Cerebral Taurine Levels are Associated with Brain Edema and Delayed Cerebral Infarction in Patients with Aneurysmal Subarachnoid Hemorrhage.

Science.gov (United States)

Kofler, Mario; Schiefecker, Alois; Ferger, Boris; Beer, Ronny; Sohm, Florian; Broessner, Gregor; Hackl, Werner; Rhomberg, Paul; Lackner, Peter; Pfausler, Bettina; Thomé, Claudius; Schmutzhard, Erich; Helbok, Raimund

2015-12-01

Cerebral edema and delayed cerebral infarction (DCI) are common complications after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome. Experimental data suggest that the amino acid taurine is released into the brain extracellular space secondary to cytotoxic edema and brain tissue hypoxia, and therefore may serve as a biomarker for secondary brain injury after aSAH. On the other hand, neuroprotective mechanisms of taurine treatment have been described in the experimental setting. We analyzed cerebral taurine levels using high-performance liquid chromatography in the brain extracellular fluid of 25 consecutive aSAH patients with multimodal neuromonitoring including cerebral microdialysis (CMD). Patient characteristics and clinical course were prospectively recorded. Associations with CMD-taurine levels were analyzed using generalized estimating equations with an autoregressive process to handle repeated observations within subjects. CMD-taurine levels were highest in the first days after aSAH (11.2 ± 3.2 µM/l) and significantly decreased over time (p taurine levels compared to those without (Wald = 7.3, df = 1, p taurine supplementation and brain extracellular taurine (p = 0.6). Moreover, a significant correlation with brain extracellular glutamate (r = 0.82, p taurine levels were found in patients with brain edema or DCI after aneurysmal subarachnoid hemorrhage. Its value as a potential biomarker deserves further investigation.

Cerebral autoregulation control of blood flow in the brain

CERN Document Server

Payne, Stephen

2016-01-01

This Brief provides a comprehensive introduction to the control of blood flow in the brain. Beginning with the basic physiology of autoregulation, the author goes on to discuss measurement techniques, mathematical models, methods of analysis, and relevant clinical conditions, all within this single volume. The author draws together this disparate field, and lays the groundwork for future research directions. The text gives an up-to-date review of the state of the art in cerebral autoregulation, which is particularly relevant as cerebral autoregulation moves from the laboratory to the bedside. Cerebral Autoregulation will be useful to researchers in the physical sciences such as mathematical biology, medical physics, and biomedical engineering whose work is concerned with the brain. Researchers in the medical sciences and clinicians dealing with the brain and blood flow, as well as industry professionals developing techniques such as ultrasound, MRI, and CT will also find this Brief of interest.

[Research on brain white matter network in cerebral palsy infant].

Science.gov (United States)

Li, Jun; Yang, Cheng; Wang, Yuanjun; Nie, Shengdong

2017-10-01

Present study used diffusion tensor image and tractography to construct brain white matter networks of 15 cerebral palsy infants and 30 healthy infants that matched for age and gender. After white matter network analysis, we found that both cerebral palsy and healthy infants had a small-world topology in white matter network, but cerebral palsy infants exhibited abnormal topological organization: increased shortest path length but decreased normalize clustering coefficient, global efficiency and local efficiency. Furthermore, we also found that white matter network hub regions were located in the left cuneus, precuneus, and left posterior cingulate gyrus. However, some abnormal nodes existed in the frontal, temporal, occipital and parietal lobes of cerebral palsy infants. These results indicated that the white matter networks for cerebral palsy infants were disrupted, which was consistent with previous studies about the abnormal brain white matter areas. This work could help us further study the pathogenesis of cerebral palsy infants.

Blood-brain barrier dysfunction and amyloid precursor protein accumulation in microvascular compartment following ischemia-reperfusion brain injury with 1-year survival.

Science.gov (United States)

Pluta, R

2003-01-01

This study examined the late microvascular consequences of brain ischemia due to cardiac arrest in rats. In reacted vibratome sections scattered foci of extravasated horseradish peroxidase were noted throughout the brain and did not appear to be restricted to any specific area of brain. Ultrastructural investigation of leaky sites frequently presented platelets adhering to the endothelium of venules and capillaries. Endothelial cells demonstrated pathological changes with evidence of perivascular astrocytic swelling. At the same time, we noted C-terminal of amyloid precursor protein/beta-amyloid peptide (CAPP/betaA) deposits in cerebral blood vessels, with a halo of CAPP/betaA immunoreactivity in the surrounding parenchyma suggested diffusion of CAPP/betaA out of the vascular compartment. Changes predominated in the hippocampus, cerebral and entorhinal cortex, corpus callosum, thalamus, basal ganglia and around the lateral ventricles. These data implicate delayed abnormal endothelial function of vessels following ischemia-reperfusion brain injury as a primary event in the pathogenesis of the recurrent cerebral infarction.

Fused cerebral organoids model interactions between brain regions.

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Bagley, Joshua A; Reumann, Daniel; Bian, Shan; Lévi-Strauss, Julie; Knoblich, Juergen A

2017-07-01

Human brain development involves complex interactions between different regions, including long-distance neuronal migration or formation of major axonal tracts. Different brain regions can be cultured in vitro within 3D cerebral organoids, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a coculture method combining brain regions of choice within one organoid tissue. By fusing organoids of dorsal and ventral forebrain identities, we generate a dorsal-ventral axis. Using fluorescent reporters, we demonstrate CXCR4-dependent GABAergic interneuron migration from ventral to dorsal forebrain and describe methodology for time-lapse imaging of human interneuron migration. Our results demonstrate that cerebral organoid fusion cultures can model complex interactions between different brain regions. Combined with reprogramming technology, fusions should offer researchers the possibility to analyze complex neurodevelopmental defects using cells from neurological disease patients and to test potential therapeutic compounds.

Utility of evaluation of cerebral circulation for brain-oriented intensive care

International Nuclear Information System (INIS)

Honda, Mitsuru; Sakata, Yoshihito; Ichibayashi, Ryo; Yoshihara, Katsunori; Noguchi, Yoshitaka; Seiki, Yoshikatsu; Machida, Keiichi; Sase, Shigeru

2007-01-01

Severe traumatic brain injury is widely known to cause a dynamic change in CBF. Especially, a decrease in cerebral blood flow (CBF) has been reported. In the present study we measured CBF, mean transit time (MTT) and cerebral blood volume (CBV). Our purpose was to investigate the possibility to estimate the outcome and severity by using these physiological parameters and the utility of cerebral circulation evaluation for brain-oriented intensive care. In 54 patients with traumatic brain injury, Xe-CT and perfusion CT were performed at the same time in the phase II (Day 1-3). We measured CBF by using Xe-CT and MTT by using Perfusion CT and calculated CBV by using AZ-7000 W 98 computer system. The results were correlated with the outcome and the values of CBF and MTT. Significant differences in CBF and MTT were found between a favorable outcome group and a poor outcome group. We could evaluate the condition of cerebral circulation for patients with traumatic brain injury by analyzing the values of CBF and MTT. In conclusion, these parameters can be helpfull for the optimal management and outcome improvement for the patients with severe traumatic brain injury. (author)

microRNA in Cerebral Spinal Fluid as Biomarkers of Alzheimer’s Disease Risk After Brain Injury

Science.gov (United States)

2017-08-01

AWARD NUMBER: W81XWH-15-1-0318 TITLE: microRNA in Cerebral Spinal Fluid as Biomarkers of Alzheimer’s Disease Risk After Brain Injury...After Brain Injury 5b. GRANT NUMBER AZ14046 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) J 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER...responses to brain injury that precede, and likely drive, changes in protein expression that lead to the development of AD. We have additional preliminary

Automated analysis for early signs of cerebral infarctions on brain X-ray CT images

International Nuclear Information System (INIS)

Oshima, Kazuki; Hara, Takeshi; Zhou, X.; Muramatsu, Chisako; Fujita, Hiroshi; Sakashita, Keiji

2010-01-01

t-PA (tissue plasminogen activator) thrombolysis is an effective clinical treatment for the acute cerebral infarction by breakdown to blood clots. However there is a risk of hemorrhage with its use. The guideline of the treatment is denying cerebral hemorrhage and widespread Early CT sign (ECS) on CT images. In this study, we analyzed the CT value of normal brain and ECS with normal brain model by comparing patient brain CT scan with a statistical normal model. Our method has constructed normal brain models consisted of 60 normal brain X-ray CT images. We calculated Z-score based on statistical model for 16 cases of cerebral infarction with ECS, 3 cases of cerebral infarction without ECS, and 25 cases of normal brain. The results of statistical analysis showed that there was a statistically significant difference between control and abnormal groups. This result implied that the automated detection scheme for ECS by using Z-score would be a possible application for brain computer-aided diagnosis (CAD). (author)

Volatile anesthetics influence blood-brain barrier integrity by modulation of tight junction protein expression in traumatic brain injury.

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Serge C Thal

Full Text Available Disruption of the blood-brain barrier (BBB results in cerebral edema formation, which is a major cause for high mortality after traumatic brain injury (TBI. As anesthetic care is mandatory in patients suffering from severe TBI it may be important to elucidate the effect of different anesthetics on cerebral edema formation. Tight junction proteins (TJ such as zonula occludens-1 (ZO-1 and claudin-5 (cl5 play a central role for BBB stability. First, the influence of the volatile anesthetics sevoflurane and isoflurane on in-vitro BBB integrity was investigated by quantification of the electrical resistance (TEER in murine brain endothelial monolayers and neurovascular co-cultures of the BBB. Secondly brain edema and TJ expression of ZO-1 and cl5 were measured in-vivo after exposure towards volatile anesthetics in native mice and after controlled cortical impact (CCI. In in-vitro endothelial monocultures, both anesthetics significantly reduced TEER within 24 hours after exposure. In BBB co-cultures mimicking the neurovascular unit (NVU volatile anesthetics had no impact on TEER. In healthy mice, anesthesia did not influence brain water content and TJ expression, while 24 hours after CCI brain water content increased significantly stronger with isoflurane compared to sevoflurane. In line with the brain edema data, ZO-1 expression was significantly higher in sevoflurane compared to isoflurane exposed CCI animals. Immunohistochemical analyses revealed disruption of ZO-1 at the cerebrovascular level, while cl5 was less affected in the pericontusional area. The study demonstrates that anesthetics influence brain edema formation after experimental TBI. This effect may be attributed to modulation of BBB permeability by differential TJ protein expression. Therefore, selection of anesthetics may influence the barrier function and introduce a strong bias in experimental research on pathophysiology of BBB dysfunction. Future research is required to investigate

Double-tracer autoradiographic study of protein synthesis and glucose consumption in rats with focal cerebral ischemia

DEFF Research Database (Denmark)

Christensen, Thomas; Balchen, T; Bruhn, T

1999-01-01

A double-tracer autoradiographic method for simultaneous measurement of regional glucose utilization (rCMRglc) and regional protein synthesis (PS) in consecutive brain sections is described and applied to study the metabolism of the ischemic penumbra 2 h after occlusion of the middle cerebral...... artery (MCAO) in rats. In halothane anesthesia, the left middle cerebral artery was permanently occluded. Two hours after MCAO an i.v. bolus injection of 14C-deoxyglucose and 3H-leucine was given and circulated for 45 min. Two sets of brain sections were processed for quantitative autoradiography....... Neighboring brain sections exposed an X-ray film (3H-insensitive), and a 3H-sensitive for determination of rCMRglc and PS, respectively. Sections for PS determination were washed in trichloroacetic acid (TCA) prior to film exposure in order to remove 14C-deoxyglucose and unincorporated 3H-leucine. Regional...

A Stepwise Approach: Decreasing Infection in Deep Brain Stimulation for Childhood Dystonic Cerebral Palsy.

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Johans, Stephen J; Swong, Kevin N; Hofler, Ryan C; Anderson, Douglas E

2017-09-01

Dystonia is a movement disorder characterized by involuntary muscle contractions, which cause twisting movements or abnormal postures. Deep brain stimulation has been used to improve the quality of life for secondary dystonia caused by cerebral palsy. Despite being a viable treatment option for childhood dystonic cerebral palsy, deep brain stimulation is associated with a high rate of infection in children. The authors present a small series of patients with dystonic cerebral palsy who underwent a stepwise approach for bilateral globus pallidus interna deep brain stimulation placement in order to decrease the rate of infection. Four children with dystonic cerebral palsy who underwent a total of 13 surgical procedures (electrode and battery placement) were identified via a retrospective review. There were zero postoperative infections. Using a multistaged surgical plan for pediatric patients with dystonic cerebral palsy undergoing deep brain stimulation may help to reduce the risk of infection.

Volumetric Magnetic Resonance Imaging Study of Brain and Cerebellum in Children with Cerebral Palsy.

Science.gov (United States)

Kułak, Piotr; Maciorkowska, Elżbieta; Gościk, Elżbieta

2016-01-01

Introduction. Quantitative magnetic resonance imaging (MRI) studies are rarely used in the diagnosis of patients with cerebral palsy. The aim of present study was to assess the relationships between the volumetric MRI and clinical findings in children with cerebral palsy compared to control subjects. Materials and Methods. Eighty-two children with cerebral palsy and 90 age- and sex-matched healthy controls were collected. Results. The dominant changes identified on MRI scans in children with cerebral palsy were periventricular leukomalacia (42%) and posthemorrhagic hydrocephalus (21%). The total brain and cerebellum volumes in children with cerebral palsy were significantly reduced in comparison to controls. Significant grey matter volume reduction was found in the total brain in children with cerebral palsy compared with the control subjects. Positive correlations between the age of the children of both groups and the grey matter volumes in the total brain were found. Negative relationship between width of third ventricle and speech development was found in the patients. Positive correlations were noted between the ventricles enlargement and motor dysfunction and mental retardation in children with cerebral palsy. Conclusions. By using the voxel-based morphometry, the total brain, cerebellum, and grey matter volumes were significantly reduced in children with cerebral palsy.

Exercise induces the release of heat shock protein 72 from the human brain in vivo

OpenAIRE

Lancaster, G. I.; Møller, K.; Nielsen, B.; Secher, N. H.; Febbraio, M. A.; Nybo, L.

2004-01-01

The present study tested the hypothesis that in response to physical stress the human brain has the capacity to release heat shock protein 72 (Hsp72) in vivo. Therefore, 6 humans (males) cycled for 180 minutes at 60% of their maximal oxygen uptake, and the cerebral Hsp72 response was determined on the basis of the internal jugular venous to arterial difference and global cerebral blood flow. At rest, there was a net balance of Hsp72 across the brain, but after 180 minutes of exercise, we were...

