rats with ischemia reperfusion. A total of 60 male Wistar rats were randomly divided into the normal group, sham group, diabetic cerebral infarction group and single cerebral infarction group according to the random number table, with 15 rats in each group. The high sucrose diet and intraperitoneal injection of streptozotocin were performed for the modeling of diabetic rats, while the thread-occlusion method was employed to build the model of cerebral ischemia reperfusion. The immunohistochemical staining was performed to detect the expression of angiostatin, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in the brain tissue. The expression of angiostatin after the reperfusion in the brain tissue of rats in the single cerebral infarction group and diabetic cerebral infarction group was increased 6 h after the reperfusion, reached to the peak on 1 d and then decreased gradually. The expression of angiostatin in the diabetic cerebral infarction group 6 h, 1 d, 3 d and 7 d after the reperfusion was significantly higher than that in the single cerebral infarction group (P < 0.05). VEGF began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak at 6 h and then decreased gradually. The expression of VEGF in the diabetic cerebral infarction group at each time point after the reperfusion was significantly lower than that in the single cerebral infarction group (P < 0.05). MMP-9 began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak on 1 d and then decreased gradually. The expression of MMP-9 in the diabetic cerebral infarction group at each time point after the reperfusion was significantly

  13. Synchronization patterns in cerebral blood flow and peripheral blood pressure under minor stroke

    NASA Astrophysics Data System (ADS)

    Chen, Zhi; Ivanov, Plamen C.; Hu, Kun; Stanley, H. Eugene; Novak, Vera

    2003-05-01

    Stroke is a leading cause of death and disability in the United States. The autoregulation of cerebral blood flow that adapts to changes in systemic blood pressure is impaired after stroke. We investigate blood flow velocities (BFV) from right and left middle cerebral arteries (MCA) and beat-to-beat blood pressure (BP) simultaneously measured from the finger, in 13 stroke and 11 healthy subjects using the mean value statistics and phase synchronization method. We find an increase in the vascular resistance and a much stronger cross-correlation with a time lag up to 20 seconds with the instantaneous phase increment of the BFV and BP signals for the subjects with stroke compared to healthy subjects.

  14. The impact of age on cerebral perfusion, oxygenation and metabolism during exercise in humans

    PubMed Central

    Braz, Igor D.

    2015-01-01

    Abstract Age is one of the most important risk factors for dementia and stroke. Examination of the cerebral circulatory responses to acute exercise in the elderly may help to pinpoint the mechanisms by which exercise training can reduce the risk of brain diseases, inform the optimization of exercise training programmes and assist with the identification of age‐related alterations in cerebral vascular function. During low‐to‐moderate intensity dynamic exercise, enhanced neuronal activity is accompanied by cerebral perfusion increases of ∼10–30%. Beyond ∼60–70% maximal oxygen uptake, cerebral metabolism remains elevated but perfusion in the anterior portion of the circulation returns towards baseline, substantively because of a hyperventilation‐mediated reduction in the partial pressure of arterial carbon dioxide (P aC O2) and cerebral vasoconstriction. Cerebral perfusion is lower in older individuals, both at rest and during incremental dynamic exercise. Nevertheless, the increase in the estimated cerebral metabolic rate for oxygen and the arterial–internal jugular venous differences for glucose and lactate are similar in young and older individuals exercising at the same relative exercise intensities. Correction for the age‐related reduction in P aC O2 during exercise by the provision of supplementary CO2 is suggested to remove ∼50% of the difference in cerebral perfusion between young and older individuals. A multitude of candidates could account for the remaining difference, including cerebral atrophy, and enhanced vasoconstrictor and blunted vasodilatory pathways. In summary, age‐related reductions in cerebral perfusion during exercise are partly associated with a lower P aC O2 in exercising older individuals; nevertheless the cerebral extraction of glucose, lactate and oxygen appear to be preserved. PMID:26435295

  15. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of white matter lesions on MRI: the evaluation of vascular care in Alzheimer's disease (EVA) study.

    PubMed

    Richard, Edo; Gouw, Alida A; Scheltens, Philip; van Gool, Willem A

    2010-03-01

    White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, P=0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease.

  16. Cerebral Microbleeds in Patients with Dementia with Lewy Bodies and Parkinson Disease Dementia.

    PubMed

    Kim, S W; Chung, S J; Oh, Y-S; Yoon, J H; Sunwoo, M K; Hong, J Y; Kim, J-S; Lee, P H

    2015-09-01

    The burden of amyloid β is greater in patients with dementia with Lewy bodies than in those with Parkinson disease dementia, and an increased amyloid β load is closely related to a higher incidence of cerebral microbleeds. Here, we investigated the prevalence and topography of cerebral microbleeds in patients with dementia with Lewy bodies and those with Parkinson disease dementia to examine whether cerebral microbleeds are more prevalent in patients with dementia with Lewy bodies than in those with Parkinson disease dementia. The study population consisted of 42 patients with dementia with Lewy bodies, 88 patients with Parkinson disease dementia, and 35 controls who underwent brain MR imaging with gradient recalled-echo. Cerebral microbleeds were classified as deep, lobar, or infratentorial. The frequency of cerebral microbleeds was significantly greater in patients with dementia with Lewy bodies (45.2%) than in those with Parkinson disease dementia (26.1%) or in healthy controls (17.1%; P = .017). Lobar cerebral microbleeds were observed more frequently in the dementia with Lewy bodies group (40.5%) than in the Parkinson disease dementia (17%; P = .004) or healthy control (8.6%; P = .001) group, whereas the frequencies of deep and infratentorial cerebral microbleeds did not differ among the 3 groups. Logistic regression analyses revealed that, compared with the healthy control group, the dementia with Lewy bodies group was significantly associated with the presence of lobar cerebral microbleeds after adjusting for age, sex, nonlobar cerebral microbleeds, white matter hyperintensities, and other vascular risk factors (odds ratio, 4.39 [95% CI, 1.27-15.25]). However, compared with the healthy control group, the Parkinson disease dementia group was not significantly associated with lobar cerebral microbleeds. This study showed that patients with dementia with Lewy bodies had a greater burden of cerebral microbleeds and exhibited a lobar predominance of cerebral

  17. Individual housing-based socioeconomic status predicts risk of accidental falls among adults.

    PubMed

    Ryu, Euijung; Juhn, Young J; Wheeler, Philip H; Hathcock, Matthew A; Wi, Chung-Il; Olson, Janet E; Cerhan, James R; Takahashi, Paul Y

    2017-07-01

    Accidental falls are a major public health concern among people of all ages. Little is known about whether an individual-level housing-based socioeconomic status measure is associated with the risk of accidental falls. Among 12,286 Mayo Clinic Biobank participants residing in Olmsted County, Minnesota, subjects who experienced accidental falls between the biobank enrollment and September 2014 were identified using ICD-9 codes evaluated at emergency departments. HOUSES (HOUsing-based Index of SocioEconomic Status), a socioeconomic status measure based on individual housing features, was also calculated. Cox regression models were utilized to assess the association of the HOUSES (in quartiles) with accidental fall risk. Seven hundred eleven (5.8%) participants had at least one emergency room visit due to an accidental fall during the study period. Subjects with higher HOUSES were less likely to experience falls in a dose-response manner (hazard ratio: 0.58; 95% confidence interval: 0.44-0.76 for comparing the highest to the lowest quartile). In addition, the HOUSES was positively associated with better health behaviors, social support, and functional status. The HOUSES is inversely associated with accidental fall risk requiring emergency care in a dose-response manner. The HOUSES may capture falls-related risk factors through housing features and socioeconomic status-related psychosocial factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Procedures, placement, and risks of further abuse after Munchausen syndrome by proxy, non-accidental poisoning, and non-accidental suffocation

    PubMed Central

    Davis, P; McClure, R; Rolfe, K; Chessman, N; Pearson, S; Sibert, J; Meadow, R

    1998-01-01

    OBJECTIVES—To investigate outcome, management, and prevention in Munchausen syndrome by proxy, non-accidental poisoning, and non-accidental suffocation.
DESIGN—Ascertainment through British Paediatric Surveillance Unit and questionnaires to responding paediatricians.
SETTING—The UK and Republic of Ireland, September 1992 to August 1994.
SUBJECTS—Children under 14 years diagnosed with the above.
MAIN OUTCOME MEASURES—Placement and child protection measures for victims and siblings; morbidity and reabuse rates for victims; abuse of siblings; prosecution of perpetrators.
RESULTS—Outcome data for 119 with median follow up of 24 months (range 12 to 44 months). No previously diagnosed factitious disease was found to have been caused by genuine disease. Forty six children were allowed home without conditions at follow up. Children who had suffered from suffocation, non-accidental poisoning, direct harm, and those under 5 years were less likely to go home.
 Twenty seven (24%) children still had symptoms or signs as a result of the abuse at follow up; 108/120 were originally on a child protection register and 35/111 at follow up. Twenty nine per cent (34/118) of the perpetrators had been prosecuted and most convicted; 17% of the milder cases of Munchausen syndrome by proxy allowed home were reabused. Evidence in siblings suggests that in 50% of families with a suffocated child and 40% with non-accidental poisoning there would be further abuse, some fatal.
CONCLUSIONS—This type of abuse is severe with high mortality, morbidity, family disruption, reabuse, and harm to siblings. A very cautious approach for child protection with reintroduction to home only if circumstances are especially favourable is advised. Paediatric follow up by an expert in child protection should also occur.

 PMID:9613350

  19. Elevated Markers of Vascular Remodeling and Arterial Stiffness Are Associated with Neurocognitive Function in Older HIV+ Adults on Suppressive Antiretroviral Therapy

    PubMed Central

    Montoya, Jessica L.; Iudicello, Jennifer; Fazeli, Pariya L.; Hong, Suzi; Potter, Michael; Ellis, Ronald J.; Grant, Igor; Letendre, Scott L.; Moore, David J.

    2016-01-01

    Background HIV is associated with elevated markers of vascular remodeling that may contribute to arterial fibrosis and stiffening, and changes in pulse pressure (PP). These changes may, in turn, deleteriously affect autoregulation of cerebral blood flow and neurocognitive function. Methods To evaluate these mechanisms, we studied markers of vascular remodeling, PP, and neurocognitive function among older (≥50 years of age) HIV-infected (HIV+; n = 72) and HIV-seronegative (HIV-; n = 36) adults. Participants completed standardized neurobehavioral and neuromedical assessments. Neurocognitive functioning was evaluated using a well-validated comprehensive battery. Three plasma biomarkers of vascular remodeling (i.e., angiopoietin 2, Tie-2, and vascular endothelial growth factor; VEGF) were collected. Results HIV+ and HIV- participants had similar levels of plasma Ang-2 (p = .48), Tie-2 (p = .27), VEGF (p = .18), and PP (p = .98). In a multivariable regression model, HIV interacted with Tie-2 (β = .41, p < .01) and VEGF (β = −.43, p = .01) on neurocognitive function, such that lower Tie-2 and higher VEGF values were associated with worse neurocognitive function for HIV+ participants. Greater Tie-2 values were associated with increased PP (r = .31, p < .01). In turn, PP demonstrated a quadratic association with neurocognitive function (β = −.33, p = .01), such that lower and higher, relative to mean sample, PP values were associated with worse neurocognitive function. Conclusions These findings indicate that vascular remodeling and altered cerebral blood flow autoregulation contribute to neurocognitive function. Furthermore, HIV moderates the association between vascular remodeling and neurocognitive function but not the association between PP and neurocognitive function. PMID:27828873

  20. Betulinic acid, a natural PDE inhibitor restores hippocampal cAMP/cGMP and BDNF, improve cerebral blood flow and recover memory deficits in permanent BCCAO induced vascular dementia in rats.

    PubMed

    Kaundal, Madhu; Zameer, Saima; Najmi, Abul Kalam; Parvez, Suhel; Akhtar, Mohd

    2018-08-05

    Vascular dementia (VaD) is the second most common form of senile dementia, embraces memory deficits, neuroinflammation, executive function damage, mood and behavioral changes and abnormal cerebral blood flow. The purpose of the study was to explore the therapeutic potential of betulinic acid in bilateral common carotid artery occlusion (BCCAO) induced VaD in experimental rats. VaD was induced by BCCAO in rats and betulinic acid (10 and 15 mg/kg/day po) was administered 1 week after surgery. The cerebral blood pressure of the animal was recorded before and after the treatment using Laser Doppler flow meter. Object recognition task for non-spatial, Morris water maze for spatial and locomotor activity was performed to evaluate behavioral changes in rats. At the end of the study, animals were decapitated and hippocampus was separated to perform biochemical, neuroinflammatory and second messengers cAMP/cGMP analysis. Histology was done to study the brain pathophysiology. BCCAO surgery was able to significantly impaired memory in rats as observed behavioral and biochemical parameters. Moreover, BA demonstrated a neuroprotective effect in a dose-dependent manner. BA was able to re-establish cerebral blood flow, restore behavioral parameters and showed significant improvements in the as cAMP,cGMP and BDNF levels, restrain the oxidative stress and inflammatory parameters. In histopathology, betulinic acid treated groups showed a decrease in microgliosis and less pathological abnormalities comparable to diseased rat's brain. The observed effect might be attributed to the neuroprotective potential of betulinic acid and its ability to restore cognitive impairment and hippocampal neurochemistry in VaD. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Arterial changes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in relation to pathogenesis of diffuse myelin loss of cerebral white matter: examination of cerebral medullary arteries by reconstruction of serial sections of an autopsy case.

    PubMed

    Okeda, Riki; Arima, Kunimasa; Kawai, Mitsuru

    2002-11-01

    There is little information regarding the pathogenesis underlying diffuse myelin loss in the cerebral white matter and sparing of the U fibers in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), in which the medial smooth muscle cells of systemic arteries are characteristically involved. We sought to examine the precise extent and severity of changes in the cerebral arteries in an autopsy case of CADASIL in relation to pathogenesis of the diffuse myelin loss. We reconstructed 1000 serial sections of the frontal cerebral medullary arteries of an autopsy subject, which was the first identified Japanese case of CADASIL, as confirmed by the presence of ultrastructural deposits of granular osmiophilic material in the media of some visceral arteries and by genetic analysis. We reconstructed 11 medullary arteries of the frontal lobe showing diffuse myelin loss and atrophy of the white matter with sparing of the U fibers. All of these showed complete loss of medial smooth muscle cells over their entire length and severe adventitial fibrosis. Although intimal fibrosis or hyalinosis was present, luminal occlusion was scarce. These changes were also observed in the small and large arachnoidal arteries but were relatively mild in the latter and in the cortical and subcortical medullary arteries. These arterial changes resulted in transformation of the cerebral arteries, in particular almost all the medullary arteries, to a so-called earthen pipe state. This supports the reported findings of a reduction in vascular reactivity to fluctuations in CO2 levels and systemic blood pressure in CADASIL.

  2. 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

  3. Severe visual loss and cerebral infarction after injection of hyaluronic acid gel.

    PubMed

    Kim, Eung Gyu; Eom, Tae Kyung; Kang, Seok Joo

    2014-01-01

    We report a case of a 23-year-old man with cerebral infarction and permanent visual loss after injection of a hyaluronic acid gel filler for augmentation rhinoplasty. The patient was admitted to the hospital with complaints of loss of vision in the right eye, facial paralysis on the right side, and paralysis of the left limbs with severe pain during augmentation rhinoplasty with filler injection. Brain magnetic resonance imaging and computed tomography showed ophthalmic artery obstruction and right middle cerebral artery infarction. Acute thrombolysis was performed to treat the infarction; however, the patient's condition did not improve. Intracerebral hemorrhage in the right temporal/frontal/occipital/parietal lobe, subarachnoid hemorrhage, and midline shifting were observed on brain computed tomography after 24 hours after thrombolysis. Emergency decompressive craniectomy was performed. After the surgery, the patient continued to experience drowsiness, with no improvement in visual loss and motor weakness. Three months later, he could walk with cane. This case indicates that surgeons who administer filler injections should be familiar with the possibility of accidental intravascular injection and should explain the adverse effects of fillers to patients before surgery.

  4. 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.

  5. Rutin protects against cognitive deficits and brain damage in rats with chronic cerebral hypoperfusion.

    PubMed

    Qu, Jie; Zhou, Qiong; Du, Ying; Zhang, Wei; Bai, Miao; Zhang, Zhuo; Xi, Ye; Li, Zhuyi; Miao, Jianting

    2014-08-01

    Chronic cerebral hypoperfusion is a critical causative factor for the development of cognitive decline and dementia in the elderly, which involves many pathophysiological processes. Consequently, inhibition of several pathophysiological pathways is an attractive therapeutic strategy for this disorder. Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage caused by chronic cerebral hypoperfusion remains unknown. Here, we investigated the neuroprotective effect of rutin on cognitive impairments and the potential mechanisms underlying its action in rats with chronic cerebral hypoperfusion. We used Sprague-Dawley rats with permanent bilateral common carotid artery occlusion (BCCAO), a well-established model of chronic cerebral hypoperfusion. After rutin treatment for 12 weeks, the neuroprotective effect of rutin in rats was evaluated by behavioural tests, biochemical and histopathological analyses. BCCAO rats showed marked cognitive deficits, which were improved by rutin treatment. Moreover, BCCAO rats exhibited central cholinergic dysfunction, oxidative damage, inflammatory responses and neuronal damage in the cerebral cortex and hippocampus, compared with sham-operated rats. All these effects were significantly alleviated by treatment with rutin. Our results provide new insights into the pharmacological actions of rutin and suggest that rutin has multi-targeted therapeutical potential on cognitive deficits associated with conditions with chronic cerebral hypoperfusion such as vascular dementia and Alzheimer's disease. © 2014 The British Pharmacological Society.

  6. Accidental fetal lacerations during cesarean delivery: experience in an Italian level III university hospital.

    PubMed

    Dessole, Salvatore; Cosmi, Erich; Balata, Antonio; Uras, Luisa; Caserta, Donatella; Capobianco, Giampiero; Ambrosini, Guido

    2004-11-01

    The purpose of this study was to investigate the incidence, type, location, and risk factors of accidental fetal lacerations during cesarean delivery. Total deliveries, cesarean deliveries, and neonatal records for documented accidental fetal lacerations were reviewed retrospectively in our level III university hospital. The gestational age, the presenting part of the fetus, the cesarean delivery indication, the type of incision, and the surgeon who performed the procedure were recorded. Cesarean deliveries were divided into scheduled, unscheduled, and emergency procedures. Fetal lacerations were divided into mild, moderate, and severe. Neonatal follow-up examinations regarding laceration sequelae were available for 6 months. Of 14926 deliveries, 3108 women were delivered by cesarean birth (20.82%). Neonatal records documented 97 accidental fetal lacerations. Of these accidental lacerations, 94 were mild; 2 were moderate, and 1 was severe. The overall rate of accidental fetal laceration per cesarean delivery was 3.12%; the accidental laceration rate in the cohort of fetuses was 2.46%. The crude odds ratios were 0.34 for scheduled procedures, 0.57 for unscheduled procedures, and 1.7 for emergency procedures. The risk for fetal accidental lacerations was higher in fetuses who underwent emergency cesarean birth and lower for unscheduled and scheduled cesarean births (P < .001). Fetal accidental laceration may occur during cesarean delivery; the incidence is significantly higher during emergency cesarean delivery compared with elective procedures. The patient should be counseled about the occurrence of fetal laceration during cesarean delivery to avoid litigation.

  7. Voluntary respiratory control and cerebral blood flow velocity upon ice-water immersion.

    PubMed

    Mantoni, Teit; Rasmussen, Jakob Højlund; Belhage, Bo; Pott, Frank Christian

    2008-08-01

    In non-habituated subjects, cold-shock response to cold-water immersion causes rapid reduction in cerebral blood flow velocity (approximately 50%) due to hyperventilation, increasing risk of syncope, aspiration, and drowning. Adaptation to the response is possible, but requires several cold immersions. This study examines whether thorough instruction enables non-habituated persons to attenuate the ventilatory component of cold-shock response. There were nine volunteers (four women) who were lowered into a 0 degrees C immersion tank for 60 s. Middle cerebral artery mean velocity (CBFV) was measured together with ventilatory parameters and heart rate before, during, and after immersion. Within seconds after immersion in ice-water, heart rate increased significantly from 95 +/- 8 to 126 +/- 7 bpm (mean +/- SEM). Immersion was associated with an elevation in respiratory rate (from 12 +/- 3 to 21 +/- 5 breaths, min(-1)) and tidal volume (1022 +/- 142 to 1992 +/- 253 ml). Though end-tidal carbon dioxide tension decreased from 4.9 +/- 0.13 to 3.9 +/- 0.21 kPa, CBFV was insignificantly reduced by 7 +/- 4% during immersion with a brief nadir of 21 +/- 4%. Even without prior cold-water experience, subjects were able to suppress reflex hyperventilation following ice-water immersion, maintaining the cerebral blood flow velocity at a level not associated with impaired consciousness. This study implies that those susceptible to accidental cold-water immersion could benefit from education in cold-shock response and the possibility of reducing the ventilatory response voluntarily.

  8. Hemodialysis as a treatment of severe accidental hypothermia.

    PubMed

    Caluwé, Rogier; Vanholder, Raymond; Dhondt, Annemieke

    2010-03-01

    We describe a case of severe accidental hypothermia (core body temperature 23.2 degrees C) successfully treated with hemodialysis in a diabetic patient with preexisting renal insufficiency. Consensus exists about cardiopulmonary bypass as the treatment of choice in cases of severe accidental hypothermia with cardiac arrest. Prospective randomized controlled trials comparing the different rewarming modalities for hemodynamically stable patients with hypothermia, however, are lacking. In our opinion, the choice of a rewarming technique should be patient tailored, knowing that hemodialysis is an efficient, minimally invasive, and readily available technique with the advantage of providing electrolyte support.

  9. Planning-free cerebral blood flow territory mapping in patients with intracranial arterial stenosis

    PubMed Central

    Arteaga, Daniel F; Strother, Megan K; Davis, L Taylor; Fusco, Matthew R; Faraco, Carlos C; Roach, Brent A; Scott, Allison O

    2016-01-01

    A noninvasive method for quantifying cerebral blood flow and simultaneously visualizing cerebral blood flow territories is vessel-encoded pseudocontinuous arterial spin labeling MRI. However, obstacles to acquiring such information include limited access to the methodology in clinical centers and limited work on how clinically acquired vessel-encoded pseudocontinuous arterial spin labeling data correlate with gold-standard methods. The purpose of this work is to develop and validate a semiautomated pipeline for the online quantification of cerebral blood flow maps and cerebral blood flow territories from planning-free vessel-encoded pseudocontinuous arterial spin labeling MRI with gold-standard digital subtraction angiography. Healthy controls (n = 10) and intracranial atherosclerotic disease patients (n = 34) underwent 3.0 T MRI imaging including vascular (MR angiography) and hemodynamic (cerebral blood flow-weighted arterial spin labeling) MRI. Patients additionally underwent catheter and/or CT angiography. Variations in cross-territorial filling were grouped according to diameters of circle of Willis vessels in controls. In patients, Cohen’s k-statistics were computed to quantify agreement in perfusion patterns between vessel-encoded pseudocontinuous arterial spin labeling and angiography. Cross-territorial filling patterns were consistent with circle of Willis anatomy. The intraobserver Cohen's k-statistics for cerebral blood flow territory and digital subtraction angiography perfusion agreement were 0.730 (95% CI = 0.593–0.867; reader one) and 0.708 (95% CI = 0.561–0.855; reader two). These results support the feasibility of a semiautomated pipeline for evaluating major neurovascular cerebral blood flow territories in patients with intracranial atherosclerotic disease. PMID:27389177

  10. A descriptive study of accidental skeletal injuries and non-accidental skeletal injuries of child maltreatment.

    PubMed

    Ghanem, Maha A H; Moustafa, Tarek A; Megahed, Haidy M; Salama, Naglaa; Ghitani, Sara A

    2018-02-01

    Lack of awareness and recognition of child maltreatment is the major reason behind underreporting. All victims often interact with the health care system for routine or emergency care. In several research works, non-accidental fractures are the second most common injury in maltreated children and it is represented up to one-third of cases. To determine the incidence of different types of accidental and non-accidental skeletal injuries among children, estimate the severity of injuries according to the modified injury severity score and to determine the degree of fractures either closed or opened (Gustiloe-Anderson open fracture classification). Moreover, identifying fractures resulting from child abuse and neglect. This aimed for early recognition of non-accidental nature of fractures in child maltreatment that can prevent further morbidity and mortality. A descriptive study was carried out on all children (109) with skeletal injuries who were admitted to both Main Alexandria and El-Hadara Orthopedic and Traumatology University Hospitals during six months. History, physical examination and investigations were done for the patients. A detailed questionnaire was taken to diagnose child abuse and neglect. Gustiloe-Anderson open fracture classification was used to estimate the degree of open fractures. Out of 109 children, twelve cases (11%) were categorized as child maltreatment. One case was physical abuse, eight cases (7.3%) were child neglect and three cases (2.8%) were labour exploitation. Road traffic accidents (RTA) was the commonest cause of skeletal injuries followed by falling from height. Regarding falls, they included 4 cases of stair falls in neglected children and another four cases of falling from height (balcony/window). The remaining 36 cases of falls were accidental. The skeletal injuries were in the form of fractures in 99 cases, dislocation in two cases, both fracture and/or dislocation in three cases, and bone deformity from brachial plexus injury

  11. 21 CFR 369.9 - General warnings re accidental ingestion by children.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false General warnings re accidental ingestion by... SERVICES (CONTINUED) DRUGS FOR HUMAN USE INTERPRETATIVE STATEMENTS RE WARNINGS ON DRUGS AND DEVICES FOR OVER-THE-COUNTER SALE Definitions and Interpretations § 369.9 General warnings re accidental ingestion...

  12. 21 CFR 369.9 - General warnings re accidental ingestion by children.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false General warnings re accidental ingestion by... SERVICES (CONTINUED) DRUGS FOR HUMAN USE INTERPRETATIVE STATEMENTS RE WARNINGS ON DRUGS AND DEVICES FOR OVER-THE-COUNTER SALE Definitions and Interpretations § 369.9 General warnings re accidental ingestion...

  13. Magnetic Resonance Imaging Criteria for Thrombolysis in Hyperacute Cerebral Infarction

    PubMed Central

    AHMETGJEKAJ, ILIR; KABASHI-MUÇAJ, SERBEZE; LASCU, LUANA CORINA; KABASHI, ANTIGONA; BONDARI, A.; BONDARI, SIMONA; DEDUSHI-HOTI, KRESHNIKE; BIÇAKU, ARDIAN; SHATRI, JETON

    2014-01-01

    Purpose: Selection of patients with cerebral infarction for MRI that is suitable for thrombolytic therapy as an emerging application. Although the efficiency of the therapy with i.v. tissue plasminogen activator (tPA) within 3 hours after onset of symptoms has been proven in selected patients with CT, now these criteria are determined by MRI, as the data we gather are fast and accurate in the first hours. Material and methods: MRI screening in patients with acute cerebral infarction before application of thrombolytic therapy was done in a UCC Mannheim in Germany. Unlike trials with CT, MRI studies demonstrated the benefits of therapy up to 6 hours after the onset of symptoms. We studied 21 patients hospitalized in Clinic of Neuroradiology at University Clinical Centre in Mannheim-Germany. They all undergo brain MRI evaluation for stroke. This article reviews literature that has followed application of thrombolysis in patients with cerebral infarction based on MRI. Results: We have analyzed the MRI criteria for i.v. application of tPA at this University Centre. Alongside the personal viewpoints of clinicians, survey reveals a variety of clinical aspects and MRI features that are opened for further more exploration: therapeutic effects, the use of the MRI angiography, dynamics, and other. Conclusions: MRI is a tested imaging method for rapid evaluation of patients with hyperacute cerebral infarction, replacing the use of CT imaging and clinical features. MRI criteria for thrombolytic therapy are being applied in some cerebral vascular centres. In Kosovo, the application of thrombolytic therapy has not started yet. PMID:25729591

  14. Magnetic resonance imaging criteria for thrombolysis in hyperacute cerebral infarction.

    PubMed

    Ahmetgjekaj, Ilir; Kabashi-Muçaj, Serbeze; Lascu, Luana Corina; Kabashi, Antigona; Bondari, A; Bondari, Simona; Dedushi-Hoti, Kreshnike; Biçaku, Ardian; Shatri, Jeton

    2014-01-01

    Selection of patients with cerebral infarction for MRI that is suitable for thrombolytic therapy as an emerging application. Although the efficiency of the therapy with i.v. tissue plasminogen activator (tPA) within 3 hours after onset of symptoms has been proven in selected patients with CT, now these criteria are determined by MRI, as the data we gather are fast and accurate in the first hours. MRI screening in patients with acute cerebral infarction before application of thrombolytic therapy was done in a UCC Mannheim in Germany. Unlike trials with CT, MRI studies demonstrated the benefits of therapy up to 6 hours after the onset of symptoms. We studied 21 patients hospitalized in Clinic of Neuroradiology at University Clinical Centre in Mannheim-Germany. They all undergo brain MRI evaluation for stroke. This article reviews literature that has followed application of thrombolysis in patients with cerebral infarction based on MRI. We have analyzed the MRI criteria for i.v. application of tPA at this University Centre. Alongside the personal viewpoints of clinicians, survey reveals a variety of clinical aspects and MRI features that are opened for further more exploration: therapeutic effects, the use of the MRI angiography, dynamics, and other. MRI is a tested imaging method for rapid evaluation of patients with hyperacute cerebral infarction, replacing the use of CT imaging and clinical features. MRI criteria for thrombolytic therapy are being applied in some cerebral vascular centres. In Kosovo, the application of thrombolytic therapy has not started yet.

  15. Smooth muscle‐generated methylglyoxal impairs endothelial cell‐mediated vasodilatation of cerebral microvessels in type 1 diabetic rats

    PubMed Central

    Alomar, Fadhel; Singh, Jaipaul; Jang, Hee‐Seong; Rozanzki, George J; Shao, Chun Hong; Padanilam, Babu J; Mayhan, William G

    2016-01-01

    Background and Purpose Endothelial cell‐mediated vasodilatation of cerebral arterioles is impaired in individuals with Type 1 diabetes (T1D). This defect compromises haemodynamics and can lead to hypoxia, microbleeds, inflammation and exaggerated ischaemia‐reperfusion injuries. The molecular causes for dysregulation of cerebral microvascular endothelial cells (cECs) in T1D remains poorly defined. This study tests the hypothesis that cECs dysregulation in T1D is triggered by increased generation of the mitochondrial toxin, methylglyoxal, by smooth muscle cells in cerebral arterioles (cSMCs). Experimental Approach Endothelial cell‐mediated vasodilatation, vascular transcytosis inflammation, hypoxia and ischaemia‐reperfusion injury were assessed in brains of male Sprague‐Dawley rats with streptozotocin‐induced diabetes and compared with those in diabetic rats with increased expression of methylglyoxal‐degrading enzyme glyoxalase‐I (Glo‐I) in cSMCs. Key Results After 7–8 weeks of T1D, endothelial cell‐mediated vasodilatation of cerebral arterioles was impaired. Microvascular leakage, gliosis, macrophage/neutrophil infiltration, NF‐κB activity and TNF‐α levels were increased, and density of perfused microvessels was reduced. Transient occlusion of a mid‐cerebral artery exacerbated ischaemia‐reperfusion injury. In cSMCs, Glo‐I protein was decreased, and the methylglyoxal‐synthesizing enzyme, vascular adhesion protein 1 (VAP‐1) and methylglyoxal were increased. Restoring Glo‐I protein in cSMCs of diabetic rats to control levels via gene transfer, blunted VAP‐1 and methylglyoxal increases, cECs dysfunction, microvascular leakage, inflammation, ischaemia‐reperfusion injury and increased microvessel perfusion. Conclusions and Implications Methylglyoxal generated by cSMCs induced cECs dysfunction, inflammation, hypoxia and exaggerated ischaemia‐reperfusion injury in diabetic rats. Lowering methylglyoxal produced by cSMCs may be a

  16. [Experimental study of angiography using vascular interventional robot-2(VIR-2)].

    PubMed

    Tian, Zeng-min; Lu, Wang-sheng; Liu, Da; Wang, Da-ming; Guo, Shu-xiang; Xu, Wu-yi; Jia, Bo; Zhao, De-peng; Liu, Bo; Gao, Bao-feng

    2012-06-01

    To verify the feasibility and safety of new vascular interventional robot system used in vascular interventional procedures. Vascular interventional robot type-2 (VIR-2) included master-slave parts of body propulsion system, image navigation systems and force feedback system, the catheter movement could achieve under automatic control and navigation, force feedback was integrated real-time, followed by in vitro pre-test in vascular model and cerebral angiography in dog. Surgeon controlled vascular interventional robot remotely, the catheter was inserted into the intended target, the catheter positioning error and the operation time would be evaluated. In vitro pre-test and animal experiment went well; the catheter can enter any branch of vascular. Catheter positioning error was less than 1 mm. The angiography operation in animal was carried out smoothly without complication; the success rate of the operation was 100% and the entire experiment took 26 and 30 minutes, efficiency was slightly improved compared with the VIR-1, and the time what staff exposed to the DSA machine was 0 minute. The resistance of force sensor can be displayed to the operator to provide a security guarantee for the operation. No surgical complications. VIR-2 is safe and feasible, and can achieve the catheter remote operation and angiography; the master-slave system meets the characteristics of traditional procedure. The three-dimensional image can guide the operation more smoothly; force feedback device provides remote real-time haptic information to provide security for the operation.

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

    PubMed

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

    2007-05-01

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

  18. [Relation between expression of cerebral beta-APP in the chronic alcoholism rats and death caused by TSAH].

    PubMed

    Wei, Lai; Lei, Huai-Cheng; Yu, Xiao-Jun; Lai, Xiao-Ping; Qian, Hong; Xu, Xiao-Hu; Zhu, Fang-Cheng

    2013-04-01

    By observing the cerebral beta-amyloid precursor protein (beta-APP) expression in the chronic alcoholism rats with slight cerebral injury, to discuss the correlation of chronic alcoholism and death caused by traumatic subarachnoid haemorrhage (TSAH). Sixty male SD rats were randomly divided into watering group, watering group with strike, alcoholism group and alcoholism group with strike. Among them, the alcohol was used for continuous 4 weeks in alcoholism groups and the concussion was made in groups with strike. In each group, HE staining and immunohistochemical staining of the cerebral tissues were done and the results were analyzed by the histopathologic image system. In watering group, there was no abnormal. In watering group with strike, mild neuronic congestion was found. In alcoholism group, vascular texture on cerebral surface was found. And the neurons arranged in disorder with dilated intercellular space. In alcoholism group with strike, diffuse congestion on cerebral surface was found. And there was TSAH with thick-layer patches around brainstem following irregular axonotmesis. The quantity of beta-APP IOD in alcoholism group was significantly higher in the frontal lobe, hippocampus, cerebellum, brainstem than those in watering group with strike and alcoholism group with strike. The cerebral tissues with chronic alcoholism, due to the decreasing tolerance, could cause fatal TSAH and pathological changes in cerebral tissues of rats under slight cerebral injury.