Correlation of glucose metabolism in brain cells and brain morphological changes with clinical typing in children with cerebral palsy

Institute of Scientific and Technical Information of China (English)

Qiongxiang Zhai; Huixian Qiao; Jiqing Liu

2006-01-01

BACKGROUND:It is widely known that fluorino-18-fluorodeoxyglucose positron emission tomography(18F-FDG PET)is commonly used to evaluate and diagnose epilepsy;however,whether it is beneficial to understand functional metabolism of bra in cells so as to reflect injured site and degree of brain cells or not should be studied further.OBJECTIVE:To evaluate the correlation between glucose metabolism and clinical typling as well as the conelation between active function of brain cells and degree of brain injury among children with cerbral palsy with 18F-FDG PET and MRI and compare the results of them.DESIGN:Case analysis.SETTING:Department of Pediatrics,People's Hospital of Guangdong Province.PARTICIPANTS:A total of 31 children with cerebral palsy were selected from Out-patient Clinic and In-patient Department of People's Hospital of Guangdong Province from July 2001 to August 2004.Based on clinical criteria of cerebral palsy,patients were classified into spasm(n=10),gradual movement(n=4),mixed type(n =13)and ataxia(n=4).There were 18 boys and 13 girls aged from 10 months to 4 years.All of them were met the diagnostic criteria of cerebral palsy and all parents of them were told the facts.Exclusion cdteria:Patients who had cerebral palsy caused by genetic metabolism disease were excluded.METHODS:①All children accepted MRI examination after hospitalization with Philips Acs NT 15T superconductling magnetic resonance scanner.②All children were fasted for 4 hours.And then,PET image of brain was collected based on T+EID type.If obvious hypermetabolism or hypometabolism region successively occurred on two layers, the image was regarded as abnormality. ③Different correlations of various abnormal greups of MRI and vadous types of cerebral palsy with PET image were compared and analyzed with Erusal-Willas rank sum test.MAIN OUTCOME MEASURES:①Results of 18F-FDG PET;②Results of MRI examination;③Correlation of variously abnormal groups of MRI and various types of cerebral

Acupuncture inhibits Notch1 and Hes1 protein expression in the basal ganglia of rats with cerebral hemorrhage

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Wei Zou

2015-01-01

Full Text Available Notch pathway activation maintains neural stem cells in a proliferating state and increases nerve repair capacity. To date, studies have rarely focused on changes or damage to signal transduction pathways during cerebral hemorrhage. Here, we examined the effect of acupuncture in a rat model of cerebral hemorrhage. We examined four groups: in the control group, rats received no treatment. In the model group, cerebral hemorrhage models were established by infusing non-heparinized blood into the brain. In the acupuncture group, modeled rats had Baihui (DU20 and Qubin (GB7 acupoints treated once a day for 30 minutes. In the DAPT group, modeled rats had 0.15 μg/mL DAPT solution (10 mL infused into the brain. Immunohistochemistry and western blot results showed that acupuncture effectively inhibits Notch1 and Hes1 protein expression in rat basal ganglia. These inhibitory effects were identical to DAPT, a Notch signaling pathway inhibitor. Our results suggest that acupuncture has a neuroprotective effect on cerebral hemorrhage by inhibiting Notch-Hes signaling pathway transduction in rat basal ganglia after cerebral hemorrhage.

Measurement of local cerebral protein synthesis in vivo: influence of recycling of amino acids derived from protein degradation

International Nuclear Information System (INIS)

Smith, C.B.; Deibler, G.E.; Eng, N.; Schmidt, K.; Sokoloff, L.

1988-01-01

A quantitative autoradiographic method for the determination of local rates of protein synthesis in brain in vivo is being developed. The method employs L-[1- 14 C]leucine as the radiolabeled tracer. A comprehensive model has been designed that takes into account intracellular and extracellular spaces, intracellular compartmentation of leucine, and the possibility of recycling of unlabeled leucine derived from steady-state degradation of protein into the precursor pool for protein synthesis. We have evaluated the degree of recycling by measuring the ratio of the steady-state precursor pool distribution space for labeled leucine to that of unlabeled leucine. The values obtained were 0.58 in whole brain and 0.47 in liver. These results indicate that there is significant recycling of unlabeled amino acids derived from steady-state protein degradation in both tissues. Any method for the determination of rates of cerebral protein synthesis in vivo with labeled tracers that depends on estimation of precursor pool specific activity in tissue from measurements in plasma must take this recycling into account

Lycium barbarum Extracts Protect the Brain from Blood-Brain Barrier Disruption and Cerebral Edema in Experimental Stroke

Science.gov (United States)

Yang, Di; Li, Suk-Yee; Yeung, Chung-Man; Chang, Raymond Chuen-Chung; So, Kwok-Fai; Wong, David; Lo, Amy C. Y.

2012-01-01

Background and Purpose Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model. Methods C57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO. Results LBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains. Conclusions Seven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke. PMID:22438957

SHORT-TERM MEMORY IS INDEPENDENT OF BRAIN PROTEIN SYNTHESIS

Energy Technology Data Exchange (ETDEWEB)

Davis, Hasker P.; Rosenzweig, Mark R.; Jones, Oliver W.

1980-09-01

Male Swiss albino CD-1 mice given a single injection of a cerebral protein synthesis inhibitor, anisomycin (ANI) (1 mg/animal), 20 min prior to single trial passive avoidance training demonstrated impaired retention at tests given 3 hr, 6 hr, 1 day, and 7 days after training. Retention was not significantly different from saline controls when tests were given 0.5 or 1.5 hr after training. Prolonging inhibition of brain protein synthesis by giving either 1 or 2 additional injections of ANI 2 or 2 and 4 hr after training did not prolong short-term retention performance. The temporal development of impaired retention in ANI treated mice could not be accounted for by drug dosage, duration of protein synthesis inhibition, or nonspecific sickness at test. In contrast to the suggestion that protein synthesis inhibition prolongs short-term memory (Quinton, 1978), the results of this experiment indicate that short-term memory is not prolonged by antibiotic drugs that inhibit cerebral protein synthesis. All evidence seems consistent with the hypothesis that short-term memory is protein synthesis independent and that the establishment of long-term memory depends upon protein synthesis during or shortly after training. Evidence for a role of protein synthesis in memory maintenance is discussed.

Long-term evolution of cerebral hemodynamics after brain irradiation in the rat

International Nuclear Information System (INIS)

Keyeux, A.; Ochrymowicz-Bemelmans, D.

1985-01-01

Long-term evolution of radioisotope indices, evaluating respectively the cerebral blood flow (CBF), the cerebral blood volume (CBV) and the cephalic specific distribution space of iodoantipyrine (ΔIAP) of rat, was studied after brain irradiation at 20 Gy. Radioinduced hemodynamic alterations evidenced by this approach are biphasic and support the prominent role of circulation impairment in the genesis of delayed brain radionecrosis [fr

Neuroprotective effect of TAT-14-3-3ε fusion protein against cerebral ischemia/reperfusion injury in rats.

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Yuanjun Zhu

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

Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

Science.gov (United States)

Wattanathorn, Jintanaporn; Jittiwat, Jinatta; Tongun, Terdthai; Muchimapura, Supaporn; Ingkaninan, Kornkanok

2011-01-01

Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia. PMID:21197427

Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

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Jintanaporn Wattanathorn

2011-01-01

Full Text Available Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO. Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GSH-Px in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.

Cerebral Metabolism and the Role of Glucose Control in Acute Traumatic Brain Injury.

Science.gov (United States)

Buitrago Blanco, Manuel M; Prashant, Giyarpuram N; Vespa, Paul M

2016-10-01

This article reviews key concepts of cerebral glucose metabolism, neurologic outcomes in clinical trials, the biology of the neurovascular unit and its involvement in secondary brain injury after traumatic brain insults, and current scientific and clinical data that demonstrate a better understanding of the biology of metabolic dysfunction in the brain, a concept now known as cerebral metabolic energy crisis. The use of neuromonitoring techniques to better understand the pathophysiology of the metabolic crisis is reviewed and a model that summarizes the triphasic view of cerebral metabolic disturbance supported by existing scientific data is outlined. The evidence is summarized and a template for future research provided. Copyright © 2016 Elsevier Inc. All rights reserved.

Immunochemical characterization of the brain glutamate binding protein

International Nuclear Information System (INIS)

Roy, S.

1986-01-01

A glutamate binding protein (GBP) was purified from bovine and rat brain to near homogeneity. Polyclonal antibodies were raised against this protein. An enzyme-linked-immunosorbent-assay was used to quantify and determine the specificity of the antibody response. The antibodies were shown to strongly react with bovine brain GBP and the analogous protein from rat brain. The antibodies did not show any crossreactivity with the glutamate metabolizing enzymes, glutamate dehydrogenase, glutamine synthetase and glutamyl transpeptidase, however it crossreacted moderately with glutamate decarboxylase. The antibodies were also used to define the possible physiologic activity of GBP in synaptic membranes. The antibodies were shown: (i) to inhibit the excitatory amino-acid stimulation of thiocyanate (SCN)flux, (ii) had no effect on transport of L-Glutamic acid across the synaptic membrane, and (iii) had no effect on the depolarization-induced release of L-glutamate. When the anti-GBP antibodies were used to localize and quantify the GBP distribution in various subcellular fractions and in brain tissue samples, it was found that the hippocampus had the highest immunoreactivity followed by the cerebral cortex, cerebellar cortex and caudate-putamen. The distribution of immunoreactivity in the subcellular fraction were as follows: synaptic membranes > crude mitochondrial fraction > homogenate > myelin. In conclusion these studies suggest that: (a) the rat brain GBP and the bovine brain GBP are immunologically homologous protein, (b) there are no structural similarities between the GBP and the glutamate metabolizing enzymes with the exception of glutamate decarboxylase and (c) the subcellular and regional distribution of the GBP immunoreactivity followed a similar pattern as observed for L-[ 3 H]-binding

Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia

Science.gov (United States)

Kim, Jae Hwan; Lee, Yong Woo; Park, Kyung Ah; Lee, Won Taek; Lee, Jong Eun

2010-01-01

Brain edema is frequently shown after cerebral ischemia. It is an expansion of brain volume because of increasing water content in brain. It causes to increase mortality after stroke. Agmatine, formed by the decarboxylation of -arginine by arginine decarboxylase, has been shown to be neuroprotective in trauma and ischemia models. The purpose of this study was to investigate the effect of agmatine for brain edema in ischemic brain damage and to evaluate the expression of aquaporins (AQPs). Results showed that agmatine significantly reduced brain swelling volume 22 h after 2 h middle cerebral artery occlusion in mice. Water content in brain tissue was clearly decreased 24 h after ischemic injury by agmatine treatment. Blood–brain barrier (BBB) disruption was diminished with agmatine than without. The expressions of AQPs-1 and -9 were well correlated with brain edema as water channels, were significantly decreased by agmatine treatment. It can thus be suggested that agmatine could attenuate brain edema by limitting BBB disruption and blocking the accumulation of brain water content through lessening the expression of AQP-1 after cerebral ischemia. PMID:20029450

Cerebral circulation, metabolism, and blood-brain barrier of rats in hypocapnic hypoxia

International Nuclear Information System (INIS)

Beck, T.; Krieglstein, J.

1987-01-01

The effects of hypoxic hypoxia on physiological variables, cerebral circulation, cerebral metabolism, and blood-brain barrier were investigated in conscious, spontaneously breathing rats by exposing them to an atmosphere containing 7% O 2 . Hypoxia affected a marked hypotension, hypocapnia and alkalosis. Cortical tissue high-energy phosphates and glucose content were not affected by hypoxia, glucose 6-phosphate lactate, and pyruvate levels were significantly increased. Blood-brain barrier permeability, regional brain glucose content and lumped constant were not changed by hypoxia. Local cerebral glucose utilization (LCGU) rose by 40-70% of control values in gray matter and by 80-90% in white matter. Under hypoxia, columns of increased and decreased LCGU and were detectable in cortical gray matter. Color-coded [ 14 C]2-deoxy-D-glucose autoradiograms of rat brain are shown. Local cerebral blood flow (LCBF) increased by 50-90% in gray matter and by up to 180% in white matter. Coupling between LCGU and LCBF in hypoxia remained unchanged. The data suggests a stimulation of glycolysis, increased glucose transport into the cell, and increased hexokinase activity. The physiological response of gray and white matter to hypoxia obviously differs. Uncoupling of the relation between LCGU and LCBF does not occur

Suppressing Receptor-Interacting Protein 140: a New Sight for Salidroside to Treat Cerebral Ischemia.

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Chen, Tong; Ma, Zhanqiang; Zhu, Lingpeng; Jiang, Wenjiao; Wei, Tingting; Zhou, Rui; Luo, Fen; Zhang, Kai; Fu, Qiang; Ma, Chunhua; Yan, Tianhua

2016-11-01

The purpose of the current study was to detect the effect of salidroside (Sal) on cerebral ischemia and explore its potential mechanism. Middle cerebral artery occlusion (MCAO) was performed to investigate the effects of Sal on cerebral ischemia. The rats were randomly divided into five groups: sham group, vehicle group, clopidogrel (7.5 mg/kg) group, Sal (20 mg/kg) group, and Sal (40 mg/kg) group. SH-SY5Y cells were exposed to ischemia-reperfusion (I/R) injury to verify the protective effect of Sal in vitro. We also built the stable receptor-interacting protein 140 (RIP140)-overexpressing SH-SY5Y cells. The results showed that Sal significantly reduces brain infarct size and cerebral edema. Sal could effectively decrease the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in serum of the MCAO rats and supernatant of I/R-induced SH-SY5Y cells. Immunohistochemical and Western blot results demonstrated that Sal inhibited RIP140-mediated inflammation and apoptosis in the MCAO rats and SH-SY5Y cells. In addition, we further confirmed that RIP140/NF-κB signaling plays a crucial role by evaluating the protein expression in RIP140-overexpressing SH-SY5Y cells. Our findings suggested that Sal could be used as an effective neuroprotective agent for cerebral ischemia due to its significant effect on preventing neuronal cell injury after cerebral ischemia both in vivo and in vitro by the inhibitions of RIP140-mediated inflammation and apoptosis.

Cerebral Vascular Injury in Traumatic Brain Injury.

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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.

Development of a cerebral circulation model for the automatic control of brain physiology.

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Utsuki, T

2015-01-01

In various clinical guidelines of brain injury, intracranial pressure (ICP), cerebral blood flow (CBF) and brain temperature (BT) are essential targets for precise management for brain resuscitation. In addition, the integrated automatic control of BT, ICP, and CBF is required for improving therapeutic effects and reducing medical costs and staff burden. Thus, a new model of cerebral circulation was developed in this study for integrative automatic control. With this model, the CBF and cerebral perfusion pressure of a normal adult male were regionally calculated according to cerebrovascular structure, blood viscosity, blood distribution, CBF autoregulation, and ICP. The analysis results were consistent with physiological knowledge already obtained with conventional studies. Therefore, the developed model is potentially available for the integrative control of the physiological state of the brain as a reference model of an automatic control system, or as a controlled object in various control simulations.

The Effects of Blast Exposure on Protein Deimination in the Brain

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Peter J. Attilio

2017-01-01

Full Text Available Oxidative stress and calcium excitotoxicity are hallmarks of traumatic brain injury (TBI. While these early disruptions may be corrected over a relatively short period of time, long-lasting consequences of TBI including impaired cognition and mood imbalances can persist for years, even in the absence of any evidence of overt injury based on neuroimaging. This investigation examined the possibility that disordered protein deimination occurs as a result of TBI and may thus contribute to the long-term pathologies of TBI. Protein deimination is a calcium-activated, posttranslational modification implicated in the autoimmune diseases rheumatoid arthritis and multiple sclerosis, where aberrant deimination creates antigenic epitopes that elicit an autoimmune attack. The present study utilized proteomic analyses to show that blast TBI alters the deimination status of proteins in the porcine cerebral cortex. The affected proteins represent a small subset of the entire brain proteome and include glial fibrillary acidic protein and vimentin, proteins reported to be involved in autoimmune-based pathologies. The data also indicate that blast injury is associated with an increase in immunoglobulins in the brain, possibly representing autoantibodies directed against novel protein epitopes. These findings indicate that aberrant protein deimination is a biomarker for blast TBI and may therefore underlie chronic neuropathologies of head injury.

Cerebral blood flow of the non-affected brain in patients with malignant brain tumors as studied by SPECT

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Araki, Yuzo; Imao, Yukinori; Hirata, Toshifumi; Ando, Takashi; Sakai, Noboru; Yamada, Hiroshi

1990-01-01

In 40 patients (age range, 20-69 years) receiving radiation and chemotherapy for brain tumors, the mean cerebral blood flow (mCBF) in the non-affected area has been examined by single photon emission CT (SPECT) with Xe-133. Forty volunteers (age range, 25-82 years) served as controls. Although mCBF during external irradiation was transiently increased, it was significantly decreased at 3 months after beginning of external irradiation compared with that in the control group. Factors responsible for the decrease in mCBF were radiation doses, lesion volume, the degree of cerebral atrophy, and age; this was more pronounced when chemotherapy such as ACNU was combined with radiation. A decreased mCBF was independent of intraoperative radiation combined with external radiation and either local or whole brain irradiation. SPECT with Xe-133 was useful in determining minute changes in cerebral blood flow that precedes parenchymal brain damage. (N.K.)

Abnormalities of Microcirculation and Intracranial and Cerebral Perfusion Pressures in Severe Brain Injury

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Yu. A. Churlyaev

2008-01-01

Full Text Available Objective: to evaluate the states of microcirculation, cerebral perfusion intracranial pressures in patients with isolated severe brain injury (SBI and to determine their possible relationships. Subjects and methods. 148 studies were performed in 16 victims with SBI. According to the outcome of brain traumatic disease, the patients were divided into two groups: 1 those who had a good outcome (n=8 and 2 those who had a fatal outcome (n=8. Microcirculation was examined by skin laser Doppler flowmetry using a LAKK-01 capillary blood flow laser analyzer (LAZMA Research-and-Production Association, Russian Federation. All the victims underwent surgical interventions to remove epi-, subdural, and intracerebral hematomas. A Codman subdural/intraparenchymatous intracranial pressure (ICD sensor (Johnson & Johnson, United Kingdom was intraoperatively inserted in the victims. Cerebral perfusion pressure (CPP was calculated using the generally accepted formula: CPP = MBP (mean blood pressure — ICD. ICD, CPP, and microcirculation were studied on postoperative days 1, 3, 5, and 7. Their values were recorded simultaneously. Ninety and 58 studies were conducted in the group of patients with good and fatal outcomes, respectively. Results. No correlation between the changes in MBP, ICD, and microcirculatory parameters suggested that the value of ICD was determined by the nature of brain damage and it was the leading and determining indicator in the diagnosis and treatment of secondary cerebral lesions. The amplitude of low-frequency fluctuations directly correlated with ICD, which indicated that they might be used to evaluate cerebral perfusion and impaired cerebral circulation indirectly in victims with severe brain injury. Conclusion. The laser Doppler flowmetric technique makes it possible not only to qualitatively, but also quantitatively determine changes in the tissue blood flow system in severe brain injury. With this technique, both the local and central

Cerebral microdialysis for protein biomarker monitoring in the neurointensive care setting

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Lars Tomas Hillered

2014-12-01

Full Text Available Cerebral microdialysis (MD was introduced as a neurochemical monitoring tool in the early 1990s and is currently well established for the sampling of low molecular weight biomarkers of energy metabolic perturbation and cellular distress in the neurointensive care (NIC setting. There is now a growing interest in MD for intracerebral sampling of protein biomarkers of secondary injury mechanisms in acute traumatic and neurovascular brain injury in the NIC community. The initial enthusiasm over the opportunity to sample protein biomarkers with high molecular weight cut-off (MWCO MD catheters has dampened somewhat with the emerging realization of inherent problems with this methodology including protein adhesion, protein-protein interaction and biofouling, leading to unstable MD catheter performance (i.e. fluid recovery and extraction efficiency. This review will focus on the results of a multidisciplinary collaborative effort, within the Uppsala Berzelii Centre for Neurodiagnostics during the past several years, to study the features of the complex process of high MWCO MD for protein biomarkers. This research has led to new methodology showing robust in vivo performance with optimized fluid recovery and improved extraction efficiency, allowing for more accurate biomarker monitoring. In combination with evolving analytical methodology allowing for multiplex biomarker analysis in ultra-small MD samples a new opportunity opens up for high-resolution temporal mapping of secondary injury cascades, such as neuroinflammation and other cell injury reactions directly in the injured human brain. Such data may provide an important basis for improved characterization of complex injuries, e.g. traumatic and neurovascular brain injury, and help in defining targets and treatment windows for neuroprotective drug development

Expression and deposition of basement membrane proteins by brain capillary endothelial cells in a primary murine model of the blood-brain barrier

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Thomsen, Maj Schneider; Birkelund, Svend; Larsen, Annette Burkhart

2016-01-01

The blood-brain barrier (BBB) represents the interface between the blood and the brain parenchyma and consists of endothelial cells which are tightly sealed together by tight junction proteins. The endothelial cells are in addition supported by pericytes, which are embedded in the vascular basement...... of the present study was to create four different in vitro constructs of the murine BBB to characterise if the expression and secretion of basement membrane proteins by the murine brain capillary endothelial cells (mBCECs) was affected by co-culturing with pericytes, mixed glial cells, or both. Primary m......BCECs and pericytes were isolated from brains of adult mice. Mixed glial cells were prepared from cerebral cortices of newborn mice. The mBCECs were grown as mono-culture, or co-cultured with pericytes, mixed glial cells, or both. To study the expression of basement membrane proteins RT-qPCR, mass spectrometry...

Characterization of the regulatory subunit from brain cyclic AMP-dependent protein kinase II

International Nuclear Information System (INIS)

Stein, J.C.

1985-01-01

Tryptic peptides derived from the regulatory subunits of brain and heart cAMP-dependent protein kinase II were mapped by reverse phase HPLC. At 280 nm, 15 unique peptides were found only in the heart RII digest, while 5 other peptides were obtained only from brain RII. At 210 nm, 13 brain-RII specific and 15 heart-RII specific tryptic peptides were identified and resolved. Two-dimensional mapping analyses revealed that several 37 P-labeled tryptic fragments derived from the autophosphorylation and the photoaffinity labeled cAMP-binding sites of brain RII were separate and distinct from the 32 P-peptides isolated from similarly treated heart RII. The tryptic phosphopeptide containing the autophosphorylation site in brain RII was purified. The sequence and phosphorylation site is: Arg-Ala-Ser(P)-Val-Cys-Ala-Glu-Ala-Tyr-Asn-Pro-Asp-Glu-Glu-Glu-Asp-Asp-Ala-Glu. Astrocytes and neurons exhibit high levels of the brain RII enzyme, while oligodendrocytes contain the heart RII enzyme. Monoclonal antibodies to bovine cerebral cortex RII were made and characterized. The antibodies elucidated a subtle difference between membrane-associated and cytosolic RII from cerebral cortex

Breaking down brain barrier breaches in cerebral malaria

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Petersen, Jens E V; Lavstsen, Thomas; Craig, Alister

2016-01-01

Recent findings have linked brain swelling to death in cerebral malaria (CM). These observations have prompted a number of investigations into the mechanisms of this pathology with the goal of identifying potential therapeutic targets. In this issue of the JCI, Gallego-Delgado and colleagues...

Utility of cerebral circulation evaluation in acute traumatic brain injuries

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Honda, Mitsuru; Sakata, Yoshihito; Haga, Daisuke; Nomoto, Jun; Noguchi, Yoshitaka; Seiki, Yoshikatsu; Machida, Keiichi; Sase, Shigeru

2007-01-01

Severe traumatic brain injury (TBI) is well-known to cause dynamic changes in cerebral blood flow (CBF). Specifically, TBI has been reported to cause decreases in cerebral blood flow (CBF). In this study, we measured CBF, mean transit time (MTT) and cerebral blood volume (CBV) after TBI. Our purpose was investigate the possibility of assessing TBI outcome and severity with these physiological parameters, and the clinical utility of cerebral circulation evaluation for brain-oriented intensive care. In 37 patients with TBI, xenon-enhanced CT (Xe-CT) and perfusion CT were performed on days 1-3 post-event (phase II). We measured CBF using Xe-CT and MTT by Perfusion CT and calculated CBV using an AZ-7000W98 computer system. Relative intra cranicol pressure (ICP) and CBF showed significant negative correlations. Relative ICP and MTT showed significant positive correlations. Outcomes, correlated with valuse of CBF and MIT. Significant differences in CBF and MTT were found between favorable outcome group (good recovery (GR) and moderate disability (MD)) and poor outcome group (severe disability (SD), vegetative state (VS), and dead (D)). We could estimate the outcome of patients after TBI by analyzing values of CBF and MTT with a probability of 74%. We evaluated cerebral circulation status in patients with TBI by CBF and MTT. These tests can help to optimize management and improve outcome in patients with severe TBI. (author)

Neuroenergetic Response to Prolonged Cerebral Glucose Depletion after Severe Brain Injury and the Role of Lactate.

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Patet, Camille; Quintard, Hervé; Suys, Tamarah; Bloch, Jocelyne; Daniel, Roy T; Pellerin, Luc; Magistretti, Pierre J; Oddo, Mauro

2015-10-15

Lactate may represent a supplemental fuel for the brain. We examined cerebral lactate metabolism during prolonged brain glucose depletion (GD) in acute brain injury (ABI) patients monitored with cerebral microdialysis (CMD). Sixty episodes of GD (defined as spontaneous decreases of CMD glucose from normal to low [brain oxygen and blood lactate remained normal. Dynamics of lactate and glucose supply during GD were further studied by analyzing the relationships between blood and CMD samples. There was a strong correlation between blood and brain lactate when LPR was normal (r = 0.56; p 25. The correlation between blood and brain glucose also decreased from r = 0.62 to r = 0.45. These findings in ABI patients suggest increased cerebral lactate delivery in the absence of brain hypoxia when glucose availability is limited and support the concept that lactate acts as alternative fuel.

The selective value of computed tomography of the brain in Cerebritis due to systemic lupus erythematosus

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Gaylis, N.B.; Altman, R.D.; Ostrov, S.; Quencer, R.

1982-01-01

Systemic lupus erythematosus (SLE) and steroid effects on the brain were measured by computed tomography (CT). Of 14 patients with SLE cerebritis, 10 (71%) had marked cortical atrophy and 4 (29%) minimal atrophy. None were normal by CT. Controls included 22 patients with SLE without cerebritis receiving cortiocosteroids; this group had normal CT scans in 16 (73%) and minimal cortical atrophy in the remaining 6 (27%). Follow-up CT on 5 patients with cerebritis was unchanged. CT of the brain is a minimally invasive technique for documenting SLE cerebritis. CT may also help differentiate cerebritis from the neuropsychiatric side effects of corticosteroids

Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

International Nuclear Information System (INIS)

Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona; Husain, Nuzhat; Srivastava, Savita; Rathore, Ram K.S.; Sarma, Manoj K.; Malik, Gyanendra K.; Das, Vinita; Pradhan, Mandakini; Pandey, Chandra M.; Narayana, Ponnada A.

2009-01-01

In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA ≤ 28 weeks for frontal cortical region and GA≤22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

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Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona [Sanjay Gandhi Post Graduate Institute of Medical Sciences, Department of Radiodiagnosis, Lucknow, UP (India); Husain, Nuzhat; Srivastava, Savita [CSM Medical University, Department of Pathology, Lucknow (India); Rathore, Ram K.S.; Sarma, Manoj K. [Indian Institute of Technology, Department of Mathematics and Statistics, Kanpur (India); Malik, Gyanendra K. [CSM Medical University, Department of Pediatrics, Lucknow (India); Das, Vinita [CSM Medical University, Department of Obstetrics and Gynecology, Lucknow (India); Pradhan, Mandakini [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Medical Genetics, Lucknow (India); Pandey, Chandra M. [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Biostatistics, Lucknow (India); Narayana, Ponnada A. [University of Texas Medical School at Houston, Department of Diagnostic and Interventional Imaging, Houston, TX (United States)

2009-09-15

In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA {<=} 28 weeks for frontal cortical region and GA{<=}22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

A quantitative brain map of experimental cerebral malaria pathology.

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Patrick Strangward

2017-03-01

Full Text Available 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.

A quantitative brain map of experimental cerebral malaria pathology.

Science.gov (United States)

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.