  19. Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries.

    PubMed

    Rutkai, Ibolya; Dutta, Somhrita; Katakam, Prasad V; Busija, David W

    2015-11-01

    Mitochondrial respiration has never been directly examined in intact cerebral arteries. We tested the hypothesis that mitochondrial energetics of large cerebral arteries ex vivo are sex dependent. The Seahorse XFe24 analyzer was used to examine mitochondrial respiration in isolated cerebral arteries from adult male and female Sprague-Dawley rats. We examined the role of nitric oxide (NO) on mitochondrial respiration under basal conditions, using N(ω)-nitro-l-arginine methyl ester, and following pharmacological challenge using diazoxide (DZ), and also determined levels of mitochondrial and nonmitochondrial proteins using Western blot, and vascular diameter responses to DZ. The components of mitochondrial respiration including basal respiration, ATP production, proton leak, maximal respiration, and spare respiratory capacity were elevated in females compared with males, but increased in both male and female arteries in the presence of the NOS inhibitor. Although acute DZ treatment had little effect on mitochondrial respiration of male arteries, it decreased the respiration in female arteries. Levels of mitochondrial proteins in Complexes I-V and the voltage-dependent anion channel protein were elevated in female compared with male cerebral arteries. The DZ-induced vasodilation was greater in females than in males. Our findings show that substantial sex differences in mitochondrial respiratory dynamics exist in large cerebral arteries and may provide the mechanistic basis for observations that the female cerebral vasculature is more adaptable after injury. Copyright © 2015 the American Physiological Society.

  20. Brain vascular heterogeneity: implications for disease pathogenesis and design of in vitro blood-brain barrier models.

    PubMed

    Noumbissi, Midrelle E; Galasso, Bianca; Stins, Monique F

    2018-04-23

    The vertebrate blood-brain barrier (BBB) is composed of cerebral microvascular endothelial cells (CEC). The BBB acts as a semi-permeable cellular interface that tightly regulates bidirectional molecular transport between blood and the brain parenchyma in order to maintain cerebral homeostasis. The CEC phenotype is regulated by a variety of factors, including cells in its immediate environment and within functional neurovascular units. The cellular composition of the brain parenchyma surrounding the CEC varies between different brain regions; this difference is clearly visible in grey versus white matter. In this review, we discuss evidence for the existence of brain vascular heterogeneity, focusing on differences between the vessels of the grey and white matter. The region-specific differences in the vasculature of the brain are reflective of specific functions of those particular brain areas. This BBB-endothelial heterogeneity may have implications for the course of pathogenesis of cerebrovascular diseases and neurological disorders involving vascular activation and dysfunction. This heterogeneity should be taken into account when developing BBB-neuro-disease models representative of specific brain areas.

  1. LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-β.

    PubMed

    Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

    2012-11-14

    Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer's disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in cerebrovasculature, in particular in vascular smooth muscle cells. Previous studies have indicated a role of LRP1 in endothelial cells in transcytosing Aβ out of the brain across the BBB; however, whether this represents a significant pathway for brain Aβ clearance remains controversial. Here, we demonstrate that Aβ can be cleared locally in the cerebrovasculature by an LRP1-dependent endocytic pathway in smooth muscle cells. The uptake and degradation of both endogenous and exogenous Aβ were significantly reduced in LRP1-suppressed human brain vascular smooth muscle cells. Conditional deletion of Lrp1 in vascular smooth muscle cell in amyloid model APP/PS1 mice accelerated brain Aβ accumulation and exacerbated Aβ deposition as amyloid plaques and CAA without affecting Aβ production. Our results demonstrate that LRP1 is a major Aβ clearance receptor in cerebral vascular smooth muscle cell and a disturbance of this pathway contributes to Aβ accumulation. These studies establish critical functions of the cerebrovasculature system in Aβ metabolism and identify a new pathway involved in the pathogenesis of both AD and CAA.

  2. LRP1 in Brain Vascular Smooth Muscle Cells Mediates Local Clearance of Alzheimer's Amyloid-β

    PubMed Central

    Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

    2012-01-01

    Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer’s disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in cerebrovasculature, in particular in vascular smooth muscle cells. Previous studies have indicated a role of LRP1 in endothelial cells in transcytosing Aβ out of the brain across the BBB; however, whether this represents a significant pathway for brain Aβ clearance remains controversial. Here, we demonstrate that Aβ can be cleared locally in the cerebrovasculature by an LRP1-dependent endocytic pathway in smooth muscle cells. The uptake and degradation of both endogenous and exogenous Aβ were significantly reduced in LRP1-suppressed human brain vascular smooth muscle cells. Conditional deletion of Lrp1 in vascular smooth muscle cell in amyloid model APP/PS1 mice accelerated brain Aβ accumulation and exacerbated Aβ deposition as amyloid plaques and CAA without affecting Aβ production. Our results demonstrate that LRP1 is a major Aβ clearance receptor in cerebral vascular smooth muscle cell and a disturbance of this pathway contributes to Aβ accumulation. These studies establish critical functions of the cerebrovasculature system in Aβ metabolism and identify a new pathway involved in the pathogenesis of both AD and CAA. PMID:23152628

  3. Night work, long work weeks, and risk of accidental injuries. A register-based study.

    PubMed

    Larsen, Ann D; Hannerz, Harald; Møller, Simone V; Dyreborg, Johnny; Bonde, Jens Peter; Hansen, Johnni; Kolstad, Henrik A; Hansen, Åse Marie; Garde, Anne Helene

    2017-11-01

    Objectives The aims of this study were to (i) investigate the association between night work or long work weeks and the risk of accidental injuries and (ii) test if the association is affected by age, sex or socioeconomic status. Methods The study population was drawn from the Danish version of the European Labour Force Survey from 1999-2013. The current study was based on 150 438 participants (53% men and 47% women). Data on accidental injuries were obtained at individual level from national health registers. We included all 20-59-year-old employees working ≥32 hours a week at the time of the interview. We used Poisson regression to estimate the relative rates (RR) of accidental injuries as a function of night work or long work weeks (>40 hours per week) adjusted for year of interview, sex, age, socioeconomic status (SES), industry, and weekly working hours or night work. Age, sex and SES were included as two-way interactions. Results We observed 23 495 cases of accidental injuries based on 273 700 person years at risk. Exposure to night work was statistically significantly associated with accidental injuries (RR 1.11, 99% CI 1.06-1.17) compared to participants with no recent night work. No associations were found between long work weeks (>40 hours) and accidental injuries. Conclusion We found a modest increased risk of accidental injuries when reporting night work. No associations between long work weeks and risk of accidental injuries were observed. Age, sex and SES showed no trends when included as two-way interactions.

  4. Combined Direct and Indirect Cerebral Revascularization Using Local and Flow-Through Flaps.

    PubMed

    Azadgoli, Beina; Leland, Hyuma A; Wolfswinkel, Erik M; Bakhsheshian, Joshua; Russin, Jonathan J; Carey, Joseph N

    2018-02-01

     Extracranial-intracranial bypass is indicated in ischemic disease such as moyamoya, certain intracranial aneurysms, and other complex neurovascular diseases. In this article, we present our series of local and flow-through flaps for cerebral revascularization as an additional tool to provide direct and indirect revascularization and/or soft tissue coverage.  A retrospective review of a prospectively maintained database was performed identifying nine patients. Ten direct arterial bypass procedures with nine indirect revascularization and/or soft tissue reconstruction were performed.  Indications for arterial bypass included intracranial aneurysm ( n  = 2) and moyamoya disease ( n  = 8). Indications for soft tissue transfer included infected cranioplasty (one) and indirect cerebral revascularization (eight). Four flow-through flaps and five pedicled flaps were used including a flow-through radial forearm fasciocutaneous flap (one), flow-through radial forearm fascial flaps (three), and pedicled temporoparietal fascial (TPF) flaps with distal end anastomosis (five). The superficial temporal vessels (seven) and facial vessels (two) were used as the vascular inflow. Arterial bypass was established into the middle cerebral artery (six) and anterior communicating artery (three). There were no intraoperative complications. All flaps survived with no donor-site complications. In one case of flow-through TPF flap, the direct graft failed, but the indirect flap remained vascularized.  Local and flow-through flaps can improve combined direct and indirect revascularization and provide soft tissue reconstruction. Minimal morbidity has been encountered in early outcomes though long-term results remain under investigation for these combined neurosurgery and plastic surgery procedures.  The level of evidence is IV. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. Macro-to-micro cortical vascular imaging underlies regional differences in ischemic brain

    NASA Astrophysics Data System (ADS)

    Dziennis, Suzan; Qin, Jia; Shi, Lei; Wang, Ruikang K.

    2015-05-01

    The ability to non-invasively monitor and quantify hemodynamic responses down to the capillary level is important for improved diagnosis, treatment and management of neurovascular disorders, including stroke. We developed an integrated multi-functional imaging system, in which synchronized dual wavelength laser speckle contrast imaging (DWLS) was used as a guiding tool for optical microangiography (OMAG) to test whether detailed vascular responses to experimental stroke in male mice can be evaluated with wide range sensitivity from arteries and veins down to the capillary level. DWLS enabled rapid identification of cerebral blood flow (CBF), prediction of infarct area and hemoglobin oxygenation over the whole mouse brain and was used to guide the OMAG system to hone in on depth information regarding blood volume, blood flow velocity and direction, vascular architecture, vessel diameter and capillary density pertaining to defined regions of CBF in response to ischemia. OMAG-DWLS is a novel imaging platform technology to simultaneously evaluate multiple vascular responses to ischemic injury, which can be useful in improving our understanding of vascular responses under pathologic and physiological conditions, and ultimately facilitating clinical diagnosis, monitoring and therapeutic interventions of neurovascular diseases.

  6. The big chill: accidental hypothermia.

    PubMed

    Davis, Robert Allan

    2012-01-01

    A potential cause of such emergent issues as cardiac arrhythmias, hypotension, and fluid and electrolyte shifts, accidental hypothermia can be deadly, is common among trauma patients, and is often difficult to recognize. The author discusses predisposing conditions, the classic presentation, and the effects on normal thermoregulatory processes; explains how to conduct a systems assessment of the hypothermic patient; and describes crucial management strategies.

  7. Increased brain injury and vascular leakage after pretreatment with p38-inhibitor SB203580 in transient ischemia.

    PubMed

    Lennmyr, F; Ericsson, A; Gerwins, P; Ahlström, H; Terént, A

    2003-11-01

    Focal cerebral ischemia activates intracellular signaling pathways including the mitogen-activated protein kinase p38, which may be involved in the process of ischemic brain injury. In this study, the effect of pretreatment with the p38-inhibitor SB203580 on infarct size and blood-brain barrier (BBB) breakdown was investigated with magnetic resonance imaging (MRI). Rats were given SB203580 (n = 6) or vehicle (n = 6) in the right lateral ventricle prior to transient (90 min) middle cerebral artery occlusion (MCAO) on the left side. The rats were examined with serial MRI during MCAO, at reperfusion and after 1 and 4 days. The mean infarct size on T2-weighted images after 1 day was significantly higher in the SB203580-treated group than in controls (300 +/- 95 mm3 vs 126 +/- 75 mm3; P < 0.01). Vascular gadolinium leakage, indicating BBB breakdown, was significantly larger in the SB203580-treated group than in controls after 1 day (median leakage score 18.5; range 15-21 vs 6.5; 4-17; P < 0.05) and 4 days (11; 6-15 vs 3.5; 1-9; P < 0.05), although no significant difference was seen initially. Pretreatment with SB203580 may aggravate ischemic brain injury and cerebral vascular leakage in the present model of transient ischemia.

  8. Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats.

    PubMed

    Brooks, Steven D; DeVallance, Evan; d'Audiffret, Alexandre C; Frisbee, Stephanie J; Tabone, Lawrence E; Shrader, Carl D; Frisbee, Jefferson C; Chantler, Paul D

    2015-12-01

    The metabolic syndrome (MetS) is highly prevalent in the North American population and is associated with increased risk for development of cerebrovascular disease. This study determined the structural and functional changes in the middle cerebral arteries (MCA) during the progression of MetS and the effects of chronic pharmacological interventions on mitigating vascular alterations in obese Zucker rats (OZR), a translationally relevant model of MetS. The reactivity and wall mechanics of ex vivo pressurized MCA from lean Zucker rats (LZR) and OZR were determined at 7-8, 12-13, and 16-17 wk of age under control conditions and following chronic treatment with pharmacological agents targeting specific systemic pathologies. With increasing age, control OZR demonstrated reduced nitric oxide bioavailability, impaired dilator (acetylcholine) reactivity, elevated myogenic properties, structural narrowing, and wall stiffening compared with LZR. Antihypertensive therapy (e.g., captopril or hydralazine) starting at 7-8 wk of age blunted the progression of arterial stiffening compared with OZR controls, while treatments that reduced inflammation and oxidative stress (e.g., atorvastatin, rosiglitazone, and captopril) improved NO bioavailability and vascular reactivity compared with OZR controls and had mixed effects on structural remodeling. These data identify specific functional and structural cerebral adaptations that limit cerebrovascular blood flow in MetS patients, contributing to increased risk of cognitive decline, cerebral hypoperfusion, and ischemic stroke; however, these pathological adaptations could potentially be blunted if treated early in the progression of MetS. Copyright © 2015 the American Physiological Society.

  9. The Feasibility of a Structured Cognitive Training Protocol to Address Progressive Cognitive Decline in Individuals with Vascular Dementia

    ERIC Educational Resources Information Center

    Mayer, Jamie F.; Bishop, Lilli A.; Murray, Laura L.

    2012-01-01

    Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, better known as CADASIL, is a rare, genetic form of early-onset vascular dementia. The purpose of this study was to use a modified version of Attention Process Training--II (APT-II; Sohlberg, Johnson, Paule, Raskin, & Mateer, 2001) with an…

  10. Prediction of vascular abnormalities on CT angiography in patients with acute headache.

    PubMed

    Alons, Imanda M E; Goudsmit, Ben F J; Jellema, Korné; van Walderveen, Marianne A A; Wermer, Marieke J H; Algra, Ale

    2018-05-09

    Patients with acute headache increasingly undergo CT-angiography (CTA) to evaluate underlying vascular causes. The aim of this study is to determine clinical and non-contrast CT (NCCT) criteria to select patients who might benefit from CTA. We retrospectively included patients with acute headache who presented to the emergency department of an academic medical center and large regional teaching hospital and underwent NCCT and CTA. We identified factors that increased the probability of finding a vascular abnormality on CTA, performed multivariable regression analyses and determined discrimination with the c-statistic. A total of 384 patients underwent NCCT and CTA due to acute headache. NCCT was abnormal in 194 patients. Among these, we found abnormalities in 116 cases of which 99 aneurysms. In the remaining 190 with normal NCCT we found abnormalities in 12 cases; four unruptured aneurysms, three cerebral venous thrombosis', two reversible cerebral vasoconstriction syndromes, two cervical arterial dissections and one cerebellar infarction. In multivariable analysis abnormal NCCT, lowered consciousness and presentation within 6 hr of headache onset were independently associated with abnormal CTA. The c-statistic of abnormal NCCT alone was 0.80 (95% CI: 0.75-0.80), that also including the other two variables was 0.84 (95% CI: 0.80-0.88). If NCCT was normal no other factors could help identify patients at risk for abnormalities. In patients with acute headache abnormal NCCT is the strongest predictor of a vascular abnormality on CTA. If NCCT is normal no other predictors increase the probability of finding an abnormality on CTA and diagnostic yield is low. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

  11. Activation of PPAR-γ by pioglitazone attenuates oxidative stress in aging rat cerebral arteries through upregulating UCP2.

    PubMed

    Wang, Peijian; Li, Binghu; Cai, Guocai; Huang, Mingqing; Jiang, Licheng; Pu, Jing; Li, Lu; Wu, Qi; Zuo, Li; Wang, Qiulin; Zhou, Peng

    2014-12-01

    Increasing amounts of evidence implicate oxidative stress as having a pivotal role in age-related cerebrovascular dysfunction, which is an important risk factor for the development of cerebrovascular disease. Previous studies have shown that the activation of the expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) in vascular endothelial cells results in an improvement of vascular function. Pioglitazone, a well-known PPAR-γ agonist, protects against oxidative stress in the rostral ventrolateral medulla by the upregulation of mitochondrial uncoupling protein 2 (UCP2). In this study, we sought to explore the effects and the underlying mechanisms of pioglitazone on age-related oxidative stress elevation and cerebrovascular dysfunction in aging rat cerebral arteries. A natural aging model was constructed and used in these experiments. One-month oral administration of pioglitazone (20 mg·kg·d) ameliorated the production of reactive oxygen species, promoted endothelial nitric oxide synthase phosphorylation and increased the nitric oxide available, thus improving endothelium-dependent relaxation in aging rat cerebral arteries. One-month pioglitazone administration also restored PPAR-γ expression and increased the levels of UCP2 in aging rat cerebral arteries. Using in vitro studies, we demonstrated that pioglitazone attenuated reactive oxygen species levels in aging human umbilical vein endothelial cells through PPAR-γ activation. Furthermore, we found that this occurs in an UCP2-dependent manner. Our study demonstrated that the activation of PPAR-γ by pioglitazone protected against oxidative stress damage in aging cerebral arteries by upregulating UCP2. PPAR-γ may be a new target in treating age-related cerebrovascular dysfunction.

  12. Accidental Falls Among Geriatric Patients: Can More Be Prevented?

    PubMed Central

    Johnson, Edwin T.

    1985-01-01

    The potential for accidental falls among geriatric patients is of mounting concern. Two hundred forty-one accidental falls over a 12-month period at the VA Medical Center were analyzed retrospectively and the literature reviewed in order to highlight factors that have bearing on the incidence and severity of falls. If a patient's potential for falling could be identified through a grading system based on these premonitory features, preventive measures might be more clearly focused where needed to reduce this frequent hazard in our hospital population. PMID:4046062

  13. Patent Foramen Ovale in Patients with Cerebral Infarction: A Transesophageal Echocradigraphy Study

    NASA Technical Reports Server (NTRS)

    Petty, George W.; Khandheria, Bijoy K.; Chu, Chu-Pin; Sicks, JoRean D.; Whisnant, Jack P.

    1997-01-01

    Patent foramen ovale was detected in 37 patients (32%). Mean age was similar in those with (60 years) and those without (64 years) PFO. Patent foramen ovale was more frequent among men (39%) than women (20%, P=.03). Patients with PFO had a lower frequency of atrial fibrillation, diabetes me!litus, hypertension, and peripheral vascular disease compared with those without PFO. There was no difference in frequency of the following characteristics in patients with PFO compared with those without PFO: pulmonary embolus, chronic obstructive pulmonary disease, pulmonary hypertension, peripheral embolism, prior cerebral infarction, nosocomial cerebral infarction, Valsalva maneuver at the time of cerebral infarction, recent surgery, or hemorrhagic transformation of cerebral infarction. Patent foramen ovale was found in 22 (40%) of 55 patients with infarcts of uncertain cause and in 15 (25%) of 61 with infarcts of known cause (cardioembolic, 21%; large vessel atherostenosis, 25%; lacune, 40%) (P=.08). When the analysis was restricted to patients who underwent Valsalva maneuver, PFO with right to left or bidirectional shunt was found in 19 (50%) of 38 patients with infarcts of uncertain cause and in 6 (20%) of 30 with infarcts of known cause (P=.Ol). Conclusion: Although PFO was over-represented in patients with infarcts of uncertain cause in our and other studies, it has a high frequency among patients with cerebral infarction of all types. The relation between PFO and stroke requires further study.

  14. Epidemiology of Munchausen syndrome by proxy, non-accidental poisoning, and non-accidental suffocation.

    PubMed Central

    McClure, R J; Davis, P M; Meadow, S R; Sibert, J R

    1996-01-01

    A two year prospective study was performed to determine the epidemiology of Munchausen syndrome by proxy, non-accidental poisoning, and non-accidental suffocation in the UK and the Republic of Ireland. Cases were notified to the British Paediatric Association Surveillance Unit from September 1992 to August 1994 if a formal case conference had been held for the first time during that period to discuss any of the above conditions. A total of 128 cases were identified: 55 suffered Munchausen syndrome by proxy alone, 15 poisoning, and 15 suffocation; 43 suffered more than one type of abuse. The majority of children were aged under 5 years, the median age being 20 months. On 85% of occasions the perpetrator was the child's mother. In 42% of families with more than one child, a sibling had previously suffered some form of abuse. Eighty five per cent of notifying paediatricians considered the probability of their diagnosis as virtually certain before a case conference was convened. The commonest drugs used to poison were anticonvulsants; opiates were the second commonest. Sixty eight children suffered severe illness of whom eight died. The combined annual incidence of these conditions in children aged under 16 years is at least 0.5/100,000, and for children aged under 1, at least 2.8/100,000. PMID:8813872

  15. Cerebral microbleeds: different prevalence, topography, and risk factors depending on dementia diagnosis—the Karolinska Imaging Dementia Study.

    PubMed

    Shams, S; Martola, J; Granberg, T; Li, X; Shams, M; Fereshtehnejad, S M; Cavallin, L; Aspelin, P; Kristoffersen-Wiberg, M; Wahlund, L O

    2015-04-01

    Cerebral microbleeds are thought to represent cerebral amyloid angiopathy when in lobar regions of the brain and hypertensive arteriopathy when in deep and infratentorial locations. By studying cerebral microbleeds, their topography, and risk factors, we aimed to gain an insight into the vascular and amyloid pathology of dementia diagnoses and increase the understanding of cerebral microbleeds in dementia. We analyzed 1504 patients (53% women; mean age, 63 ± 10 years; 10 different dementia diagnoses) in this study. All patients underwent MR imaging as part of the dementia investigation, and all their clinical parameters were recorded. Among the 1504 patients with dementia, 22% had cerebral microbleeds. Cerebral microbleed topography was predominantly lobar (P = .01) and occipital (P = .007) in Alzheimer disease. Patients with cerebral microbleeds were significantly older (P < .001), were more frequently male (P < .001), had lower cognitive scores (P = .006), and more often had hypertension (P < .001). Risk factors for cerebral microbleeds varied depending on the dementia diagnosis. Odds ratios for having cerebral microbleeds increased with the number of risk factors (hypertension, hyperlipidemia, diabetes, male sex, and age 65 and older) in the whole patient group and increased differently in the separate dementia diagnoses. Prevalence, topography, and risk factors of cerebral microbleeds vary depending on the dementia diagnosis and reflect the inherent pathology of different dementia diagnoses. Because cerebral microbleeds are seen as possible predictors of intracerebral hemorrhage, their increasing prevalence with an increasing number of risk factors, as shown in our study, may require taking the number of risk factors into account when deciding on anticoagulant therapy in dementia. © 2015 by American Journal of Neuroradiology.

  16. Effects of accidental hypothermia on posttraumatic complications and outcome in multiple trauma patients.

    PubMed

    Mommsen, P; Andruszkow, H; Frömke, C; Zeckey, C; Wagner, U; van Griensven, M; Frink, M; Krettek, C; Hildebrand, F

    2013-01-01

    Accidental hypothermia seems to predispose multiple trauma patients to the development of posttraumatic complications, such as Systemic Inflammatory Response Syndrome (SIRS), sepsis, Multiple Organ Dysfunction Syndrome (MODS), and increased mortality. However, the role of accidental hypothermia as an independent prognostic factor is controversially discussed. The aim of the present study was to evaluate the incidence of accidental hypothermia in multiple trauma patients and its effects on the development of posttraumatic complications and mortality. Inclusion criteria for patients in this retrospective study (2005-2009) were an Injury Severity Score (ISS) ≥16, age ≥16 years, admission to our Level I trauma centre within 6h after the accident. Accidental hypothermia was defined as body temperature less than 35°C measured within 2 h after admission, but always before first surgical procedure in the operation theatre. The association between accidental hypothermia and the development of posttraumatic complications as well as mortality was investigated. Statistical analysis was performed with χ(2)-test, Student's t-test, ANOVA and logistic regression. Statistical significance was considered at p<0.05. 310 multiple trauma patients were enrolled in the present study. Patients' mean age was 41.9 (SD 17.5) years, the mean injury severity score was 29.7 (SD 10.2). The overall incidence of accidental hypothermia was 36.8%. The overall incidence of posttraumatic complications was 77.4% (SIRS), 42.9% (sepsis) and 7.4% (MODS), respectively. No association was shown between accidental hypothermia and the development of posttraumatic complications. Overall, 8.7% died during the posttraumatic course. Despite an increased mortality rate in hypothermic patients, hypothermia failed to be an independent risk factor for mortality in multivariate analysis. Accidental hypothermia is very common in multiply injured patients. However, it could be assumed that the increase of

  17. Assessing Intracranial Vascular Compliance Using Dynamic Arterial Spin Labeling

    PubMed Central

    Yan, Lirong; Liu, Collin Y.; Smith, Robert X.; Jog, Mayank; Langham, Michael; Krasileva, Kate; Chen, Yufen; Ringman, John M.; Wang, Danny J.J.

    2015-01-01

    Vascular compliance (VC) is an important marker for a number of cardiovascular diseases and dementia, which is typically assessed in central and peripheral arteries indirectly by quantifying pulse wave velocity (PWV), and/or pulse pressure waveform. To date, very few methods are available for the quantification of intracranial VC. In the present study, a novel MRI technique for in-vivo assessment of intracranial VC was introduced, where dynamic arterial spin labeling (ASL) scans were synchronized with the systolic and diastolic phases of the cardiac cycle. VC is defined as the ratio of change in arterial cerebral blood volume (ΔCBV) and change in arterial pressure (ΔBP). Intracranial VC was assessed in different vascular components using the proposed dynamic ASL method. Our results show that VC mainly occurs in large arteries, gradually decreases in small arteries and arterioles. The comparison of intracranial VC between young and elderly subjects shows that aging is accompanied by a reduction of intracranial VC, in good agreement with the literature. Furthermore, a positive association between intracranial VC and cerebral perfusion measured using pseudo-continuous ASL with 3D GRASE MRI was observed independent of aging effects, suggesting loss of VC is associated with a decline in perfusion. Finally, a significant positive correlation between intracranial and central (aortic arch) VC was observed using an ungated phase-contrast 1D projection PWV technique. The proposed dynamic ASL method offers a promising approach for assessing intracranial VC in a range of cardiovascular diseases and dementia. PMID:26364865

  18. Acute impact of drinking coffee on the cerebral and systemic vasculature.

    PubMed

    Washio, Takuro; Sasaki, Hiroyuki; Ogoh, Shigehiko

    2017-05-01

    Previous studies have suggested that the risk of ischemic stroke increases immediately after drinking coffee. Indeed, drinking coffee, that is, caffeine, acutely increases arterial stiffness as well as blood pressure and peripheral vascular resistance. On the other hand, it has been reported that arterial stiffening is associated with elevation in the pulsatility index (PI) of cerebral blood flow (CBF), which increases the risk of brain disease. However, the effect of drinking coffee on the PI of the CBF and its interaction with arterial stiffness remain unknown. Against this background, we hypothesized that an acute increase in arterial stiffness induced by drinking coffee augments cerebral pulsatile stress. To test this hypothesis, in 10 healthy young men we examined the effects of drinking coffee on the PI of middle cerebral artery blood velocity (MCAv) and brachial-ankle pulse wave velocity (baPWV) as indices of cerebral pulsatile stress and arterial stiffness, respectively. Mean arterial blood pressure and baPWV were higher ( P  < 0.01 and P  = 0.02), whereas mean MCA V and mean cerebrovascular conductance index were lower upon drinking coffee ( P  = 0.02 and P  < 0.01) compared with a placebo (decaffeinated coffee). However, there was no difference in the PI of MCAv between drinking coffee and the placebo condition. These findings suggest that drinking coffee does not increase cerebral pulsatile stress acutely despite an elevation in arterial stiffness in the systemic circulation. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  19. Dental pain as a risk factor for accidental acetaminophen overdose: a case-control study.

    PubMed

    Vogel, Jody; Heard, Kennon J; Carlson, Catherine; Lange, Chad; Mitchell, Garrett

    2011-11-01

    Patients frequent take acetaminophen to treat dental pain. One previous study found a high rate of overuse of nonprescription analgesics in an emergency dental clinic. The purpose of this study is to determine if patients with dental pain are more likely to be treated for accidental acetaminophen poisoning than patients with other types of pain. We conducted a case-control study at 2 urban hospitals. Cases were identified by chart review of patients who required treatment for accidental acetaminophen poisoning. Controls were self-reported acetaminophen users taking therapeutic doses identified during a survey of emergency department patients. For our primary analysis, the reason for taking acetaminophen was categorized as dental pain or not dental pain. Our primary outcome was the odds ratio of accidental overdose to therapeutic users after adjustment for age, sex, alcoholism, and use of combination products using logistic regression. We identified 73 cases of accidental acetaminophen poisoning and 201 therapeutic users. Fourteen accidental overdose patients and 4 therapeutic users reported using acetaminophen for dental pain. The adjusted odds ratio for accidental overdose due to dental pain compared with other reasons for use was 12.8 (95% confidence interval, 4.2-47.6). We found that patients with dental pain are at increased risk to accidentally overdose on acetaminophen compared with patients taking acetaminophen for other reasons. Emergency physicians should carefully question patients with dental pain about overuse of analgesics. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Inhibition of SUR1 Decreases the Vascular Permeability of Cerebral Metastases1

    PubMed Central

    Thompson, Eric M; Pishko, Gregory L; Muldoon, Leslie L; Neuwelt, Edward A

    2013-01-01

    Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage. We investigated if inhibiting SUR1 reduces cerebral edema due to metastases, the most common brain tumor, and explored the putative association of SUR1 and the endothelial tight junction protein, zona occludens-1 (ZO-1). Nude rats were intracerebrally implanted with small cell lung carcinoma (SCLC) LX1 or A2058 melanoma cells (n = 36). Rats were administered vehicle, glyburide (4.8 µg twice, orally), or dexamethasone (0.35 mg, intravenous). Blood-tumor barrier (BTB) permeability (Ktrans) was evaluated before and after treatment using dynamic contrast-enhanced magnetic resonance imaging. SUR1 and ZO-1 expression was evaluated using immunofluorescence and Western blots. In both models, SUR1 expression was significantly increased (P < .05) in tumors. In animals with SCLC, control mean Ktrans (percent change ± standard error) was 101.8 ± 36.6%, and both glyburide (-21.4 ± 14.2%, P < .01) and dexamethasone (-14.2 ± 13.1%, P < .01) decreased BTB permeability. In animals with melanoma, compared to controls (117.1 ± 43.4%), glyburide lowered BTB permeability increase (3.2 ± 15.4%, P < .05), while dexamethasone modestly lowered BTB permeability increase (63.1 ± 22.1%, P > .05). Both glyburide (P < .001) and dexamethasone (P < .01) decreased ZO-1 gap formation. By decreasing ZO-1 gaps, glyburide was at least as effective as dexamethasone at halting increased BTB permeability caused by SCLC and melanoma. Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema. PMID:23633925

  1. Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment.

    PubMed

    Skrobot, Olivia A; Attems, Johannes; Esiri, Margaret; Hortobágyi, Tibor; Ironside, James W; Kalaria, Rajesh N; King, Andrew; Lammie, George A; Mann, David; Neal, James; Ben-Shlomo, Yoav; Kehoe, Patrick G; Love, Seth

    2016-11-01

    There are no generally accepted protocols for post-mortem assessment in cases of suspected vascular cognitive impairment. Neuropathologists from seven UK centres have collaborated in the development of a set of vascular cognitive impairment neuropathology guidelines (VCING), representing a validated consensus approach to the post-mortem assessment and scoring of cerebrovascular disease in relation to vascular cognitive impairment. The development had three stages: (i) agreement on a sampling protocol and scoring criteria, through a series of Delphi method surveys; (ii) determination of inter-rater reliability for each type of pathology in each region sampled (Gwet's AC2 coefficient); and (iii) empirical testing and validation of the criteria, by blinded post-mortem assessment of brain tissue from 113 individuals (55 to 100 years) without significant neurodegenerative disease who had had formal cognitive assessments within 12 months of death. Fourteen different vessel and parenchymal pathologies were assessed in 13 brain regions. Almost perfect agreement (AC2 > 0.8) was found when the agreed criteria were used for assessment of leptomeningeal, cortical and capillary cerebral amyloid angiopathy, large infarcts, lacunar infarcts, microhaemorrhage, larger haemorrhage, fibrinoid necrosis, microaneurysms, perivascular space dilation, perivascular haemosiderin leakage, and myelin loss. There was more variability (but still reasonably good agreement) in assessment of the severity of arteriolosclerosis (0.45-0.91) and microinfarcts (0.52-0.84). Regression analyses were undertaken to identify the best predictors of cognitive impairment. Seven pathologies-leptomeningeal cerebral amyloid angiopathy, large infarcts, lacunar infarcts, microinfarcts, arteriolosclerosis, perivascular space dilation and myelin loss-predicted cognitive impairment. Multivariable logistic regression determined the best predictive models of cognitive impairment. The preferred model included moderate

  2. Ischemic brain injury in cerebral amyloid angiopathy

    PubMed Central

    van Veluw, Susanne J; Greenberg, Steven M

    2016-01-01

    Cerebral amyloid angiopathy (CAA) is a common form of cerebral small vessel disease and an important risk factor for intracerebral hemorrhage and cognitive impairment. While the majority of research has focused on the hemorrhagic manifestation of CAA, its ischemic manifestations appear to have substantial clinical relevance as well. Findings from imaging and pathologic studies indicate that ischemic lesions are common in CAA, including white-matter hyperintensities, microinfarcts, and microstructural tissue abnormalities as detected with diffusion tensor imaging. Furthermore, imaging markers of ischemic disease show a robust association with cognition, independent of age, hemorrhagic lesions, and traditional vascular risk factors. Widespread ischemic tissue injury may affect cognition by disrupting white-matter connectivity, thereby hampering communication between brain regions. Challenges are to identify imaging markers that are able to capture widespread microvascular lesion burden in vivo and to further unravel the etiology of ischemic tissue injury by linking structural magnetic resonance imaging (MRI) abnormalities to their underlying pathophysiology and histopathology. A better understanding of the underlying mechanisms of ischemic brain injury in CAA will be a key step toward new interventions to improve long-term cognitive outcomes for patients with CAA. PMID:25944592

  3. Non-invasive assessment of intratumoral vascularity using arterial spin labeling: A comparison to susceptibility-weighted imaging for the differentiation of primary cerebral lymphoma and glioblastoma.