Inhibitory Effect on Cerebral Inflammatory Response following Traumatic Brain Injury in Rats: A Potential Neuroprotective Mechanism of N-Acetylcysteine

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Gang Chen

2008-01-01

Full Text Available Although N-acetylcysteine (NAC has been shown to be neuroprotective for traumatic brain injury (TBI, the mechanisms for this beneficial effect are still poorly understood. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. However, it has not been investigated whether NAC modulates TBI-induced cerebral inflammatory response. In this work, we investigated the effect of NAC administration on cortical expressions of nuclear factor kappa B (NF-κB and inflammatory proteins such as interleukin-1β (IL-1β, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, and intercellular adhesion molecule-1 (ICAM-1 after TBI. As a result, we found that NF-κB, proinflammatory cytokines, and ICAM-1 were increased in all injured animals. In animals given NAC post-TBI, NF-κB, IL-1β, TNF-α, and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after NAC treatment. NAC administration reduced brain edema, BBB permeability, and apoptotic index in the injured brain. The results suggest that post-TBI NAC administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which NAC ameliorates secondary brain damage following TBI.

Study of cerebral metabolism of glucose in normal human brain correlated with age

International Nuclear Information System (INIS)

Si, M.

2007-01-01

Full text: The objective was to determine whether cerebral metabolism in various regions of the brain differs with advancing age by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They (with the age ranging from 21 to 88; mean age+/-SD: 49.77+/-13.51) were selected with: (i)absence of clear focal brain lesions (epilepsy.cerebrovascular diseases etc);(ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes;(iii) absence of psychiatric disorders and abuse of drugs and alcohol. They were sub grouped into six groups with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose were matched. All subgroups were compared to the control group of 31-40 years old (84 samples; mean age+/-SD: 37.15+/-2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later, their brains were scanned for 10min. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2) .The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three-dimensional localized by MNI Space utility (MSU) software. Results:Relative hypometabolic brain areas detected are mainly in the cortical structures such as bilateral prefrontal cortex, superior temporal gyrus(BA22), parietal cortex (inferior parietal lobule and precuneus(BA40, insula(BA13)), parahippocampal gyrus and amygdala (p<0.01).It is especially apparent in the prefrontal cortex (BA9)and sensory-motor cortex(BA5, 7) (p<0.001), while basal ganglia and cerebellum remained metabolically unchanged with advancing age. Conclusions Regional cerebral metabolism of glucose shows a descent tendency with aging, especially in the prefrontal cortex (BA9)and

Alpha-Tocopherol Reduces Brain Edema and Protects Blood-Brain Barrier Integrity following Focal Cerebral Ischemia in Rats.

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Haghnejad Azar, Adel; Oryan, Shahrbanoo; Bohlooli, Shahab; Panahpour, Hamdollah

2017-01-01

This study was conducted to examine the neuroprotective effects of α-tocopherol against edema formation and disruption of the blood-brain barrier (BBB) following transient focal cerebral ischemia in rats. Ninety-six male Sprague-Dawley rats were divided into 3 major groups (n = 32 in each), namely the sham, and control and α-tocopherol-treated (30 mg/kg) ischemic groups. Transient focal cerebral ischemia (90 min) was induced by occlusion of the left middle cerebral artery. At the end of the 24-hour reperfusion period, the animals were randomly selected and used for 4 investigations (n = 8) in each of the 3 main groups: (a) assessment of neurological score and measurement of infarct size, (b) detection of brain edema formation by the wet/dry method, (c) evaluation of BBB permeability using the Evans blue (EB) extravasation technique, and (d) assessment of the malondialdehyde (MDA) and reduced glutathione (GSH) concentrations using high-performance liquid chromatography methods. Induction of cerebral ischemia in the control group produced extensive brain edema (brain water content 83.8 ± 0.11%) and EB leakage into brain parenchyma (14.58 ± 1.29 µg/g) in conjunction with reduced GSH and elevated MDA levels (5.86 ± 0.31 mmol/mg and 63.57 ± 5.42 nmol/mg, respectively). Treatment with α-tocopherol significantly lowered brain edema formation and reduced EB leakage compared with the control group (p < 0.001, 80.1 ± 0.32% and 6.66 ± 0.87 µg/g, respectively). Meanwhile, treatment with α-tocopherol retained tissue GSH levels and led to a lower MDA level (p < 0.01, 10.17 ± 0.83 mmol/mg, and p < 0.001, 26.84 ± 4.79 nmol/mg, respectively). Treatment with α-tocopherol reduced ischemic edema formation and produced protective effects on BBB function following ischemic stroke occurrence. This effect could be through increasing antioxidant activity. © 2016 S. Karger AG, Basel.

Delayed astrocytic contact with cerebral blood vessels in FGF-2 deficient mice does not compromise permeability properties at the developing blood-brain barrier.

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Saunders, Norman R; Dziegielewska, Katarzyna M; Unsicker, Klaus; Ek, C Joakim

2016-11-01

The brain functions within a specialized environment tightly controlled by brain barrier mechanisms. Understanding the regulation of barrier formation is important for understanding brain development and may also lead to finding new ways to deliver pharmacotherapies to the brain; access of many potentially promising drugs is severely hindered by these barrier mechanisms. The cellular composition of the neurovascular unit of the blood-brain barrier proper and their effects on regulation of its function are beginning to be understood. One hallmark of the neurovascular unit in the adult is the astroglial foot processes that tightly surround cerebral blood vessels. However their role in barrier formation is still unclear. In this study we examined barrier function in newborn, juvenile and adult mice lacking fibroblast growth factor-2 (FGF-2), which has been shown to result in altered astroglial differentiation during development. We show that during development of FGF-2 deficient mice the astroglial contacts with cerebral blood vessels are delayed compared with wild-type animals. However, this delay did not result in changes to the permeability properties of the blood brain barrier as assessed by exclusion of either small or larger sized molecules at this interface. In addition cerebral vessels were positive for tight-junction proteins and we observed no difference in the ultrastructure of the tight-junctions. The results indicate that the direct contact of astroglia processes to cerebral blood vessels is not necessary for either the formation of the tight-junctions or for basic permeability properties and function of the blood-brain barrier. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1201-1212, 2016. © 2016 Wiley Periodicals, Inc.

Glucose transporter of the human brain and blood-brain barrier

International Nuclear Information System (INIS)

Kalaria, R.N.; Gravina, S.A.; Schmidley, J.W.; Perry, G.; Harik, S.I.

1988-01-01

We identified and characterized the glucose transporter in the human cerebral cortex, cerebral microvessels, and choroid plexus by specific D-glucose-displaceable [3H]cytochalasin B binding. The binding was saturable, with a dissociation constant less than 1 microM. Maximal binding capacity was approximately 7 pmol/mg protein in the cerebral cortex, approximately 42 pmol/mg protein in brain microvessels, and approximately 27 pmol/mg protein in the choroid plexus. Several hexoses displaced specific [3H]cytochalasin B binding to microvessels in a rank-order that correlated well with their known ability to cross the blood-brain barrier; the only exception was 2-deoxy-D-glucose, which had much higher affinity for the glucose transporter than the natural substrate, D-glucose. Irreversible photoaffinity labeling of the glucose transporter of microvessels with [3H]cytochalasin B, followed by solubilization and polyacrylamide gel electrophoresis, labeled a protein band with an average molecular weight of approximately 55,000. Monoclonal and polyclonal antibodies specific to the human erythrocyte glucose transporter immunocytochemically stained brain blood vessels and the few trapped erythrocytes in situ, with minimal staining of the neuropil. In the choroid plexus, blood vessels did not stain, but the epithelium reacted positively. We conclude that human brain microvessels are richly endowed with a glucose transport moiety similar in molecular weight and antigenic characteristics to that of human erythrocytes and brain microvessels of other mammalian species

Clinical and neuroradiological studies of eclampsia. Cerebral vasospasm and relation to the brain edema

Energy Technology Data Exchange (ETDEWEB)

Ito, Yasuhiro; Niwa, Hisayoshi; Ando, Tetsuo; Yasuda, Takeshi; Yanagi, Tsutomu [Nagoya Daini Red Cross Hospital, Aichi (Japan)

1995-04-01

Clinical and neuroradiological studies involving cerebral angiography were conducted in four patients with eclampsia. In three cases (case 1, 2 and 4), neurological focal signs, abnormal low density areas on cranial CT and T{sub 2} high intensity areas on cranial MRI disappeared within a month. But in one case (case 3), cerebral infarction occurred and right hemiparesis and aphasia persisted. Cerebral angiography in the acute phase demonstrated vasospasm in all cases and arterial occlusion in the middle cerebral artery due to vasospasm in case 3. Angiography demonstrated several types of spasms, including diffuse, peripheral and multi local. Furthermore, in some cases, diffuse vasospasms were recognized at the siphon and extracranial portions of the internal carotid artery. In one case (Case 4), segmental vasospasms were detected in the bilateral vertebral arteries. Three to four weeks later, follow-up cerebral angiography was performed in three cases. Cerebral vasospasms had partially or completely recovered. Subarachnoid hemorrhage (SAH) was excluded by lumbar puncture and neuroradiological findings in all cases. We concluded that eclampsia itself causes cerebral vasospasm and that the mechanism of vasospasm is different from that of SAH, since cerebral vasospasm occurred in the extracranial cerebral arteries. We suspected that cerebral vasospasm in eclampsia causes cerebral ischemia, which leads to cytotoxic edema and dysfunction of the blood-brain barrier (BBB) and cerebral autoregulation. With this background, brain edema, especially vasogenic edema, may easily occur and clinical symptoms of eclampsia may appear when the blood pressure rapidly increases. (author).

Clinical and neuroradiological studies of eclampsia. Cerebral vasospasm and relation to the brain edema

International Nuclear Information System (INIS)

Ito, Yasuhiro; Niwa, Hisayoshi; Ando, Tetsuo; Yasuda, Takeshi; Yanagi, Tsutomu

1995-01-01

Clinical and neuroradiological studies involving cerebral angiography were conducted in four patients with eclampsia. In three cases (case 1, 2 and 4), neurological focal signs, abnormal low density areas on cranial CT and T 2 high intensity areas on cranial MRI disappeared within a month. But in one case (case 3), cerebral infarction occurred and right hemiparesis and aphasia persisted. Cerebral angiography in the acute phase demonstrated vasospasm in all cases and arterial occlusion in the middle cerebral artery due to vasospasm in case 3. Angiography demonstrated several types of spasms, including diffuse, peripheral and multi local. Furthermore, in some cases, diffuse vasospasms were recognized at the siphon and extracranial portions of the internal carotid artery. In one case (Case 4), segmental vasospasms were detected in the bilateral vertebral arteries. Three to four weeks later, follow-up cerebral angiography was performed in three cases. Cerebral vasospasms had partially or completely recovered. Subarachnoid hemorrhage (SAH) was excluded by lumbar puncture and neuroradiological findings in all cases. We concluded that eclampsia itself causes cerebral vasospasm and that the mechanism of vasospasm is different from that of SAH, since cerebral vasospasm occurred in the extracranial cerebral arteries. We suspected that cerebral vasospasm in eclampsia causes cerebral ischemia, which leads to cytotoxic edema and dysfunction of the blood-brain barrier (BBB) and cerebral autoregulation. With this background, brain edema, especially vasogenic edema, may easily occur and clinical symptoms of eclampsia may appear when the blood pressure rapidly increases. (author)

Basal ganglia germinoma in children with associated ipsilateral cerebral and brain stem hemiatrophy

Energy Technology Data Exchange (ETDEWEB)

Ozelame, Rodrigo V.; Shroff, Manohar; Wood, Bradley; Bouffet, Eric; Bartels, Ute; Drake, James M.; Hawkins, Cynthia; Blaser, Susan [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, Ontario (Canada)

2006-04-15

Germinoma is the most common and least-malignant intracranial germ cell tumor, usually found in the midline. Germinoma that arises in the basal ganglia, called ectopic germinoma, is a rare and well-documented entity representing 5% to 10% of all intracranial germinomas. The association of cerebral and/or brain stem atrophy with basal ganglia germinoma on CT and MRI is found in 33% of the cases. To review the literature and describe the CT and MRI findings of basal ganglia germinoma in children, known as ectopic germinoma, with associated ipsilateral cerebral and brain stem hemiatrophy. Three brain CT and six brain MRI studies performed in four children at two institutions were retrospectively reviewed. All patients were male (case 1, 14 years; case 2, 13 years; case 3, 9 years; case 4, 13 years), with pathologically proved germinoma arising in the basal ganglia, and associated ipsilateral cerebral and/or brain stem hemiatrophy on the first imaging study. It is important to note that three of these children presented with cognitive decline, psychosis and slowly progressive hemiparesis as their indication for imaging. Imaging results on initial scans were varied. In all patients, the initial study showed ipsilateral cerebral and/or brain stem hemiatrophy, representing Wallerian degeneration. All patients who underwent CT imaging presented with a hyperdense or calcified lesion in the basal ganglia on unenhanced scans. Only one of these lesions had a mass effect on the surrounding structures. In one of these patients a large, complex, heterogeneous mass appeared 15 months later. Initial MR showed focal or diffusely increased T2 signal in two cases and heterogeneous signal in the other two. (orig.)

Basal ganglia germinoma in children with associated ipsilateral cerebral and brain stem hemiatrophy

International Nuclear Information System (INIS)

Ozelame, Rodrigo V.; Shroff, Manohar; Wood, Bradley; Bouffet, Eric; Bartels, Ute; Drake, James M.; Hawkins, Cynthia; Blaser, Susan

2006-01-01

Germinoma is the most common and least-malignant intracranial germ cell tumor, usually found in the midline. Germinoma that arises in the basal ganglia, called ectopic germinoma, is a rare and well-documented entity representing 5% to 10% of all intracranial germinomas. The association of cerebral and/or brain stem atrophy with basal ganglia germinoma on CT and MRI is found in 33% of the cases. To review the literature and describe the CT and MRI findings of basal ganglia germinoma in children, known as ectopic germinoma, with associated ipsilateral cerebral and brain stem hemiatrophy. Three brain CT and six brain MRI studies performed in four children at two institutions were retrospectively reviewed. All patients were male (case 1, 14 years; case 2, 13 years; case 3, 9 years; case 4, 13 years), with pathologically proved germinoma arising in the basal ganglia, and associated ipsilateral cerebral and/or brain stem hemiatrophy on the first imaging study. It is important to note that three of these children presented with cognitive decline, psychosis and slowly progressive hemiparesis as their indication for imaging. Imaging results on initial scans were varied. In all patients, the initial study showed ipsilateral cerebral and/or brain stem hemiatrophy, representing Wallerian degeneration. All patients who underwent CT imaging presented with a hyperdense or calcified lesion in the basal ganglia on unenhanced scans. Only one of these lesions had a mass effect on the surrounding structures. In one of these patients a large, complex, heterogeneous mass appeared 15 months later. Initial MR showed focal or diffusely increased T2 signal in two cases and heterogeneous signal in the other two. (orig.)