    PubMed

    Furtner, J; Schöpf, V; Preusser, M; Asenbaum, U; Woitek, R; Wöhrer, A; Hainfellner, J A; Wolfsberger, S; Prayer, D

    2014-05-01

    Using conventional MRI methods, the differentiation of primary cerebral lymphomas (PCNSL) and other primary brain tumors, such as glioblastomas, is difficult due to overlapping imaging characteristics. This study was designed to discriminate tumor entities using normalized vascular intratumoral signal intensity values (nVITS) obtained from pulsed arterial spin labeling (PASL), combined with intratumoral susceptibility signals (ITSS) from susceptibility-weighted imaging (SWI). Thirty consecutive patients with glioblastoma (n=22) and PCNSL (n=8), histologically classified according to the WHO brain tumor classification, were included. MRIs were acquired on a 3T scanner, and included PASL and SWI sequences. nVITS was defined by the signal intensity ratio between the tumor and the contralateral normal brain tissue, as obtained by PASL images. ITSS was determined as intratumoral low signal intensity structures detected on SWI sequences and were divided into four different grades. Potential differences in the nVITS and ITSS between glioblastomas and PCNSLs were revealed using statistical testing. To determine sensitivity, specificity, and diagnostic accuracy, as well as an optimum cut-off value for the differentiation of PCNSL and glioblastoma, a receiver operating characteristic analysis was used. We found that nVITS (p=0.011) and ITSS (p=0.001) values were significantly higher in glioblastoma than in PCNSL. The optimal cut-off value for nVITS was 1.41 and 1.5 for ITSS, with a sensitivity, specificity, and accuracy of more than 95%. These findings indicate that nVITS values have a comparable diagnostic accuracy to ITSS values in differentiating glioblastoma and PCNSL, offering a completely non-invasive and fast assessment of tumoral vascularity in a clinical setting. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Vascular complications in patients with aldosterone producing adenoma in Japan: comparative study with essential hypertension. The Research Committee of Disorders of Adrenal Hormones in Japan.

    PubMed

    Takeda, R; Matsubara, T; Miyamori, I; Hatakeyama, H; Morise, T

    1995-05-01

    The incidence of vascular complications in 224 patients with aldosterone-producing adenoma (APA) which was proven on adrenal surgery, was compared to that in 224 sex- and age-matched patients with essential hypertension (EHT). The incidence of cerebral hemorrhage was significantly higher (p < 0.05) in the patients with APA when compared to the EHT group. On the other hand, the incidence of myocardial infarction and/or congestive heart failure in the APA group was lower, although this difference did not reach statistical significance. Diastolic blood pressure in the APA group was significantly higher (p < 0.001) in the EHT group. However, a significant difference in diastolic blood pressure was not detected between the APA groups with and without vascular complications, whereas in the EHT group diastolic blood pressure was significantly higher (p < 0.001) in cases with vascular complications as compared to those without complications. As a possible factor contributing to the higher incidence of cerebral hemorrhage in the APA group, proteinuria was suggested. It was recommended that patients with primary aldosteronism should undergo operation when localization of the APA is established.

  5. Play dough as an educational tool for visualization of complicated cerebral aneurysm anatomy.

    PubMed

    Eftekhar, Behzad; Ghodsi, Mohammad; Ketabchi, Ebrahim; Ghazvini, Arman Rakan

    2005-05-10

    Imagination of the three-dimensional (3D) structure of cerebral vascular lesions using two-dimensional (2D) angiograms is one of the skills that neurosurgical residents should achieve during their training. Although ongoing progress in computer software and digital imaging systems has facilitated viewing and interpretation of cerebral angiograms enormously, these facilities are not always available. We have presented the use of play dough as an adjunct to the teaching armamentarium for training in visualization of cerebral aneurysms in some cases. The advantages of play dough are low cost, availability and simplicity of use, being more efficient and realistic in training the less experienced resident in comparison with the simple drawings and even angiographic views from different angles without the need for computers and similar equipment. The disadvantages include the psychological resistance of residents to the use of something in surgical training that usually is considered to be a toy, and not being as clean as drawings or computerized images. Although technology and computerized software using the patients' own imaging data seems likely to become more advanced in the future, use of play dough in some complicated cerebral aneurysm cases may be helpful in 3D reconstruction of the real situation.

  6. Play dough as an educational tool for visualization of complicated cerebral aneurysm anatomy

    PubMed Central

    Eftekhar, Behzad; Ghodsi, Mohammad; Ketabchi, Ebrahim; Ghazvini, Arman Rakan

    2005-01-01

    Background Imagination of the three-dimensional (3D) structure of cerebral vascular lesions using two-dimensional (2D) angiograms is one of the skills that neurosurgical residents should achieve during their training. Although ongoing progress in computer software and digital imaging systems has facilitated viewing and interpretation of cerebral angiograms enormously, these facilities are not always available. Methods We have presented the use of play dough as an adjunct to the teaching armamentarium for training in visualization of cerebral aneurysms in some cases. Results The advantages of play dough are low cost, availability and simplicity of use, being more efficient and realistic in training the less experienced resident in comparison with the simple drawings and even angiographic views from different angles without the need for computers and similar equipment. The disadvantages include the psychological resistance of residents to the use of something in surgical training that usually is considered to be a toy, and not being as clean as drawings or computerized images. Conclusion Although technology and computerized software using the patients' own imaging data seems likely to become more advanced in the future, use of play dough in some complicated cerebral aneurysm cases may be helpful in 3D reconstruction of the real situation. PMID:15885141

  7. [Behavioural problems and personality change related to cerebral amyloid angiopathy].

    PubMed

    Gahr, Maximilian; Connemann, Bernhard J; Schönfeldt-Lecuona, Carlos

    2012-11-01

    Cerebral amyloid angiopathy (CAA) belongs to the group of amyloidoses that are characterized by the deposition of insoluble and tissue-damaging amyloid proteins. Spontaneous intracerebral hemorrhage is the common clinical presentation of CAA resulting from the degenerative effect of beta amyloid on the cerebral vascular system. Though CAA is rather a neurological disease psychiatric symptoms can occur and even dominate the clinical picture. A case report is presented in order to illustrate the association between CAA and psychiatric symptoms. We report the case of a 54-year-old female patient with radiologic references to a probable CAA and mild cognitive impairment who developed behavioural difficulties and personality change that necessitated a psychiatric treatment. Psychiatric symptoms were most likely due to CAA. CAA can be associated with psychiatric symptoms and hence should be considered in the treatment of elderly patients with behavioural problems or personality changes. Diagnostic neuroimaging and examination of cerebrospinal fluid is recommended. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Regional brain blood flow and cerebral hemispheric oxygen consumption during acute hypoxaemia in the llama fetus

    PubMed Central

    Llanos, Aníbal J; Riquelme, Raquel A; Sanhueza, Emilia M; Herrera, Emilio; Cabello, Gertrudis; Giussani, Dino A; Parer, Julian T

    2002-01-01

    Unlike fetal animals of lowland species, the llama fetus does not increase its cerebral blood flow during an episode of acute hypoxaemia. This study tested the hypothesis that the fetal llama brain maintains cerebral hemispheric O2 consumption by increasing cerebral O2 extraction rather than decreasing cerebral oxygen utilisation during acute hypoxaemia. Six llama fetuses were surgically instrumented under general anaesthesia at 217 days of gestation (term ca 350 days) with vascular and amniotic catheters in order to carry out cardiorespiratory studies. Following a control period of 1 h, the llama fetuses underwent 3 × 20 min episodes of progressive hypoxaemia, induced by maternal inhalational hypoxia. During basal conditions and during each of the 20 min of hypoxaemia, fetal cerebral blood flow was measured with radioactive microspheres, cerebral oxygen extraction was calculated, and fetal cerebral hemispheric O2 consumption was determined by the modified Fick principle. During hypoxaemia, fetal arterial O2 tension and fetal pH decreased progressively from 24 ± 1 to 20 ± 1 Torr and from 7.36 ± 0.01 to 7.33 ± 0.01, respectively, during the first 20 min episode, to 16 ± 1 Torr and 7.25 ± 0.05 during the second 20 min episode and to 14 ± 1 Torr and 7.21 ± 0.04 during the final 20 min episode. Fetal arterial partial pressure of CO2 (Pa,CO2, 42 ± 2 Torr) remained unaltered from baseline throughout the experiment. Fetal cerebral hemispheric blood flow and cerebral hemispheric oxygen extraction were unaltered from baseline during progressive hypoxaemia. In contrast, a progressive fall in fetal cerebral hemispheric oxygen consumption occurred during the hypoxaemic challenge. In conclusion, these data do not support the hypothesis that the fetal llama brain maintains cerebral hemispheric O2 consumption by increasing cerebral hemispheric O2 extraction. Rather, the data show that in the llama fetus, a reduction in cerebral hemispheric metabolism occurs during acute

  9. The contribution of CXCL12-expressing radial glia cells to neuro-vascular patterning during human cerebral cortex development

    PubMed Central

    Errede, Mariella; Girolamo, Francesco; Rizzi, Marco; Bertossi, Mirella; Roncali, Luisa; Virgintino, Daniela

    2014-01-01

    This study was conducted on human developing brain by laser confocal and transmission electron microscopy (TEM) to make a detailed analysis of important features of blood-brain barrier (BBB) microvessels and possible control mechanisms of vessel growth and differentiation during cerebral cortex vascularization. The BBB status of cortex microvessels was examined at a defined stage of cortex development, at the end of neuroblast waves of migration, and before cortex lamination, with BBB-endothelial cell markers, namely tight junction (TJ) proteins (occludin and claudin-5) and influx and efflux transporters (Glut-1 and P-glycoprotein), the latter supporting evidence for functional effectiveness of the fetal BBB. According to the well-known roles of astroglia cells on microvessel growth and differentiation, the early composition of astroglia/endothelial cell relationships was analyzed by detecting the appropriate astroglia, endothelial, and pericyte markers. GFAP, chemokine CXCL12, and connexin 43 (Cx43) were utilized as markers of radial glia cells, CD105 (endoglin) as a marker of angiogenically activated endothelial cells (ECs), and proteoglycan NG2 as a marker of immature pericytes. Immunolabeling for CXCL12 showed the highest level of the ligand in radial glial (RG) fibers in contact with the growing cortex microvessels. These specialized contacts, recognizable on both perforating radial vessels and growing collaterals, appeared as CXCL12-reactive en passant, symmetrical and asymmetrical, vessel-specific RG fiber swellings. At the highest confocal resolution, these RG varicosities showed a CXCL12-reactive dot-like content whose microvesicular nature was confirmed by ultrastructural observations. A further analysis of RG varicosities reveals colocalization of CXCL12 with Cx43, which is possibly implicated in vessel-specific chemokine signaling. PMID:25360079

  10. Involving Parents in Indicated Early Intervention for Childhood PTSD Following Accidental Injury

    ERIC Educational Resources Information Center

    Cobham, Vanessa E.; March, Sonja; De Young, Alexandra; Leeson, Fiona; Nixon, Reginald; McDermott, Brett; Kenardy, Justin

    2012-01-01

    Accidental injuries represent the most common type of traumatic event to which a youth is likely to be exposed. While the majority of youth who experience an accidental injury will recover spontaneously, a significant proportion will go on to develop Post-Traumatic Stress Disorder (PTSD). And yet, there is little published treatment outcome…

  11. Methods for the correction of vascular artifacts in PET O-15 water brain-mapping studies

    NASA Astrophysics Data System (ADS)

    Chen, Kewei; Reiman, E. M.; Lawson, M.; Yun, Lang-sheng; Bandy, D.; Palant, A.

    1996-12-01

    While positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) can be used to map brain regions that are involved in normal and pathological human behaviors, measurements in the anteromedial temporal lobe can be confounded by the combined effects of radiotracer activity in neighboring arteries and partial-volume averaging. The authors now describe two simple methods to address this vascular artifact. One method utilizes the early frames of a dynamic PET study, while the other method utilizes a coregistered magnetic resonance image (MRI) to characterize the vascular region of interest (VROI). Both methods subsequently assign a common value to each pixel in the VROI for the control (baseline) scan and the activation scan. To study the vascular artifact and to demonstrate the ability of the proposed methods correcting the vascular artifact, four dynamic PET scans were performed in a single subject during the same behavioral state. For each of the four scans, a vascular scan containing vascular activity was computed as the summation of the images acquired 0-60 s after radiotracer administration, and a control scan containing minimal vascular activity was computed as the summation of the images acquired 20-80 s after radiotracer administration. t-score maps calculated from the four pairs of vascular and control scans were used to characterize regional blood flow differences related to vascular activity before and after the application of each vascular artifact correction method. Both methods eliminated the observed differences in vascular activity, as well as the vascular artifact observed in the anteromedial temporal lobes. Using PET data from a study of normal human emotion, these methods permitted the authors to identify rCBF increases in the anteromedial temporal lobe free from the potentially confounding, combined effects of vascular activity and partial-volume averaging.

  12. Dengue fever with diffuse cerebral hemorrhages, subdural hematoma and cranial diabetes insipidus.

    PubMed

    Jayasinghe, Nayomi Shermila; Thalagala, Eranga; Wattegama, Milanka; Thirumavalavan, Kanapathipillai

    2016-05-10

    Neurological manifestations in dengue fever occur in <1 % of the patients and known to be due to multisystem dysfunction secondary to vascular leakage. Occurrence of wide spread cerebral haemorrhages with subdural hematoma during the leakage phase without profound thrombocytopenia and occurrence of cranial diabetes insipidus are extremely rare and had not been reported in published literature earlier, thus we report the first case. A 24 year old previously healthy lady was admitted on third day of fever with thrombocytopenia. Critical phase started on fifth day with evidence of pleural effusion and moderate ascites. Thirty one hours into critical phase she developed headache, altered level of consciousness, limb rigidity and respiratory depression without definite seizures. Non-contrast CT brain done at tertiary care level revealed diffuse intracranial haemorrhages and sub arachnoid haemorrhages in right frontal, parietal, occipital lobes and brainstem, cerebral oedema with an acute subdural hematoma in right temporo- parietal region. Her platelet count was 40,000 at this time with signs of vascular leakage. She was intubated and ventilated with supportive care. Later on she developed features of cranial diabetes insipidus and it responded to intranasal desmopressin therapy. In spite of above measures signs of brainstem herniation developed and she succumbed to the illness on day 8. Dengue was confirmed serologically. Exact pathophysiological mechanism of diffuse cerebral haemorrhages without profound thrombocytopenia is not well understood. Increased awareness and high degree of clinical suspicion is needed among clinicians for timely diagnosis of this extremely rare complication of dengue fever. We postulate that immunological mechanisms may play a role in pathogenesis. However further comprehensive research and studies are needed to understand the pathophysiological mechanisms leading to this complication.

  13. Information entropy-based fitting of the disease trajectory of brain ischemia-induced vascular cognitive impairment.

    PubMed

    Liu, Lin; Huo, Ju; Zhao, Ying; Tian, Yu

    2012-03-25

    The present study investigated the disease trajectory of vascular cognitive impairment using the entropy of information in a neural network mathematical simulation based on the free radical and excitatory amino acids theories. Glutamate, malondialdehyde, and inducible nitric oxide synthase content was significantly elevated, but acetylcholine, catalase, superoxide dismutase, glutathione peroxidase and constitutive nitric oxide synthase content was significantly decreased in our vascular cognitive impairment model. The fitting curves for each factor were obtained using Matlab software. Nineteen, 30 and 49 days post ischemia were the main output time frames of the influence of these seven factors. Our results demonstrated that vascular cognitive impairment involves multiple factors. These factors include excitatory amino acid toxicity and nitric oxide toxicity. These toxicities disrupt the dynamic equilibrium of the production and removal of oxygen free radicals after cerebral ischemia, reducing the ability to clear oxygen free radicals and worsening brain injury.

  14. The Dual Role of Cerebral Autoregulation and Collateral Flow in the Circle of Willis After Major Vessel Occlusion.

    PubMed

    Kennedy McConnell, Flora; Payne, Stephen

    2017-08-01

    Ischaemic stroke is a leading cause of death and disability. Autoregulation and collateral blood flow through the circle of Willis both play a role in preventing tissue infarction. To investigate the interaction of these mechanisms a one-dimensional steady-state model of the cerebral arterial network was created. Structural variants of the circle of Willis that present particular risk of stroke were recreated by using a network model coupled with: 1) a steady-state physiological model of cerebral autoregulation; and 2) one wherein the cerebral vascular bed was modeled as a passive resistance. Simulations were performed in various conditions of internal carotid and vertebral artery occlusion. Collateral flow alone is unable to ensure adequate blood flow ([Formula: see text] normal flow) to the cerebral arteries in several common variants during internal carotid artery occlusion. However, compared to a passive model, cerebral autoregulation is better able to exploit available collateral flow and maintain flows within [Formula: see text] of baseline. This is true for nearly all configurations. Hence, autoregulation is a crucial facilitator of collateral flow through the circle of Willis. Impairment of this response during ischemia will severely impact cerebral blood flows and tissue survival, and hence, autoregulation should be monitored in this situation.

  15. Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading glioma cells

    PubMed Central

    Watkins, Stacey; Robel, Stefanie; Kimbrough, Ian F.; Robert, Stephanie M.; Ellis-Davies, Graham; Sontheimer, Harald

    2014-01-01

    Astrocytic endfeet cover the entire cerebral vasculature and serve as exchange sites for ions, metabolites, and energy substrates from the blood to the brain. They maintain endothelial tight junctions that form the blood-brain barrier (BBB) and release vasoactive molecules that regulate vascular tone. Malignant gliomas are highly invasive tumors that use the perivascular space for invasion and co-opt existing vessels as satellite tumors form. Here we use a clinically relevant mouse model of glioma and find that glioma cells, as they populate the perivascular space of pre-existing vessels, displace astrocytic endfeet from endothelial or vascular smooth muscle cells. This causes a focal breach in the BBB. Furthermore, astrocyte-mediated gliovascular coupling is lost, and glioma cells seize control over regulation of vascular tone through Ca2+-dependent release of K+. These findings have important clinical implications regarding blood flow in the tumor-associated brain and the ability to locally deliver chemotherapeutic drugs in disease. PMID:24943270

  16. 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

  17. Mixed vascular nevus syndrome: a report of four new cases and a literature review.

    PubMed

    Ruggieri, Martino; Polizzi, Agata; Strano, Serena; Schepis, Carmelo; Morano, Massimiliano; Belfiore, Giuseppe; Palmucci, Stefano; Foti, Pietro Valerio; Pirrone, Concetta; Sofia, Vito; David, Emanuele; Salpietro, Vincenzo; Mankad, Kshitij; Milone, Pietro

    2016-10-01

    Mixed vascular nevus (or nevus vascularis mixtus) represents an admixture of cutaneous vascular malformations of the telangiectatic type and angiospastic spots of nevus anemicus. It can occur as an purely cutaneous trait or as a hallmark of a neurocutaneous phenotype (mixed vascular nevus syndrome) characterised by the combination of: (I) paired vascular (telangiectatic and anemic) twin nevi and brain abnormalities of the Dyke-Davidoff-Masson type (i.e., crossed cerebral/cerebellar hemiatrophy with hypoplasia of the ipsilateral cerebral vessels and homolateral hypertrophy of the skull and sinuses (hyperpneumatisation) with contralateral hemispheric hypertrophy); or (II) paired vascular twin nevi and brain malformations of the Dyke-Davidoff-Masson type in association with systemic abnormalities consisting in facial asymmetry, skeletal anomalies (i.e., Legg-Calvé-Perthes-like disease) and disorders of autoimmunity (i.e., diabetes, thyroiditis). In 2014, Happle proposed to name the syndrome with the eponym Ruggieri-Leech syndrome. Review of the existing literature on nevus vascularis mixtus and information on our personal experience on new cases and follow-up of previously reported cases by some of us. The existing literature revealed 4 previous studies including 33 cases with an inferred purely cutaneous trait and 3 cases with a combination of paired vascular twin nevi and brain malformation of the Dyke-Davidoff-Masson type. Our personal experience includes 4 unpublished patients (1 female and 3 males; currently aged 2 to 34 years) seen and followed-up at our Institutions in Italy who had: paired vascular nevi involving either the face (n=2) or the face and parts of the body (n=2); facial asymmetry (n=4); mild to moderate facial dysmorphic features (n=2); developmental delay (n=3); seizures/stroke-like episodes and associated hemiplegia (n=4); muscular hypotrophy (n=2); mild to moderate hemispheric atrophy (n=4); skull osseous hypertrophy (n=4); hyperpneumatisation

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

    PubMed

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

    2015-08-01

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

  19. Asymptomatic cervicocerebral atherosclerosis, intracranial vascular resistance and cognition: the AsIA-neuropsychology study.

    PubMed

    López-Olóriz, Jorge; López-Cancio, Elena; Arenillas, Juan F; Hernández, María; Jiménez, Marta; Dorado, Laura; Barrios, Maite; Soriano-Raya, Juan José; Miralbell, Júlia; Cáceres, Cynthia; Forés, Rosa; Pera, Guillem; Dávalos, Antoni; Mataró, Maria

    2013-10-01

    Carotid atherosclerosis has emerged as a relevant contributor to cognitive impairment and dementia whereas the role of intracranial stenosis and vascular resistance in cognition remains unknown. This study aims to assess the association of asymptomatic cervicocerebral atherosclerosis and intracranial vascular resistance with cognitive performance in a large dementia-free population. The Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) Neuropsychology Study included 747 Caucasian subjects older than 50 with a moderate-high vascular risk (assessed by REGICOR score) and without history of neither symptomatic vascular disease nor dementia. Extracranial and transcranial color-coded duplex ultrasound examination was performed to assess carotid intima-media thickness (IMT), presence of carotid plaques (ECAD group), intracranial stenosis (ICAD group), and middle cerebral artery pulsatility index (MCA-PI) as a measure of intracranial vascular resistance. Neuropsychological assessment included tests in three cognitive domains: visuospatial skills and speed, verbal memory and verbal fluency. In univariate analyses, carotid IMT, ECAD and MCA-PI were associated with lower performance in almost all cognitive domains, and ICAD was associated with poor performance in some visuospatial and verbal cognitive tests. After adjustment for age, sex, vascular risk score, years of education and depressive symptoms, ECAD remained associated with poor performance in the three cognitive domains and elevated MCA-PI with worse performance in visuospatial skills and speed. Carotid plaques and increased intracranial vascular resistance are independently associated with low cognitive functioning in Caucasian stroke and dementia-free subjects. We failed to find an independent association of intracranial large vessel stenosis with cognitive performance. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. An Active Contour Model Based on Adaptive Threshold for Extraction of Cerebral Vascular Structures.

    PubMed

    Wang, Jiaxin; Zhao, Shifeng; Liu, Zifeng; Tian, Yun; Duan, Fuqing; Pan, Yutong

    2016-01-01

    Cerebral vessel segmentation is essential and helpful for the clinical diagnosis and the related research. However, automatic segmentation of brain vessels remains challenging because of the variable vessel shape and high complex of vessel geometry. This study proposes a new active contour model (ACM) implemented by the level-set method for segmenting vessels from TOF-MRA data. The energy function of the new model, combining both region intensity and boundary information, is composed of two region terms, one boundary term and one penalty term. The global threshold representing the lower gray boundary of the target object by maximum intensity projection (MIP) is defined in the first-region term, and it is used to guide the segmentation of the thick vessels. In the second term, a dynamic intensity threshold is employed to extract the tiny vessels. The boundary term is used to drive the contours to evolve towards the boundaries with high gradients. The penalty term is used to avoid reinitialization of the level-set function. Experimental results on 10 clinical brain data sets demonstrate that our method is not only able to achieve better Dice Similarity Coefficient than the global threshold based method and localized hybrid level-set method but also able to extract whole cerebral vessel trees, including the thin vessels.

  1. [Effects of combined action of radon baths and transcranial magnetotherapy on cerebral circulation in patients in an intermediate period of a mild craniocerebral trauma].

    PubMed

    Moliavchikova, O V; Cherevashchenko, L A; Grinzaĭd, Iu M; Aĭvazov, V N; Zhuravlev, M E

    2007-01-01

    The authors propose combined therapy improving cerebral circulation in patients in an intermediate period of a mild craniocerebral trauma. The combination consists of radon baths and transcranial magnetotherapy which raise blood volume filling, relieve vascular resistance, improve venous outflow.

  2. Strategic Role of Frontal White Matter Tracts in Vascular Cognitive Impairment: A Voxel-Based Lesion-Symptom Mapping Study in CADASIL

    ERIC Educational Resources Information Center

    Duering, Marco; Zieren, Nikola; Herve, Dominique; Jouvent, Eric; Reyes, Sonia; Peters, Nils; Pachai, Chahin; Opherk, Christian; Chabriat, Hugues; Dichgans, Martin

    2011-01-01

    Cerebral small vessel disease is the most common cause of vascular cognitive impairment. It typically manifests with lacunar infarcts and ischaemic white matter lesions. However, little is known about how these lesions relate to the cognitive symptoms. Previous studies have found a poor correlation between the burden of ischaemic lesions and…

  3. The accidental mentor: Australian rural nurses developing supportive relationships in the workplace.

    PubMed

    Mills, J E; Francis, K; Bonner, A

    2007-01-01

    Like the fictional 'Accidental Tourist', an author who does not plan to write about travel, the accidental mentor is an experienced rural nurse who does not plan to be a mentor, and yet assumes that role with new or novice rural nurses as a result of them encountering a critical incident. Accidental mentoring is a short-term relationship that provides support for the new or novice nurse in managing the incident, while maintaining their level of confidence. This article describes the findings from a constructivist grounded theory study that examined Australian rural nurses' experiences of mentoring, including evidence for a new concept of mentoring - accidental mentoring. Constructivist grounded theory is a research methodology that focuses on issues of importance for participants around an area of common interest - in this case Australian rural nurse mentoring. In this study, seven participants were interviewed, generating nine transcripts. These were analysed using a process of concurrent data generation and analysis. In addition, the literature regarding rural nurse workforce and mentoring was incorporated as a source of data, using collective frame analysis. Rural nurses live their work, which predisposes them to developing supportive relationships with new or novice rural nurses. Supportive relationships range from preceptoring, to accidental mentoring, mentoring and deep friendship, depending on the level of trust and engagement that is established between the partners and the amount of time they spend together. Accidental mentoring is a short-term relationship that is prompted by experienced rural nurses observing a new or novice rural nurse experiencing a critical incident. Findings are presented that illustrate a new concept of accidental mentoring not present in the current literature around nurse mentoring. A series of recommendations are included that suggest strategies for improved rural nurse retention as an outcome of recognising and developing such

  4. Purpose in Life and Cerebral Infarcts in Community Dwelling Older Persons

    PubMed Central

    Yu, Lei; Boyle, Patricia A.; Wilson, Robert S.; Levine, Steven R.; Schneider, Julie A.; Bennett, David A.

    2015-01-01

    Background and Purpose Purpose in life, the sense that life has meaning and direction, is associated with reduced risks of adverse health outcomes. However, it remains unknown whether purpose in life protects against the risk of cerebral infarcts among community-dwelling older persons. We tested the hypothesis that greater purpose in life is associated with lower risk of cerebral infarcts. Methods Participants came from the Rush Memory and Aging Project. Each participant completed a standard measure of purpose in life. Uniform neuropathologic examination identified macroscopic infarcts and microinfarcts, blinded to clinical information. Association of purpose in life with cerebral infarcts was examined in ordinal logistic regression models using a semiquantitative outcome. Results 453 participants were included in the analyses. The mean score on the measure of purpose was 3.5 (Standard Deviation=0.47, range=2.1-5.0). Macroscopic infarcts were found in 154 (34.0 %) persons, and microinfarcts were found in 128 (28.3%) persons. Greater purpose in life was associated with a lower odds of having one or more macroscopic infarcts (Odds Ratio=0.535, 95% Confidence Interval=0.346-0.826, p=.005), but we did not find association with microinfarcts (Odds Ratio=0.780, 95% Confidence Interval=0.495-1.229, p=.283). These results persisted after adjusting for vascular risk factors of body mass index, history of smoking, diabetes, and blood pressure, as well as measures of negative affect, physical activity, and clinical stroke. The association with macroscopic infarcts was driven by lacunar infarcts, and was independent of cerebral atherosclerosis and arteriolosclerosis. Conclusions Purpose in life may affect risk for cerebral infarcts, specifically macroscopic lacunar infarcts. PMID:25791714

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

    PubMed

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

    2017-01-01

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

  6. Patients with advanced Parkinson's disease with and without freezing of gait: a comparative analysis of vascular lesions using brain MRI.

    PubMed

    Gallardo, M J; Cabello, J P; Pastor, C; Muñoz-Torrero, J J; Carrasco, S; Ibañez, R; Vaamonde, J

    2014-05-01

    Freezing of gait (FOG) is one of the most disabling and enigmatic symptoms in Parkinson's disease. Vascular lesions, observed in magnetic resonance imaging (MRI) scans, may produce or exacerbate this symptom. The study includes 22 patients with Parkinson's disease subjects, 12 with freezing of gait and 10 without. All patients underwent an MRI scan and any vascular lesions were analysed using the modified Fazekas scale. Patients with FOG scored higher on the modified Fazekas scale than the rest of the group. Although the two groups contained the same percentage of patients with vascular lesions (50% in both groups), lesion load was higher in the group of patients with FOG. Vascular lesions in the periventricular area and deep white matter seem to be the most involved in the development of FOG. Vascular lesions may contribute to the onset or worsening of FOG in patients with PD. This study suggests that cerebral vascular disease should be considered in patients with FOG. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  7. Effect of type 1 diabetes on the production and vasoactivity of hydrogen sulfide in rat middle cerebral arteries

    PubMed Central

    Streeter, Elosie Y; Badoer, Emilio; Woodman, Owen L; Hart, Joanne L

    2013-01-01

    Hydrogen sulfide (H2S) is produced endogenously in vascular tissue and has both vasoregulation and antioxidant effects. This study examines the effect of diabetes-induced oxidative stress on H2S production and function in rat middle cerebral arteries. Diabetes was induced in rats with streptozotocin (50 mg/kg, i.v.). Middle cerebral artery function was examined using a small vessel myograph and superoxide anion generation measured using nicotinamide adenine dinucleotide phosphate (NADPH)-dependent lucigenin-enhanced chemiluminescence. Cystathionine-γ-lyase (CSE) mRNA expression was measured via RT-PCR. Diabetic rats had elevated blood glucose and significantly reduced cerebral artery endothelial function. Maximum vasorelaxation to the H2S donor NaHS was unaffected in diabetic cerebral arteries and was elicited via a combination of K+, Cl−, and Ca2+ channel modulation, although the contribution of Cl− channels was significantly less in the diabetic cerebral arteries. Vasorelaxation to the H2S precursor l-cysteine and CSE mRNA were significantly increased in diabetic cerebral arteries. Cerebral artery superoxide production was significantly increased in diabetes, but this increase was attenuated ex vivo by incubation with the H2S donor NaHS. These data confirm that cerebral artery endothelial dysfunction and oxidative stress occurs in diabetes. Endogenous H2S production and activity is upregulated in cerebral arteries in this model of diabetes. Vasorelaxation responses to exogenous H2S are preserved and exogenous H2S attenuates the enhanced cerebral artery generated superoxide observed in the diabetic group. These data suggest that upregulation of endogenous H2S in diabetes may play an antioxidant and vasoprotective role. PMID:24303182

  8. MRI assessment of cerebral oxygen metabolism in cocaine-addicted individuals: Hypoactivity and dose dependence

    PubMed Central

    Liu, Peiying; Lu, Hanzhang; Filbey, Francesca M.; Tamminga, Carol A.; Cao, Yan; Adinoff, Bryon

    2014-01-01

    Long-term cocaine use is known to negatively impact neural and cerebrovascular systems. However, the use of imaging markers to separately assess these parameters remains challenging. The primary reason is that most functional imaging markers such as cerebral blood flow, functional connectivity, and task-evoked functional MRI are known to reflect a complex interplay between neural and vascular components, thus the interpretation of the results is not straightforward. The goal of the present study is to examine neural-activity-specific changes in cocaine addiction, using cerebral metabolic rate of oxygen (CMRO2) as a surrogate marker of aggregated neural activity. We applied a recently developed CMRO2 technique in 13 cocaine-addicted subjects and 13 age and gender matched control subjects, and examined the impact of long-term cocaine use on CMRO2. Our results showed that CMRO2 in cocaine-addicted subjects (152±16 μmol/100g/min) is significantly lower (p=0.031) than that in controls (169±20 μmol/100g/min). Furthermore, the severity of this decreased metabolism is associated with lifetime cocaine use (p=0.05). Additionally, the CMRO2 reduction was accompanied by a trend of decrease in cerebral blood flow (p=0.058), but venous oxygenation was unaffected (p=0.96), which suggested that the CMRO2 change may be attributed to a vascular deficiency in chronic cocaine users. To our knowledge, this is the first study to measure CMRO2 in cocaine addicted individuals. Our findings suggest that CMRO2 may be a promising approach for assessing the long-term effects of cocaine use on the brain. PMID:24757009

  9. Cerebral aneurysm

    MedlinePlus Videos and Cool Tools

    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 ...

  10. Use of the 2.8 French Progreat microcatheter in diagnostic cerebral angiography.

    PubMed

    Griauzde, Julius; Gemmete, Joseph J; Shastri, Ravi; Pandey, Aditya S; Chaudhary, Neeraj

    2017-01-01

    Tortuous vascular anatomy poses a significant challenge to performing diagnostic cerebral angiography. To report a new cerebral angiography technique for overcoming tortuous aortic and supra-aortic anatomy using a 2.8 French (F) Progreat microcatheter (0.028 inch (internal diameter) (Terumo; Somerset, New Jersey, USA) to obtain a diagnostic cerebral angiogram. A retrospective analysis of consecutive cases undergoing diagnostic cerebral angiography at our institution between 1 January 2013 and 30 November 2015 in which a 2.8F Progreat microcatheter was used. Clinical and operative notes were reviewed and correlated with imaging. Radiologic imaging, including CT, MRI, and digital subtraction angiography, was reviewed. Neurologic, systemic, and local complications were recorded on the basis of clinical follow-up results after each angiographic examination. Events that occurred within 24 h of the angiography were considered to be complications of the procedure. Initial attempts at catheterization of the target vessel with various 4F and 5F catheters were unsuccessful owing to tortuosity, atherosclerotic disease, or occlusion of the catheter in the target vessel. Microcatheterization of the target vessel was successful in 59/62 (95%) target vessels. A diagnostic cerebral angiogram with a power injection was obtained in 59 (100%) of the successfully catheterized vessels. In one case, angiography proceeded to aneurysm coiling after over-the-wire exchange. In two cases, angiography proceeded to mechanical thrombectomy after over-the-wire exchange. No procedural complications were seen. The 2.8F Progreat microcatheter can be used to obtain a diagnostic cerebral angiogram in patients with anatomic challenges limiting catheterization by standard techniques. 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/.

  11. Simultaneous two-photon imaging of cerebral oxygenation and capillary blood flow in atherosclerotic mice

    NASA Astrophysics Data System (ADS)

    Lu, Xuecong; Li, Baoqiang; Moeini, Mohammad; Lesage, Frédéric

    2017-02-01

    Gradual changes in brain microvasculature and cerebral capillary blood flow occurring with atherosclerosis may significantly contribute to cognition decline due to their role in brain tissue oxygenation. However, previous stud- ies of the relationship between cerebral capillary blood flow and brain tissue oxygenation are limited. This study aimed to investigate vascular and concomitant changes in brain tissue pO2 with atherosclerosis. Experiments in young healthy C57B1/6 mice (n=6 , WT), young atherosclerotic mice (n=6 , ATX Y) and old atherosclerotic mice (n=6 , ATX O) were performed imaging on the left sensory-motor cortex at resting state under urethane (1.5 g/kg) anesthesia using two-photon fluorescence microscopy. The results showed that pO2 around capillaries, correlated with red blood cell (RBC) flux, increased with atherosclerosis.

  12. Vascular basement membranes as pathways for the passage of fluid into and out of the brain.

    PubMed

    Morris, Alan W J; Sharp, Matthew MacGregor; Albargothy, Nazira J; Fernandes, Rute; Hawkes, Cheryl A; Verma, Ajay; Weller, Roy O; Carare, Roxana O

    2016-05-01

    In the absence of conventional lymphatics, drainage of interstitial fluid and solutes from the brain parenchyma to cervical lymph nodes is along basement membranes in the walls of cerebral capillaries and tunica media of arteries. Perivascular pathways are also involved in the entry of CSF into the brain by the convective influx/glymphatic system. The objective of this study is to differentiate the cerebral vascular basement membrane pathways by which fluid passes out of the brain from the pathway by which CSF enters the brain. Experiment 1: 0.5 µl of soluble biotinylated or fluorescent Aβ, or 1 µl 15 nm gold nanoparticles was injected into the mouse hippocampus and their distributions determined at 5 min by transmission electron microscopy. Aβ was distributed within the extracellular spaces of the hippocampus and within basement membranes of capillaries and tunica media of arteries. Nanoparticles did not enter capillary basement membranes from the extracellular spaces. Experiment 2: 2 µl of 15 nm nanoparticles were injected into mouse CSF. Within 5 min, groups of nanoparticles were present in the pial-glial basement membrane on the outer aspect of cortical arteries between the investing layer of pia mater and the glia limitans. The results of this study and previous research suggest that cerebral vascular basement membranes form the pathways by which fluid passes into and out of the brain but that different basement membrane layers are involved. The significance of these findings for neuroimmunology, Alzheimer's disease, drug delivery to the brain and the concept of the Virchow-Robin space are discussed.

  13. MyD88 contributes to neuroinflammatory responses induced by cerebral ischemia/reperfusion in mice

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

    Ye, Xinchun; Kong, Delian; Wang, Jun

    Myeloid differentiation primary-response protein-88 (MyD88) is one of adaptor proteins mediating Toll-like receptors (TLRs) signaling. Activation of MyD88 results in the activation of nuclear factor kappa B (NFκB) and the increase of inflammatory responses. Evidences have demonstrated that TLRs signaling contributes to cerebral ischemia/reperfusion (I/R) injury. However, the role of MyD88 in this mechanism of action is disputed and needs to be clarified. In the present study, in a mouse model of cerebral I/R, we examined the activities of NFκB and interferon factor-3 (IRF3), and the inflammatory responses in ischemic brain tissue using ELISA, Western blots, and real-time PCR. Neurologicalmore » function and cerebral infarct size were also evaluated 24 h after cerebral I/R. Our results showed that NFκB activity increased in ischemic brains, but IRF3 was not activated after cerebral I/R, in wild-type (WT) mice. MyD88 deficit inhibited the activation of NFκB, and the expression of interleukin-1β (IL-1β), IL-6, Beclin-1 (BECN1), pellino-1, and cyclooxygenase-2 (COX-2) increased by cerebral I/R compared with WT mice. Interestingly, the expression of interferon Beta 1 (INFB1) and vascular endothelial growth factor (VEGF) increased in MyD88 KO mice. Unexpectedly, although the neurological function improved in the MyD88 knockout (KO) mice, the deficit of MyD88 failed to reduce cerebral infarct size compared to WT mice. We concluded that MyD88-dependent signaling contributes to the inflammatory responses induced by cerebral I/R. MyD88 deficit may inhibit the increased inflammatory response and increase neuroprotective signaling. - Highlights: • Cerebral ischemia/reperfusion activates inflammatory responses in brain tissue. • MyD88-dependent pathway contributes to the activated inflammatory responses. • MyD88 deficit increases neuroprotective signaling in ischemic brain.« less

  14. Subgroup of ADNI Normal Controls Characterized by Atrophy and Cognitive Decline Associated With Vascular Damage

    PubMed Central

    Nettiksimmons, Jasmine; Beckett, Laurel; Schwarz, Christopher; Carmichael, Owen; Fletcher, Evan; DeCarli, Charles

    2013-01-01

    Previous work examining Alzheimer’s Disease Neuroimaging Initiative (ADNI) normal controls using cluster analysis identified a subgroup characterized by substantial brain atrophy and white matter hyperintensities (WMH). We hypothesized that these effects could be related to vascular damage. Fifty-three individuals in the suspected vascular cluster (Normal 2) were compared with 31 individuals from the cluster characterized as healthy/typical (Normal 1) on a variety of outcomes, including magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers, vascular risk factors and outcomes, cognitive trajectory, and medications for vascular conditions. Normal 2 was significantly older but did not differ on ApoE4+ prevalence. Normal 2 differed significantly from Normal 1 on all MRI measures but not on Amyloid-Beta1-42 or total tau protein. Normal 2 had significantly higher body mass index (BMI), Hachinksi score, and creatinine levels, and took significantly more medications for vascular conditions. Normal 2 had marginally significantly higher triglycerides and blood glucose. Normal 2 had a worse cognitive trajectory on the Rey’s Auditory Verbal Learning Test (RAVLT) 30-min delay test and the Functional Activity Questionnaire (FAQ). Cerebral atrophy associated with multiple vascular risks is common among cognitively normal individuals, forming a distinct subgroup with significantly increased cognitive decline. Further studies are needed to determine the clinical impact of these findings. PMID:23527743

  15. 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.

  16. The Return of an Old Worm: Cerebral Paragonimiasis Presenting with Intracerebral Hemorrhage

    PubMed Central

    Koh, Eun Jung; Kim, Seung-Ki; Wang, Kyu-Chang; Chai, Jong-Yil; Chong, Sangjoon; Park, Sung-Hye; Cheon, Jung-Eun

    2012-01-01

    Paragonimiasis is caused by ingesting crustaceans, which are the intermediate hosts of Paragonimus. The involvement of the brain was a common presentation in Korea decades ago, but it becomes much less frequent in domestic medical practices. We observed a rare case of cerebral paragonimiasis manifesting with intracerebral hemorrhage. A 10-yr-old girl presented with sudden-onset dysarthria, right facial palsy and clumsiness of the right hand. Brain imaging showed acute intracerebral hemorrhage in the left frontal area. An occult vascular malformation or small arteriovenous malformation compressed by the hematoma was initially suspected. The lesion progressed for over 2 months until a delayed surgery was undertaken. Pathologic examination was consistent with cerebral paragonimiasis. After chemotherapy with praziquantel, the patient was monitored without neurological deficits or seizure attacks for 6 months. This case alerts practicing clinicians to the domestic transmission of a forgotten parasitic disease due to environmental changes. PMID:23166429

  17. Effect of short-term exercise-heat acclimation on ventilatory and cerebral blood flow responses to passive heating at rest in humans.

    PubMed

    Fujii, Naoto; Tsuji, Bun; Honda, Yasushi; Kondo, Narihiko; Nishiyasu, Takeshi

    2015-09-01

    Hyperthermia induces hyperventilation and cerebral hypoperfusion in resting humans. We tested the hypothesis that short-term exercise-heat acclimation would alleviate those effects. Twenty healthy male subjects were divided into two groups that performed exercise training in the heat (TR-HEAT, n = 10) or cold (TR-COLD, n = 10). Before and after the training, the subjects in both groups participated in passive-heat tests at rest. Training was performed at 37°C (TR-HEAT) or 10°C (TR-COLD) and entailed four 20-min bouts of cycling at 50% peak oxygen uptake separated by 10-min recoveries daily for 6 consecutive days. After TR-HEAT, esophageal temperature was lowered when measured before and during passive heating, as was the esophageal temperature threshold for cutaneous active vasodilation, whereas plasma volume was increased (all P < 0.05). These traditional indices of successful heat acclimation were not all induced by TR-COLD (all P > 0.05). TR-HEAT had no significant effect on passive heating-induced increases in minute ventilation, even when evaluated as the esophageal temperature threshold for increases in minute ventilation and the slope relating minute ventilation to esophageal temperature (all P > 0.05). By contrast, TR-HEAT attenuated the passive heating-induced reduction in the cerebral vascular conductance index (middle cerebral artery mean blood velocity/mean arterial pressure) (all P < 0.05). TR-COLD did not attenuate the increase in minute ventilation or the decrease in the cerebral vascular conductance index observed during passive heating (all P > 0.05). These data suggest that in resting heated humans, short-term heat acclimation achieved through moderate-intensity exercise training (i.e., 50% peak oxygen uptake) in the heat does not influence hyperthermia-induced hyperventilation, but it does potentially attenuate cerebral hypoperfusion. Copyright © 2015 the American Physiological Society.

  18. Juvenile nasopharyngeal angiofibroma: vascular determinates for operative complications and tumor recurrence.

    PubMed

    Chan, Kenny H; Gao, Dexiang; Fernandez, Patrick G; Kingdom, Todd T; Kumpe, David A

    2014-03-01

    Operative complications and tumor recurrence in juvenile nasopharyngeal angiofibroma (JNA) are measurable and meaningful outcomes. This study aimed to assess the association of these two outcomes to various clinical indices and in particular, vascular determinates. Retrospective cohort study. An 18-year retrospective chart review of an academic tertiary center was undertaken. Data from clinical notes, imaging studies, and arteriograms were analyzed. Thirty-seven male (mean age, 14.4 years) patients were included in the study. Tumor stages included: IA (three), IB (three), IIA (14), IIB (three), IIC (five), IIIA (five), and IIIB (four). Four complications (cerebrospinal fluid leak, cerebral vascular accident, and two transient ocular defects) occurred. Eight recurrences occurred within 24 months following surgery. Complications were associated with estimated intraoperative blood loss (EBL) (P = .045). Tumor recurrence was associated with feeding vessels from the contralateral internal carotid artery (ICA) (P = .017). EBL was significantly associated with surgical technique used. EBL, tumor stage, and tumor vascular supply were significantly associated with each other. Vascular factors were associated with JNA complication and tumor recurrence. EBL might affect complications, and contralateral ICA as a feeding vessel might affect recurrence. EBL was influenced by procedure choice and was interrelated to size and vascular supply of the tumor. This study bolsters the need to decrease intraoperative blood loss by preoperative embolization and use of endoscopic removal techniques. Furthermore, when branches of the ICA are found to be feeding vessels, greater surgical attention for a dry surgical field is encouraged. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  19. [Accidental hypothermia].

    PubMed

    Soteras Martínez, Iñigo; Subirats Bayego, Enric; Reisten, Oliver

    2011-07-09

    Accidental hypothermia is an infrequent and under-diagnosed pathology, which causes fatalities every year. Its management requires thermometers to measure core temperature. An esophageal probe may be used in a hospital situation, although in moderate hypothermia victims epitympanic measurement is sufficient. Initial management involves advance life support and body rewarming. Vigorous movements can trigger arrhythmia which does not use to respond to medication or defibrillation until the body reaches 30°C. External, passive rewarming is the method of choice for mild hypothermia and a supplementary method for moderate or severe hypothermia. Active external rewarming is indicated for moderate or severe hypothermia or mild hypothermia that has not responded to passive rewarming. Active internal rewarming is indicated for hemodynamically stable patients suffering moderate or severe hypothermia. Patients with severe hypothermia, cardiac arrest or with a potassium level below 12 mmol/l may require cardiopulmonary bypass treatment. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  20. Demonstration of elevation and localization of Rho-kinase activity in the brain of a rat model of cerebral infarction.

    PubMed

    Yano, Kazuo; Kawasaki, Koh; Hattori, Tsuyoshi; Tawara, Shunsuke; Toshima, Yoshinori; Ikegaki, Ichiro; Sasaki, Yasuo; Satoh, Shin-ichi; Asano, Toshio; Seto, Minoru

    2008-10-10

    Evidence that Rho-kinase is involved in cerebral infarction has accumulated. However, it is uncertain whether Rho-kinase is activated in the brain parenchyma in cerebral infarction. To answer this question, we measured Rho-kinase activity in the brain in a rat cerebral infarction model. Sodium laurate was injected into the left internal carotid artery, inducing cerebral infarction in the ipsilateral hemisphere. At 6 h after injection, increase of activating transcription factor 3 (ATF3) and c-Fos was found in the ipsilateral hemisphere, suggesting that neuronal damage occurs. At 0.5, 3, and 6 h after injection of laurate, Rho-kinase activity in extracts of the cerebral hemispheres was measured by an ELISA method. Rho-kinase activity in extracts of the ipsilateral hemisphere was significantly increased compared with that in extracts of the contralateral hemisphere at 3 and 6 h but not 0.5 h after injection of laurate. Next, localization of Rho-kinase activity was evaluated by immunohistochemical analysis in sections of cortex and hippocampus including infarct area 6 h after injection of laurate. Staining for phosphorylation of myosin-binding subunit (phospho-MBS) and myosin light chain (phospho-MLC), substrates of Rho-kinase, was elevated in neuron and blood vessel, respectively, in ipsilateral cerebral sections, compared with those in contralateral cerebral sections. These findings indicate that Rho-kinase is activated in neuronal and vascular cells in a rat cerebral infarction model, and suggest that Rho-kinase could be an important target in the treatment of cerebral infarction.

  1. Measuring the visual salience of alignments by their non-accidentalness.

    PubMed

    Blusseau, S; Carboni, A; Maiche, A; Morel, J M; Grompone von Gioi, R

    2016-09-01

    Quantitative approaches are part of the understanding of contour integration and the Gestalt law of good continuation. The present study introduces a new quantitative approach based on the a contrario theory, which formalizes the non-accidentalness principle for good continuation. This model yields an ideal observer algorithm, able to detect non-accidental alignments in Gabor patterns. More precisely, this parameterless algorithm associates with each candidate percept a measure, the Number of False Alarms (NFA), quantifying its degree of masking. To evaluate the approach, we compared this ideal observer with the human attentive performance on three experiments of straight contours detection in arrays of Gabor patches. The experiments showed a strong correlation between the detectability of the target stimuli and their degree of non-accidentalness, as measured by our model. What is more, the algorithm's detection curves were very similar to the ones of human subjects. This fact seems to validate our proposed measurement method as a convenient way to predict the visibility of alignments. This framework could be generalized to other Gestalts. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Accidental Head Injury: A Real Life Experience.

    ERIC Educational Resources Information Center

    Blakely, Jim

    1988-01-01

    The adult victim of accidental head injury as a result of an automobile accident recounts his experiences as a brain injured adult with such problems as poor balance, poor speech, spasticity, and lack of fine motor movement. He emphasizes his determination to get on with his life. (DB)

  3. Neuropilin 2 deficiency does not affect cortical neuronal viability in response to oxygen-glucose-deprivation and transient middle cerebral artery occlusion.

    PubMed

    Hou, Sheng T; Jiang, Susan X; Slinn, Jacqueline; O'Hare, Michael; Karchewski, Laurie

    2010-04-01

    Neuropilin 2 (NRP2) is a type I transmembrane protein that binds to distinct members of the class III secreted Semaphorin subfamily. NRP2 plays important roles in repulsive axon guidance, angiogenesis and vasculogenesis through partnering with co-receptors such as vascular endothelial growth factor receptors (VEGFRs) during development. Emerging evidence also suggests that NRP2 contributes to injury response and environment changes in adult brains. In this study, we examined the contribution of NRP2 gene to cerebral ischemia-induced brain injury using NRP2 deficient mouse. To our surprise, the lack of NRP2 expression does not affect the outcome of brain injury induced by transient occlusion of the middle cerebral artery (MCAO) in mouse. The cerebral vasculature in terms of the middle cerebral artery anatomy and microvessel density in the cerebral cortex of NRP2 deficient homozygous (NRP2(-/-)) mice are normal and almost identical to those of the heterozygous (NRP2(+/-)) and wild type (NRP2(+/+)) littermates. MCAO (1h) and 24h reperfusion caused a brain infarction of 23% (compared to the contralateral side) in NRP2(-/-) mice, which is not different from those in NRP2(+/- and +/+) mice at 22 and 21%, respectively (n=19, p>0.05). Correspondingly, NRP2(-/-) mouse also showed a similar level of deterioration of neurological functions after stroke compared with their NRP2(+/- and +/+) littermates. Oxygen-glucose-deprivation (OGD) caused a significant neuronal death in NRP2(-/-) cortical neurons, at the level similar to that in NRP(+/+) cortical neurons (72% death in NRP(-/-) neurons vs. 75% death in NRP2(+/+) neurons; n=4; p>0.05). Together, these loss-of-function studies demonstrated that despite of its critical role in neuronal guidance and vascular formation during development, NRP2 expression dose not affect adult brain response to cerebral ischemia. Crown Copyright 2009. Published by Elsevier Ireland Ltd. All rights reserved.

  4. Upregulation of contractile endothelin type B receptors by lipid-soluble cigarette smoking particles in rat cerebral arteries via activation of MAPK

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

    Sandhu, Hardip, E-mail: sandhu.hardip@gmail.co; Xu, Cang Bao; Edvinsson, Lars

    2010-11-15

    Cigarette smoke exposure increases the risk of stroke. However, the underlying molecular mechanisms are poorly understood. Endothelin system plays key roles in the pathogenesis of stroke. The present study was designed to examine if lipid-soluble (dimethyl sulfoxide-soluble) cigarette smoke particles (DSP) induces upregulation of contractile endothelin type B (ET{sub B}) receptors in rat cerebral arteries and if activation of mitogen activated protein kinase (MAPK) and nuclear factor-kappaB (NF-{kappa}B) mediate the upregulation of contractile endothelin receptors in the cerebral arteries. Rat middle cerebral arteries were isolated and organ cultured in serum free medium for 24 h in the presence of DSPmore » with or without specific inhibitors: MEK specific (U0126), p38 specific (SB202190), JNK specific (SP600125), NF-{kappa}B specific (BMS-345541) or (IMD-0354), transcription inhibitor (actinomycin D), or translation blocker (cycloheximide). Contractile responses to the ET{sub B} receptor agonist sarafotoxin 6c were investigated by a sensitive myograph. The expression of the ET{sub B} receptors were studied at mRNA and protein levels using quantitative real time PCR and immunohistochemistry, respectively. Results show that organ culture per se induced transcriptional upregulation of contractile ET{sub B} receptors in the cerebral vascular smooth muscle cells. This upregulation was further increased at the translational level by addition of DSP to the organ culture, but this increase was not seen by addition of nicotine or water-soluble cigarette smoke particles to the organ culture. The increased upregulation of contractile ET{sub B} receptors by DSP was abrogated by U0126, SP600125, actinomycin D, and cycloheximide, suggesting that the underlying molecular mechanisms involved in this process include activation of MEK and JNK MAPK-mediated transcription and translation of new contractile ET{sub B} receptors. Thus, the MAPK-mediated upregulation of contractile ET

  5. Paediatric femur fractures at the emergency department: accidental or not?

    PubMed Central

    Vrolijk-Bosschaart, Thekla F; Bakx, Roel; Van Rijn, Rick R.

    2016-01-01

    Only a small proportion of all paediatric fractures is caused by child abuse or neglect, especially in highly prevalent long bone fractures. It can be difficult to differentiate abusive fractures from non-abusive fractures. This article focuses on femoral fractures in young children. Based on three cases, this article presents a forensic evidence-based approach to differentiate between accidental and non-accidental causes of femoral fractures. We describe three cases of young children who were presented to the emergency department because of a suspected femur fracture. Although in all cases, the fracture had a similar location and appearance, the clinical history and developmental stage of the child led to three different conclusions. In the first two cases, an accidental mechanism was a plausible conclusion, although in the second case, neglect of parental supervision was the cause for concern. In the third case, a non-accidental injury was diagnosed and appropriate legal prosecution followed. Any doctor treating children should always be aware of the possibility of child abuse and neglect in children with injuries, especially in young and non-mobile children presenting with an unknown trauma mechanism. If a suspicion of child abuse or neglect arises, a thorough diagnostic work-up should be performed, including a full skeletal survey according to the guidelines of the Royal College of Radiologists and the Royal College of Paediatrics and Child Health. In order to make a good assessment, the radiologist reviewing the skeletal survey needs access to all relevant clinical and social information. PMID:26642309

  6. Risk assessment for stonecutting enterprises Accidental risks in the course of petroleum production and stone extraction

    NASA Astrophysics Data System (ADS)

    Aleksandrova, A. J.; Timofeeva, S. S.

    2018-01-01

    The paper is devoted to the assessment of accidental risks occurring at the works engaged in stone extracting and petroleum production. Two basic kinds of accidents common for stone extracting and petroleum production have been chosen to be discussed in the part under consideration. The most dangerous accidental situation characteristic for a stone milling line is an unsanctioned explosion, UE, of blasting agents used for the development of stone deposits. The analysis of a risk occurrence in certain accidental situations is to be carried out. With reference to petroleum extraction, a combustibles and lubricants (C & L) explosion is the most dangerous of characteristic accidental situations. To reveal the most probable causes of accidental situations to be realized, a graph of cause and effect relations has been constructed for each of the accidental situations most probable causes to real situation of an accident. Disasters of a natural origin are the most probable causes of unsanctioned explosions at the deposits of stone raw materials. Technology related natural disasters are the most probable causes of unsanctioned explosions to be realized at multiple well platforms engaged in petroleum production.

  7. IGF-1 deficiency impairs cerebral myogenic autoregulation in hypertensive mice.

    PubMed

    Toth, Peter; Tucsek, Zsuzsanna; Tarantini, Stefano; Sosnowska, Danuta; Gautam, Tripti; Mitschelen, Matthew; Koller, Akos; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2014-12-01

    Aging impairs autoregulatory protection in the brain, exacerbating hypertension-induced cerebromicrovascular injury, neuroinflammation, and development of vascular cognitive impairment. Despite the importance of the age-related decline in circulating insulin-like growth factor-1 (IGF-1) levels in cerebrovascular aging, the effects of IGF-1 deficiency on functional adaptation of cerebral arteries to high blood pressure remain elusive. To determine whether IGF-1 deficiency impairs autoregulatory protection, hypertension was induced in control and IGF-1-deficient mice (Igf1(f/f)+TBG-iCre-AAV8) by chronic infusion of angiotensin-II. In hypertensive control mice, cerebral blood flow (CBF) autoregulation was extended to higher pressure values and the pressure-induced tone of middle cerebral arteries (MCAs) was increased. In hypertensive IGF-1-deficient mice, autoregulation was markedly disrupted, and MCAs did not show adaptive increases in myogenic tone. In control mice, the mechanism of adaptation to hypertension involved upregulation of TRPC channels in MCAs and this mechanism was impaired in hypertensive IGF-1-deficient mice. Likely downstream consequences of cerebrovascular autoregulatory dysfunction in hypertensive IGF-1-deficient mice included exacerbated disruption of the blood-brain barrier and neuroinflammation (microglia activation and upregulation of proinflammatory cytokines and chemokines), which were associated with impaired hippocampal cognitive function. Collectively, IGF-1 deficiency impairs autoregulatory protection in the brain of hypertensive mice, potentially exacerbating cerebromicrovascular injury and neuroinflammation mimicking the aging phenotype.

  8. Modelling Ischemic Stroke and Temperature Intervention Using Vascular Porous Method

    NASA Astrophysics Data System (ADS)

    Blowers, Stephen; Valluri, Prashant; Marshall, Ian; Andrews, Peter; Harris, Bridget; Thrippleton, Michael

    2017-11-01

    In the event of cerebral infarction, a region of tissue is supplied with insufficient blood flow to support normal metabolism. This can lead to an ischemic reaction which incurs cell death. Through a reduction of temperature, the metabolic demand can be reduced, which then offsets the onset of necrosis. This allows extra time for the patient to receive medical attention and could help prevent permanent brain damage from occurring. Here, we present a vascular-porous (VaPor) blood flow model that can simulate such an event. Cerebral blood flow is simulated using a combination of 1-Dimensional vessels embedded in 3-Dimensional porous media. This allows for simple manipulation of the structure and determining the effect of an obstructed vessel. Results show regional temperature increase of 1-1.5°C comparable with results from literature (in contrast to previous simpler models). Additionally, the application of scalp cooling in such an event dramatically reduces the temperature in the affected region to near hypothermic temperatures, which points to a potential rapid form of first intervention.

  9. Accidental poisoning with detomidine and butorphanol.

    PubMed

    Hannah, N

    2010-09-01

    This is a case report concerning a veterinarian who spilled detomidine and butorphanol on dermatitic hands while sedating a horse. This resulted in acute poisoning from which the patient spontaneously recovered with supportive management. Veterinarians often suffer from occupational dermatitis and handle strong sedatives with no gloves while working around unpredictable animals. Thus, this group is at risk of accidental self-poisoning from this method.

  10. Accidental hypothermia in a healthy quadriplegic patient.

    PubMed

    Altus, P; Hickman, J W; Nord, H J

    1985-03-01

    An otherwise healthy 28-year-old quadriplegic patient was admitted to the hospital with a core temperature of 76 degrees F secondary to accidental hypothermia. Her neurologic disability was detrimental to thermoregulation by decreasing her ability to shiver actively and to vasoconstrict. The relationship between shivering and thermoregulation is discussed.

  11. Presenilin 1 mutation decreases both calcium and contractile responses in cerebral arteries.

    PubMed

    Toussay, Xavier; Morel, Jean-Luc; Biendon, Nathalie; Rotureau, Lolita; Legeron, François-Pierre; Boutonnet, Marie-Charlotte; Cho, Yoon H; Macrez, Nathalie

    2017-10-01

    Mutations or upregulation in presenilin 1 (PS1) gene are found in familial early-onset Alzheimer's disease or sporadic late-onset Alzheimer's disease, respectively. PS1 has been essentially studied in neurons and its mutation was shown to alter intracellular calcium (Ca 2+ ) signals. Here, we showed that PS1 is expressed in smooth muscle cells (SMCs) of mouse cerebral arteries, and we assessed the effects of the deletion of exon 9 of PS1 (PS1dE9) on Ca 2+ signals and contractile responses of vascular SMC. Agonist-induced contraction of cerebral vessels was significantly decreased in PS1dE9 both in vivo and ex vivo. Spontaneous activity of Ca 2+ sparks through ryanodine-sensitive channels (RyR) was unchanged, whereas the RyR-mediated Ca 2+ -release activated by caffeine was shorter in PS1dE9 SMC when compared with control. Moreover, PS1dE9 mutation decreased the caffeine-activated capacitive Ca 2+ entry, and inhibitors of SERCA pumps reversed the effects of PS1dE9 on Ca 2+ signals. PS1dE9 mutation also leads to the increased expression of SERCA3, phospholamban, and RyR3. These results show that PS1 plays a crucial role in the cerebrovascular system and the vascular reactivity is decreased through altered Ca 2+ signals in PS1dE9 mutant mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Cryptotanshinone exhibits therapeutical effects on cerebral stroke through the PI3K/AKT‑eNOS signaling pathway.

    PubMed

    Zhu, Weixin; Qiu, Weihong; Lu, Ailan

    2017-12-01

    Cerebral stroke is a kind of acute cerebrovascular disease with high incidence, morbidity and disability. Treatments against various types of cerebral stroke are limited at preventive measurements due to the lack of effective therapeutic method. The present study aimed to investigate the protective effect of cryptotanshinone (CPT) on cerebral stroke, and investigate the possible mechanism involved in order to develop a novel therapy against stoke. The phosphoinositide 3‑kinase membrane translocation of cerebral stroke rats pretreated with CPT at various concentrations were measured, as well as the phosphorylation of protein kinase B (AKT) and endothelial nitric oxide synthase (eNOS). Additionally, the expression level of B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and vascular endothelial growth factor were also assessed using western blotting and reverse transcription‑quantitative polymerase chain reaction. Furthermore, biochemical tests were used to measure the activity of superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) in both the cerebral cortex and peripheral blood. As a result, CPT‑pretreated rats presented declined phosphoinositide 3‑kinase (PI3K) and AKT expression levels, indicating that the PI3K/AKT signaling pathway was inhibited. Increased Bcl‑2 and NO levels in both the cerebral cortex and peripheral blood demonstrated the anti‑apoptosis and blood vessel protection effect of CPT. Furthermore, increased SOD activity and declined MDA levels demonstrated suppressed lipid peroxidation. In conclusion, CPT exhibited a protective effect against cerebral stroke through inhibition of the PI3K/AKT‑eNOS signaling pathway. These results suggested the potential of CPT as a promising agent in the treatment of cerebral stroke.

  13. Imaging putative foetal cerebral blood oxygenation using susceptibility weighted imaging (SWI).

    PubMed

    Yadav, Brijesh Kumar; Krishnamurthy, Uday; Buch, Sagar; Jella, Pavan; Hernandez-Andrade, Edgar; Yeo, Lami; Korzeniewski, Steven J; Trifan, Anabela; Hassan, Sonia S; Haacke, E Mark; Romero, Roberto; Neelavalli, Jaladhar

    2018-05-01

    To evaluate the magnetic susceptibility, ∆χ v , as a surrogate marker of venous blood oxygen saturation, S v O 2 , in second- and third-trimester normal human foetuses. Thirty-six pregnant women, having a mean gestational age (GA) of 31 2/7 weeks, underwent magnetic resonance imaging (MRI). Susceptibility-weighted imaging (SWI) data from the foetal brain were acquired. ∆χ v of the superior sagittal sinus (SSS) was quantified using MR susceptometry from the intra-vascular phase measurements. Assuming the magnetic property of foetal blood, ∆χ do , is the same as that of adult blood, S v O 2 was derived from the measured Δχ v . The variation of ∆χ v and S v O 2 , as a function of GA, was statistically evaluated. The mean ∆χ v in the SSS in the second-trimester (n = 8) and third-trimester foetuses (n = 28) was found to be 0.34± 0.06 ppm and 0.49 ±0.05 ppm, respectively. Correspondingly, the derived S v O 2 values were 69.4% ±3.27% and 62.6% ±3.25%. Although not statistically significant, an increasing trend (p = 0.08) in Δχ v and a decreasing trend (p = 0.22) in S v O 2 with respect to advancing gestation was observed. We report cerebral venous blood magnetic susceptibility and putative oxygen saturation in healthy human foetuses. Cerebral oxygen saturation in healthy human foetuses, despite a slight decreasing trend, does not change significantly with advancing gestation. • Cerebral venous magnetic susceptibility and oxygenation in human foetuses can be quantified. • Cerebral venous oxygenation was not different between second- and third-trimester foetuses. • Foetal cerebral venous oxygenation does not change significantly with advancing gestation.

  14. 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 ...

  15. Vascular and Inflammatory Factors in the Pathophysiology of Blast-Induced Brain Injury

    PubMed Central

    Elder, Gregory A.; Gama Sosa, Miguel A.; De Gasperi, Rita; Stone, James Radford; Dickstein, Dara L.; Haghighi, Fatemeh; Hof, Patrick R.; Ahlers, Stephen T.