Impaired cerebral autoregulation and brain injury in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

Science.gov (United States)

Massaro, An N; Govindan, R B; Vezina, Gilbert; Chang, Taeun; Andescavage, Nickie N; Wang, Yunfei; Al-Shargabi, Tareq; Metzler, Marina; Harris, Kari; du Plessis, Adre J

2015-08-01

Impaired cerebral autoregulation may contribute to secondary injury in newborns with hypoxic-ischemic encephalopathy (HIE). Continuous, noninvasive assessment of cerebral pressure autoregulation can be achieved with bedside near-infrared spectroscopy (NIRS) and systemic mean arterial blood pressure (MAP) monitoring. This study aimed to evaluate whether impaired cerebral autoregulation measured by NIRS-MAP monitoring during therapeutic hypothermia and rewarming relates to outcome in 36 newborns with HIE. Spectral coherence analysis between NIRS and MAP was used to quantify changes in the duration [pressure passivity index (PPI)] and magnitude (gain) of cerebral autoregulatory impairment. Higher PPI in both cerebral hemispheres and gain in the right hemisphere were associated with neonatal adverse outcomes [death or detectable brain injury by magnetic resonance imaging (MRI), P < 0.001]. NIRS-MAP monitoring of cerebral autoregulation can provide an ongoing physiological biomarker that may help direct care in perinatal brain injury. Copyright © 2015 the American Physiological Society.

Molecular pathophysiology of cerebral edema

Science.gov (United States)

Gerzanich, Volodymyr; Simard, J Marc

2015-01-01

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

Preliminary application of SPECT three dimensional brain imaging in normal controls and patients with cerebral infarction

Energy Technology Data Exchange (ETDEWEB)

Zhaosheng, Luan; Pengyong,; Xiqin, Sun; Wei, Wang; Huisheng, Liu; Wen, Zhou [88 Hospital PLA, Taian, SD (China). Dept. of Nuclear Medicine

1992-11-01

10 normal controls and 32 cerebral infarction patients were examined with SPECT three-dimensional (3D) and sectional imaging. The result shows that 3D brain imaging has significant value in the diagnosis of cerebral infarction. 3D brain imaging is superior to sectional imaging in determining the location and size of superficial lesions. For the diagnosis of deep lesions, it is better to combine 3D brain imaging with sectional imaging. The methodology of 3D brain imaging is also discussed.

Preliminary application of SPECT three dimensional brain imaging in normal controls and patients with cerebral infarction

International Nuclear Information System (INIS)

Luan Zhaosheng; Pengyong; Sun Xiqin; Wang Wei; Liu Huisheng; Zhou Wen

1992-01-01

10 normal controls and 32 cerebral infarction patients were examined with SPECT three-dimensional (3D) and sectional imaging. The result shows that 3D brain imaging has significant value in the diagnosis of cerebral infarction. 3D brain imaging is superior to sectional imaging in determining the location and size of superficial lesions. For the diagnosis of deep lesions, it is better to combine 3D brain imaging with sectional imaging. The methodology of 3D brain imaging is also discussed

Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation

DEFF Research Database (Denmark)

Madsen, P L; Hasselbalch, S G; Hagemann, L P

1995-01-01

fraction of the activation-induced excess glucose uptake. These data confirm earlier reports that brain activation can induce resetting of the cerebral oxygen/glucose consumption ratio, and indicate that the resetting persists for a long period after cerebral activation has been terminated and physiologic......Global cerebral blood flow (CBF), global cerebral metabolic rates for oxygen (CMRO2), and for glucose (CMRglc), and lactate efflux were measured during rest and during cerebral activation induced by the Wisconsin card sorting test. Measurements were performed in healthy volunteers using the Kety......-Schmidt technique. Global CMRO2 was unchanged during cerebral activation, whereas global CBF and global CMRglc both increased by 12%, reducing the molar ratio of oxygen to glucose consumption from 6.0 during baseline conditions to 5.4 during activation. Data obtained in the period following cerebral activation...

Blood-brain barrier and cerebral blood flow: Age differences in hemorrhagic stroke

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Semyachkina-Glushkovskaya Oxana

2015-11-01

Full Text Available Neonatal stroke is similar to the stroke that occurs in adults and produces a significant morbidity and long-term neurologic and cognitive deficits. There are important differences in the factors, clinical events and outcomes associated with the stroke in infants and adults. However, mechanisms underlying age differences in the stroke development remain largely unknown. Therefore, treatment guidelines for neonatal stroke must extrapolate from the adult data that is often not suitable for children. The new information about differences between neonatal and adult stroke is essential for identification of significant areas for future treatment and effective prevention of neonatal stroke. Here, we studied the development of stress-induced hemorrhagic stroke and possible mechanisms underlying these processes in newborn and adult rats. Using histological methods and magnetic resonance imaging, we found age differences in the type of intracranial hemorrhages. Newborn rats demonstrated small superficial bleedings in the cortex while adult rats had more severe deep bleedings in the cerebellum. Using Doppler optical coherent tomography, we found higher stress-reactivity of the sagittal sinus to deleterious effects of stress in newborn vs. adult rats suggesting that the cerebral veins are more vulnerable to negative stress factors in neonatal vs. adult brain in rats. However, adult but not newborn rats demonstrated the stroke-induced breakdown of blood brain barrier (BBB permeability. The one of possible mechanisms underlying the higher resistance to stress-related stroke injures of cerebral vessels in newborn rats compared with adult animals is the greater expression of two main tight junction proteins of BBB (occludin and claudin-5 in neonatal vs. mature brain in rats.

rLj-RGD3, a Novel Recombinant Toxin Protein from Lampetra japonica, Protects against Cerebral Reperfusion Injury Following Middle Cerebral Artery Occlusion Involving the Integrin-PI3K/Akt Pathway in Rats.

Directory of Open Access Journals (Sweden)

Qian Lu

Full Text Available The RGD-toxin protein Lj-RGD3 is a naturally occurring 118 amino acid peptide that can be obtained from the salivary gland of the Lampetra japonica fish. This unique peptide contains 3 RGD (Arg-Gly-Asp motifs in its primary structure. Lj-RGD3 is available in recombinant form (rLj-RGD3 and can be produced in large quantities using DNA recombination techniques. The pharmacology of the three RGD motif-containing peptides has not been studied. This study investigated the protective effects of rLj-RGD3, a novel polypeptide, against ischemia/reperfusion-induced damage to the brain caused by middle cerebral artery occlusion (MCAO in a rat stroke model. We also explored the mechanism by which rLj-RGD3 acts by measuring protein and mRNA expression levels, with an emphasis on the FAK and integrin-PI3K/Akt anti-apoptosis pathways.rLj-RGD3 was obtained from the buccal secretions of Lampetra japonica using gene recombination technology. Sprague Dawley (SD rats were randomly divided into the following seven groups: a sham group; a vehicle-treated (VT group; 100.0 μg·kg-1, 50.0 μg·kg-1 and 25.0 μg·kg-1 dose rLj-RGD3 groups; and two positive controls, including 1.5 mg·kg-1 Edaravone (ED and 100.0 μg·kg-1 Eptifibatide (EP. MCAO was induced using a model consisting of 2 h of ischemia and 24 h of reperfusion. Behavioral changes were observed in the normal and operation groups after focal cerebral ischemia/reperfusion was applied. In addition, behavioral scores were evaluated at 4 and 24 h after reperfusion. Brain infarct volumes were determined based on 2,3,5-triphenyltetrazolium chloride (TTC staining. Pathological changes in brain tissues were observed using hematoxylin and eosin (H&E staining. Moreover, neuronal apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL assays. We determined the expression levels of focal adhesion kinase (FAK, phosphatidyl inositol 3-kinase (PI3K, protein kinase B

Aquaporin-11: A channel protein lacking apparent transport function expressed in brain

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Tsunenari Takashi

2006-05-01

Full Text Available Abstract Background The aquaporins are a family of integral membrane proteins composed of two subfamilies: the orthodox aquaporins, which transport only water, and the aquaglyceroporins, which transport glycerol, urea, or other small solutes. Two recently described aquaporins, numbers 11 and 12, appear to be more distantly related to the other mammalian aquaporins and aquaglyceroporins. Results We report on the characterization of Aquaporin-11 (AQP11. AQP11 RNA and protein is found in multiple rat tissues, including kidney, liver, testes and brain. AQP11 has a unique distribution in brain, appearing in Purkinje cell dendrites, hippocampal neurons of CA1 and CA2, and cerebral cortical neurons. Immunofluorescent staining of Purkinje cells indicates that AQP11 is intracellular. Unlike other aquaporins, Xenopus oocytes expressing AQP11 in the plasma membrane failed to transport water, glycerol, urea, or ions. Conclusion AQP11 is functionally distinct from other proteins of the aquaporin superfamily and could represent a new aquaporin subfamily. Further studies are necessary to elucidate the role of AQP11 in the brain.

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

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Brandi D Freeman

2016-03-01

Full Text Available 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.

HTLV-I associated myelopathy with multiple spotty areas in cerebral white matter and brain stem by MRI

Energy Technology Data Exchange (ETDEWEB)

Hara, Yasuo; Takahashi, Mitsuo; Yoshikawa, Hiroo; Yorifuji, Shirou; Tarui, Seiichiro

1988-01-01

A 48-year-old woman was admitted with complaints of urinary incontinence and gait disturbance, both of which had progressed slowly without any sign of remission. Family history was not contributory. Neurologically, extreme spasticity was recoginized in the lower limbs. Babinski sign was positive bilaterally. Flower-like atypical lymphocytes were seen in blood. Positive anti-HTLV-I antibody was confirmed in serum and spinal fluid by western blot. She was diagnosed as having HTLV-I associated myelopathy (HAM). CT reveald calcification in bilateral globus pallidus, and MRI revealed multiple spotty areas in cerebral white matter and brain stem, but no spinal cord lesion was detectable. Electrophysiologically, brain stem auditory evoked potential (BAEP) suggested the presence of bilateral brain stem lesions. Neither median nor posterior tibial nerve somatosensory evoked potentials were evoked, a finding suggesting the existence of spinal cord lesion. In this case, the lesion was not confined to spinal cord, it was also observed in brain stem and cerebral white matter. Such distinct lesions in cerebral white matter and brain stem have not been reported in patients with HAM. It is suggested that HTLV-I is probably associated with cerebral white matter and brain stem.

Positron emission tomography and cerebral metabolism

International Nuclear Information System (INIS)

Comar, D.; Maziere, M.; Zarifian, E.; Naquet, R.

1979-01-01

The association of new methods of labelling with short lived radioisotopes and of visualisation 'in vivo' of these labelled molecules by emission tomography, provide the possibility of studying brain metabolism at different levels. Two examples will illustrate the possibilities of this methodology. Cerebral metabolism of methionine- 11 C in phenylketonutic patients: The cerebral uptake of methionine was measured in 24 PKU children aged 1 to 40 months on a low protein diet. Ten of them were examined twice at intervals of several months. Stopping the diet for one week leads to an increase in blood phenylalanine and to a significant important decrease in brain uptake of labelled methionine. Futhermore, for children under treatment having a low phenylalanine blood concentration, brain uptake of methionine decreases with age between 1 and 40 months. These results suggest that the treatment of this disease should be started as soon as possible after birth. Cerebral metabolism of psychoactive drugs: The study of the brain distribution and kinetics of psychoactive drugs may help in understanding their mode of action. Chlorpromazine- 11 C was administered i.v. to schyzophrenic patients not previously treated with neuroleptics. In all patients the brain uptake of the drug was high and rapid, and was localized mainly in the grey matter, probably in proportion to the blood flow. Non-specific binding of this drug to brain proteins prevented visualization of specific binding to dopaminergic or αnor-adrenergic receptors. Specific receptor binding of benzodiazepines was however visualized in the brain of baboons after injection of 11 C-flunitrazepam (specific activity = 600 Ci/μmole) and subsequent displacement of this radioactive ligand by a pharmacological dose of Lorazepam

Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats.

Science.gov (United States)

Ahmed, Maha A E; El Morsy, Engy M; Ahmed, Amany A E

2014-08-21

Interruption to blood flow causes ischemia and infarction of brain tissues with consequent neuronal damage and brain dysfunction. Pomegranate extract is well tolerated, and safely consumed all over the world. Interestingly, pomegranate extract has shown remarkable antioxidant and anti-inflammatory effects in experimental models. Many investigators consider natural extracts as novel therapies for neurodegenerative disorders. Therefore, this study was carried out to investigate the protective effects of standardized pomegranate extract against cerebral ischemia/reperfusion-induced brain injury in rats. Adult male albino rats were randomly divided into sham-operated control group, ischemia/reperfusion (I/R) group, and two other groups that received standardized pomegranate extract at two dose levels (250, 500 mg/kg) for 15 days prior to ischemia/reperfusion (PMG250+I/R, and PMG500+I/R groups). After I/R or sham operation, all rats were sacrificed and brains were harvested for subsequent biochemical analysis. Results showed reduction in brain contents of MDA (malondialdehyde), and NO (nitric oxide), in addition to enhancement of SOD (superoxide dismutase), GPX (glutathione peroxidase), and GRD (glutathione reductase) activities in rats treated with pomegranate extract prior to cerebral I/R. Moreover, pomegranate extract decreased brain levels of NF-κB p65 (nuclear factor kappa B p65), TNF-α (tumor necrosis factor-alpha), caspase-3 and increased brain levels of IL-10 (interleukin-10), and cerebral ATP (adenosine triphosphate) production. Comet assay showed less brain DNA (deoxyribonucleic acid) damage in rats protected with pomegranate extract. The present study showed, for the first time, that pre-administration of pomegranate extract to rats, can offer a significant dose-dependent neuroprotective activity against cerebral I/R brain injury and DNA damage via antioxidant, anti-inflammatory, anti-apoptotic and ATP-replenishing effects. Copyright © 2014 Elsevier Inc

Effects of hyperbaric treatment in cerebral air embolism on intracranial pressure, brain oxygenation, and brain glucose metabolism in the pig

NARCIS (Netherlands)

van Hulst, Robert A.; Drenthen, Judith; Haitsma, Jack J.; Lameris, Thomas W.; Visser, Gerhard H.; Klein, Jan; Lachmann, Burkhard

2005-01-01

OBJECTIVE: To evaluate the effects of hyperbaric oxygen treatment after cerebral air embolism on intracranial pressure, brain oxygenation, brain glucose/lactate metabolism, and electroencephalograph. DESIGN: Prospective animal study. SETTING: Hyperbaric chamber. SUBJECTS: Eleven Landrace/Yorkshire

Cerebral amyloid angiopathy-related inflammation presenting with steroid-responsive higher brain dysfunction: case report and review of the literature

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Maeda Yasushi

2011-09-01

Full Text Available Abstract A 56-year-old man noticed discomfort in his left lower limb, followed by convulsion and numbness in the same area. Magnetic resonance imaging (MRI showed white matter lesions in the right parietal lobe accompanied by leptomeningeal or leptomeningeal and cortical post-contrast enhancement along the parietal sulci. The patient also exhibited higher brain dysfunction corresponding with the lesions on MRI. Histological pathology disclosed β-amyloid in the blood vessels and perivascular inflammation, which highlights the diagnosis of cerebral amyloid angiopathy (CAA-related inflammation. Pulse steroid therapy was so effective that clinical and radiological findings immediately improved. CAA-related inflammation is a rare disease, defined by the deposition of amyloid proteins within the leptomeningeal and cortical arteries associated with vasculitis or perivasculitis. Here we report a patient with CAA-related inflammation who showed higher brain dysfunction that improved with steroid therapy. In cases with atypical radiological lesions like our case, cerebral biopsy with histological confirmation remains necessary for an accurate diagnosis.