    2015-01-01

    Blast-related traumatic brain injury (TBI) has received much recent attention because of its frequency in the conflicts in Iraq and Afghanistan. This renewed interest has led to a rapid expansion of clinical and animal studies related to blast. In humans, high-level blast exposure is associated with a prominent hemorrhagic component. In animal models, blast exerts a variety of effects on the nervous system including vascular and inflammatory effects that can be seen with even low-level blast exposures which produce minimal or no neuronal pathology. Acutely, blast exposure in animals causes prominent vasospasm and decreased cerebral blood flow along with blood-brain barrier breakdown and increased vascular permeability. Besides direct effects on the central nervous system, evidence supports a role for a thoracically mediated effect of blast; whereby, pressure waves transmitted through the systemic circulation damage the brain. Chronically, a vascular pathology has been observed that is associated with alterations of the vascular extracellular matrix. Sustained microglial and astroglial reactions occur after blast exposure. Markers of a central and peripheral inflammatory response are found for sustained periods after blast injury and include elevation of inflammatory cytokines and other inflammatory mediators. At low levels of blast exposure, a microvascular pathology has been observed in the presence of an otherwise normal brain parenchyma, suggesting that the vasculature may be selectively vulnerable to blast injury. Chronic immune activation in brain following vascular injury may lead to neurobehavioral changes in the absence of direct neuronal pathology. Strategies aimed at preventing or reversing vascular damage or modulating the immune response may improve the chronic neuropsychiatric symptoms associated with blast-related TBI. PMID:25852632

  16. Mixed vascular nevus syndrome: a report of four new cases and a literature review

    PubMed Central

    Polizzi, Agata; Strano, Serena; Schepis, Carmelo; Morano, Massimiliano; Belfiore, Giuseppe; Palmucci, Stefano; Foti, Pietro Valerio; Pirrone, Concetta; Sofia, Vito; David, Emanuele; Salpietro, Vincenzo; Mankad, Kshitij; Milone, Pietro

    2016-01-01

    Background Mixed vascular nevus (or nevus vascularis mixtus) represents an admixture of cutaneous vascular malformations of the telangiectatic type and angiospastic spots of nevus anemicus. It can occur as an purely cutaneous trait or as a hallmark of a neurocutaneous phenotype (mixed vascular nevus syndrome) characterised by the combination of: (I) paired vascular (telangiectatic and anemic) twin nevi and brain abnormalities of the Dyke-Davidoff-Masson type (i.e., crossed cerebral/cerebellar hemiatrophy with hypoplasia of the ipsilateral cerebral vessels and homolateral hypertrophy of the skull and sinuses (hyperpneumatisation) with contralateral hemispheric hypertrophy); or (II) paired vascular twin nevi and brain malformations of the Dyke-Davidoff-Masson type in association with systemic abnormalities consisting in facial asymmetry, skeletal anomalies (i.e., Legg-Calvé-Perthes-like disease) and disorders of autoimmunity (i.e., diabetes, thyroiditis). In 2014, Happle proposed to name the syndrome with the eponym Ruggieri-Leech syndrome. Methods Review of the existing literature on nevus vascularis mixtus and information on our personal experience on new cases and follow-up of previously reported cases by some of us. Results The existing literature revealed 4 previous studies including 33 cases with an inferred purely cutaneous trait and 3 cases with a combination of paired vascular twin nevi and brain malformation of the Dyke-Davidoff-Masson type. Our personal experience includes 4 unpublished patients (1 female and 3 males; currently aged 2 to 34 years) seen and followed-up at our Institutions in Italy who had: paired vascular nevi involving either the face (n=2) or the face and parts of the body (n=2); facial asymmetry (n=4); mild to moderate facial dysmorphic features (n=2); developmental delay (n=3); seizures/stroke-like episodes and associated hemiplegia (n=4); muscular hypotrophy (n=2); mild to moderate hemispheric atrophy (n=4); skull osseous hypertrophy

  17. Thromboxane A2-induced bi-directional regulation of cerebral arterial tone.

    PubMed

    Neppl, Ronald L; Lubomirov, Lubomir T; Momotani, Ko; Pfitzer, Gabriele; Eto, Masumi; Somlyo, Avril V

    2009-03-06

    Myosin light chain phosphatase plays a critical role in modulating smooth muscle contraction in response to a variety of physiologic stimuli. A downstream target of the RhoA/Rho-kinase and nitric oxide (NO)/cGMP/cyclic GMP-dependent kinase (cGKI) pathways, myosin light chain phosphatase activity reflects the sum of both calcium sensitization and desensitization pathways through phosphorylation and dephosphorylation of the myosin phosphatase targeting subunit (MYPT1). As cerebral blood flow is highly spatio-temporally modulated under normal physiologic conditions, severe perturbations in normal cerebral blood flow, such as in cerebral vasospasm, can induce neurological deficits. In nonpermeabilized cerebral vessels stimulated with U-46619, a stable mimetic of endogenous thromboxane A2 implicated in the etiology of cerebral vasospasm, we observed significant increases in contractile force, RhoA activation, regulatory light chain phosphorylation, as well as phosphorylation of MYPT1 at Thr-696, Thr-853, and surprisingly Ser-695. Inhibition of nitric oxide signaling completely abrogated basal MYPT1 Ser-695 phosphorylation and significantly increased and potentiated U-46619-induced MYPT1 Thr-853 phosphorylation and contractile force, indicating that NO/cGMP/cGKI signaling maintains basal vascular tone through active inhibition of calcium sensitization. Surprisingly, a fall in Ser-695 phosphorylation did not result in an increase in phosphorylation of the Thr-696 site. Although activation of cGKI with exogenous cyclic nucleotides inhibited thromboxane A2-induced MYPT1 membrane association, RhoA activation, contractile force, and regulatory light chain phosphorylation, the anticipated decreases in MYPT1 phosphorylation at Thr-696/Thr-853 were not observed, indicating that the vasorelaxant effects of cGKI are not through dephosphorylation of MYPT1. Thus, thromboxane A2 signaling within the intact cerebral vasculature induces "buffered" vasoconstrictions, in which both the

  18. Effect of acute exposure to hypergravity (GX vs. GZ) on dynamic cerebral autoregulation

    NASA Technical Reports Server (NTRS)

    Serrador, J. M.; Wood, S. J.; Picot, P. A.; Stein, F.; Kassam, M. S.; Bondar, R. L.; Rupert, A. H.; Schlegel, T. T.

    2001-01-01

    We examined the effects of 30 min of exposure to either +3GX (front-to-back) or +GZ (head-to-foot) centrifugation on cerebrovascular responses to 80 degrees head-up tilt (HUT) in 14 healthy individuals. Both before and after +3 GX or +3 GZ centrifugation, eye-level blood pressure (BP(eye)), end tidal PCO2 (PET(CO2)), mean cerebral flow velocity (CFV) in the middle cerebral artery (transcranial Doppler ultrasound), cerebral vascular resistance (CVR), and dynamic cerebral autoregulatory gain (GAIN) were measured with subjects in the supine position and during subsequent 80 degrees HUT for 30 min. Mean BP(eye) decreased with HUT in both the GX (n = 7) and GZ (n = 7) groups (P < 0.001), with the decrease being greater after centrifugation only in the GZ group (P < 0.05). PET(CO2) also decreased with HUT in both groups (P < 0.01), but the absolute level of decrease was unaffected by centrifugation. CFV decreased during HUT more significantly after centrifugation than before centrifugation in both groups (P < 0.02). However, these greater decreases were not associated with greater increases in CVR. In the supine position after centrifugation compared with before centrifugation, GAIN increased in both groups (P < 0.05, suggesting an autoregulatory deficit), with the change being correlated to a measure of otolith function (the linear vestibulo-ocular reflex) in the GX group (r = 0.76, P < 0.05) but not in the GZ group (r = 0.24, P = 0.60). However, GAIN was subsequently restored to precentrifugation levels during postcentrifugation HUT (i.e., as BP(eye) decreased), suggesting that both types of centrifugation resulted in a leftward shift of the cerebral autoregulation curve. We speculate that this leftward shift may have been due to vestibular activation (especially during +GX) or potentially to an adaptation to reduced cerebral perfusion pressure during +GZ.

  19. Bioprinting for vascular and vascularized tissue biofabrication.

    PubMed

    Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

    2017-03-15

    Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision

  20. Transcranial Doppler-determined change in posterior cerebral artery blood flow velocity does not reflect vertebral artery blood flow during exercise.

    PubMed

    Washio, Takuro; Sasaki, Hiroyuki; Ogoh, Shigehiko

    2017-04-01

    We examined whether a change in posterior cerebral artery flow velocity (PCAv) reflected the posterior cerebral blood flow in healthy subjects during both static and dynamic exercise. PCAv and vertebral artery (VA) blood flow, as an index of posterior cerebral blood flow, were continuously measured during an exercise trial using transcranial Doppler (TCD) ultrasonography and Doppler ultrasound, respectively. Static handgrip exercise significantly increased both PCAv and VA blood flow. Increasing intensity of dynamic exercise further increased VA blood flow from moderate exercise, while PCAv decreased to almost resting level. During both static and dynamic exercise, the PCA cerebrovascular conductance (CVC) index significantly decreased from rest (static and high-intensity dynamic exercise, -11.5 ± 12.2% and -18.0 ± 16.8%, means ± SD, respectively) despite no change in the CVC of VA. These results indicate that vasoconstriction occurred at PCA but not VA during exercise-induced hypertension. This discrepancy in vascular response to exercise between PCA and VA may be due to different cerebral arterial characteristics. Therefore, to determine the effect of exercise on posterior cerebral circulation, at least, we need to carefully consider which cerebral artery to measure, regardless of exercise mode. NEW & NOTEWORTHY We examined whether transcranial Doppler-determined flow velocity in the posterior cerebral artery can be used as an index of cerebral blood flow during exercise. However, the changes in posterior cerebral artery flow velocity during exercise do not reflect vertebral artery blood flow. Copyright © 2017 the American Physiological Society.

  1. Neuroblast survival depends on mature vascular network formation after mouse stroke: role of endothelial and smooth muscle progenitor cell co-administration.

    PubMed

    Nih, Lina R; Deroide, Nicolas; Leré-Déan, Carole; Lerouet, Dominique; Soustrat, Mathieu; Levy, Bernard I; Silvestre, Jean-Sébastien; Merkulova-Rainon, Tatiana; Pocard, Marc; Margaill, Isabelle; Kubis, Nathalie

    2012-04-01

    Pro-angiogenic cell-based therapies constitute an interesting and attractive approach to enhancing post-stroke neurogenesis and decreasing neurological deficit. However, most new stroke-induced neurons die during the first few weeks after ischemia, thus impairing total recovery. Although the neovascularization process involves different cell types and various growth factors, most cell therapy protocols are based on the biological effects of single-cell-type populations or on the administration of heterogeneous populations of progenitors, namely human cord blood-derived CD34(+) cells, with scarce vascular progenitor cells. Tight cooperation between endothelial cells and smooth muscle cells/pericytes is critical for the development of functional neovessels. We hypothesized that neuroblast survival in stroke brain depends on mature vascular network formation. In this study, we injected a combination of endothelial progenitor cells (EPCs) and smooth muscle progenitor cells (SMPCs), isolated from human umbilical cord blood, into a murine model of permanent focal ischemia induced by middle cerebral artery occlusion. The co-administration of SMPCs and EPCs induced enhanced angiogenesis and vascular remodeling in the peri-infarct and infarct areas, where vessels exhibited a more mature phenotype. This activation of vessel growth resulted in the maintenance of neurogenesis and neuroblast migration to the peri-ischemic cortex. Our data suggest that a mature vascular network is essential for neuroblast survival after cerebral ischemia, and that co-administration of EPCs and SMPCs may constitute a novel therapeutic strategy for improving the treatment of stroke. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  2. Accidental introductions of natural enemies: causes and implications

    USDA-ARS?s Scientific Manuscript database

    Accidental introductions of natural enemies, including parasitoid and predatory groups, may exceed species introduced intentionally. Several factors favor this: a general surge in international trade; lack of surveillance for species that are not associated with live plants or animals; inability to ...

  3. In vivo assessment of the human cerebral microcirculation and its glycocalyx: A technical report.

    PubMed

    Haeren, R H L; Rijkers, K; Schijns, O E M G; Dings, J; Hoogland, G; van Zandvoort, M A M J; Vink, H; van Overbeeke, J J

    2018-06-01

    . Because of their eminent role in cerebral homeostasis, this method may significantly add to research on the role of vascular pathophysiology underling various neurological disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. [Impact of heat waves on non-accidental deaths in Jinan, China].

    PubMed

    Zhang, J; Liu, S Q; Zhou, L; Gong, S P; Liu, Y L; Zhang, Y; Zhang, J

    2016-02-20

    To assess the impact of heat waves on non-accidental deaths, and to investigate the influencing factors for deaths caused by heat waves in Jinan, China. Daily death data and meteorological data for summer days with or without heat waves in Jinan from 2012 to 2014 were collected, and a cross-over analysis was conducted to evaluate the influence of heat waves on non-accidental deaths and deaths caused by other reasons. The univariate and multivariate logistic regression models were used to investigate the influencing factors for deaths caused by heat waves. The risks of non-accidental deaths and deaths caused by circulation system diseases during the days with heat waves were 1.82 times(95% CI: 1.47~2.36) and 1.53 times(95% CI: 1.14~2.07) those during the days without heat waves. The multivariate logistic regression analysis showed that old age(≥75 years)(OR=1.184, 95% CI: 1.068~1.313), low educational level(OR=1.187, 95% CI: 1.064~1.324), and deaths outside hospital(OR=1.105, 95% CI: 1.009~1.210) were associated with the high risk of deaths during the days with heat waves. Heat waves significantly increase the risk of non-accidental deaths and deaths caused by circulation system diseases in Jinan, and the deaths during the days with heat waves are related to age, educational level, and place of death.

  5. An alternative approach for computing seismic response with accidental eccentricity

    NASA Astrophysics Data System (ADS)

    Fan, Xuanhua; Yin, Jiacong; Sun, Shuli; Chen, Pu

    2014-09-01

    Accidental eccentricity is a non-standard assumption for seismic design of tall buildings. Taking it into consideration requires reanalysis of seismic resistance, which requires either time consuming computation of natural vibration of eccentric structures or finding a static displacement solution by applying an approximated equivalent torsional moment for each eccentric case. This study proposes an alternative modal response spectrum analysis (MRSA) approach to calculate seismic responses with accidental eccentricity. The proposed approach, called the Rayleigh Ritz Projection-MRSA (RRP-MRSA), is developed based on MRSA and two strategies: (a) a RRP method to obtain a fast calculation of approximate modes of eccentric structures; and (b) an approach to assemble mass matrices of eccentric structures. The efficiency of RRP-MRSA is tested via engineering examples and compared with the standard MRSA (ST-MRSA) and one approximate method, i.e., the equivalent torsional moment hybrid MRSA (ETM-MRSA). Numerical results show that RRP-MRSA not only achieves almost the same precision as ST-MRSA, and is much better than ETM-MRSA, but is also more economical. Thus, RRP-MRSA can be in place of current accidental eccentricity computations in seismic design.

  6. Experience with intubated patients does not affect the accidental extubation rate in pediatric intensive care units and intensive care nurseries.

    PubMed

    Frank, B S; Lewis, R J

    1997-06-01

    Accidental extubation is a potentially serious event for pediatric or neonatal patients with respiratory failure, especially in clinical settings in which personnel capable of performing reintubation may not be readily available. Thus the rate of accidental extubation in small intensive care units that operate without 24-hour in-house physician availability may be an important quality assurance indicator. The objective of this study were to determine the accidental extubation rate at a single small pediatric intensive care unit (PICU) and compare it with published reports. This study was carried out in a six-bed PICU at Washoe Medical Center in Reno, Nevada, with a relatively low level of patient acuity, as measured by PRISM score and the frequency of intubation, and without 24-hour in-house physician availability. All intubated patients admitted during the 5-year period from January 1, 1989 to December 31, 1993 were included. The primary outcome measure was the occurrence of accidental extubation. We observed only two accidental extubations in 1,749 intubated-patient-days (IPD) (0.114 accidental extubations/100 IPD [95% confidence interval 0.014-0.413 accidental extubations/ 100 IPD]). This rate of accidental extubation was compared with data in published reports from neonatal intensive care units (NICUs) and PICUs, which ranged from 0.14 accidental extubations/100 IPD to 4.36 accidental extubations/100 IPD. The dependence of the observed accidental extubation rate on unit size and institutional experience with intubated patients, as measured by the average number of intubated patients, was examined. We found no evidence that the accidental extubation rate is higher in smaller units or units with less institutional experience. Low rates can be achieved in small units with low acuity.

  7. Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia.

    PubMed

    Panickar, Kiran S; Jang, Saebyeol

    2013-08-01

    Cerebral ischemia is caused by an interruption of blood flow to the brain which generally leads to irreversible brain damage. Ischemic injury is associated with vascular leakage, inflammation, tissue injury, and cell death. Cellular changes associated with ischemia include impairment of metabolism, energy failure, free radical production, excitotoxicity, altered calcium homeostasis, and activation of proteases all of which affect brain functioning and also contribute to longterm disabilities including cognitive decline. Inflammation, mitochondrial dysfunction, increased oxidative/nitrosative stress, and intracellular calcium overload contribute to brain injury including cell death and brain edema. However, there is a paucity of agents that can effectively reduce cerebral damage and hence considerable attention has focused on developing newer agents with more efficacy and fewer side-effects. Polyphenols are natural compounds with variable phenolic structures and are rich in vegetables, fruits, grains, bark, roots, tea, and wine. Most polyphenols have antioxidant, anti-inflammatory, and anti-apoptotic properties and their protective effects on mitochondrial functioning, glutamate uptake, and regulating intracellular calcium levels in ischemic injury in vitro have been demonstrated. This review will assess the current status of the potential effects of polyphenols in reducing cerebral injury and improving cognitive function in ischemia in animal and human studies. In addition, the review will also examine available patents in nutrition and agriculture that relates to cerebral ischemic injury with an emphasis on plant polyphenols.

  8. Contribution of the vertebral artery to cerebral circulation in the rat snake Elaphe obsoleta

    NASA Technical Reports Server (NTRS)

    Zippel, K. C.; Lillywhite, H. B.; Mladinich, C. R.; Hargens, A. (Principal Investigator)

    1998-01-01

    Blood supplying the brain in vertebrates is carried primarily by the carotid vasculature. In most mammals, cerebral blood flow is supplemented by the vertebral arteries, which anastomose with the carotids at the base of the brain. In other tetrapods, cerebral blood is generally believed to be supplied exclusively by the carotid vasculature, and the vertebral arteries are usually described as disappearing into the dorsal musculature between the heart and head. There have been several reports of a vertebral artery connection with the cephalic vasculature in snakes. We measured regional blood flows using fluorescently labeled microspheres and demonstrated that the vertebral artery contributes a small but significant fraction of cerebral blood flow (approximately 13% of total) in the rat snake Elaphe obsoleta. Vascular casts of the anterior vessels revealed that the vertebral artery connection is indirect, through multiple anastomoses with the inferior spinal artery, which connects with the carotid vasculature near the base of the skull. Using digital subtraction angiography, fluoroscopy, and direct observations of flow in isolated vessels, we confirmed that blood in the inferior spinal artery flows craniad from a point anterior to the vertebral artery connections. Such collateral blood supply could potentially contribute to the maintenance of cerebral circulation during circumstances when craniad blood flow is compromised, e.g., during the gravitational stress of climbing.

  9. Methylene Blue Modulates β-Secretase, Reverses Cerebral Amyloidosis, and Improves Cognition in Transgenic Mice*

    PubMed Central

    Mori, Takashi; Koyama, Naoki; Segawa, Tatsuya; Maeda, Masahiro; Maruyama, Nobuhiro; Kinoshita, Noriaki; Hou, Huayan; Tan, Jun; Town, Terrence

    2014-01-01

    Amyloid precursor protein (APP) proteolysis is required for production of amyloid-β (Aβ) peptides that comprise β-amyloid plaques in the brains of patients with Alzheimer disease (AD). Here, we tested whether the experimental agent methylene blue (MB), used for treatment of methemoglobinemia, might improve AD-like pathology and behavioral deficits. We orally administered MB to the aged transgenic PSAPP mouse model of cerebral amyloidosis and evaluated cognitive function and cerebral amyloid pathology. Beginning at 15 months of age, animals were gavaged with MB (3 mg/kg) or vehicle once daily for 3 months. MB treatment significantly prevented transgene-associated behavioral impairment, including hyperactivity, decreased object recognition, and defective spatial working and reference memory, but it did not alter nontransgenic mouse behavior. Moreover, brain parenchymal and cerebral vascular β-amyloid deposits as well as levels of various Aβ species, including oligomers, were mitigated in MB-treated PSAPP mice. These effects occurred with inhibition of amyloidogenic APP proteolysis. Specifically, β-carboxyl-terminal APP fragment and β-site APP cleaving enzyme 1 protein expression and activity were attenuated. Additionally, treatment of Chinese hamster ovary cells overexpressing human wild-type APP with MB significantly decreased Aβ production and amyloidogenic APP proteolysis. These results underscore the potential for oral MB treatment against AD-related cerebral amyloidosis by modulating the amyloidogenic pathway. PMID:25157105

  10. A novel atherothrombotic model of ischemic stroke induced by injection of collagen into the cerebral vasculature

    PubMed Central

    Schunke, Kathryn J.; Toung, Thomas K.; Zhang, Jian; Pathak, Arvind P.; Xu, Jiadi; Zhang, Jiangyang; Koehler, Raymond C.; Faraday, Nauder

    2017-01-01

    Background Most ischemic strokes in humans are caused by ruptured arterial atheroma, which activate platelets and produce thrombi that occlude cerebral vessels. Methods To simulate these events, we threaded a catheter through the internal carotid artery toward the middle cerebral artery (MCA) orifice and injected collagen directly into the cerebral circulation of male C57Bl/6 mice and Wistar rats. Results Laser-Doppler flowmetry demonstrated reductions in cerebral blood flow (CBF) of ~80% in mice and ~60% in rats. CBF spontaneously increased but remained depressed after catheter withdrawal. Magnetic resonance imaging showed that ipsilateral CBF was reduced at 3 h after collagen injection and markedly improved at 48 h. Micro-computed tomography revealed reduced blood vessel density in the ipsilateral MCA territory at 3 h. Gross examination of excised brains revealed thrombi within ipsilateral cerebral arteries at 3 h, but not 24 h, after collagen injection. Immunofluorescence microscopy confirmed that platelets and fibrinogen/fibrin were major components of these thrombi at both macrovascular and microvascular levels. Cerebral infarcts comprising ~30% of hemispheric volume and neurobehavioral deficits were observed 48 h after ischemic injury in both mice and rats. Comparison with existing methods Collagen injection caused brain injury that was similar in magnitude and variability to mechanical MCA occlusion or injection of a pre-formed clot; however, alterations in CBF and the mechanism of vascular occlusion were more consistent with clinical ischemic stroke. Conclusion This novel rodent model of ischemic stroke has pathophysiologic characteristics consistent with clinical atherothrombotic stroke, is technically feasible, and creates reproducible brain injury. PMID:25314906

  11. A Nonlinear Dynamic Approach Reveals a Long-Term Stroke Effect on Cerebral Blood Flow Regulation at Multiple Time Scales

    PubMed Central

    Hu, Kun; Lo, Men-Tzung; Peng, Chung-Kang; Liu, Yanhui; Novak, Vera

    2012-01-01

    Cerebral autoregulation (CA) is an important vascular control mechanism responsible for relatively stable cerebral blood flow despite changes of systemic blood pressure (BP). Impaired CA may leave brain tissue unprotected against potentially harmful effects of BP fluctuations. It is generally accepted that CA is less effective or even inactive at frequencies >∼0.1 Hz. Without any physiological foundation, this concept is based on studies that quantified the coupling between BP and cerebral blood flow velocity (BFV) using transfer function analysis. This traditional analysis assumes stationary oscillations with constant amplitude and period, and may be unreliable or even invalid for analysis of nonstationary BP and BFV signals. In this study we propose a novel computational tool for CA assessment that is based on nonlinear dynamic theory without the assumption of stationary signals. Using this method, we studied BP and BFV recordings collected from 39 patients with chronic ischemic infarctions and 40 age-matched non-stroke subjects during baseline resting conditions. The active CA function in non-stroke subjects was associated with an advanced phase in BFV oscillations compared to BP oscillations at frequencies from ∼0.02 to 0.38 Hz. The phase shift was reduced in stroke patients even at > = 6 months after stroke, and the reduction was consistent at all tested frequencies and in both stroke and non-stroke hemispheres. These results provide strong evidence that CA may be active in a much wider frequency region than previously believed and that the altered multiscale CA in different vascular territories following stroke may have important clinical implications for post-stroke recovery. Moreover, the stroke effects on multiscale cerebral blood flow regulation could not be detected by transfer function analysis, suggesting that nonlinear approaches without the assumption of stationarity are more sensitive for the assessment of the coupling of nonstationary

  12. Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes

    PubMed Central

    Kelly-Cobbs, Aisha I.; Prakash, Roshini; Li, Weiguo; Pillai, Bindu; Hafez, Sherif; Coucha, Maha; Johnson, Maribeth H.; Ogbi, Safia N.; Fagan, Susan C.

    2013-01-01

    Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies. PMID:23335797

  13. Accidental Kähler moduli inflation

    NASA Astrophysics Data System (ADS)

    Maharana, Anshuman; Rummel, Markus; Sumitomo, Yoske

    2015-09-01

    We study a model of accidental inflation in type IIB string theory where inflation occurs near the inflection point of a small Kähler modulus. A racetrack structure helps to alleviate the known concern that string-loop corrections may spoil Kähler Moduli Inflation unless having a significant suppression via the string coupling or a special brane setup. Also, the hierarchy of gauge group ranks required for the separation between moduli stabilization and inflationary dynamics is relaxed. The relaxation becomes more significant when we use the recently proposed D-term generated racetrack model.

  14. Gastroschisis, destructive brain lesions, and placental infarction in the second trimester suggest a vascular pathogenesis.

    PubMed

    Folkerth, Rebecca D; Habbe, Donald M; Boyd, Theonia K; McMillan, Kristin; Gromer, Jessica; Sens, Mary Ann; Elliott, Amy J

    2013-01-01

    The cause and pathogenesis of gastroschisis are uncertain. We report the autopsy and placental pathology of a stillbirth at 20 gestational weeks, in which gastroschisis was accompanied by destructive lesions in the cerebral cortex and brainstem, as well as cardiac calcification, consistent with ischemic injury during the 2nd trimester. An important potential underlying mechanism explaining the fetal abnormalities is the presence of infarcts in the placenta, indicative at this gestational age of maternal vascular underperfusion. The association of gastroschisis with ischemic lesions in the brain, heart, and placenta in this case supports the concept that gastroschisis, at least in some instances, may result from vascular event(s) causing disruption of the fetal abdominal wall and resulting in the extrusion of the abdominal organs, as well as hypoxic-ischemic brain and cardiac injury.

  15. Choices of Stent and Cerebral Protection in the Ongoing ACST-2 Trial: A Descriptive Study.

    PubMed

    de Waard, D D; Halliday, A; de Borst, G J; Bulbulia, R; Huibers, A; Casana, R; Bonati, L H; Tolva, V

    2017-05-01

    Several plaque and lesion characteristics have been associated with an increased risk for procedural stroke during or shortly after carotid artery stenting (CAS). While technical advancements in stent design and cerebral protection devices (CPD) may help reduce the procedural stroke risk, and anatomy remains important, tailoring stenting procedures according to plaque and lesion characteristics might be a useful strategy in reducing stroke associated with CAS. In this descriptive report of the ongoing Asymptomatic Carotid Surgery Trial-2 (ACST-2), it was assessed whether choice for stent and use or type of CPD was influenced by plaque and lesion characteristics. Trial patients who underwent CAS between 2008 and 2015 were included in this study. Chi-square statistics were used to study the effects of plaque echolucency, ipsilateral preocclusive disease (90-99%), and contralateral high-grade stenosis (>50%) or occlusion of the carotid artery on interventionalists' choice for stent and CPD. Differences in treatment preference between specialties were also analysed. In this study, 831 patients from 88 ACST-2 centres were included. Almost all procedures were performed by either interventional radiologists (50%) or vascular surgeons (45%). Plaque echolucency, ipsilateral preocclusive disease (90-99%), and significant contralateral stenosis (>50%) or occlusion did not affect the choice of stent or either the use of cerebral protection and type of CPD employed (i.e., filter/flow reversal). Vascular surgeons used a CPD significantly more often than interventional radiologists (98.6% vs. 76.3%; p < .001), but this choice did not appear to be dependent on patient characteristics. In ACST-2, plaque characteristics and severity of stenosis did not primarily determine interventionalists' choice of stent or use or type of CPD, suggesting that other factors, such as vascular anatomy or personal and centre preference, may be more important. Stent and CPD use was highly

  16. Patterns of accidental deaths in Kuwait: a retrospective descriptive study from 2003-2009.

    PubMed

    Al-Kandary, Nadia; Al-Waheeb, Salah

    2015-03-28

    Accidents are a preventable cause of death. Unfortunately it accounts for a large number of deaths in many societies. In Kuwait, road traffic accidents (RTA) is the leading cause of death in young people. The study investigated the patterns of accidental deaths in Kuwait, one of the Gulf States which incorporates a wide variety of multi-ethnic communities. The study was retrospective from 2003-2009. Data of forensic cases were collected from the general department of criminal evidence (GDCE) in the ministry of interior (MOI).We attempted to find out causes of accidental death and the prevelance of each cause. Furthermore, the relationship of demographic factors (eg. Age, sex, marital status and nationality) with each cause of accidental death in Kuwait were studied. The material of this study constituted a total of 4886 reported accidental deaths referred for Medico-legal examination. Road traffic accidents was by far the most prevalent cause of death (64.6%) followed by fall from height (13.1%). Poisoning and mine explosions were amongst the least common causes. The government of Kuwait needs to take strong measures to promote safety in the workplace and households by educational campaigns.

  17. Osborn waves in severe accidental hypothermia secondary to prolonged immobilization and malnutrition.

    PubMed

    Rotondi, Francesco; Manganelli, Fiore; Candelmo, Fiore; Marino, Luciano; Di Lorenzo, Emilio; Alfano, Ferdinando; Stanco, Giovanni; Rosato, Giuseppe

    2010-07-01

    We report the case of a 77-year-old man, in whom accidental hypothermia was secondary to prolonged immobilization and malnutrition. The electrocardiogram showed typical Osborn waves, which disappeared with the rewarming of the patient. The diagnosis of hypothermia is easy in patients with a history of prolonged exposure to a cold environment but accidental hypothermia may also occur as a consequence of prolonged immobilization and malnutrition. ECG analysis is very important for a correct and fast diagnosis.

  18. Ten-year risk of stroke in patients with previous cerebral infarction and the impact of carotid surgery in the Asymptomatic Carotid Surgery Trial.

    PubMed

    Streifler, Jonathan Y; den Hartog, Anne G; Pan, Samuel; Pan, Hongchao; Bulbulia, Richard; Thomas, Dafydd J; Brown, Martin M; Halliday, Alison

    2016-12-01

    Silent brain infarcts are common in patients at increased risk of stroke and are associated with a poor prognosis. In patients with asymptomatic carotid stenosis, similar adverse associations were claimed, but the impact of previous infarction or symptoms on the beneficial effects of carotid endarterectomy is not clear. Our aim was to evaluate the impact of prior cerebral infarction in patients enrolled in the Asymptomatic Carotid Surgery Trial, a large trial with 10-year follow-up in which participants whose carotid stenosis had not caused symptoms for at least six months were randomly allocated either immediate or deferred carotid endarterectomy. The first Asymptomatic Carotid Surgery Trial included 3120 patients. Of these, 2333 patients with baseline brain imaging were identified and divided into two groups irrespective of treatment assignment, 1331 with evidence of previous cerebral infarction, defined as a history of ischemic stroke or transient ischemic attack > 6 months prior to randomization or radiological evidence of an asymptomatic infarct (group 1) and 1002 with normal imaging and no prior stroke or transient ischemic attack (group 2). Stroke and vascular deaths were compared during follow-up, and the impact of carotid endarterectomy was observed in both groups. Baseline characteristics of patients with and without baseline brain imaging were broadly similar. Of those included in the present report, male gender and hypertension were more common in group 1, while mean ipsilateral stenosis was slightly greater in group 2. At 10 years follow-up, stroke was more common among participants with cerebral infarction before randomization (absolute risk increase 5.8% (1.8-9.8), p = 0.004), and the risk of stroke and vascular death was also higher in this group (absolute risk increase 6.9% (1.9-12.0), p = 0.007). On multivariate analysis, prior cerebral infarction was associated with a greater risk of stroke (hazard ratio = 1.51, 95% confidence

  19. Mechanics and Composition of Middle Cerebral Arteries from Simulated Microgravity Rats with and without 1-h/d –Gx Gravitation

    PubMed Central

    Cheng, Jiu-Hua; Zhang, Li-Fan; Gao, Fang; Bai, Yun-Gang; Boscolo, Marco; Huang, Xiao-Feng; Zhang, Xiang

    2014-01-01

    Background To elucidate further from the biomechanical aspect whether microgravity-induced cerebral vascular mal-adaptation might be a contributing factor to postflight orthostatic intolerance and the underlying mechanism accounting for the potential effectiveness of intermittent artificial gravity (IAG) in preventing this adverse effect. Methodology/Principal Findings Middle cerebral arteries (MCAs) were isolated from 28-day SUS (tail-suspended, head-down tilt rats to simulate microgravity effect), S+D (SUS plus 1-h/d −Gx gravitation by normal standing to simulate IAG), and CON (control) rats. Vascular myogenic reactivity and circumferential stress-strain and axial force-pressure relationships and overall stiffness were examined using pressure arteriography and calculated. Acellular matrix components were quantified by electron microscopy. The results demonstrate that myogenic reactivity is susceptible to previous pressure-induced, serial constrictions. During the first-run of pressure increments, active MCAs from SUS rats can strongly stiffen their wall and maintain the vessels at very low strains, which can be prevented by the simulated IAG countermeasure. The strains are 0.03 and 0.14 respectively for SUS and S+D, while circumferential stress being kept at 0.5 (106 dyn/cm2). During the second-run pressure steps, both the myogenic reactivity and active stiffness of the three groups declined. The distensibility of passive MCAs from S+D is significantly higher than CON and SUS, which may help to attenuate the vasodilatation impairment at low levels of pressure. Collagen and elastin percentages were increased and decreased, respectively, in MCAs from SUS and S+D as compared with CON; however, elastin was higher in S+D than SUS rats. Conclusions Susceptibility to previous myogenic constrictions seems to be a self-limiting protective mechanism in cerebral small resistance arteries to prevent undue cerebral vasoconstriction during orthostasis at 1-G environment

  20. Risk factors and prevention of vascular complications in polycythemia vera.

    PubMed

    Barbui, T; Finazzi, G

    1997-01-01

    Risk factors for vascular complications in polycythemia vera (PV) include laboratory and clinical findings. Among laboratory values, the hematocrit has been clearly associated with thrombosis, particularly in the cerebral circulation. Platelet count is a possible but not yet clearly established predictor of vascular complications. Platelet function tests are of little help in prognostic evaluation because most attempts to correlate these abnormalities with clinical events have been disappointing. Clinical predictors of thrombosis include increasing age and a previous history of vascular events. Identifying risk factors for thrombosis is important to initiate therapy. Phlebotomy is associated with an increased incidence of thrombosis in the first 3 to 5 years, whereas chemotherapy may induce a higher risk of secondary malignancies after 7 to 10 years of follow-up. New cytoreductive drugs virtually devoid of mutagenic risk include interferon-alpha and anagrelide, but their role in reducing thrombotic complications remains to be demonstrated. Antithrombotic drugs, such as aspirin, are frequently used in PV, despite doubts regarding safety and efficacy. Two recent studies from the Gruppo Italiano Studio Policitemia Vera (GISP) assessed the rate of major thrombosis as well as the tolerability of low-dose aspirin in PV patients. These investigations created a favorable scenario for launching a European collaborative clinical trial (ECLAP study) aimed at testing the efficacy of low-dose aspirin in preventing thrombosis and prolonging survival in patients with PV.

  1. 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 ...