Computed tomography in severe protein energy malnutrition.

OpenAIRE

Househam, K C; de Villiers, J F

1987-01-01

Computed tomography of the brain was performed on eight children aged 1 to 4 years with severe protein energy malnutrition. Clinical features typical of kwashiorkor were present in all the children studied. Severe cerebral atrophy or brain shrinkage according to standard radiological criteria was present in every case. The findings of this study suggest considerable cerebral insult associated with severe protein energy malnutrition.

Cerebral control and survival after stereotactic radiotherapy of brain metastases

International Nuclear Information System (INIS)

Arnold, Elmar Till

2014-01-01

This retrospective study, including 275 patients who underwent stereotactic radiotherapy due to brain metastases between 2003 and 2008, investigates influencing factors regarding cerebral control and survival, symptomatic effects and a potential benefit for patients older than 70 years. We were able to identify risk factors for remote brain failure which leads to a therapeutic recommendation. Furthermore we confirm a positive symptomatic effect and a benefit of stereotactic readiotherapy for patients over 70 years.

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

Science.gov (United States)

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

2008-04-01

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

Immunochemical method for quantitative evaluation of vasogenic brain edema following cold injury of rat brain

Energy Technology Data Exchange (ETDEWEB)

Bodsch, W; Huerter, T; Hossmann, K A [Max-Planck-Institut fuer Hirnforschung, Koeln (Germany, F.R.). Forschungsstelle fuer Hirnkreislauf-Forschung

1982-10-07

An immunochemical method is described for quantitative assessment of serum proteins and hemoglobin content in brain tissue homogenates. Using a combination of affinity chromatography and radioimmunoassay, the sensitivity of the method is 50 ng hemoglobin and 100 ng serum protein per assay, respectively. The method was used to measure cerebral hematocrit, blood volume and serum protein extravasation in rat brain at various times following cold injury. In control rats cerebral blood volume was 6.88 +- 0.15 ml/100 g and cerebral hematocrit 26.4 +- 0.86% (means +- S.E.). Following cold injury blood volume did not significantly change, but there was a gradual increase of extravasated serum proteins, reaching a maximum of 21.54 +- 2.76 mg/g d.w. after 8 hours. Thereafter protein content gradually declined, but even after 64 h it was distinctly increased. Protein extravasation was partly dissociated from the increase of brain water and sodium which reached a maximum already after 2 h and which normalized within 32 and 64 h, respectively. It is concluded that edema fluid associated with cold injury is not simply an ultrafiltrate of blood serum but consists of cytotoxic and vasogenic components which follow a different time course both during formation and resolution of edema.

Immunochemical method for quantitative evaluation of vasogenic brain edema following cold injury of rat brain

International Nuclear Information System (INIS)

Bodsch, W.; Huerter, T.; Hossmann, K.-A.

1982-01-01

An immunochemical method is described for quantitative assessment of serum proteins and hemoglobin content in brain tissue homogenates. Using a combination of affinity chromatography and radioimmunoassay, the sensitivity of the method is 50 ng hemoglobin and 100 ng serum protein per assay, respectively. The method was used to measure cerebral hematocrit, blood volume and serum protein extravasation in rat brain at various times following cold injury. In control rats cerebral blood volume was 6.88 +- 0.15 ml/100 g and cerebral hematocrit 26.4 +- 0.86% (means +- S.E.). Following cold injury blood volume did not significantly change, but there was a gradual increase of extravasated serum proteins, reaching a maximum of 21.54 +- 2.76 mg/g d.w. after 8 hours. Thereafter protein content gradually declined, but even after 64 h it was distinctly increased. Protein extravasation was partly dissociated from the increase of brain water and sodium which reached a maximum already after 2 h and which normalized within 32 and 64 h, respectively. It is concluded that edema fluid associated with cold injury is not simply an ultrafiltrate of blood serum but consists of cytotoxic and vasogenic components which follow a different time course both during formation and resolution of edema. (Auth.)

Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

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Najmeh Kabiri

2016-09-01

Full Text Available The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99. Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly higher than the Sham group, although right hemispheres in all of the treated groups illustrated higher brain water content than the left ones. Brain anti-oxidant capacity elevated in the ischemic rats treated with Kombucha and in the Sham group. Brain and plasma malondialdehyde concentrations significantly decreased in both of the ischemic groups injected with Kombucha. The findings suggest that Kombucha tea could be useful for the prevention of cerebral damage.

Comparison of Tc-99m ECD brain SPECT between patients with delayed development and cerebral palsy

International Nuclear Information System (INIS)

Cho, I.; Chun, K.; Won, K.; Lee, H.; Jang, S.; Lee, J.

2002-01-01

Purpose: In previous study, thalamic or cerebellar hypoperfusion were reported in patients with cerebral palsy. This study was performed to evaluate cerebral perfusion abnormalities using Tc-99m ECD brain SPECT in patients with delayed motor development. Methods: Nineteen patients (9 boys, 10 girls, mean age 25.5 months) with delayed development underwent brain SPECT after injection of 185∼370 MBq of Tc-99m ECD. The imaging was obtained between 30 minutes and 1hr after injection. The patients were divided clinically as follows, patients with delayed development (n=5) and patients with cerebral palsy (n=14) who has delayed development and abnormal movement. The clinical subtypes of cerebral palsy were spastic quadriplegia (n=5), spastic diplegia (n=6) and spastic hemiplegia (n=3). In each group, decrease of cerebral perfusion was evaluated visually as mild, moderate and severe and quantitation of cerebral perfusion after Lassen's correction was also obtained. Results: SPECT findings showed normal or mildly decreased thalamic perfusion in patients with delayed development and severe decrease of thalamic or cerebellar perfusion in patients with spastic quadriplegia. In patients with spastic diplegia, mild decrease of perfusion was observed in thalamus. In quantified data, thalamic perfusion was lowest in patients with spastic quadriplegia and highest in patients with delayed development, but there were no statistically significant differences. Conclusion: Brain SPECT with Tc-99m ECD has a role in the detection of perfusion abnormalities in patients with delayed development and cerebral palsy

[How can we determine the best cerebral perfusion pressure in pediatric traumatic brain injury?].

Science.gov (United States)

Vuillaume, C; Mrozek, S; Fourcade, O; Geeraerts, T

2013-12-01

The management of cerebral perfusion pressure (CPP) is the one of the main preoccupation for the care of paediatric traumatic brain injury (TBI). The physiology of cerebral autoregulation, CO2 vasoreactivity, cerebral metabolism changes with age as well as the brain compliance. Low CPP leads to high morbidity and mortality in pediatric TBI. The recent guidelines for the management of CPP for the paediatric TBI indicate a CPP threshold 40-50 mmHg (infants for the lower and adolescent for the upper). But we must consider the importance of age-related differences in the arterial pressure and CPP. The best CPP is the one that allows to avoid cerebral ischaemia and oedema. In this way, the adaptation of optimal CPP must be individual. To assess this objective, interesting tools are available. Transcranial Doppler can be used to determine the best level of CPP. Other indicators can predict the impairment of autoregulation like pressure reactivity index (PRx) taking into consideration the respective changes in ICP and CPP. Measurement of brain tissue oxygen partial pressure is an other tool that can be used to determine the optimal CPP. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

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Shen J

2017-09-01

Full Text Available Junyi Shen, Zhiming Zhao, Wei Shang, Chunli Liu, Beibei Zhang, Lingjie Zhao, Hui Cai Department of Integrated Traditional and Western Medicine, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China Abstract: Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1 has a wide variety of therapeutic values for central nervous system (CNS diseases for the neuron protective effects. However, the blood–brain barrier (BBB restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H, Rg1, and OX26 antibody, targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction. Keywords: poly-γ-glutamic acid, ginsenoside Rg1, OX26, blood–brain barrier

Strain differences in the response to morphine on incorporation of 3H-lysine into rat brain protein

International Nuclear Information System (INIS)

Ford, D.H.; Rhines, R.K.; Levi, M.A.

1977-01-01

The effect of morphine on the specific activity (SA) of lysine in the plasma free amino acid (FFA) fraction and in the cerebral cortical FAA and protein fractions, as well as on the specific accumulation and incorporation, was determined in male Sprague-Dawley and Wistar rats at various time intervals after intravenous injection of drug and amino acid into unanesthetized animals. The lysine SA was higher in Sprague-Dawley than in Wistar rats in the plasma and brain FAA fraction and in the protein fraction. In the SD strain, morphine decreased the SA of plasma FAA significantly, but had only slight effects in the Wistar strain. In the cortical gray matter, morphine elevated the SA of lysine significantly in both strains. SA of the lysine in cerebral cortical protein increased in both strains with time. When the data for the free amino acids were expressed in terms of specific accumulation, the observed rates were higher in the Sprague-Dawley animals and reached a point of maximal concentration, which was not observed in animals of the Wistar strain. Morphine elevated the levels of specific accumulation of lysine into the cortical free amino acid pool in both strains of rat. It is concluded that Sprague-Dawley and Wistar rats are not equivalent in relation to the accumulation of an amino acid in the brain FAA pool from the plasma and that the effect of morphine on specific incorporation of lysine into brain protein is greater in Wistar rats. (author)

Corvitin restores metallothionein and glial fibrillary acidic protein levels in rat brain affected by pituitrin-izadrin

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H. N. Shiyntum; O. O. Dovban; Y. P. Kovalchuk; T. Ya. Yaroshenko2; G. A. Ushakova1

2017-01-01

In this research, we investigated the effect of pituitrin-izadrin induced injury on the levels of metallothionein (MT) and soluble and filament forms of glial fibrillary acidic protein (GFAP) in the hippocampus, cerebellum, thalamus, and the cerebral cortex, and examined the effect of corvitin on the brain under the noted changes. Our results showed oppositely directed changes – a decrease in the level of MT and an increase in GFAP in the rat brain, with a tendency to astrogliosis development...

The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice

International Nuclear Information System (INIS)

Hua, Fang; Wang, Jun; Sayeed, Iqbal; Ishrat, Tauheed; Atif, Fahim; Stein, Donald G.

2009-01-01

TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NF-κB and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-κB activity and phosphorylation of the inhibitor of kappa B (IκBα) increased in ischemic brains, but IRF3, inhibitor of κB kinase complex-ε (IKKε), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-κB activity or p-IκBα induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-κB signaling and brain injury after acute cerebral I/R.

Prospective comparative study of brain protection in total aortic arch replacement: deep hypothermic circulatory arrest with retrograde cerebral perfusion or selective antegrade cerebral perfusion.

Science.gov (United States)

Okita, Y; Minatoya, K; Tagusari, O; Ando, M; Nagatsuka, K; Kitamura, S

2001-07-01

The purpose of this study was to compare the results of total aortic arch replacement using two different methods of brain protection, particularly with respect to neurologic outcome. From June 1997, 60 consecutive patients who underwent total arch replacement through a midsternotomy were alternately allocated to one of two methods of brain protection: deep hypothermic circulatory arrest with retrograde cerebral perfusion (RCP: 30 patients) or with selective antegrade cerebral perfusion (SCP: 30 patients). Preoperative and postoperative (3 weeks) brain CT scan, neurological examination, and cognitive function tests were performed. Serum 100b protein was assayed before and after the cardiopulmonary bypass, as well as 24 hours and 48 hours after the operation. Hospital mortality occurred in 2 patients in the RCP group (6.6%) and 2 in the SCP group (6.6%). New strokes occurred in 1 (3.3%) of the RCP group and in 2 (6.6%) of the SCP group (p = 0.6). The incidence of transient brain dysfunction was significantly higher in the RCP group than in the SCP group (10, 33.3% vs 4, 13.3%, p = 0.05). Except in patients with strokes, S-100b values showed no significant differences in the two groups (RCP: SCP, prebypass 0.01+/-0.04: 0.05+/-0.16, postbypass 2.17+/-0.94: 1.97+/-1.00, 24 hours 0.61+/-0.36: 0.60+/-0.37, 48 hours 0.36+/-0.45: 0.46+/-0.40 microg/L, p = 0.7). There were no intergroup differences in the scores of memory decline (RCP 0.74+/-0.99; SCP 0.55+/-1.19, p = 0.6), orientation (RCP 1.11+/-1.29; SCP 0.50+/-0.76, p = 0.08), or intellectual function (RCP 1.21+/-1.27; SCP 1.05+/-1.15, p = 0.7). Both methods of brain protection for patients undergoing total arch replacement resulted in acceptable levels of mortality and morbidity. However, the prevalence of transient brain dysfunction was significantly higher in patients with the RCP.

Brain Size and Cerebral Glucose Metabolic Rate in Nonspecific Retardation and Down Syndrome.

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Haier, Richard J.; And Others

1995-01-01

Brain size and cerebral glucose metabolic rate were determined for 10 individuals with mild mental retardation (MR), 7 individuals with Down syndrome (DS), and 10 matched controls. MR and DS groups both had brain volumes of about 80% compared to controls, with variance greatest within the MR group. (SLD)

Brain scan in cerebral ischemia. An experimental model in the rat

International Nuclear Information System (INIS)

Turner, J.H.

1975-01-01

A rapid embolic method for consistent induction of stroke in the rat is described. Brain scans were performed using a micro-pinhole collimator system, and the value of the model for studies in localization of radiopharmaceuticals in cerebral ischemia is demonstrated

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

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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.