  2. Randomized comparison of distal and proximal cerebral protection during carotid artery stenting.

    PubMed

    Cano, Manuel N; Kambara, Antônio M; de Cano, Silvia J F; Pezzi Portela, Luiz Antônio; Paes, Ângela Tavares; Costa, J Ribamar; Abizaid, Alexandre Antônio Cunha; Moreira, Samuel Martins; Sousa, Amanda G M R; Sousa, J Eduardo Moraes Rego

    2013-11-01

    This study sought to randomly compare cerebral protection with ANGIOGUARD (Cordis Corporation, Bridgewater, New Jersey) with Mo.Ma (Invatec/Medtronic Vascular Inc, Santa Rosa, California) during carotid artery stenting (CAS), using diffusion-weighted magnetic resonance imaging (DW-MRI) to detect new ischemic cerebral lesions. The number, size, and location of lesions were analyzed. The choice of the type of cerebral protection during CAS is controversial. From July 2008 to July 2011, 60 patients undergoing CAS were randomized to ANGIOGUARD or Mo.Ma, distributed by chance, 30 patients for each group. All patients underwent DW-MRI before and after CAS. An independent neuroradiologist blinded to the cerebral protection used analyzed the images. Univariate and multivariate logistic models were fitted to analyze new ischemic lesions. Alternatively, a propensity score approach was used to reduce the bias due to differences between the groups. For the number of lesions, we used Poisson regression models. New ischemic lesions seen on DW-MRI were present in 63.3% of the ANGIOGUARD group versus 66.7% of the Mo.Ma cohort (p = 0.787). The number of ischemic cerebral lesions per patient, when present, was significantly lower in the Mo.Ma group (a median of 6 lesions per patient vs. a median of 10 in the ANGIOGUARD, p < 0.001). Most lesions were small (<0.5 mm) and localized in the ipsilateral territory. One patient in the ANGIOGUARD group had a minor stroke during CAS (1.66%). New ischemic lesions seen on DW-MRI were present in both groups in >60%, but the number of lesions per patient was greater in the ANGIOGUARD group. No death or disabling stroke occurred during at least 1 year of follow-up in both cohorts. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  3. The effectiveness of high-flow regional cerebral perfusion in Norwood stage I palliation.

    PubMed

    Miyaji, Kagami; Miyamoto, Takashi; Kohira, Satoshi; Yoshii, Takeshi; Itatani, Kei-Ichi; Sato, Hajime; Inoue, Nobuyuki

    2011-11-01

    Regional cerebral perfusion (RCP) has been shown to provide cerebral circulatory support during Norwood procedure. In our institution, high-flow RCP (HFRCP) from the right innominate artery has been induced to keep sufficient cerebral and somatic oxygen delivery via collateral vessels. We studied the effectiveness of HFRCP to regional cerebral and somatic tissue oxygenation in Norwood stage I palliation. Seventeen patients, who underwent the Norwood procedure, were separated into two groups: group C (n=6) using low-flow RCP and group H (n=11) using HFRCP (mean flow: 54 vs 92mlkg(-1)min(-1), P<0.0001). The mean duration of RCP was 64±10min (range, 49-86min) under the moderate hypothermia. Chlorpromazine (3.0mgkg(-1)) was given to group H patients before and during RCP to increase RCP flow. The mean radial arterial pressure was kept <50mmHg during RCP. To clarify the effectiveness of HFRCP for cerebral and somatic tissue oxygenation, cerebral regional oxygen saturation (rSO(2)) and systemic venous oxygenation (SvO(2)) during RCP were compared between the two groups. Changes in the lactate level before and after RCP, and changes in the blood urea nitrogen (BUN), creatinine, lactate dehydrogenase (LDH), and creatinine kinase (CK) levels before and after surgery, were also compared between the groups. Mean rSO(2) was 82.9±9.0% in group H and 65.9±10.7% in group C (P<0.05). Mean SvO(2) during RCP was 98.2±4.3% in group H and 85.4±9.7% in group C (P<0.01). During RCP, lactate concentration significantly increased in group C compared with that in group H (P<0.001). After surgery, the LDH and CK levels significantly increased in group C compared with that in group H (P<0.05). Our study revealed that HFRCP preserved sufficient cerebral and somatic tissue oxygenation during the Norwood procedure. The reduction of vascular resistance of collateral vessels increased both cerebral and somatic blood flow, resulting in improved tissue oxygen delivery. Copyright © 2011

  4. 49 CFR 192.751 - Prevention of accidental ignition.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Prevention of accidental ignition. 192.751 Section 192.751 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY TRANSPORTATION OF NATURAL AND OTHER GAS BY PIPELINE:...

  5. Glioblastoma: Vascular Habitats Detected at Preoperative Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging Predict Survival.

    PubMed

    Juan-Albarracín, Javier; Fuster-Garcia, Elies; Pérez-Girbés, Alexandre; Aparici-Robles, Fernando; Alberich-Bayarri, Ángel; Revert-Ventura, Antonio; Martí-Bonmatí, Luis; García-Gómez, Juan M

    2018-06-01

    Purpose To determine if preoperative vascular heterogeneity of glioblastoma is predictive of overall survival of patients undergoing standard-of-care treatment by using an unsupervised multiparametric perfusion-based habitat-discovery algorithm. Materials and Methods Preoperative magnetic resonance (MR) imaging including dynamic susceptibility-weighted contrast material-enhanced perfusion studies in 50 consecutive patients with glioblastoma were retrieved. Perfusion parameters of glioblastoma were analyzed and used to automatically draw four reproducible habitats that describe the tumor vascular heterogeneity: high-angiogenic and low-angiogenic regions of the enhancing tumor, potentially tumor-infiltrated peripheral edema, and vasogenic edema. Kaplan-Meier and Cox proportional hazard analyses were conducted to assess the prognostic potential of the hemodynamic tissue signature to predict patient survival. Results Cox regression analysis yielded a significant correlation between patients' survival and maximum relative cerebral blood volume (rCBV max ) and maximum relative cerebral blood flow (rCBF max ) in high-angiogenic and low-angiogenic habitats (P < .01, false discovery rate-corrected P < .05). Moreover, rCBF max in the potentially tumor-infiltrated peripheral edema habitat was also significantly correlated (P < .05, false discovery rate-corrected P < .05). Kaplan-Meier analysis demonstrated significant differences between the observed survival of populations divided according to the median of the rCBV max or rCBF max at the high-angiogenic and low-angiogenic habitats (log-rank test P < .05, false discovery rate-corrected P < .05), with an average survival increase of 230 days. Conclusion Preoperative perfusion heterogeneity contains relevant information about overall survival in patients who undergo standard-of-care treatment. The hemodynamic tissue signature method automatically describes this heterogeneity, providing a set of vascular habitats with high

  6. Hemorrhagic shock-induced cerebral bioenergetic imbalance is corrected by pharmacologic treatment with EF24 in a rat model

    PubMed Central

    Rao, Geeta; Xie, Jun; Hedrick, Andria; Awasthi, Vibhudutta

    2015-01-01

    Maintenance of cerebral viability and function is an important goal of critical care in victims of injury due to ischemia and hypovolemia. As part of the multiple organ dysfunction syndrome, the brain function after trauma is influenced by systemic inflammatory response. We investigated the effect of EF24, an anti-inflammatory bis-chalcone, on cerebral bioenergetics in a rat model of 45% hemorrhagic shock. The rats were treated with EF24 (0.4 mg/kg) or EF24 with an artificial oxygen carrier liposome-encapsulated hemoglobin (LEH). The volume of LEH administered was equal to the shed blood. The brain was collected after 6 h of shock for biochemical assays. EF24 treatment showed significant recovery of ATP, phosphocreatine, and NAD/NADH ratio. It also increased citrate synthase activity and cytochrome c oxidase subunit IV expression which were reduced in shock brain. Furthermore, it reduced the shock-induced accumulation of pyruvate and pyruvate dehydrogenase kinase-1 expression, suggesting that EF24 treatment improves cerebral energetics by restoring perturbed pyruvate metabolism in the mitochondria. These effects of EF24 were associated with reduced poly(ADP-ribose) polymerase cleavage and a significant improvement in the levels of nerve growth factor and brain-derived neurotrophic factor in shock brain. Co-administration of LEH with EF24 was only marginally more effective as compared to the treatment with EF24 alone. These results show that EF24 treatment sets up a pro-survival phenotype in shock by resurrecting cerebral bioenergetics. Since EF24 was effective in the absence of accompanying fluid resuscitation, it has potential utility as a pre-hospital pharmacotherapy in shock due to accidental blood loss. PMID:26232641

  7. 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.

  8. Suicide and accidental deaths in children and adolescents in England and Wales, 2001-2010.

    PubMed

    Windfuhr, Kirsten; While, David; Hunt, Isabelle M; Shaw, Jenny; Appleby, Louis; Kapur, Nav

    2013-12-01

    To investigate the impact of narrative verdicts on suicide statistics among 10-19-year-olds; to identify the number and rate of suicide and accidental deaths, particularly in 10-14-year-olds. National cohort study. England and Wales. Mid-year population estimates from the Office for National Statistics (ONS) were used to calculate rates per 100,000 population for suicide (undetermined and suicide verdicts) and accidental deaths (poisoning, hanging) for those aged 10-14 and 15-19. Trends in rates over time (2001-2010) were investigated using Poisson regression. Interaction tests were carried out to determine differences in trends between the two time periods (2001-2005 and 2006-2010). There were 1523 suicides (2.25/100,000). Suicide rates were highest in those aged 15-19 years (4.04/100,000) and in males (3.14/100,000). Between 2001 and 2010, rates significantly decreased among those aged 15-19 years (incidence rate-ratio (IRR): 0.95; 95% CI 0.93 to 0.97), with no change in rates of accidental deaths (IRR: 1.01, 95% CI 0.95 to 1.07). However, there was a significant interaction between the two time periods for accidental poisonings (2001-2005: IRR: 0.79 (95% CI 0.69 to 0.91); 2006-2010: IRR: 1.01 (95% CI 0.89 to 1.15), interaction p=0.012) and accidental hangings (2001-2005: IRR: 0.93 (95% CI 0.76 to 1.14); 2006-2010: IRR: 1.25 (95% CI 1.04 to 1.49), interaction=0.01) Undetermined deaths significantly decreased among females aged 15-19 yeras (IRR: 0.93; 95% CI 0.88 to 0.98). There were no significant trends among 10-14-year-olds. Rates of suicide are higher among older adolescents and males. There was a significant fall in suicide rates in males aged 15-19 years that was not accounted for by changes in rates of accidental death. The absence of a significant trend in suicide or accidental deaths in those aged 10-14 years may have been the result of small numbers. However, monitoring should continue to identify longitudinal trends in all young people.

  9. Prevention of accidental exposure in radiotherapy: the risk matrix approach.

    PubMed

    Vilaragut, J J; Duménigo, C; Delgado, J M; Morales, J; McDonnell, J D; Ferro, R; Ortiz López, P; Ramírez, M L; Pérez Mulas, A; Papadopulos, S; Gonçalves, M; López Morones, R; Sánchez Cayuela, C; Cascajo Castresana, A; Somoano, F; Álvarez, C; Guillén, A; Rodríguez, M; Pereira, P P; Nader, A

    2013-02-01

    Knowledge and lessons from past accidental exposures in radiotherapy are very helpful in finding safety provisions to prevent recurrence. Disseminating lessons is necessary but not sufficient. There may be additional latent risks for other accidental exposures, which have not been reported or have not occurred, but are possible and may occur in the future if not identified, analyzed, and prevented by safety provisions. Proactive methods are available for anticipating and quantifying risk from potential event sequences. In this work, proactive methods, successfully used in industry, have been adapted and used in radiotherapy. Risk matrix is a tool that can be used in individual hospitals to classify event sequences in levels of risk. As with any anticipative method, the risk matrix involves a systematic search for potential risks; that is, any situation that can cause an accidental exposure. The method contributes new insights: The application of the risk matrix approach has identified that another group of less catastrophic but still severe single-patient events may have a higher probability, resulting in higher risk. The use of the risk matrix approach for safety assessment in individual hospitals would provide an opportunity for self-evaluation and managing the safety measures that are most suitable to the hospital's own conditions.

  10. Cardiovascular and Postural Control Interactions during Hypergravity: Effects on Cerebral Autoregulation in Males and Females

    NASA Astrophysics Data System (ADS)

    Goswami, Nandu; Blaber, Andrew; Bareille, Marie-Pierre; Beck, Arnaud; Avan, Paul; Bruner, Michelle; Hinghofer-Szalkay, Helmut

    2012-07-01

    Orthostatic intolerance remains a problem upon return to Earth from the microgravity environment of spaceflight. A variety of conditions including hypovolemia, cerebral vasoconstriction, cerebral or peripheral vascular disease, or cardiac arrhythmias may result in syncope if the person remains upright. Current research indicates that there is a greater dependence on visual and somatosensory information at the beginning of space flight with a decreased otolith gain during prolonged space flight (Herault et al., 2002). The goal of the research is to further our understanding of the fundamental adaptive homeostatic mechanisms involved in gravity related changes in cardiovascular and postural function. Cardiovascular, cerebrovascular, and postural sensory motor control systems in male and female participants before, during, and after exposure to graded levels of hyper-G were investigated. Hypotheses: 1) Activation of skeletal muscle pump will be directly related to the degree of orthostatic stress. 2) Simultaneous measurement of heart rate, blood pressure and postural sway will predict cardio-postural stability. Blood pressure and heart rate (means and variability), postural sway, center of pressure (COP), baroreflex function, calf blood flow, middle cerebral artery blood flow, non-invasive intracranial pressure measurements, and two-breath CO2 were measured. Results from the study will be used to provide an integrated insight into mechanisms of cardio-postural control and cerebral autoregulation, which are important aspects of human health in flights to Moon, Mars and distant planets.

  11. Cerebral basis of posttraumatic stress disorder following the Chernobyl disaster.

    PubMed

    Loganovsky, Konstantin N; Zdanevich, Nataliya A

    2013-04-01

    Whether posttraumatic stress disorder (PTSD) following radiation emergency has psychopathological, neurocognitive, and neurophysiological peculiarities is at issue. The goal was to explore the features and cerebral basis of "radiation" PTSD in the survivors of the Chernobyl accident. Subjects and Methods The cross-sectional study included 241 people, 219 of whom have been diagnosed with PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria, among them 115 clean-up workers of the Chernobyl accident (34 with acute radiation sickness), 76 evacuees from the Chernobyl exclusion zone, 28 veterans of the war in Afghanistan, and 22 healthy unexposed individuals. Psychometric examinations, neurocognitive assessments, computerized electroencephalography, and cerebral vascular Doppler were used. "Radiation" PTSD includes "flashforward" phenomena and anticipating stress (projection of fear and danger to the future); somatoform disorders (depression, trait and state anxiety); and neurocognitive deficit (impaired memory and attention, auditory-verbal memory and learning, proactive and retroactive interference, cerebellar and stem symptoms, intellectual changes). The intima-media component, thickness of common carotid arteries, and common and left internal carotid arteries stenosis rates are increased in the liquidators. Changes of bioelectrical brain activity as a decrease of beta- and theta-power, together with an increase of alpha-power, were found in the Chernobyl accident survivors with PTSD. PTSD following radiation emergency is characterized by comorbidity of psychopathology, neurocognitive deficit, and cerebrovascular pathology with increased risk of cerebral atherosclerosis and stroke. The cerebral basis of this PTSD is proposed to be an abnormal communication between the pyramidal cells of the neocortex and the hippocampus, and deep brain structures. It is recommended that a system of emergency and long-term psychological

  12. Accidental Chlorine Gas Intoxication: Evaluation of 39 Patients

    PubMed Central

    Sever, Mustafa; Mordeniz, Cengiz; Sever, Fidan; Dokur, Mehmet

    2009-01-01

    Background Chlorine is a known pulmonary irritant gas that may cause acute damage in the respiratory system. In this paper, the socio-demographic and clinical characteristics of 39 accidentally exposed patients to chlorine gas are reported and different emergency treatment modalities are also discussed. Methods Two emergency departments applications were retrospectively analyzed for evaluation of accidental chlorine gas exposure for year 2007. Patients were classified into 3 groups according to severity of clinical and laboratory findings based on the literature and duration of land of stay in the emergency department. The first group was slightly exposed (discharged within 6 hours), second group moderately exposed (treated and observed for 24 hours), and third group was severely exposed (hospitalized). Most of the patients were initially treated with a combination of humidified oxygen, corticosteroids, and bronchodilators. Results The average age was 17.03 ± 16.01 years (95% CI). Seven (17.9%) of them were female and 29 (74.4%) were children. Twenty-four patients (61.5%) were included in the first, nine (23.1%) were in second and six (15.4%) were in the third group. The presenting symptoms were cough, nausea, and vomiting and conjunctiva hyperemia for the first group, first groups symptoms plus dyspnea for the second group. Second groups symptoms plus palpitation, weakness and chest tightness were for the third group. Cough and dyspnea were seen in 64.1% and 30.8% of the patients respectively. No patients died. Conclusions The authors recommend that non symptomatic or slightly exposed patients do not need any specific treatment or symptomatic treatment is sufficient. Keywords Accidental; Chlorine exposure; Chlorine gas; Chlorine intoxication; Emergency department PMID:22481989

  13. Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain.

    PubMed

    Iliff, Jeffrey J; Wang, Minghuan; Zeppenfeld, Douglas M; Venkataraman, Arun; Plog, Benjamin A; Liao, Yonghong; Deane, Rashid; Nedergaard, Maiken

    2013-11-13

    CSF from the subarachnoid space moves rapidly into the brain along paravascular routes surrounding penetrating cerebral arteries, exchanging with brain interstitial fluid (ISF) and facilitating the clearance of interstitial solutes, such as amyloid β, in a pathway that we have termed the "glymphatic" system. Prior reports have suggested that paravascular bulk flow of CSF or ISF may be driven by arterial pulsation. However, cerebral arterial pulsation could not be directly assessed. In the present study, we use in vivo two-photon microscopy in mice to visualize vascular wall pulsatility in penetrating intracortical arteries. We observed that unilateral ligation of the internal carotid artery significantly reduced arterial pulsatility by ~50%, while systemic administration of the adrenergic agonist dobutamine increased pulsatility of penetrating arteries by ~60%. When paravascular CSF-ISF exchange was evaluated in real time using in vivo two-photon and ex vivo fluorescence imaging, we observed that internal carotid artery ligation slowed the rate of paravascular CSF-ISF exchange, while dobutamine increased the rate of paravascular CSF-ISF exchange. These findings demonstrate that cerebral arterial pulsatility is a key driver of paravascular CSF influx into and through the brain parenchyma, and suggest that changes in arterial pulsatility may contribute to accumulation and deposition of toxic solutes, including amyloid β, in the aging brain.

  14. 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

  15. Prevalence of middle cerebral artery stenosis in asymptomatic subjects of more than 40 years age group: a transcranial Doppler study.

    PubMed

    Sada, Sujay; Reddy, Yugandhar; Rao, Sampath; Alladi, Suvarna; Kaul, Subash

    2014-01-01

    Middle cerebral artery (MCA) disease is the most common vascular lesion in stroke. Transcranial Doppler (TCD) is a non-invasive bedside screening method for assessing cerebral blood flow. To investigate the prevalence of MCA stenosis in asymptomatic but high-risk individuals for stroke. Prospective study between December 2011 and December 2013. Vascular risk factors considered included: hypertension (HTN), diabetes mellitus, smoking, alcohol consumption, coronary artery disease (CAD), peripheral vascular disease (PVD), hypercholesterolemia and obesity. TCD was performed with portable machine through the temporal windows by use of a standardized protocol. Of the 427 subjects, 374 were analyzed; males 264 (70.6%) and females 110 (29.4%). Mean age was 54.2 ± 7.6 years. The frequency of the risk factors was: HTN 287 (76.7%), diabetes 220 (58.8%), CAD 120 (32.1%), hypercholesterolemia 181 (48.4%), smoking 147 (39.3%), alcohol 99 (26.5%), obesity 198 (52.9%) and PVD 8 (2.1%). Of the 374 subjects, 27 (7.2%) had intracranial arterial stenosis and the rest had normal intracranial arteries. On univariate analysis, subjects with higher age, HTN, CAD, smoking and hypercholesterolemia had higher risk of having intracranial arterial stenosis (P < 0.05). Multivariate analysis showed HTN and CAD are independent risk factors for intracranial arterial stenosis. Overall prevalence of intracranial arterial stenosis is 7.2% in high-risk population sample from Hyderabad in South India. HTN and CAD are independent risk factors for the development of intracranial arterial stenosis.

  16. Accidental poisoning with autumn crocus.

    PubMed

    Gabrscek, Lucija; Lesnicar, Gorazd; Krivec, Bojan; Voga, Gorazd; Sibanc, Branko; Blatnik, Janja; Jagodic, Boris

    2004-01-01

    We describe a case of a 43-yr-old female with severe multiorgan injury after accidental poisoning with Colchicum autumnale, which was mistaken for wild garlic (Allium ursinum). Both plants grow on damp meadows and can be confused in the spring when both plants have leaves but no blossoms. The autumn crocus contains colchicine, which inhibits cellular division. Treatment consisted of supportive care, antibiotic therapy, and granulocyte-directed growth factor. The patient was discharged from the hospital after three weeks. Three years after recovery from the acute poisoning, the patient continued to complain of muscle weakness and intermittent episodes of hair loss.

  17. Duration of time on shift before accidental blood or body fluid exposure for housestaff, nurses, and technicians.

    PubMed

    Green-McKenzie, Judith; Shofer, Frances S

    2007-01-01

    Shift work has been found to be associated with an increased rate of errors and accidents among healthcare workers (HCWs), but the effect of shift work on accidental blood and body fluid exposure sustained by HCWs has not been well characterized. To determine the duration of time on shift before accidental blood and body fluid exposure in housestaff, nurses, and technicians and the proportion of housestaff who sustain a blood and body fluid exposure after 12 hours on duty. This retrospective, descriptive study was conducted during a 24-month period at a large urban teaching hospital. Participants were HCWs who sustained an accidental blood and body fluid exposure. Housestaff were on duty significantly longer than both nursing staff (P=.02) and technicians (P<.0001) before accidental blood and body fluid exposure. Half of the blood and body fluid exposures sustained by housestaff occurred after being on duty 8 hours or more, and 24% were sustained after being on duty 12 hours or more. Of all HCWs, 3% reported an accidental blood and body fluid exposure, with specific rates of 7.9% among nurses, 9.4% among housestaff, and 3% among phlebotomists. Housestaff were significantly more likely to have longer duration of time on shift before blood and body fluid exposure than were the other groups. Almost one-quarter of accidental blood and body fluid exposures to housestaff were incurred after they had been on duty for 12 hours or more. Housestaff sustained a higher rate of accidental blood and body fluid exposures than did nursing staff and technicians.

  18. A prospective cohort study of non-fatal accidental overdose among street youth: the link with suicidal ideation.

    PubMed

    Richer, Isabelle; Bertrand, Karine; Vandermeerschen, Jill; Roy, Elise

    2013-07-01

    Drug overdose and suicide are the two leading causes of death among street youth. The literature discusses the two faces of drug overdose: accidental act and suicide attempt. Some authors have stated that accidental overdoses may be a hidden expression of suicidal ideation. This study longitudinally examined the relationship between recent suicidal ideations and non-fatal accidental drug overdoses among street youth. Between July 2001 and December 2005, 858 street youth (14-23 years old) were recruited for a prospective cohort study. Youth were eligible if, in the previous year, they had been without a place to sleep more than once or had used the services of street youth agencies on a regular basis (≥3). Participants completed baseline questionnaires and follow-up interviews were carried out every 6 months. Mixed-effect logistic regression models were conducted. Apart from suicidal ideation and accidental drug overdose, variables considered in the model were age, sex, problematic alcohol use, homelessness, injection drug use and polydrug use (≥3 drugs). Accidental drug overdose was significantly associated with suicidal ideation (adjusted odds ratio 1.88; 95% confidence interval 1.23-2.54). Homelessness, injection drug use and polydrug use were also significant in the final model. Results show that, during follow up, suicidal ideation independently increased risks of accidental overdose. They also underscore the need for interventions beyond educational prevention. Primary care practitioners should investigate suicidal ideations and behaviours of street youth in treatment for accidental overdose. © 2012 Australasian Professional Society on Alcohol and other Drugs.

  19. Sorcin modulation of Ca2+ sparks in rat vascular smooth muscle cells

    PubMed Central

    Rueda, Angélica; Song, Ming; Toro, Ligia; Stefani, Enrico; Valdivia, Héctor H

    2006-01-01

    Spontaneous, local Ca2+ release events or Ca2+ sparks by ryanodine receptors (RyRs) are important determinants of vascular tone and arteriolar resistance, but the mechanisms that modulate their properties in smooth muscle are poorly understood. Sorcin, a Ca2+-binding protein that associates with cardiac RyRs and quickly stops Ca2+ release in the heart, provides a potential mechanism to modulate Ca2+ sparks in vascular smooth muscle, but little is known about the functional role of sorcin in this tissue. In this work, we characterized the expression and intracellular location of sorcin in aorta and cerebral artery and gained mechanistic insights into its functional role as a modulator of Ca2+ sparks. Sorcin is present in endothelial and smooth muscle cells, as assessed by immunocytochemical and Western blot analyses. Smooth muscle sorcin translocates from cytosolic to membranous compartments in a Ca2+-dependent manner and associates with RyRs, as shown by coimmunoprecipitation and immunostaining experiments. Ca2+ sparks recorded in saponin-permeabilized vascular myocytes have increased frequency, duration and spatial spread but reduced amplitude with respect to Ca2+ sparks in intact cells, suggesting that permeabilization disrupts the normal organization of RyRs and releases diffusible substances that control Ca2+ spark properties. Perfusion of 2 μm sorcin onto permeabilized myocytes reduced the amplitude, duration and spatial spread of Ca2+ sparks, demonstrating that sorcin effectively regulates Ca2+ signalling in vascular smooth muscle. Together with a dense distribution in the perimeter of the cell along a pool of RyRs, these properties make sorcin a viable candidate to modulate vascular tone in smooth muscle. PMID:16931553

  20. Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies.

    PubMed

    Sadick, Maliha; Müller-Wille, René; Wildgruber, Moritz; Wohlgemuth, Walter A

    2018-06-06

    Vascular anomalies are a diagnostic and therapeutic challenge. They require dedicated interdisciplinary management. Optimal patient care relies on integral medical evaluation and a classification system established by experts in the field, to provide a better understanding of these complex vascular entities.  A dedicated classification system according to the International Society for the Study of Vascular Anomalies (ISSVA) and the German Interdisciplinary Society of Vascular Anomalies (DiGGefA) is presented. The vast spectrum of diagnostic modalities, ranging from ultrasound with color Doppler, conventional X-ray, CT with 4 D imaging and MRI as well as catheter angiography for appropriate assessment is discussed.  Congenital vascular anomalies are comprised of vascular tumors, based on endothelial cell proliferation and vascular malformations with underlying mesenchymal and angiogenetic disorder. Vascular tumors tend to regress with patient's age, vascular malformations increase in size and are subdivided into capillary, venous, lymphatic, arterio-venous and combined malformations, depending on their dominant vasculature. According to their appearance, venous malformations are the most common representative of vascular anomalies (70 %), followed by lymphatic malformations (12 %), arterio-venous malformations (8 %), combined malformation syndromes (6 %) and capillary malformations (4 %).  The aim is to provide an overview of the current classification system and diagnostic characterization of vascular anomalies in order to facilitate interdisciplinary management of vascular anomalies.   · Vascular anomalies are comprised of vascular tumors and vascular malformations, both considered to be rare diseases.. · Appropriate treatment depends on correct classification and diagnosis of vascular anomalies, which is based on established national and international classification systems, recommendations and guidelines.. · In the classification

  1. Non-accidental salt poisoning.

    PubMed Central

    Meadow, R

    1993-01-01

    The clinical features of 12 children who incurred non-accidental salt poisoning are reported. The children usually presented to hospital in the first six months of life with unexplained hypernatraemia and associated illness. Most of the children suffered repetitive poisoning before detection. The perpetrator was believed to the mother for 10 children, the father for one, and either parent for one. Four children had serum sodium concentrations above 200 mmol/l. Seven children had incurred other fabricated illness, drug ingestion, physical abuse, or failure to thrive/neglect. Two children died; the other 10 remained healthy in alternative care. Features are described that should lead to earlier detection of salt poisoning; the importance of checking urine sodium excretion, whenever hypernatraemia occurs, is stressed. PMID:8503665

  2. Self-reported Hearing Difficulty and Risk of Accidental Injury in US Adults, 2007 to 2015.

    PubMed

    Lin, Harrison W; Mahboubi, Hossein; Bhattacharyya, Neil

    2018-03-22

    Accidental injuries are a leading cause of morbidity and mortality in the United States. Hearing problems may be associated with an increased risk for such injuries. To investigate associations between hearing difficulty and risk of accidental injuries among US adults. Cross-sectional analysis of responses of a nationally representative sample of 232.2 million individuals 18 years or older who participated in the National Health Interview Survey from 2007 to 2015 and responded to the questions related to the hearing and injury modules. The main outcome variable was accidental injury in the preceding 3 months. Hearing status was self-reported as "excellent," "good," "a little trouble," "moderate trouble," "a lot of trouble," and "deaf." Prevalence of accidental injuries was analyzed based on demographic characteristics and hearing status. Odds ratios (ORs) and 95% CIs for injuries adjusted for demographics were calculated for degrees of hearing difficulty. A secondary outcome was association of hearing status with type of injury and was classified as driving related, work related, or leisure/sport related. Of 232.2 million US adults, 120.2 million (51.7%) were female, and 116.3 million (50.1%) considered their hearing to be less than excellent. Accidental injuries occurred in 2.8% of survey respondents. In comparison with normal-hearing adults (those with self-rated excellent or good hearing), the odds of accidental injury were higher in those with a little trouble hearing (4.1%; OR, 1.6; 95% CI, 1.5-1.8), moderate trouble hearing (4.2%; OR, 1.7; 95% CI, 1.4-1.9), and a lot of trouble hearing (4.8%; OR, 1.9; 95% CI, 1.6-2.3). Work- and leisure-related injuries were more prevalent among those with self-perceived hearing difficulty. Multivariate analysis, adjusted for age and sex, revealed leisure-related injuries was most consistently associated with various degrees of hearing difficulty. Odds ratios were 1.2 (95% CI, 1.0-1.4) in those with a little trouble hearing

  3. 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 ...

  4. Cerebral Hemodynamics in the Elderly: A Transcranial Doppler Study in the Einstein Aging Study Cohort.

    PubMed

    Yang, Dixon; Cabral, Digna; Gaspard, Emmanuel N; Lipton, Richard B; Rundek, Tatjana; Derby, Carol A

    2016-09-01

    We sought to describe the relationship between age, sex, and race/ethnicity with transcranial Doppler hemodynamic characteristics from major intracerebral arterial segments in a large elderly population with varying demographics. We analyzed 369 stroke-free participants aged 70 years and older from the Einstein Aging Study. Single-gate, nonimaging transcranial Doppler sonography, a noninvasive sonographic technique that assesses real-time cerebrovascular hemodynamics, was used to interrogate 9 cerebral arterial segments. Individual Doppler spectra and cerebral blood flow velocities were acquired, and the pulsatility index and resistive index were calculated by the device's automated waveform-tracking function. Multiple linear regression models were used to examine the independent associations of age, sex, and race/ethnicity with transcranial Doppler measures, adjusting for hypertension, history of myocardial infarction or revascularization, and history of diabetes. Among enrolled participants, 303 individuals had at least 1 vessel insonated (mean age [SD], 80 [6] years; 63% women; 58% white; and 32% black). With age, transcranial Doppler measures of mean blood flow velocity were significantly decreased in the basilar artery (P = .001) and posterior cerebral artery (right, P = .003; left, P = .02). Pulsatility indices increased in the left middle cerebral artery (P = .01) and left anterior cerebral artery (P = .03), and the resistive index was increased in the left middle cerebral artery (P = .007) with age. Women had higher pulsatility and resistive indices compared to men in several vessels. We report a decreased mean blood flow velocity and weakly increased arterial pulsatility and resistance with aging in a large elderly stroke-free population. These referential trends in cerebrovascular hemodynamics may carry important implications in vascular diseases associated with advanced age, increased risk of cerebrovascular disease, cognitive decline, and dementia.

  5. Correlation between cerebral hemodynamic and perfusion pressure changes in non-human primates

    NASA Astrophysics Data System (ADS)

    Ruesch, A.; Smith, M. A.; Wollstein, G.; Sigal, I. A.; Nelson, S.; Kainerstorfer, J. M.

    2017-02-01

    The mechanism that maintains a stable blood flow in the brain despite changes in cerebral perfusion pressure (CPP), and therefore guaranties a constant supply of oxygen and nutrients to the neurons, is known as cerebral auto-regulation (CA). In a certain range of CPP, blood flow is mediated by a vasomotor adjustment in vascular resistance through dilation of blood vessels. CA is known to be impaired in diseases like traumatic brain injury, Parkinson's disease, stroke, hydrocephalus and others. If CA is impaired, blood flow and pressure changes are coupled and thee oxygen supply might be unstable. Lassen's blood flow auto-regulation curve describes this mechanism, where a plateau of stable blood flow in a specific range of CPP corresponds to intact auto-regulation. Knowing the limits of this plateau and maintaining CPP within these limits can improve patient outcome. Since CPP is influenced by both intracranial pressure and arterial blood pressure, long term changes in either can lead to auto-regulation impairment. Non-invasive methods for monitoring blood flow auto-regulation are therefore needed. We propose too use Near infrared spectroscopy (NIRS) too fill this need. NIRS is an optical technique, which measures microvascular changes in cerebral hemoglobin concentration. We performed experiments on non-human primates during exsanguination to demonstrate that thee limits of blood flow auto-regulation can be accessed with NIRS.

  6. Insomnia medication use and the probability of an accidental event in an older adult population

    PubMed Central

    Avidan, Alon Y; Palmer, Liisa A; Doan, Justin F; Baran, Robert W

    2010-01-01

    Objective: This study examined the risk of accidental events in older adults prescribed a sedating antidepressant, long-acting benzodiazepine, short-acting benzodiazepine, and nonbenzodiazepine, relative to a reference group (selective melatonin receptor agonist). Methods: This was a retrospective cohort analysis of older adults (≥65 years) with newly initiated pharmacological treatment of insomnia. Data were collected from the Thomson MarketScan® Medicare Supplemental and Coordination of Benefits databases (January 1, 2000, through June 30, 2006). Probit models were used to evaluate the probability of an accidental event. Results: Data were analyzed for 445,329 patients. Patients taking a long-acting benzodiazepine (1.21 odds ratio [OR]), short-acting benzodiazepine (1.16 OR), or nonbenzodiazepine (1.12 OR) had a significantly higher probability of experiencing an accidental event during the first month following treatment initiation compared with patients taking the reference medication (P < 0.05 for all). A significantly higher probability of experiencing an accidental event was also observed during the 3-month period following the initiation of treatment (1.62 long-acting benzodiazepine, 1.60 short-acting benzodiazepine, 1.48 nonbenzodiazepine, and 1.56 sedating antidepressant; P < 0.05). Conclusions: Older adults taking an SAD or any of the benzodiazepine receptor agonists appear to have a greater risk of an accidental event compared with a reference group taking an MR. PMID:21701634

  7. [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.

  8. Computational modelling of the cerebral cortical microvasculature: effect of x-ray microbeams versus broad beam irradiation

    NASA Astrophysics Data System (ADS)

    Merrem, A.; Bartzsch, S.; Laissue, J.; Oelfke, U.

    2017-05-01

    Microbeam Radiation Therapy is an innovative pre-clinical strategy which uses arrays of parallel, tens of micrometres wide kilo-voltage photon beams to treat tumours. These x-ray beams are typically generated on a synchrotron source. It was shown that these beam geometries allow exceptional normal tissue sparing from radiation damage while still being effective in tumour ablation. A final biological explanation for this enhanced therapeutic ratio has still not been found, some experimental data support an important role of the vasculature. In this work, the effect of microbeams on a normal microvascular network of the cerebral cortex was assessed in computer simulations and compared to the effect of homogeneous, seamless exposures at equal energy absorption. The anatomy of a cerebral microvascular network and the inflicted radiation damage were simulated to closely mimic experimental data using a novel probabilistic model of radiation damage to blood vessels. It was found that the spatial dose fractionation by microbeam arrays significantly decreased the vascular damage. The higher the peak-to-valley dose ratio, the more pronounced the sparing effect. Simulations of the radiation damage as a function of morphological parameters of the vascular network demonstrated that the distribution of blood vessel radii is a key parameter determining both the overall radiation damage of the vasculature and the dose-dependent differential effect of microbeam irradiation.

  9. The Association between Dust Storms and Daily Non-Accidental Mortality in the United States, 1993-2005.

    PubMed

    Crooks, James Lewis; Cascio, Wayne E; Percy, Madelyn S; Reyes, Jeanette; Neas, Lucas M; Hilborn, Elizabeth D

    2016-11-01

    The impact of dust storms on human health has been studied in the context of Asian, Saharan, Arabian, and Australian storms, but there has been no recent population-level epidemiological research on the dust storms in North America. The relevance of dust storms to public health is likely to increase as extreme weather events are predicted to become more frequent with anticipated changes in climate through the 21st century. We examined the association between dust storms and county-level non-accidental mortality in the United States from 1993 through 2005. Dust storm incidence data, including date and approximate location, are taken from the U.S. National Weather Service storm database. County-level mortality data for the years 1993-2005 were acquired from the National Center for Health Statistics. Distributed lag conditional logistic regression models under a time-stratified case-crossover design were used to study the relationship between dust storms and daily mortality counts over the whole United States and in Arizona and California specifically. End points included total non-accidental mortality and three mortality subgroups (cardiovascular, respiratory, and other non-accidental). We estimated that for the United States as a whole, total non-accidental mortality increased by 7.4% (95% CI: 1.6, 13.5; p = 0.011) and 6.7% (95% CI: 1.1, 12.6; p = 0.018) at 2- and 3-day lags, respectively, and by an average of 2.7% (95% CI: 0.4, 5.1; p = 0.023) over lags 0-5 compared with referent days. Significant associations with non-accidental mortality were estimated for California (lag 2 and 0-5 day) and Arizona (lag 3), for cardiovascular mortality in the United States (lag 2) and Arizona (lag 3), and for other non-accidental mortality in California (lags 1-3 and 0-5). Dust storms are associated with increases in lagged non-accidental and cardiovascular mortality. Citation: Crooks JL, Cascio WE, Percy MS, Reyes J, Neas LM, Hilborn ED. 2016. The association between dust storms

  10. Dynamic magnetic resonance imaging assessment of vascular targeting agent effects in rat intracerebral tumor models

    PubMed Central

    Muldoon, Leslie L.; Gahramanov, Seymur; Li, Xin; Marshall, Deborah J.; Kraemer, Dale F.; Neuwelt, Edward A.

    2011-01-01

    We used dynamic MRI to evaluate the effects of monoclonal antibodies targeting brain tumor vasculature. Female athymic rats with intracerebral human tumor xenografts were untreated or treated with intetumumab, targeting αV-integrins, or bevacizumab, targeting vascular endothelial growth factor (n = 4–6 per group). Prior to treatment and at 1, 3, and 7 days after treatment, we performed standard MRI to assess tumor volume, dynamic susceptibility-contrast MRI with the blood-pool iron oxide nanoparticle ferumoxytol to evaluate relative cerebral blood volume (rCBV), and dynamic contrast-enhanced MRI to assess tumor vascular permeability. Tumor rCBV increased by 27 ± 13% over 7 days in untreated rats; intetumumab increased tumor rCBV by 65 ± 10%, whereas bevacizumab reduced tumor rCBV by 31 ± 10% at 7 days (P < .001 for group and day). Similarly, intetumumab increased brain tumor vascular permeability compared with controls at 3 and 7 days after treatment, whereas bevacizumab decreased tumor permeability within 24 hours (P = .0004 for group, P = .0081 for day). All tumors grew over the 7-day assessment period, but bevacizumab slowed the increase in tumor volume on MRI. We conclude that the vascular targeting agents intetumumab and bevacizumab had diametrically opposite effects on dynamic MRI of tumor vasculature in rat brain tumor models. Targeting αV-integrins increased tumor vascular permeability and blood volume, whereas bevacizumab decreased both measures. These findings have implications for chemotherapy delivery and antitumor efficacy. PMID:21123368

  11. Cerebral hemodynamic and metabolic changes caused by brain retraction after aneurysmal subarachnoid hemorrhage.

    PubMed

    Yundt, K D; Grubb, R L; Diringer, M N; Powers, W J

    1997-03-01

    The cerebral hemodynamic and metabolic effects of aneurysmal subarachnoid hemorrhage are complex. To investigate the impact of surgical retraction, we analyzed position emission tomography (PET) studies that measured the regional cerebral metabolic rate for oxygen, regional oxygen extraction fraction, and regional cerebral blood flow in four patients before and after right frontotemporal craniotomies for clipping of ruptured anterior circulation aneurysms. Preoperative studies were conducted 1 day before surgery and postoperative studies 6 to 17 days after surgery. No patient had hydrocephalus or intracerebral hematoma. At the time of the second PET study, none of the patients had signs of clinical vasospasm. Regional measurements were obtained from the right ventrolateral frontal and anterior temporal regions corresponding to the area of retraction and compared to the same regions in the opposite hemisphere. To establish a quantitative means to differentiate between hemodynamic and metabolic changes related to arterial vasospasm and those caused by brain retraction, we studied a second group of preoperative patients, who had undergone PET during angiographic and clinical vasospasm. There was a 45% reduction in regional cerebral metabolic rate for oxygen (1.87 +/- 0.22 to 1.04 +/- 0.28 ml 100 g-1 min-1) and 32% reduction in regional oxygen extraction fraction (0.41 +/- 0.04 to 0.28 +/- 0.03) in the region of retraction but no change in the opposite hemisphere (paired t test; P = 0.042 and 0.003, respectively). There was no change in regional cerebral blood flow in any region. Brain retraction produced a focal area of tissue injury at the site of retractor blade placement, as compared to more diffuse vascular territory changes produced by vasospasm. This reduction in the cerebral metabolic rate of oxygen and the oxygen extraction fraction indicates a primary reduction in metabolism and uncoupling of flow and metabolism (luxury perfusion). Similar findings of luxury

  12. 21 CFR 1002.20 - Reporting of accidental radiation occurrences.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the Director, Center for Devices and Radiological Health, all accidental radiation occurrences... grounds include, but are not necessarily limited to, professional, scientific, or medical facts or... occurred. (b) Such reports shall be addressed to the Center for Devices and Radiological Health, ATTN...

  13. 21 CFR 1002.20 - Reporting of accidental radiation occurrences.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... the Director, Center for Devices and Radiological Health, all accidental radiation occurrences... grounds include, but are not necessarily limited to, professional, scientific, or medical facts or... occurred. (b) Such reports shall be addressed to Food and Drug Administration, Center for Devices and...

  14. [Processes of logical thought in a case of cerebral vascular lesion].

    PubMed

    Blanco Men ndez, R; Aguado Balsas, A M

    Reasoning and logical thought processes have traditionally been attributed to frontal lobe function or,on the other hand, have been considered as diffuse functions of the brain. However, there is today evidence enough about the possibility to find dissociations in thought processes, depending on logical structure of the experimental tasks and referring to different areas of the brain, frontal and post rolandic ones. To study possible dissociations between thought structures corresponding to categorical and relational logic, on one hand, and propositional logic on the other hand. The case of a brain injured patient with vascular etiology, localized in left frontal parietal cortex, is presented. A specific battery of reasoning tests has been administered. . A differential performance at some reasoning experimental tasks has been found depending on such logical conceptual structures. The possibility of establishing dissociations among certain logical thought and intelectual functions depending on localization of possible brain lesion (frontal versus temporal) is discussed.

  15. Determinants of suicide and accidental or violent death in the Australian HIV Observational Database.

    PubMed

    McManus, Hamish; Petoumenos, Kathy; Franic, Teo; Kelly, Mark D; Watson, Jo; O'Connor, Catherine C; Jeanes, Mark; Hoy, Jennifer; Cooper, David A; Law, Matthew G

    2014-01-01

    Rates of suicide and accidental or violent death remain high in HIV-positive populations despite significantly improved prognosis since the introduction of cART. We conducted a nested case-control study of suicide and accidental or violent death in the Australian HIV Observational Database (AHOD) between January 1999 and March 2012. For each case, 2 controls were matched by clinic, age, sex, mode of exposure and HIV-positive date to adjust for potential confounding by these covariates. Risk of suicide and accidental or violent death was estimated using conditional logistic regression. We included 27 cases (17 suicide and 10 violent/accidental death) and 54 controls. All cases were men who have sex with men (MSM) or MSM/ injecting drug use (IDU) mode of exposure. Increased risk was associated with unemployment (Odds Ratio (OR) 5.86, 95% CI: 1.69-20.37), living alone (OR 3.26, 95% CI: 1.06-10.07), suicidal ideation (OR 6.55, 95% CI: 1.70-25.21), and >2 psychiatric/cognitive risk factors (OR 4.99, 95% CI: 1.17-30.65). CD4 cell count of >500 cells/µL (OR 0.25, 95% CI: 0.07-0.87) and HIV-positive date ≥1990 (1990-1999 (OR 0.31, 95% CI: 0.11-0.89), post-2000 (OR 0.08, 95% CI: 0.01-0.84)) were associated with decreased risk. CD4 cell count ≥500 cells/µL remained a significant predictor of reduced risk (OR 0.15, 95% CI: 0.03-0.70) in a multivariate model adjusted for employment status, accommodation status and HIV-positive date. After adjustment for psychosocial factors, the immunological status of HIV-positive patients contributed to the risk of suicide and accidental or violent death. The number of psychiatric/cognitive diagnoses contributed to the level of risk but many psychosocial factors were not individually significant. These findings indicate a complex interplay of factors associated with risk of suicide and accidental or violent death.

  16. Autonomic dysfunction affects cerebral neurovascular coupling.

    PubMed

    Azevedo, Elsa; Castro, Pedro; Santos, Rosa; Freitas, João; Coelho, Teresa; Rosengarten, Bernhard; Panerai, Ronney

    2011-12-01

    Autonomic failure (AF) affects the peripheral vascular system, but little is known about its influence on cerebrovascular regulation. Patients with familial amyloidotic polyneuropathy (FAP) were studied as a model for AF. Ten mild (FAPm), 10 severe (FAPs) autonomic dysfunction FAP patients, and 15 healthy controls were monitored in supine and sitting positions for arterial blood pressure (ABP) and heart rate (HR) with arterial volume clamping, and for blood flow velocity (BFV) in posterior (PCA) and contralateral middle cerebral arteries (MCA) with transcranial Doppler. Analysis included resting BFV, cerebrovascular resistance parameters (cerebrovascular resistance index, CVRi; resistance area product, RAP; and critical closing pressure, CrCP), and neurovascular coupling through visually evoked BFV responses in PCA (gain, rate time, attenuation, and natural frequency). In non-stimulation conditions, in each position, there were no significant differences between the groups, regarding HR, BP, resting BFV, and vascular resistance parameters. Sitting ABP was higher than in supine in the three groups, although only significantly in controls. Mean BFV was lower in sitting in all the groups, lacking statistical significance only in FAPs PCA. CVRi and CrCP increased with sitting in all the groups, while RAP increased in controls but decreased in FAPm and FAPs. In visual stimulation conditions, FAPs comparing to controls had a significant decrease of natural frequency, in supine and sitting, and of rate time and gain in sitting position. These results demonstrate that cerebrovascular regulation is affected in FAP subjects with AF, and that it worsens with orthostasis.

  17. 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 ...

  18. Assessment by three-dimensional power Doppler ultrasound of cerebral blood flow perfusion in fetuses with congenital heart disease.

    PubMed

    Zeng, S; Zhou, J; Peng, Q; Tian, L; Xu, G; Zhao, Y; Wang, T; Zhou, Q

    2015-06-01

    To use three-dimensional (3D) power Doppler ultrasound to investigate cerebral blood flow perfusion in fetuses with congenital heart disease (CHD). The vascularization index (VI), flow index (FI) and vascularization flow index (VFI) in the total intracranial volume and the main arterial territories (middle cerebral artery (MCA), anterior cerebral artery (ACA) and posterior cerebral artery (PCA)) were evaluated prospectively and compared in 112 fetuses with CHD and 112 normal fetuses using 3D power Doppler. Correlations between the 3D power Doppler indices and neurodevelopment scores at 12 months of age were assessed in a subset of the CHD group, and values were compared with those of controls. Compared with the controls, the VI, FI and VFI of the total intracranial volume and the three main arteries were significantly higher in fetuses with hypoplastic left heart syndrome and left-sided obstructive lesions (P < 0.001), and the 3D power Doppler values in the ACA territory were significantly higher in fetuses with transposition of the great arteries (P < 0.01). The largest proportional increase in the blood flow perfusion indices in the fetuses with CHD relative to controls was observed in the ACA territory (P < 0.05). Among 41 cases with CHD that underwent testing, the mean Psychomotor Development Index (PDI) and Mental Development Index (MDI) scores were significantly lower than in 94 of the controls that were tested (P < 0.001). Among these CHD cases, total intracranial FI was positively correlated with PDI (r = 0.342, P = 0.029) and MDI (r = 0.339, P = 0.030), and ACA-VI and ACA-VFI were positively correlated with PDI (r = 0.377 and 0.389, P = 0.015 and 0.012, respectively) but were not correlated with MDI (r = 0.243 and 0.203, P = 0.126 and 0.204, respectively). Cerebral blood flow perfusion was increased relative to controls in most fetuses with CHD and was associated with neurodevelopment scores at 12 months

  19. Accidental Peccei-Quinn Symmetry Protected to Arbitrary Order

    NASA Astrophysics Data System (ADS)

    Di Luzio, Luca; Nardi, Enrico; Ubaldi, Lorenzo

    2017-07-01

    A S U (N )L×S U (N )R gauge theory for a scalar multiplet Y transforming in the bifundamental representation (N ,N ¯) preserves, for N >4 , an accidental U (1 ) symmetry first broken at operator dimension N . A vacuum expectation value for Y can break the symmetry to Hs=S U (N )L+R or to Hh=S U (N -1 )L×S U (N -1 )R×U (1 )L +R . In the first case the accidental U (1 ) gets also broken, yielding a pseudo-Nambu-Goldstone boson with mass suppression controlled by N . In the second case a global U (1 ) remains unbroken. The strong C P problem is solved by coupling Y to new fermions carrying color. The first case allows for a Peccei-Quinn solution with U (1 )PQ protected by the gauge symmetry up to order N . In the second case U (1 ) can get broken by condensates of the new strong dynamics, resulting in a composite axion. By coupling Y to fermions carrying only weak isospin, models for axionlike particles can be constructed.

  20. Accidental Beam Losses and Protection in the LHC

    NASA Astrophysics Data System (ADS)

    Schmidt, R.; Working Group On Machine Protection

    2005-06-01

    At top energy (proton momentum 7 TeV/c) with nominal beam parameters, each of the two LHC proton beams has a stored energy of 350 MJ threatening to damage accelerator equipment in case of accidental beam loss. It is essential that the beams are properly extracted onto the dump blocks in case of failure since these are the only elements that can withstand full beam impact. Although the energy stored in the beams at injection (450 GeV/c) is about 15 times smaller compared to top energy, the beams must still be properly extracted in case of large accidental beam losses. Failures must be detected at a sufficiently early stage and initiate a beam dump. Quenches and power converter failures will be detected by monitoring the correct functioning of the hardware systems. In addition, safe operation throughout the cycle requires the use of beam loss monitors, collimators and absorbers. Ideas of detection of fast beam current decay, monitoring of fast beam position changes and monitoring of fast magnet current changes are discussed, to provide the required redundancy for machine protection.

  1. 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.

  2. Accidental hanging by a T-shirt collar in a man with morphine intoxication: an unusual case.

    PubMed

    Kodikara, Sarathchandra; Alagiyawanna, Ramesh

    2011-09-01

    Accidental hanging is rare across all age groups, and it is even rarer in the adult population except in autoerotic asphyxia. Few cases have been reported in the literature, which describe unusual patterns of accidental hanging. This article focuses on an unusual pattern of accidental hanging of a 25-year-old man, who was in a state of morphine-induced central nervous system depression and found dead in a sitting position with the collar of his T-shirt hanging off a jutting-out root of a tree. The hanged collar acted as a ligature compressing the neck.

  3. [Assessment of maternal cerebral blood flow in patients with preeclampsia].

    PubMed

    Mandić, Vesna; Miković, Zeljko; Dukić, Milan; Vasiljević, Mladenko; Filimonović, Dejan; Bogavac, Mirjana

    2005-01-01

    Systemic vasoconstriction in preeclamptic patients increases vascular resistance, and is manifested by increased arterial blood flow velocity. The aim of the study is to evaluate if there is a change of Doppler indices in maternal medial cerbral artery (MCA) in severe preeclampsia due to: 1) severity of clinical symptoms, 2) the begining of eclamptic attack and 3) the application of anticonvulsive therapy. A prospective clinical study included 92 pregnant women, gestational age 28-36 weeks. They were divided into three groups: normotensive (n=30), mild preeclampsia (n=33), and severe preeclampsia (n=29). We investigated maternal cerebral circulation by assessing the MCA. We registrated: pulsatility index (Pi), resistance index (Ri), systolic/diastolic ratio (S/D), and the maximum systolic, end diastolic and medium velocity. Patients with severe preeclampsia were divided into two subgroups. subgroup 1 included patients without symptoms of threatening eclampsia (n=18; 62.06%); while subgroup 2 included those with symptoms of preeclampsia (n=11; 37.94%). All patients with severe preeclampsia were treated with magnesium sulfate (MgSO4), and cerebral blood flow was measured before and after the treatment. Statistical analysis was done by oneway ANOVA, Student t-test and t-paired sample test. The difference was considered to be significant if p<0.05. Significantly increased Pi, Ri and all velocities were established in the group of patients with severe preeclampsia compared with the other two groups. In the group with severe preeclamsia we registrated significantly increased values of all velocities (patients with signs of threatening eclampsia). After MgSO4 treatment in patients with severe preeclampsia significantly decreased values of Pi, Ri, S/D ratio and all velocities were registered. In the studied group of patients with severe preclampsia we found increased velocity values, Pi and Ri, especially in patients with signs of threatened eclampsia, suggesting that

  4. Mitochondrial motility and vascular smooth muscle proliferation.

    PubMed

    Chalmers, Susan; Saunter, Christopher; Wilson, Calum; Coats, Paul; Girkin, John M; McCarron, John G

    2012-12-01

    Mitochondria are widely described as being highly dynamic and adaptable organelles, and their movement is thought to be vital for cell function. Yet, in various native cells, including those of heart and smooth muscle, mitochondria are stationary and rigidly structured. The significance of the differences in mitochondrial behavior to the physiological function of cells is unclear and was studied in single myocytes and intact resistance-sized cerebral arteries. We hypothesized that mitochondrial dynamics is controlled by the proliferative status of the cells. High-speed fluorescence imaging of mitochondria in live vascular smooth muscle cells shows that the organelle undergoes significant reorganization as cells become proliferative. In nonproliferative cells, mitochondria are individual (≈ 2 μm by 0.5 μm), stationary, randomly dispersed, fixed structures. However, on entering the proliferative state, mitochondria take on a more diverse architecture and become small spheres, short rod-shaped structures, long filamentous entities, and networks. When cells proliferate, mitochondria also continuously move and change shape. In the intact pressurized resistance artery, mitochondria are largely immobile structures, except in a small number of cells in which motility occurred. When proliferation of smooth muscle was encouraged in the intact resistance artery, in organ culture, the majority of mitochondria became motile and the majority of smooth muscle cells contained moving mitochondria. Significantly, restriction of mitochondrial motility using the fission blocker mitochondrial division inhibitor prevented vascular smooth muscle proliferation in both single cells and the intact resistance artery. These results show that mitochondria are adaptable and exist in intact tissue as both stationary and highly dynamic entities. This mitochondrial plasticity is an essential mechanism for the development of smooth muscle proliferation and therefore presents a novel therapeutic

  5. 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:…

  6. The effects of L-arginine on cerebral hemodynamics after controlled cortical impact injury in the mouse.

    PubMed

    Liu, Hao; Goodman, J Clay; Robertson, Claudia S

    2002-03-01

    Traumatic brain injury (TBI) induces vascular changes that may influence neurological outcome by causing the brain to be more susceptible to secondary ischemic insults. In rat models of TBI, L-arginine administration has been shown to restore cerebral blood flow and improve neurological outcome. The purpose of this study was to determine if hypoperfusion occurs in a mouse model of TBI and if L-arginine administration has the same beneficial effects after injury in the mouse. C57BL6 mice were anesthetized with isoflurane, intubated and mechanically ventilated, and underwent a 3-m/sec, 1.5-mm deformation cortical impact injury. Five minutes after injury, L-arginine, 300 mg/kg, or saline were administered. Arterial blood pressure, intracranial pressure, and laser Doppler flow at the impact site were monitored for 3 h after the injury. The cerebral hemodynamic effects of the TBI induced by cortical impact injury were similar to that previously observed in rats. Intracranial hypertension, with ICP peaking at 46+/-2 mm Hg, and systemic hypotension both contributed to a reduction in CPP. In addition, LDF decreased significantly at the impact site. L-Arginine administration restored LDF to near baseline levels without increasing ICP. These studies demonstrate that cerebral hemodynamics can be measured in mouse models of TBI. The changes in cerebral hemodynamics are relatively simlar to those see in the rat model of cortical impact injury and suggest an important role for nitric oxide metabolism in the maintenance of cerebral blood flow following TBI.

  7. 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.

  8. [Brain Perfusion, Cognitive Functions, and Vascular Age in Middle Aged Patients With Essential Arterial Hypertension].

    PubMed

    Parfenov, V A; Ostroumova, T M; Pеrepelova, E M; Perepelov, V A; Kochetkov, A I; Ostroumova, O D

    2018-05-01

    This study aimed to assess the cognitive functions and cerebral blood flow measured with arterial spin labeling (ASL) and their possible correlations with vascular age in untreated middle-aged patients with grade 1-2 essential arterial hypertension (EAH). We examined 73 subjects aged 40-59 years (33 with EAH and 40 healthy volunteers [controls]). Neuropsychological assessment included Montreal Cognitive Assessment (MoCA), Trail Making test (part A and part B), Stroop Color and Word Test, verbal fluency test (phonemic verbal fluency and semantic verbal fluency), 10‑item word list learning task. All subjects underwent brain MRI. MRI protocol included ASL. Vascular age was calculated by two techniques - using Framingham Heart Study risk tables and SCORE project scales. Patients with EAH had lower performance on phonemic verbal fluency test and lower mean MoCA score (29.2±1.4 vs. 28.1±1.7 points) compared to controls (13.4±3.2, р=0.002; 29.2±1.4, p=0.001, respectively). White matter hyperintensities (WMH) were present in 7.5 % controls and in 51.5 % EAH patients (р=0.0002). Cerebral blood flow (CBF) in EAH patients was lower in both right (39.1±5.6 vs. 45.8±3.2 ml / 100 g / min) and left frontal lobes of the brain (39.2±6.2 и 45.2±3.6 ml / 100 g / min, respectively) compared to controls (р.

  9. [Aspects of vascular physiology in clinical and vascular surgical practice: basic principles of vascular mechanics].

    PubMed

    Nocke, H; Meyer, F; Lessmann, V

    2014-10-01

    To be able to evaluate properly a vascular problem, basic concepts of vascular physiology need to be considered, as they have been taught in physiology for a long time. This article deals with selected definitions and laws of passive vascular mechanics, subdivided into parameters of vascular filling and parameters of vascular flow. PARAMETERS OF VASCULAR FILLING: During vascular filling the transmural pressure distends the vascular wall until it is balanced by the wall tension. The extent of this distension up to the point of balance depends on the elasticity of the wall. Transmural pressure, wall tension and elasticity are defined, and their respective importance is described by clinical examples, e.g. aneurysm and varix. PARAMETERS OF VASCULAR FLOW: The vascular flow can be divided into stationary and pulsating components. Both components are relevant for the bloodstream. Since the blood flow is directed in the circuit, it can be understood in first approximation as stationary ("direct current").The direct current model uses only the average values of the pulsating variables. The great advantage of the direct current model is that it can be described with simple laws, which are not valid without reservation, but often allow a first theoretical approach to a vascular problem: Ohm's law, driving pressure, flow resistance, Hagen-Poiseuille law, wall shear stress, law of continuity, Bernoulli's equation and Reynold's number are described and associated with clinical examples.The heart is a pressure-suction pump and produces a pulsating flow, the pulse. The pulse runs with pulse wave velocity, which is much larger than the blood flow velocity, through the arterial vascular system. During propagation, the pulse has to overcome the wave resistance (impedance). Wherever the wave resistance changes, e.g., at vascular bifurcations and in the periphery, it comes to reflections. The incident (forward) and reflected (backward) waves are superimposed to yield the resulting

  10. Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid-β from the mouse brain.

    PubMed

    Hawkes, Cheryl A; Gatherer, Maureen; Sharp, Matthew M; Dorr, Adrienne; Yuen, Ho Ming; Kalaria, Rajesh; Weller, Roy O; Carare, Roxana O

    2013-04-01

    Development of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) is associated with failure of elimination of amyloid-β (Aβ) from the brain along perivascular basement membranes that form the pathways for drainage of interstitial fluid and solutes from the brain. In transgenic APP mouse models of AD, the severity of cerebral amyloid angiopathy is greater in the cerebral cortex and hippocampus, intermediate in the thalamus, and least in the striatum. In this study we test the hypothesis that age-related regional variation in (1) vascular basement membranes and (2) perivascular drainage of Aβ contribute to the different regional patterns of CAA in the mouse brain. Quantitative electron microscopy of the brains of 2-, 7-, and 23-month-old mice revealed significant age-related thickening of capillary basement membranes in cerebral cortex, hippocampus, and thalamus, but not in the striatum. Results from Western blotting and immunocytochemistry experiments showed a significant reduction in collagen IV in the cortex and hippocampus with age and a reduction in laminin and nidogen 2 in the cortex and striatum. Injection of soluble Aβ into the hippocampus or thalamus showed an age-related reduction in perivascular drainage from the hippocampus but not from the thalamus. The results of the study suggest that changes in vascular basement membranes and perivascular drainage with age differ between brain regions, in the mouse, in a manner that may help to explain the differential deposition of Aβ in the brain in AD and may facilitate development of improved therapeutic strategies to remove Aβ from the brain in AD. © 2013 The Authors Aging Cell © 2013 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

  11. Hemorrhagic shock-induced cerebral bioenergetic imbalance is corrected by pharmacologic treatment with EF24 in a rat model.

    PubMed

    Rao, Geeta; Xie, Jun; Hedrick, Andria; Awasthi, Vibhudutta

    2015-12-01

    Maintenance of cerebral viability and function is an important goal of critical care in victims of injury due to ischemia and hypovolemia. As part of the multiple organ dysfunction syndrome, the brain function after trauma is influenced by the systemic inflammatory response. We investigated the effect of EF24, an anti-inflammatory bis-chalcone, on cerebral bioenergetics in a rat model of 45% hemorrhagic shock. The rats were treated with EF24 (0.4 mg/kg) or EF24 with an artificial oxygen carrier liposome-encapsulated hemoglobin (LEH). The volume of LEH administered was equal to the shed blood. The brain was collected after 6 h of shock for biochemical assays. EF24 treatment showed significant recovery of ATP, phosphocreatine, and NAD/NADH ratio. It also increased citrate synthase activity and cytochrome c oxidase subunit IV expression which were reduced in shock brain. Furthermore, it reduced the shock-induced accumulation of pyruvate and pyruvate dehydrogenase kinase-1 expression, suggesting that EF24 treatment improves cerebral energetics by restoring perturbed pyruvate metabolism in the mitochondria. These effects of EF24 were associated with reduced poly(ADP-ribose) polymerase cleavage and a significant improvement in the levels of nerve growth factor and brain-derived neurotrophic factor in shock brain. Co-administration of LEH with EF24 was only marginally more effective as compared to the treatment with EF24 alone. These results show that EF24 treatment sets up a pro-survival phenotype in shock by resurrecting cerebral bioenergetics. Since EF24 was effective in the absence of accompanying fluid resuscitation, it has potential utility as a pre-hospital pharmacotherapy in shock due to accidental blood loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. The Accidental Transgressor: Morally-Relevant Theory of Mind

    ERIC Educational Resources Information Center

    Killen, Melanie; Mulvey, Kelly Lynn; Richardson, Cameron; Jampol, Noah; Woodward, Amanda

    2011-01-01

    To test young children's false belief theory of mind in a morally relevant context, two experiments were conducted. In Experiment 1, children (N=162) at 3.5, 5.5, and 7.5 years of age were administered three tasks: prototypic moral transgression task, false belief theory of mind task (ToM), and an "accidental transgressor" task, which measured a…

  13. Flux or speed? Examining speckle contrast imaging of vascular flows.

    PubMed

    Kazmi, S M Shams; Faraji, Ehssan; Davis, Mitchell A; Huang, Yu-Yen; Zhang, Xiaojing J; Dunn, Andrew K

    2015-07-01

    Speckle contrast imaging enables rapid mapping of relative blood flow distributions using camera detection of back-scattered laser light. However, speckle derived flow measures deviate from direct measurements of erythrocyte speeds by 47 ± 15% (n = 13 mice) in vessels of various calibers. Alternatively, deviations with estimates of volumetric flux are on average 91 ± 43%. We highlight and attempt to alleviate this discrepancy by accounting for the effects of multiple dynamic scattering with speckle imaging of microfluidic channels of varying sizes and then with red blood cell (RBC) tracking correlated speckle imaging of vascular flows in the cerebral cortex. By revisiting the governing dynamic light scattering models, we test the ability to predict the degree of multiple dynamic scattering across vessels in order to correct for the observed discrepancies between relative RBC speeds and multi-exposure speckle imaging estimates of inverse correlation times. The analysis reveals that traditional speckle contrast imagery of vascular flows is neither a measure of volumetric flux nor particle speed, but rather the product of speed and vessel diameter. The corrected speckle estimates of the relative RBC speeds have an average 10 ± 3% deviation in vivo with those obtained from RBC tracking.

  14. Proteomic profiling of the brain of mice with experimental cerebral malaria.

    PubMed

    Moussa, Ehab; Huang, Honglei; Ahras, Malika; Lall, Amar; Thezenas, Marie L; Fischer, Roman; Kessler, Benedikt M; Pain, Arnab; Billker, Oliver; Casals-Pascual, Climent

    2018-05-30

    Cerebral malaria (CM) is a severe neurological complication of malaria infection in both adults and children. In pursuit of effective treatment of CM, clinical studies, postmortem analysis and animal models have been employed to understand the pathology and identify effective interventions. In this study, a shotgun proteomics analysis was conducted to profile the proteomic signature of the brain tissue of mice with experimental cerebral malaria (ECM) in order to further understand the underlying pathology. To identify CM-associated response, proteomic signatures of the brains of C57/Bl6N mice infected with P. berghei ANKA that developed neurological syndrome were compared to those of mice infected with P. berghei NK65 that developed equally high parasite burdens without neurological signs, and to those of non-infected mice. The results show that the CM-associated response in mice that developed neurological signs comprise mainly acute-phase reaction and coagulation cascade activation, and indicate the leakage of plasma proteins into the brain parenchyma. Cerebral malaria (CM) remains a major cause of death in children. The majority of these deaths occur in sub-Saharan Africa. Even with adequate access to treatment, mortality remains high and neurological sequelae can be found in up to 20% of survivors. No adjuvant treatment to date has been shown to reduce mortality and the pathophysiology of CM is largely unknown. Experimental cerebral malaria (ECM) is a well-established model that may contribute to identify and test druggable targets. In this study we have identified the disruption of the blood-brain barrier following inflammatory and vascular injury as a mechanism of disease. In this study we report a number of proteins that could be validated as potential biomarkers of ECM. Further studies, will be required to validate the clinical relevance of these biomarkers in human CM. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Positive income shocks and accidental deaths among Cherokee Indians: a natural experiment

    PubMed Central

    Bruckner, Tim A; Brown, Ryan A; Margerison-Zilko, Claire

    2011-01-01

    Background Several studies in low-income populations report the somewhat counterintuitive finding that positive income gains adversely affect adult health. The literature posits that receipt of a large portion of annual income increases, in the short term, risk-taking behaviour and/or the consumption of health-damaging goods. This work implies the hypothesis that persons with an unexpected gain in income will exhibit an elevated risk of accidental death—the fifth leading cause of death in the USA. We test this hypothesis directly by capitalizing on a natural experiment in which Cherokee Indians in rural North Carolina received discrete lump sum payments from a new casino. Methods We applied Poisson regression to the monthly count of accidental deaths among Cherokee Indians over 204 months spanning 1990–2006. We controlled for temporal patterns in accidental deaths (e.g. seasonality and trend) as well as changes in population size. Results As hypothesized, the risk of accidental death rises above expected levels during months of the large casino payments (relative risk = 2.62; 95% confidence interval = 1.54–4.47). Exploratory analyses of ethnographic interviews and behavioural surveys support that increased vehicular travel and consumption of health-damaging goods may account for the rise in accident proneness. Conclusions Although long-term income gains may improve health in this population, our findings indicate that acute responses to large income gains, in the short term, increase risk-taking and accident proneness. We encourage further investigation of natural experiments to identify causal economic antecedents of population health. PMID:21527447

  16. The Impacts of Air Temperature on Accidental Casualties in Beijing, China.

    PubMed

    Ma, Pan; Wang, Shigong; Fan, Xingang; Li, Tanshi

    2016-11-02

    Emergency room (ER) visits for accidental casualties, according to the International Classification of Deceases 10th Revision Chapters 19 and 20, include injury, poisoning, and external causes (IPEC). Annual distribution of 187,008 ER visits that took place between 2009 and 2011 in Beijing, China displayed regularity rather than random characteristics. The annual cycle from the Fourier series fitting of the number of ER visits was found to explain 63.2% of its total variance. In this study, the possible effect and regulation of meteorological conditions on these ER visits are investigated through the use of correlation analysis, as well as statistical modeling by using the Distributed Lag Non-linear Model and Generalized Additive Model. Correlation analysis indicated that meteorological variables that positively correlated with temperature have a positive relationship with the number of ER visits, and vice versa. The temperature metrics of maximum, minimum, and mean temperatures were found to have similar overall impacts, including both the direct impact on human mental/physical conditions and indirect impact on human behavior. The lag analysis indicated that the overall impacts of temperatures higher than the 50th percentile on ER visits occur immediately, whereas low temperatures show protective effects in the first few days. Accidental casualties happen more frequently on warm days when the mean temperature is higher than 14 °C than on cold days. Mean temperatures of around 26 °C result in the greatest possibility of ER visits for accidental casualties. In addition, males were found to face a higher risk of accidental casualties than females at high temperatures. Therefore, the IPEC-classified ER visits are not pure accidents; instead, they are associated closely with meteorological conditions, especially temperature.