Sequential assessment of regional cerebral blood flow, regional cerebral blood volume, and blood-brain barrier in focal cerebral ischemia: a case report

International Nuclear Information System (INIS)

Di Piero, V.; Perani, D.; Savi, A.; Gerundini, P.; Lenzi, G.L.; Fazio, F.

1986-01-01

Regional CBF (rCBF) and regional cerebral blood volume (rCBV) were evaluated by N,N,N'-trimethyl-N'-(2)-hydroxy-3-methyl-5-[123I]iodobenzyl-1, 3-propanediamine-2 HCl- and /sup 99m/TC-labeled red blood cells, respectively, and single-photon emission computerized tomography (SPECT) in a patient with focal cerebral ischemia. Sequential transmission computerized tomography (TCT) and SPECT functional data were compared with clinical findings to monitor the pathophysiological events occurring in stroke. A lack of correlation between rCBF-rCBV distributions and blood-brain barrier (BBB) breakdown was found in the acute phase. In the face of more prolonged alteration of BBB, as seen by TCT enhancement, a rapid evolution of transient phenomena such as luxury perfusion was shown by SPECT studies. Follow-up of the patient demonstrated a correlation between the neurological recovery and a parallel relative improvement of the cerebral perfusion

Immediate CT findings following embolization of cerebral aneurysms: suggestion of blood-brain barrier or vascular permeability change

International Nuclear Information System (INIS)

Baik, Seung Kug; Kim, Yong Sun; Lee, Hui Jung; Kim, Gab Chul; Park, Jaechan

2008-01-01

Although endovascular techniques are widely used for the treatment of cerebral aneurysms, the immediate postprocedural brain CT findings have not been reported. Therefore, in the present study we assessed the immediate postprocedural brain CT findings following the uneventful coil embolization of cerebral aneurysms. Included in the study were 59 patients with 61 cerebral aneurysms after uncomplicated coil embolization. Acute subarachnoid hemorrhage was present with 32 of the 61 aneurysms. All patients underwent a brain CT scan just before and within 2 h after the endovascular treatment. If the postprocedural CT scan revealed any new findings, a follow-up CT scan and/or MRI were performed within 24 h. The variables related to the abnormal CT findings were also evaluated. Among the 61 immediate brain CT scans, 26 (43%) showed abnormal findings, including cortical contrast enhancement (n=21, 34%), subarachnoid contrast enhancement (n=8, 13%), intraventricular contrast enhancement (n=5, 8%), and striatal contrast enhancement (n=2, 3%). Single or mixed CT findings were also seen. None of the 61 aneurysms was associated with new neurological symptoms after endovascular treatment, and all patients made an uneventful recovery. Abnormal findings were more likely to be found with lower body weight and with increased corrected amounts of contrast material and heparin (P<0.05). After uneventful endovascular treatment of cerebral aneurysms, the immediate brain CT findings can reveal various patterns of abnormal contrast enhancement. Recognizing the immediate brain CT findings is important, as they can mimic various diseases. (orig.)

Vascular permeability in cerebral cavernous malformations

DEFF Research Database (Denmark)

Mikati, Abdul G; Khanna, Omaditya; Zhang, Lingjiao

2015-01-01

Patients with the familial form of cerebral cavernous malformations (CCMs) are haploinsufficient for the CCM1, CCM2, or CCM3 gene. Loss of corresponding CCM proteins increases RhoA kinase-mediated endothelial permeability in vitro, and in mouse brains in vivo. A prospective case-controlled observ...

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

Science.gov (United States)

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

[Assessment of motor and sensory pathways of the brain using diffusion-tensor tractography in children with cerebral palsy].

Science.gov (United States)

Memedyarov, A M; Namazova-Baranova, L S; Ermolina, Y V; Anikin, A V; Maslova, O I; Karkashadze, M Z; Klochkova, O A

2014-01-01

Diffusion tensor tractography--a new method of magnetic resonance imaging, that allows to visualize the pathways of the brain and to study their structural-functional state. The authors investigated the changes in motor and sensory pathways of brain in children with cerebral palsy using routine magnetic resonance imaging and diffusion-tensor tractography. The main group consisted of 26 patients with various forms of cerebral palsy and the comparison group was 25 people with normal psychomotor development (aged 2 to 6 years) and MR-picture of the brain. Magnetic resonance imaging was performed on the scanner with the induction of a magnetic field of 1,5 Tesla. Coefficients of fractional anisotropy and average diffusion coefficient estimated in regions of the brain containing the motor and sensory pathways: precentral gyrus, posterior limb of the internal capsule, thalamus, posterior thalamic radiation and corpus callosum. Statistically significant differences (p cerebral palsy in relation to the comparison group. All investigated regions, the coefficients of fractional anisotropy in children with cerebral palsy were significantly lower, and the average diffusion coefficient, respectively, higher. These changes indicate a lower degree of ordering of the white matter tracts associated with damage and subsequent development of gliosis of varying severity in children with cerebral palsy. It is shown that microstructural damage localized in both motor and sensory tracts that plays a leading role in the development of the clinical picture of cerebral palsy.

The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice

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Hua, Fang, E-mail: fhua2@emory.edu [Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, 1365B Clifton Road, Suite 5100, Atlanta, GA 30322 (United States); Wang, Jun; Sayeed, Iqbal; Ishrat, Tauheed; Atif, Fahim; Stein, Donald G. [Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, 1365B Clifton Road, Suite 5100, Atlanta, GA 30322 (United States)

2009-12-18

TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-{kappa}B). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NF-{kappa}B and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-{kappa}B activity and phosphorylation of the inhibitor of kappa B (I{kappa}B{alpha}) increased in ischemic brains, but IRF3, inhibitor of {kappa}B kinase complex-{epsilon} (IKK{epsilon}), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-{kappa}B activity or p-I{kappa}B{alpha} induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-{kappa}B signaling and brain injury after acute cerebral I/R.

Transcriptomics and proteomics analyses of the PACAP38 influenced ischemic brain in permanent middle cerebral artery occlusion model mice

Directory of Open Access Journals (Sweden)

Hori Motohide

2012-11-01

Full Text Available Abstract Introduction The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP is considered to be a potential therapeutic agent for prevention of cerebral ischemia. Ischemia is a most common cause of death after heart attack and cancer causing major negative social and economic consequences. This study was designed to investigate the effect of PACAP38 injection intracerebroventrically in a mouse model of permanent middle cerebral artery occlusion (PMCAO along with corresponding SHAM control that used 0.9% saline injection. Methods Ischemic and non-ischemic brain tissues were sampled at 6 and 24 hours post-treatment. Following behavioral analyses to confirm whether the ischemia has occurred, we investigated the genome-wide changes in gene and protein expression using DNA microarray chip (4x44K, Agilent and two-dimensional gel electrophoresis (2-DGE coupled with matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS, respectively. Western blotting and immunofluorescent staining were also used to further examine the identified protein factor. Results Our results revealed numerous changes in the transcriptome of ischemic hemisphere (ipsilateral treated with PACAP38 compared to the saline-injected SHAM control hemisphere (contralateral. Previously known (such as the interleukin family and novel (Gabra6, Crtam genes were identified under PACAP influence. In parallel, 2-DGE analysis revealed a highly expressed protein spot in the ischemic hemisphere that was identified as dihydropyrimidinase-related protein 2 (DPYL2. The DPYL2, also known as Crmp2, is a marker for the axonal growth and nerve development. Interestingly, PACAP treatment slightly increased its abundance (by 2-DGE and immunostaining at 6 h but not at 24 h in the ischemic hemisphere, suggesting PACAP activates neuronal defense mechanism early on. Conclusions This study provides a detailed inventory of PACAP influenced gene expressions

The role in thanatogenesis of generalized brain edema in ischemic cerebral infarction (computer-morphometric research

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E. A. Dyadyk

2012-12-01

Full Text Available This work presents the results of computer-morphometric study of perivascular and pericellular free (oedematous spaces in brain cortex at death from the ischemic cerebral infarction and from reasons unconnected directly with cerebral pathology. It was revealed, that the mean area of perivascular spaces (vasogenic edema index at brain infarction in 13 times exceeds such at extracerebral pathology, and mean area of pericellular spaces (cytotoxic edema index – almost in 12 times, but also it substantially differs on the degree of variation (in 2,5 times higher, than area of perivascular spaces.

Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice.

Science.gov (United States)

Cheng, Zhuo; Wang, Liping; Qu, Meijie; Liang, Huaibin; Li, Wanlu; Li, Yongfang; Deng, Lidong; Zhang, Zhijun; Yang, Guo-Yuan

2018-05-03

Ischemic stroke induced matrixmetallo-proteinase-9 (MMP-9) upregulation, which increased blood-brain barrier permeability. Studies demonstrated that mesenchymal stem cell therapy protected blood-brain barrier disruption from several cerebrovascular diseases. However, the underlying mechanism was largely unknown. We therefore hypothesized that mesenchymal stem cells reduced blood-brain barrier destruction by inhibiting matrixmetallo-proteinase-9 and it was related to intercellular adhesion molecule-1 (ICAM-1). Adult ICR male mice (n = 118) underwent 90-min middle cerebral artery occlusion and received 2 × 10 5 mesenchymal stem cell transplantation. Neurobehavioral outcome, infarct volume, and blood-brain barrier permeability were measured after ischemia. The relationship between myeloperoxidase (MPO) activity and ICAM-1 release was further determined. We found that intracranial injection of mesenchymal stem cells reduced infarct volume and improved behavioral function in experimental stroke models (p mesenchymal stem cell-treated mice compared to the control group following ischemia (p cells and myeloperoxidase activity were decreased in mesenchymal stem cell-treated mice (p mesenchymal stem cell therapy attenuated blood-brain barrier disruption in mice after ischemia. Mesenchymal stem cells attenuated the upward trend of MMP-9 and potentially via downregulating ICAM-1 in endothelial cells. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway may influence MMP-9 expression of neutrophils and resident cells, and ICAM-1 acted as a key factor in the paracrine actions of mesenchymal stem cell.

Analysis of structure-function network decoupling in the brain systems of spastic diplegic cerebral palsy.

Science.gov (United States)

Lee, Dongha; Pae, Chongwon; Lee, Jong Doo; Park, Eun Sook; Cho, Sung-Rae; Um, Min-Hee; Lee, Seung-Koo; Oh, Maeng-Keun; Park, Hae-Jeong

2017-10-01

Manifestation of the functionalities from the structural brain network is becoming increasingly important to understand a brain disease. With the aim of investigating the differential structure-function couplings according to network systems, we investigated the structural and functional brain networks of patients with spastic diplegic cerebral palsy with periventricular leukomalacia compared to healthy controls. The structural and functional networks of the whole brain and motor system, constructed using deterministic and probabilistic tractography of diffusion tensor magnetic resonance images and Pearson and partial correlation analyses of resting-state functional magnetic resonance images, showed differential embedding of functional networks in the structural networks in patients. In the whole-brain network of patients, significantly reduced global network efficiency compared to healthy controls were found in the structural networks but not in the functional networks, resulting in reduced structural-functional coupling. On the contrary, the motor network of patients had a significantly lower functional network efficiency over the intact structural network and a lower structure-function coupling than the control group. This reduced coupling but reverse directionality in the whole-brain and motor networks of patients was prominent particularly between the probabilistic structural and partial correlation-based functional networks. Intact (or less deficient) functional network over impaired structural networks of the whole brain and highly impaired functional network topology over the intact structural motor network might subserve relatively preserved cognitions and impaired motor functions in cerebral palsy. This study suggests that the structure-function relationship, evaluated specifically using sparse functional connectivity, may reveal important clues to functional reorganization in cerebral palsy. Hum Brain Mapp 38:5292-5306, 2017. © 2017 Wiley Periodicals

Cerebral ischemic injury decreases α-synuclein expression in brain tissue and glutamate-exposed HT22 cells.

Science.gov (United States)

Koh, Phil-Ok

2017-09-01

α-Synuclein is abundantly expressed in neuronal tissue, plays an essential role in the pathogenesis of neurodegenerative disorders, and exerts a neuroprotective effect against oxidative stress. Cerebral ischemia causes severe neurological disorders and neuronal dysfunction. In this study, we examined α-synuclein expression in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury and neuronal cells damaged by glutamate treatment. MCAO surgical operation was performed on male Sprague-Dawley rats, and brain samples were isolated 24 hours after MCAO. We confirmed neurological behavior deficit, infarction area, and histopathological changes following MCAO injury. A proteomic approach and Western blot analysis demonstrated a decrease in α-synuclein in the cerebral cortices after MCAO injury. Moreover, glutamate treatment induced neuronal cell death and decreased α-synuclein expression in a hippocampal-derived cell line in a dose-dependent manner. It is known that α-synuclein regulates neuronal survival, and low levels of α-synuclein expression result in cytotoxicity. Thus, these results suggest that cerebral ischemic injury leads to a reduction in α-synuclein and consequently causes serious brain damage.

A Means for the Scintigraphic Imaging of Regional Brain Dynamics. Regional Cerebral Blood Flow and Regional Cerebral Blood Volume

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Potchen, E. J.; Bentley, R.; Gerth, W.; Hill, R. L.; Davis, D. O. [Washington University School Of Medicine, St. Louis, MO (United States)

1969-05-15

The use of freely diffusable inert radioactive gas as a washout indicator to measure regional cerebral blood flow has become a standardized kinetic procedure in many laboratories. Recent investigations with this technique have led us to conclude that we can reliably distinguish regional flow with perfusion against regional flow without perfusion from the early portion of the curve. Based on a detailed study of the early curve kinetics in patients with and without cerebral vascular disease we have defined the sampling duration necessary for application of the Anger gamma camera imaging process to regional changes in cerebral radioactivity. Using a standard camera and a small computer, a procedure has been developed and based upon entire field to determine the time of maximum height followed by analysis of the data in a matrix. This will permit a contour plot presentation of calculated regional cerebral blood flow in millilitres per 100 grams perfused brain per minute. In addition, we propose to augment this data by the display of regional non-perfusion blood flow versus regional cerebral flow with perfusion. Preliminary investigation on sampling duration, and Compton scattering were prerequisite to clinical scintigraphy of regional cerebral blood flow. In addition, the method of interface for the conventional Anger gamma camera to digital computers used in this procedure are discussed. Applications to further assess regional cerebral dynamics by scintigraphy are presented. (author)

Pretreatment with Sodium Phenylbutyrate Alleviates Cerebral Ischemia/Reperfusion Injury by Upregulating DJ-1 Protein

Directory of Open Access Journals (Sweden)

Rui-Xin Yang

2017-06-01

Full Text Available Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB, against I/R injury by protecting mitochondrial dysfunction via the upregulation of DJ-1 protein. Pretreatment with SPB upregulated the DJ-1 protein level and rescued the I/R injury-induced DJ-1 decrease about 50% both in vivo and in vitro. SPB also improved cellular viability and mitochondrial function and alleviated neuronal apoptosis both in cell and animal models; these effects of SPB were abolished by DJ-1 knockdown with siRNA. Furthermore, SPB improved the survival rate about 20% and neurological functions, as well as reduced about 50% of the infarct volume and brain edema, of middle cerebral artery occlusion mice 23 h after reperfusion. Therefore, our findings demonstrate that preconditioning of SPB possesses a neuroprotective effect against cerebral I/R injury by protecting mitochondrial function dependent on the DJ-1 upregulation, suggesting that DJ-1 is a potential therapeutic target for clinical ischemic stroke.