  17. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

    PubMed

    Elomaa, Laura; Yang, Yunzhi Peter

    2017-10-01

    There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

  18. Cerebral vasoconstriction precedes orthostatic intolerance after parabolic flight

    NASA Technical Reports Server (NTRS)

    Serrador, J. M.; Shoemaker, J. K.; Brown, T. E.; Kassam, M. S.; Bondar, R. L.; Schlegel, T. T.

    2000-01-01

    The effects of brief but repeated bouts of micro- and hypergravity on cerebrovascular responses to head-up tilt (HUT) were examined in 13 individuals after (compared to before) parabolic flight. Middle cerebral artery mean flow velocity (MCA MFV; transcranial Doppler ultrasound), eye level blood pressure (BP) and end tidal CO(2) (P(ET)CO(2)) were measured while supine and during 80 degrees HUT for 30 min or until presyncope. In the postflight tests subjects were classified as being orthostatically tolerant (OT) (n = 7) or intolerant (OI) (n = 6). BP was diminished with HUT in the OT group in both tests (p < 0.05) whereas postflight BP was not different from supine in the OI group. Postflight compared to preflight, the reduction in P(ET)CO(2) with HUT (p < 0.05) increased in both groups, although significantly so only in the OI group (p < 0.05). The OI group also had a significant decrease in supine MCA MFV postflight (p < 0.05) that was unaccompanied by a change in supine P(ET)CO(2). The decrease in MCA MFV that occurred during HUT in both groups preflight (p < 0.05) was accentuated only in the OI group postflight, particularly during the final 30 s of HUT (p < 0.05). However, this accentuated decrease in MCA MFV was not correlated to the greater decrease in P(ET)CO(2) during the same period (R = 0.20, p = 0.42). Although cerebral vascular resistance (CVR) also increased in the OI group during the last 30 s of HUT postflight (p < 0.05), the dynamic autoregulatory gain was not simultaneously changed. Therefore, we conclude that in the OI individuals, parabolic flight was associated with cerebral hypoperfusion following a paradoxical augmentation of CVR by a mechanism that was not related to changes in autoregulation nor strictly to changes in P(ET)CO(2).

  19. Metabolic and vascular origins of the BOLD effect: Implications for imaging pathology and resting-state brain function.

    PubMed

    Mark, Clarisse I; Mazerolle, Erin L; Chen, J Jean

    2015-08-01

    The blood oxygenation level-dependent (BOLD) phenomenon has profoundly revolutionized neuroscience, with applications ranging from normal brain development and aging, to brain disorders and diseases. While the BOLD effect represents an invaluable tool to map brain function, it does not measure neural activity directly; rather, it reflects changes in blood oxygenation resulting from the relative balance between cerebral oxygen metabolism (through neural activity) and oxygen supply (through cerebral blood flow and volume). As such, there are cases in which BOLD signals might be dissociated from neural activity, leading to misleading results. The emphasis of this review is to develop a critical perspective for interpreting BOLD results, through a comprehensive consideration of BOLD's metabolic and vascular underpinnings. We demonstrate that such an understanding is especially important under disease or resting conditions. We also describe state-of-the-art acquisition and analytical techniques to reveal physiological information on the mechanisms underlying measured BOLD signals. With these goals in mind, this review is structured to provide a fundamental understanding of: 1) the physiological and physical sources of the BOLD contrast; 2) the extraction of information regarding oxidative metabolism and cerebrovascular reactivity from the BOLD signal, critical to investigating neuropathology; and 3) the fundamental importance of metabolic and vascular mechanisms for interpreting resting-state BOLD measurements. © 2015 Wiley Periodicals, Inc.

  20. Acute Isolated Central Facial Palsy as Manifestation of Middle Cerebral Artery Ischemia.

    PubMed

    Sands, Kara A; Shahripour, Reza Bavarsad; Kumar, Gyanendra; Barlinn, Kristian; Lyerly, Michael J; Haršány, Michal; Cure, Joel; Yakov, Yuri L; Alexandrov, Anne W; Alexandrov, Andrei V

    2016-09-01

    Isolated central facial palsy (I-CFP) is attributed to a lacunar syndrome affecting the corona radiata region or pons. We examined our acute stroke registry for patients presenting with I-CFP and localized their symptoms to a vascular lesion. Our database of consecutive patients with symptoms of acute cerebral ischemia admitted from January 2008 to December 2012 was reviewed for NIH Stroke Scale (NIHSS) scores and subcomponents. All patients with I-CFP ± dysarthria (total NIHSS ≤ 3) had contrast-enhanced MR-angiography and transcranial Doppler as standard of care. All ischemic lesions were localized by MRI within 72 hours from symptom onset. Of 2,202 patients with acute cerebral ischemia, 879 patients (35%) had NIHSS score ≤ 3 points (mean age 63 + 15 years, 46 % women). Nine patients (.4%) presented with I-CFP ± dysarthria. Of these, only 1 had a lesion in the corona radiata and patent MCA, 1 had a pontine lesion without proximal vessel occlusion (2/9, or 22%). Remaining 7 patients (78%) had flow-limiting thromboembolic mid-to-distal M1/proximal M2 MCA disease. Of these, 6 (86%) patients had a prominent early anterior temporal artery on MRA and nonlacunar ischemic lesions on MRI. Contrary to current teaching of lesion localization for an I-CFP, our study revealed the majority of acute patients presenting with this symptom had evidence of flow-limiting thromboembolic MCA disease rather than a lacunar lesion. Our findings underscore the essential role of comprehensive vascular imaging in patients presenting with I-CFP, which is commonly associated with acute flow-limiting thromboembolic MCA disease. Copyright © 2016 by the American Society of Neuroimaging.

  1. 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.

  2. Gap-free segmentation of vascular networks with automatic image processing pipeline.

    PubMed

    Hsu, Chih-Yang; Ghaffari, Mahsa; Alaraj, Ali; Flannery, Michael; Zhou, Xiaohong Joe; Linninger, Andreas

    2017-03-01

    Current image processing techniques capture large vessels reliably but often fail to preserve connectivity in bifurcations and small vessels. Imaging artifacts and noise can create gaps and discontinuity of intensity that hinders segmentation of vascular trees. However, topological analysis of vascular trees require proper connectivity without gaps, loops or dangling segments. Proper tree connectivity is also important for high quality rendering of surface meshes for scientific visualization or 3D printing. We present a fully automated vessel enhancement pipeline with automated parameter settings for vessel enhancement of tree-like structures from customary imaging sources, including 3D rotational angiography, magnetic resonance angiography, magnetic resonance venography, and computed tomography angiography. The output of the filter pipeline is a vessel-enhanced image which is ideal for generating anatomical consistent network representations of the cerebral angioarchitecture for further topological or statistical analysis. The filter pipeline combined with computational modeling can potentially improve computer-aided diagnosis of cerebrovascular diseases by delivering biometrics and anatomy of the vasculature. It may serve as the first step in fully automatic epidemiological analysis of large clinical datasets. The automatic analysis would enable rigorous statistical comparison of biometrics in subject-specific vascular trees. The robust and accurate image segmentation using a validated filter pipeline would also eliminate operator dependency that has been observed in manual segmentation. Moreover, manual segmentation is time prohibitive given that vascular trees have more than thousands of segments and bifurcations so that interactive segmentation consumes excessive human resources. Subject-specific trees are a first step toward patient-specific hemodynamic simulations for assessing treatment outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Vascular risk factor burden and new-onset depression in the community.

    PubMed

    Adams, Shayna; Conner, Sarah; Himali, Jayandra J; Beiser, Alexa; Vasan, Ramachandran S; Seshadri, Sudha; Pase, Matthew P

    2018-06-01

    Depression is associated with an increased likelihood of cardiac events and stroke. We hypothesized that the vascular risk factor burden might itself predispose to both cardiovascular events and depression. Therefore, we examined whether aggregate scores of vascular risk factor burden were associated with the new-onset of depression in the community. We studied 2023 depression- and dementia-free Framingham Heart Study (Framingham, USA) Offspring participants who attended both examination cycles 7 (1998-2001) and 8 (2005-2008). The American Heart Association Ideal Cardiovascular Health metric and the Framingham stroke risk profile were calculated at exam seven. New-onset depression was adjudicated at examination cycle eight as antidepressant medication use or Centre for Epidemiologic Studies Depression Scale scores ≥16, after a mean follow-up of 6.6years (standard deviation=0.7). Of the 2023 participants, 269 (13%) developed new-onset depression. Following adjustments for age, sex, education, and the time interval between baseline and follow-up, the odds of new-onset depression decreased by 10% for each one-point increase in ideal cardiovascular health scores (Odds Ratio [OR], 0.90; 95% confidence interval [CI] 0.81-0.99) and increased by 4% for each percentage point increase in the Framingham stroke risk profile (OR, 1.04; CI, 1.00-1.07). Results were not explained by interim clinical stroke or cerebral white matter injury. In conclusion, vascular risk factor burden was associated with the new onset of depression. Shared vascular risk factors may contribute to the increased risk of cardiovascular events observed in persons with depression. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Monoamine uptake inhibitors block alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation.

    PubMed

    Long, Cheng; Chen, Mei-Fang; Sarwinski, Susan J; Chen, Po-Yi; Si, Minliang; Hoffer, Barry J; Evans, M Steven; Lee, Tony J F

    2006-07-01

    We have proposed that activation of cerebral perivascular sympathetic alpha7-nicotinic acetylcholine receptors (alpha7-nAChRs) by nicotinic agonists releases norepinephrine, which then acts on parasympathetic nitrergic nerves, resulting in release of nitric oxide and vasodilation. Using patch-clamp electrophysiology, immunohistochemistry, and in vitro tissue bath myography, we tested this axo-axonal interaction hypothesis further by examining whether blocking norepinephrine reuptake enhanced alpha7-nAChR-mediated cerebral nitrergic neurogenic vasodilation. The results indicated that choline- and nicotine-induced alpha7-nAChR-mediated nitrergic neurogenic relaxation in endothelium-denuded isolated porcine basilar artery rings was enhanced by desipramine and imipramine at lower concentrations (0.03-0.1 microM) but inhibited at higher concentrations (0.3-10 microM). In cultured superior cervical ganglion (SCG) neurons of the pig and rat, choline (0.1-30 mM)-evoked inward currents were reversibly blocked by 1-30 microM mecamylamine, 1-30 microM methyllycaconitine, 10-300 nM alpha-bungarotoxin, and 0.1-10 microM desipramine and imipramine, providing electrophysiological evidence for the presence of similar functional alpha7-nAChRs in cerebral perivascular sympathetic neurons of pigs and rats. In alpha7-nAChR-expressing Xenopus oocytes, choline-elicited inward currents were attenuated by alpha-bungarotoxin, imipramine, and desipramine. These monoamine uptake inhibitors appeared to directly block the alpha7-nAChR, resulting in diminished nicotinic agonist-induced cerebral nitrergic vasodilation. The enhanced nitrergic vasodilation by lower concentrations of monoamine uptake inhibitors is likely due to a greater effect on monoamine uptake than on alpha7-nAChR blockade. These results further support the hypothesis of axo-axonal interaction in nitrergic regulation of cerebral vascular tone.

  5. AbetaPP/APLP2 family of Kunitz serine proteinase inhibitors regulate cerebral thrombosis.

    PubMed

    Xu, Feng; Previti, Mary Lou; Nieman, Marvin T; Davis, Judianne; Schmaier, Alvin H; Van Nostrand, William E

    2009-04-29

    The amyloid beta-protein precursor (AbetaPP) is best recognized as the precursor to the Abeta peptide that accumulates in the brains of patients with Alzheimer's disease, but less is known about its physiological functions. Isoforms of AbetaPP that contain a Kunitz-type serine proteinase inhibitor (KPI) domain are expressed in brain and, outside the CNS, in circulating blood platelets. Recently, we showed that KPI-containing forms of AbetaPP regulates cerebral thrombosis in vivo (Xu et al., 2005, 2007). Amyloid precursor like protein-2 (APLP2), a closely related homolog to AbetaPP, also possesses a highly conserved KPI domain. Virtually nothing is known of its function. Here, we show that APLP2 also regulates cerebral thrombosis risk. Recombinant purified KPI domains of AbetaPP and APLP2 both inhibit the plasma clotting in vitro. In a carotid artery thrombosis model, both AbetaPP(-/-) and APLP2(-/-) mice exhibit similar significantly shorter times to vessel occlusion compared with wild-type mice indicating a prothrombotic phenotype. Similarly, in an experimental model of intracerebral hemorrhage, both AbetaPP(-/-) and APLP2(-/-) mice produce significantly smaller hematomas with reduced brain hemoglobin content compared with wild-type mice. Together, these results indicate that AbetaPP and APLP2 share overlapping anticoagulant functions with regard to regulating thrombosis after cerebral vascular injury.

  6. Modelling dynamic changes in blood flow and volume in the cerebral vasculature.

    PubMed

    Payne, S J; El-Bouri, W K

    2018-08-01

    The cerebral microvasculature plays a key role in the transport of blood and the delivery of nutrients to the cells that perform brain function. Although recent advances in experimental imaging techniques mean that its structure and function can be interrogated to very small length scales, allowing individual vessels to be mapped to a fraction of 1 μm, these techniques currently remain confined to animal models. In-vivo human data can only be obtained at a much coarser length scale, of order 1 mm, meaning that mathematical models of the microvasculature play a key role in interpreting flow and metabolism data. However, there are close to 10,000 vessels even within a single voxel of size 1 mm 3 . Given the number of vessels present within a typical voxel and the complexity of the governing equations for flow and volume changes, it is computationally challenging to solve these in full, particularly when considering dynamic changes, such as those found in response to neural activation. We thus consider here the governing equations and some of the simplifications that have been proposed in order more rigorously to justify in what generations of blood vessels these approximations are valid. We show that two approximations (neglecting the advection term and assuming a quasi-steady state solution for blood volume) can be applied throughout the cerebral vasculature and that two further approximations (a simple first order differential relationship between inlet and outlet flows and inlet and outlet pressures, and matching of static pressure at nodes) can be applied in vessels smaller than approximately 1 mm in diameter. We then show how these results can be applied in solving flow fields within cerebral vascular networks providing a simplified yet rigorous approach to solving dynamic flow fields and compare the results to those obtained with alternative approaches. We thus provide a framework to model cerebral blood flow and volume within the cerebral vasculature

  7. Tetrahedral and polyhedral mesh evaluation for cerebral hemodynamic simulation--a comparison.

    PubMed

    Spiegel, Martin; Redel, Thomas; Zhang, Y; Struffert, Tobias; Hornegger, Joachim; Grossman, Robert G; Doerfler, Arnd; Karmonik, Christof

    2009-01-01

    Computational fluid dynamic (CFD) based on patient-specific medical imaging data has found widespread use for visualizing and quantifying hemodynamics in cerebrovascular disease such as cerebral aneurysms or stenotic vessels. This paper focuses on optimizing mesh parameters for CFD simulation of cerebral aneurysms. Valid blood flow simulations strongly depend on the mesh quality. Meshes with a coarse spatial resolution may lead to an inaccurate flow pattern. Meshes with a large number of elements will result in unnecessarily high computation time which is undesirable should CFD be used for planning in the interventional setting. Most CFD simulations reported for these vascular pathologies have used tetrahedral meshes. We illustrate the use of polyhedral volume elements in comparison to tetrahedral meshing on two different geometries, a sidewall aneurysm of the internal carotid artery and a basilar bifurcation aneurysm. The spatial mesh resolution ranges between 5,119 and 228,118 volume elements. The evaluation of the different meshes was based on the wall shear stress previously identified as a one possible parameter for assessing aneurysm growth. Polyhedral meshes showed better accuracy, lower memory demand, shorter computational speed and faster convergence behavior (on average 369 iterations less).

  8. Cerebral microbleeds, cognitive impairment, and MRI in patients with diabetes mellitus.

    PubMed

    Zhou, Hong; Yang, Juan; Xie, Peihan; Dong, Yulan; You, Yong; Liu, Jincai

    2017-07-01

    Cerebral microbleeds (CMBs), a typical imaging manifestation marker of sporadic cerebral small vessel disease, play a critical role in vascular cognitive impairment, which is often accompanied by diabetes mellitus (DM). Hence, CMBs may, in part, be responsible for the occurrence and development of cognitive impairment in patients with diabetes. Novel magnetic resonance imaging (MRI) sequences, such as susceptibility-weighted imaging and T2*-weighted gradient-echo, have the capability of noninvasively revealing CMBs in the brain. Moreover, a correlation between CMBs and cognitive impairment in patients with diabetes has been suggested in applications of functional MRI (fMRI). Since pathological changes in the brain occur prior to observable decline in cognitive function, neuroimaging may help predict the progression of cognitive impairment in diabetic patients. In this article, we review the detection of CMBs using MRI in diabetic patients exhibiting cognitive impairment. Future studies should emphasize the development and establishment of a novel MRI protocol, including fMRI, for diabetic patients with cognitive impairment to detect CMBs. A reliable MRI protocol would also be helpful in understanding the pathological mechanisms of cognitive impairment in this important patient population. Copyright © 2017. Published by Elsevier B.V.

  9. 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.

  10. Use of high-resolution 3.0-T magnetic resonance imaging to characterize atherosclerotic plaques in patients with cerebral infarction

    PubMed Central

    XU, PENG; LV, LULU; LI, SHAODONG; GE, HAITAO; RONG, YUTAO; HU, CHUNFENG; XU, KAI

    2015-01-01

    The present study aimed to evaluate the utility of high-resolution magnetic resonance imaging (MRI) in the characterization of atherosclerotic plaques in patients with acute and non-acute cerebral infarction. High-resolution MRI of unilateral stenotic middle cerebral arteries was performed to evaluate the degree of stenosis, the wall and plaque areas, plaque enhancement patterns and lumen remodeling features in 15 and 17 patients with acute and non-acute cerebral infarction, respectively. No significant difference was identified in the vascular stenosis rate between acute and non-acute patients. Overall, plaque eccentricity was observed in 29 patients, including 13 acute and 16 non-acute cases, with no significant difference identified between these groups. The wall area of stenotic arteries and the number of cases with plaque enhancement were significantly greater in the acute patients, but no significant difference in plaque or lumen area was identified between the 2 patient groups. Lumen remodeling patterns of stenotic arteries significantly differed between the acute and non-acute patients; the former predominantly demonstrated positive remodeling, and the latter group demonstrated evidence of negative remodeling. In conclusion, patients with acute and non-acute cerebral infarction exhibit specific characteristics in stenotic arteries and plaques, which can be effectively evaluated by high-resolution MRI. PMID:26668651

  11. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association.

    PubMed

    Gorelick, Philip B; Scuteri, Angelo; Black, Sandra E; Decarli, Charles; Greenberg, Steven M; Iadecola, Costantino; Launer, Lenore J; Laurent, Stephane; Lopez, Oscar L; Nyenhuis, David; Petersen, Ronald C; Schneider, Julie A; Tzourio, Christophe; Arnett, Donna K; Bennett, David A; Chui, Helena C; Higashida, Randall T; Lindquist, Ruth; Nilsson, Peter M; Roman, Gustavo C; Sellke, Frank W; Seshadri, Sudha

    2011-09-01

    This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment and dementia of later life are common. Definitions of vascular cognitive impairment (VCI), neuropathology, basic science and pathophysiological aspects, role of neuroimaging and vascular and other associated risk factors, and potential opportunities for prevention and treatment are reviewed. This statement serves as an overall guide for practitioners to gain a better understanding of VCI and dementia, prevention, and treatment. Writing group members were nominated by the writing group co-chairs on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council Scientific Statement Oversight Committee, the Council on Epidemiology and Prevention, and the Manuscript Oversight Committee. The writing group used systematic literature reviews (primarily covering publications from 1990 to May 1, 2010), previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, formulate recommendations using standard American Heart Association criteria. All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. After peer review by the American Heart Association, as well as review by the Stroke Council leadership, Council on Epidemiology and Prevention Council, and Scientific Statements Oversight Committee, the statement was approved by the American Heart Association Science Advisory and Coordinating Committee. The construct of VCI has been introduced to capture the entire spectrum of cognitive disorders associated with all forms of cerebral vascular brain injury-not solely stroke-ranging from mild cognitive impairment through fully developed dementia. Dysfunction of the neurovascular

  12. The Association between Dust Storms and Daily Non-Accidental Mortality in the United States, 1993–2005

    PubMed Central

    Crooks, James Lewis; Cascio, Wayne E.; Percy, Madelyn S.; Reyes, Jeanette; Neas, Lucas M.; Hilborn, Elizabeth D.

    2016-01-01

    Background: The impact of dust storms on human health has been studied in the context of Asian, Saharan, Arabian, and Australian storms, but there has been no recent population-level epidemiological research on the dust storms in North America. The relevance of dust storms to public health is likely to increase as extreme weather events are predicted to become more frequent with anticipated changes in climate through the 21st century. Objectives: We examined the association between dust storms and county-level non-accidental mortality in the United States from 1993 through 2005. Methods: Dust storm incidence data, including date and approximate location, are taken from the U.S. National Weather Service storm database. County-level mortality data for the years 1993–2005 were acquired from the National Center for Health Statistics. Distributed lag conditional logistic regression models under a time-stratified case-crossover design were used to study the relationship between dust storms and daily mortality counts over the whole United States and in Arizona and California specifically. End points included total non-accidental mortality and three mortality subgroups (cardiovascular, respiratory, and other non-accidental). Results: We estimated that for the United States as a whole, total non-accidental mortality increased by 7.4% (95% CI: 1.6, 13.5; p = 0.011) and 6.7% (95% CI: 1.1, 12.6; p = 0.018) at 2- and 3-day lags, respectively, and by an average of 2.7% (95% CI: 0.4, 5.1; p = 0.023) over lags 0–5 compared with referent days. Significant associations with non-accidental mortality were estimated for California (lag 2 and 0–5 day) and Arizona (lag 3), for cardiovascular mortality in the United States (lag 2) and Arizona (lag 3), and for other non-accidental mortality in California (lags 1–3 and 0–5). Conclusions: Dust storms are associated with increases in lagged non-accidental and cardiovascular mortality. Citation: Crooks JL, Cascio WE, Percy MS, Reyes

  13. Reversed Robin Hood Syndrome in the Light of Nonlinear Model of Cerebral Circulation

    NASA Astrophysics Data System (ADS)

    Piechna, A.; Cieslicki, K.

    2017-05-01

    The brain is supplied by the internal carotid and vertebro-basilar systems of vessels interconnected by arterial anastomoses and forming at the base of the brain a structure called the Circle of Willis (CoW). An active intrinsic ability of cerebral vascular bed maintains constant Cerebral Blood Flow (CBF) in a certain range of systemic pressure changes. This ability is called autoregulation and together with the redundant structure of the CoW guarantee maintaining CBF even in partial occlusion of supplying arteries. However, there are some situations when the combination of those two mechanisms causes an opposite effect called the Reversed Robin Hood Syndrome (RRHS). In this work we proposed a model of the CoW with autoregulation mechanism and investigated a RRHS which may occur in the case of Internal Carotid Artery (ICA) stenosis combined with hypercapnia. We showed and analyzed the mechanism of stealing the blood by the contralateral side of the brain. Our results were qualitatively compared with the clinical reports available in the literature.

  14. No effect of ablation of surfactant protein-D on acute cerebral infarction in mice.

    PubMed

    Lambertsen, Kate L; Østergaard, Kamilla; Clausen, Bettina H; Hansen, Søren; Stenvang, Jan; Thorsen, Stine B; Meldgaard, Michael; Kristensen, Bjarne W; Hansen, Pernille B; Sorensen, Grith L; Finsen, Bente

    2014-07-19

    Crosstalk between the immune system in the brain and the periphery may contribute to the long-term outcome both in experimental and clinical stroke. Although, the immune defense collectin surfactant protein-D (SP-D) is best known for its role in pulmonary innate immunity, SP-D is also known to be involved in extrapulmonary modulation of inflammation in mice. We investigated whether SP-D affected cerebral ischemic infarction and ischemia-induced inflammatory responses in mice. The effect of SP-D was studied by comparing the size of ischemic infarction and the inflammatory and astroglial responses in SP-D knock out (KO) and wild type (WT) mice subjected to permanent middle cerebral artery occlusion. SP-D mRNA production was assessed in isolated cerebral arteries and in the whole brain by PCR, and SP-D protein in normal appearing and ischemic human brain by immunohistochemistry. Changes in plasma SP-D and TNF were assessed by ELISA and proximity ligation assay, respectively. Infarct volumetric analysis showed that ablation of SP-D had no effect on ischemic infarction one and five days after induction of ischemia. Further, ablation of SP-D had no effect on the ischemia-induced increase in TNF mRNA production one day after induction of ischemia; however the TNF response to the ischemic insult was affected at five days. SP-D mRNA was not detected in parenchymal brain cells in either naïve mice or in mice subjected to focal cerebral ischemia. However, SP-D mRNA was detected in middle cerebral artery cells in WT mice and SP-D protein in vascular cells both in normal appearing and ischemic human brain tissue. Measurements of the levels of SP-D and TNF in plasma in mice suggested that levels were unaffected by the ischemic insult. Microglial-leukocyte and astroglial responses were comparable in SP-D KO and WT mice. SP-D synthesis in middle cerebral artery cells is consistent with SP-D conceivably leaking into the infarcted area and affecting local cytokine production

  15. Determinants of Suicide and Accidental or Violent Death in the Australian HIV Observational Database

    PubMed Central

    McManus, Hamish; Petoumenos, Kathy; Franic, Teo; Kelly, Mark D.; Watson, Jo; O’Connor, Catherine C.; Jeanes, Mark; Hoy, Jennifer; Cooper, David A.; Law, Matthew G.

    2014-01-01

    Background Rates of suicide and accidental or violent death remain high in HIV-positive populations despite significantly improved prognosis since the introduction of cART. Methods We conducted a nested case-control study of suicide and accidental or violent death in the Australian HIV Observational Database (AHOD) between January 1999 and March 2012. For each case, 2 controls were matched by clinic, age, sex, mode of exposure and HIV-positive date to adjust for potential confounding by these covariates. Risk of suicide and accidental or violent death was estimated using conditional logistic regression. Results We included 27 cases (17 suicide and 10 violent/accidental death) and 54 controls. All cases were men who have sex with men (MSM) or MSM/ injecting drug use (IDU) mode of exposure. Increased risk was associated with unemployment (Odds Ratio (OR) 5.86, 95% CI: 1.69–20.37), living alone (OR 3.26, 95% CI: 1.06–10.07), suicidal ideation (OR 6.55, 95% CI: 1.70–25.21), and >2 psychiatric/cognitive risk factors (OR 4.99, 95% CI: 1.17–30.65). CD4 cell count of >500 cells/µL (OR 0.25, 95% CI: 0.07–0.87) and HIV-positive date ≥1990 (1990–1999 (OR 0.31, 95% CI: 0.11–0.89), post-2000 (OR 0.08, 95% CI: 0.01–0.84)) were associated with decreased risk. CD4 cell count ≥500 cells/µL remained a significant predictor of reduced risk (OR 0.15, 95% CI: 0.03–0.70) in a multivariate model adjusted for employment status, accommodation status and HIV-positive date. Conclusions After adjustment for psychosocial factors, the immunological status of HIV-positive patients contributed to the risk of suicide and accidental or violent death. The number of psychiatric/cognitive diagnoses contributed to the level of risk but many psychosocial factors were not individually significant. These findings indicate a complex interplay of factors associated with risk of suicide and accidental or violent death. PMID:24586519

  16. Cerebral Autoregulation Is Minimally Influenced by the Superior Cervical Ganglion in Two- Week-Old Lambs, and Absent in Preterm Lambs Immediately Following Delivery

    PubMed Central

    Czynski, Adam J.; Terry, Michael H.; Deming, Douglas D.; Power, Gordon G.; Buchholz, John N.; Blood, Arlin B.

    2013-01-01

    Cerebral vessels in the premature newborn brain are well supplied with adrenergic nerves, stemming from the superior cervical ganglia (SCG), but their role in regulation of blood flow remains uncertain. To test this function twelve premature or two-week-old lambs were instrumented with laser Doppler flow probes in the parietal cortices to measure changes in blood flow during changes in systemic blood pressure and electrical stimulation of the SCG. In lambs delivered prematurely at ∼129 days gestation cerebral perfusion and driving pressure demonstrated a direct linear relationship throughout the physiologic range, indicating lack of autoregulation. In contrast, in lambs two-weeks of age, surgical removal of one SCG resulted in ipsilateral loss of autoregulation during pronounced hypertension. Electrical stimulation of one SCG elicited unilateral increases in cerebral resistance to blood flow in both pre-term and two-week-old lambs, indicating functioning neural pathways in the instrumented, anesthetized lambs. We conclude cerebral autoregulation is non-functional in preterm lambs following cesarean delivery. Adrenergic control of cerebral vascular resistance becomes effective in newborn lambs within two-weeks after birth but SCG-dependent autoregulation is essential only during pronounced hypertension, well above the normal range of blood pressure. PMID:24349256

  17. Microbial induction of vascular pathology in the CNS.

    PubMed

    Kang, Silvia S; McGavern, Dorian B

    2010-09-01

    The central nervous system (CNS) is a finely tuned organ that participates in nearly every aspect of our day-to-day function. Neurons lie at the core of this functional unit and maintain an active dialogue with one another as well as their fellow CNS residents (e.g. astrocytes, oligodendrocytes, microglia). Because of this complex dialogue, it is essential that the CNS milieu be tightly regulated in order to permit uninterrupted and efficient neural chemistry. This is accomplished in part by anatomical barriers that segregate vascular components from the cerebral spinal fluid (CSF) and brain parenchyma. These barriers impede entry of noxious materials and enable the CNS to maintain requisite protein and ionic balances for constant electrochemical signaling. Under homeostatic conditions, the CNS is protected by the presence of specialized endothelium/epithelium, the blood brain barrier (BBB), and the blood-CSF barrier. However, following CNS infection these protective barriers can be comprised, sometimes resulting in severe neurological complications triggered by an imbalance or blockage of neural chemistry. In some instances, these disruptions are severe enough to be fatal. This review focuses on a selection of microbes (both viruses and parasites) that compromise vascular barriers and induce neurological complications upon gaining access to the CNS. Emphasis is placed on CNS diseases that result from a pathogenic interplay between host immune defenses and the invading microbe.

  18. Microbial Induction of Vascular Pathology in the CNS

    PubMed Central

    Kang, Silvia S.

    2016-01-01

    The central nervous system (CNS) is a finely tuned organ that participates in nearly every aspect of our day-to-day function. Neurons lie at the core of this functional unit and maintain an active dialogue with one another as well as their fellow CNS residents (e.g. astrocytes, oligodendrocytes, microglia). Because of this complex dialogue, it is essential that the CNS milieu be tightly regulated in order to permit uninterrupted and efficient neural chemistry. This is accomplished in part by anatomical barriers that segregate vascular components from the cerebral spinal fluid (CSF) and brain parenchyma. These barriers impede entry of noxious materials and enable the CNS to maintain requisite protein and ionic balances for constant electrochemical signaling. Under homeostatic conditions, the CNS is protected by the presence of specialized endothelium/epithelium, the blood brain barrier (BBB), and the blood-CSF barrier. However, following CNS infection these protective barriers can be comprised, sometimes resulting in severe neurological complications triggered by an imbalance or blockage of neural chemistry. In some instances, these disruptions are severe enough to be fatal. This review focuses on a selection of microbes (both viruses and parasites) that compromise vascular barriers and induce neurological complications upon gaining access to the CNS. Emphasis is placed on CNS diseases that result from a pathogenic interplay between host immune defenses and the invading microbe. PMID:20401700

  19. Cerebral vasculopathy after 4-bromo-2,5-dimethoxyphenethylamine ingestion.

    PubMed

    Ambrose, Josiah B; Bennett, Heather D; Lee, Han S; Josephson, S Andrew

    2010-05-01

    4-bromo-2,5-dimethoxyphenethylamine (2C-B) is a designer-drug variant of 3,4-methylenedioxymethamphetamine (ecstasy) whose recreational use has increased significantly over the last 10 years. Neurologic consequences of 2C-B usage are currently unknown. A 43-year-old woman experienced severe headaches within 48 hours of taking liquid 2C-B, after which time she developed progressive encephalopathy and quadraparesis, which did not improve over several months. MRA and cerebral angiogram imaging demonstrated profound vascular abnormalities of large, medium, and small-caliber vessels with subsequent watershed infarction. Brain biopsy and cerebrospinal fluid studies ruled out an inflammatory process. This case demonstrates an idiosyncratic and devastating neurologic response to 2C-B, a recreational drug whose popularity has increased with widespread availability of online guides for its synthesis.

  20. 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- ...