Pretreatment with Sodium Phenylbutyrate Alleviates Cerebral Ischemia/Reperfusion Injury by Upregulating DJ-1 Protein.

Science.gov (United States)

Yang, Rui-Xin; Lei, Jie; Wang, Bo-Dong; Feng, Da-Yun; Huang, Lu; Li, Yu-Qian; Li, Tao; Zhu, Gang; Li, Chen; Lu, Fang-Fang; Nie, Tie-Jian; Gao, Guo-Dong; Gao, Li

2017-01-01

Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R) injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB), against I/R injury by protecting mitochondrial dysfunction via the upregulation of DJ-1 protein. Pretreatment with SPB upregulated the DJ-1 protein level and rescued the I/R injury-induced DJ-1 decrease about 50% both in vivo and in vitro . SPB also improved cellular viability and mitochondrial function and alleviated neuronal apoptosis both in cell and animal models; these effects of SPB were abolished by DJ-1 knockdown with siRNA. Furthermore, SPB improved the survival rate about 20% and neurological functions, as well as reduced about 50% of the infarct volume and brain edema, of middle cerebral artery occlusion mice 23 h after reperfusion. Therefore, our findings demonstrate that preconditioning of SPB possesses a neuroprotective effect against cerebral I/R injury by protecting mitochondrial function dependent on the DJ-1 upregulation, suggesting that DJ-1 is a potential therapeutic target for clinical ischemic stroke.

A Microarray Study of Middle Cerebral Occlusion Rat Brain with Acupuncture Intervention

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Chao Zhang

2015-01-01

Full Text Available Microarray analysis was used to investigate the changes of gene expression of ischemic stroke and acupuncture intervention in middle cerebral artery occlusion (MCAo rat brain. Results showed that acupuncture intervention had a remarkable improvement in neural deficit score, cerebral blood flow, and cerebral infarction volume of MCAo rats. Microarray analysis showed that a total of 627 different expression genes were regulated in ischemic stroke. 417 genes were upregulated and 210 genes were downregulated. A total of 361 different expression genes were regulated after acupuncture intervention. Three genes were upregulated and 358 genes were downregulated. The expression of novel genes after acupuncture intervention, including Tph1 and Olr883, was further analyzed by Real-Time Quantitative Polymerase Chain Reaction (RT-PCR. Upregulation of Tph1 and downregulation of Olr883 indicated that the therapeutic effect of acupuncture for ischemic stroke may be closely related to the suppression of poststroke depression and regulation of olfactory transduction. In conclusion, the present study may enrich our understanding of the multiple pathological process of ischemic brain injury and indicate possible mechanisms of acupuncture on ischemic stroke.

Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

OpenAIRE

Najmeh Kabiri; Mahbubeh Setorki

2016-01-01

The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99). Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly hi...

Endothelial glycocalyx on brain endothelial cells is lost in experimental cerebral malaria

DEFF Research Database (Denmark)

Hempel, Casper; Hyttel, Poul; Kurtzhals, Jørgen Al

2014-01-01

We hypothesized that the glycocalyx, which is important for endothelial integrity, is lost in severe malaria. C57BL/6 mice were infected with Plasmodium berghei ANKA, resulting in cerebral malaria, or P. chabaudi AS, resulting in uncomplicated malaria. We visualized the glycocalyx with transmission...... electron microscopy and measured circulating glycosaminoglycans by dot blot and ELISA. The glycocalyx was degraded in brain vasculature in cerebral and to a lesser degree uncomplicated malaria. It was affected on both intact and apoptotic endothelial cells. Circulating glycosaminoglycan levels suggested...

Demonstration of cerebral abnormalities in cocaine abusers with SPECT perfusion brain scans

International Nuclear Information System (INIS)

Nagel, J.S.; Tumeh, S.S.; English, R.J.; Moore, M.; Lee, V.W.; Holman, L.B.

1989-01-01

This paper reports I-123 isopropyl iodoamphetamine (IMP) single-photon emission CT (SPECT) brain scans performed on cocaine users to investigate the effects of cocaine on the cerebral perfusion in a manner similar to previous CT, angiographic and positron-emission tomographic (PET) studies. Ten asymptomatic or mildly symptomatic cocaine users, two users with major neurovascular complications, and five normal subjects were studied with IMP SPECT. Rotating-brain images of the cerebral IMP uptake were displayed by using a distance-weighted surface-projection technique and were visually analyzed for focal cortical perfusion deficits. Eleven cocaine users had multiple scattered cortical IMP defects. Frontal lobe defects were most prominent. One user had confluent defects resembling swiss cheese. Concurrent CT scans available in nine patients were negative in seven and showed infarcts in two. No similar focal findings were visible in normals

Forensic applications of cerebral single photon emission computed tomography in mild traumatic brain injury.

Science.gov (United States)

Wortzel, Hal S; Filley, Christopher M; Anderson, C Alan; Oster, Timothy; Arciniegas, David B

2008-01-01

Traumatic brain injury (TBI) is a substantial source of mortality and morbidity world wide. Although most such injuries are relatively mild, accurate diagnosis and prognostication after mild TBI are challenging. These problems are complicated further when considered in medicolegal contexts, particularly civil litigation. Cerebral single photon emission computed tomography (SPECT) may contribute to the evaluation and treatment of persons with mild TBI. Cerebral SPECT is relatively sensitive to the metabolic changes produced by TBI. However, such changes are not specific to this condition, and their presence on cerebral SPECT imaging does not confirm a diagnosis of mild TBI. Conversely, the absence of abnormalities on cerebral SPECT imaging does not exclude a diagnosis of mild TBI, although such findings may be of prognostic value. The literature does not demonstrate consistent relationships between SPECT images and neuropsychological testing or neuropsychiatric symptoms. Using the rules of evidence shaped by Daubert v. Merrell Dow Pharmaceuticals, Inc., and its progeny to analyze the suitability of SPECT for forensic purposes, we suggest that expert testimony regarding SPECT findings should be admissible only as evidence to support clinical history, neuropsychological test results, and structural brain imaging findings and not as stand-alone diagnostic data.

Cerebral blood flow and brain atrophy correlated by xenon contrast CT scanning

International Nuclear Information System (INIS)

Kitagawa, Y.; Meyer, J.S.; Tanahashi, N.; Rogers, R.L.; Tachibana, H.; Kandula, P.; Dowell, R.E.; Mortel, K.F.

1985-01-01

Correlations between cerebral blood flow (CBF) measured during stable xenon contrast CT scanning and standard CT indices of brain atrophy were investigated in the patients with senile dementia of Alzheimer type, multi-infarct dementia and idiopathic Parkinson's disease. Compared to age-matched normal volunteers, significant correlations were found in patients with idiopathic Parkinson's disease between cortical and subcortical gray matter blood flow and brain atrophy estimated by the ventricular body ratio, and mild to moderate brain atrophy were correlated with stepwise CBF reductions. However, in patients with senile dementia of Alzheimer type and multi-infarct dementia, brain atrophy was not associated with stepwise CBF reductions. Overall correlations between brain atrophy and reduced CBF were weak. Mild degrees of brain atrophy are not always associated with reduced CBF

Language Development and Brain Magnetic Resonance Imaging Characteristics in Preschool Children with Cerebral Palsy

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Choi, Ja Young; Choi, Yoon Seong; Park, Eun Sook

2017-01-01

Purpose: The purpose of this study was to investigate characteristics of language development in relation to brain magnetic resonance imaging (MRI) characteristics and the other contributing factors to language development in children with cerebral palsy (CP). Method: The study included 172 children with CP who underwent brain MRI and language…

Corvitin restores metallothionein and glial fibrillary acidic protein levels in rat brain affected by pituitrin-izadrin

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H. N. Shiyntum

2017-06-01

Full Text Available In this research, we investigated the effect of pituitrin-izadrin induced injury on the levels of metallothionein (MT and soluble and filament forms of glial fibrillary acidic protein (GFAP in the hippocampus, cerebellum, thalamus, and the cerebral cortex, and examined the effect of corvitin on the brain under the noted changes. Our results showed oppositely directed changes – a decrease in the level of MT and an increase in GFAP in the rat brain, with a tendency to astrogliosis development, under the influence of systemic deficiencies in myocardial function. The use of corvitin at a dose of 42 mg/kg for five days after a cardiac attack caused by pituitary-izadrin leads to recovery in the balance of the studied proteins.

Hypothyroidism coordinately and transiently affects myelin protein gene expression in most rat brain regions during postnatal development.

Science.gov (United States)

Ibarrola, N; Rodríguez-Peña, A

1997-03-28

To assess the role of thyroid hormone on myelin gene expression, we have studied the effect of hypothyroidism on the mRNA steady state levels for the major myelin protein genes: myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG) and 2':3'-cyclic nucleotide 3'-phosphodiesterase (CNP) in different rat brain regions, during the first postnatal month. We found that hypothyroidism reduces the levels of every myelin protein transcript, with striking differences between the different brain regions. Thus, in the more caudal regions, the effect of hypothyroidism was extremely modest, being only evident at the earlier stages of myelination. In contrast, in the striatum and the cerebral cortex the important decrease in the myelin protein transcripts is maintained beyond the first postnatal month. Therefore, thyroid hormone modulates in a synchronous fashion the expression of the myelin genes and the length of its effect depends on the brain region. On the other hand, hyperthyroidism leads to an increase of the major myelin protein transcripts above control values. Finally, lack of thyroid hormone does not change the expression of the oligodendrocyte progenitor-specific gene, the platelet derived growth factor receptor alpha.

Analysis of human cerebral functions using positron emission tomography (PET)

International Nuclear Information System (INIS)

Shibasaki, Takashi

1984-01-01

Positron emission tomography has two major advantages to analyse human cerebral functions in vivo. First, we can see the distribution of a variety of substance in the living (and doing something) human brain. Positron emitters, 11 C, 13 N, 15 O and 18 F, are made by medical cyclotron and are elements of natural substrates or easily tagged to substrate. Second, the distribution of the tracer is calculated to make a quantitative functional map in a reasonable spatial resolution over the entire brain in the same time. Not only cortical areas but also deeper structures show regional cerebral blood flow (rCBF) or local cerebral metabolic rates (LCMRs). Nowadays, PET is put to practical use for determination of mainly rCBF, LCMR for glucose (LCMRsub(glu)), LCMR for oxygen (LCMRsub(o2)) and regional cerebral blood volume (rCBV). There have been many other pilot studies, such as estimation of distribution of given neurotransmitters or modulators in the brain which also confirms the substances' role in the neuronal function, and observation of protein synthesis relating to memory function. (J.P.N.)

Anencefalia e morte cerebral (neurológica Anencephaly and brain death

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Maria Lúcia Fernandes Penna

2005-06-01

Full Text Available Vem-se discutindo no país a ética da interrupção da gravidez no caso de fetos anencéfalos. Os opositores ao aborto nesses casos apontam, entre outros argumentos, que não se trata de morte cerebral devido à presença de tronco encefálico. Neste artigo discutimos o conceito de morte cerebral e sua aplicação no que tange à anencefalia. Apontamos alguns aspectos históricos do desenvolvimento desse conceito e a importância de ser considerada a diferença entre conceito e critérios. A morte neurológica é a perda definitiva e total da consciência, enquanto a presença do tronco cerebral é apenas um critério a ser usado nos casos de lesão encefálica em encéfalos antes perfeitos. O conceito de morte cerebral se aplica completamente à ausência de córtex dos anencéfalos, o que sem dúvida permite sua retirada do útero materno. Manter juridicamente a criminalização desse procedimento é uma interferência religiosa no Estado laico e democrático, que impede o exercício de escolha pelos indivíduos segundo seu credo.Brazilian society has recently discussed the ethics of interrupting pregnancy in the case of an anencephalic fetus. In such cases, anti-abortionists contend that anencephaly is not the same as brain death, since a brainstem is present. This article discusses the concept of brain death and its application to the issue of anencephaly. We point to key historical aspects in the development of this concept and the importance of considering the difference between concept and criteria. Neurological death is the definitive and complete loss of consciousness, while the presence of a brainstem is merely a criterion to be used in cases of head injury in previously intact brains. The concept of brain death is totally applicable to the absence of cortex in a fetus with anencephaly, which without a doubt allows such a fetus to be removed from the uterus. To maintain the criminalization of this procedure by legal means represents

Nanomedicine in cerebral palsy

Science.gov (United States)

Balakrishnan, Bindu; Nance, Elizabeth; Johnston, Michael V; Kannan, Rangaramanujam; Kannan, Sujatha

2013-01-01

Cerebral palsy is a chronic childhood disorder that can have diverse etiologies. Injury to the developing brain that occurs either in utero or soon after birth can result in the motor, sensory, and cognitive deficits seen in cerebral palsy. Although the etiologies for cerebral palsy are variable, neuroinflammation plays a key role in the pathophysiology of the brain injury irrespective of the etiology. Currently, there is no effective cure for cerebral palsy. Nanomedicine offers a new frontier in the development of therapies for prevention and treatment of brain injury resulting in cerebral palsy. Nanomaterials such as dendrimers provide opportunities for the targeted delivery of multiple drugs that can mitigate several pathways involved in injury and can be delivered specifically to the cells that are responsible for neuroinflammation and injury. These materials also offer the opportunity to deliver agents that would promote repair and regeneration in the brain, resulting not only in attenuation of injury, but also enabling normal growth. In this review, the current advances in nanotechnology for treatment of brain injury are discussed with specific relevance to cerebral palsy. Future directions that would facilitate clinical translation in neonates and children are also addressed. PMID:24204146

Clinical studies of cerebral arteriosclerosis in diabetic subjects. Analysis with brain MRI study

International Nuclear Information System (INIS)

Ohashi, Makoto; Tanahashi, Hideo; Nomura, Makoto; Yamada, Yoshio; Abe, Hiroshi.

1994-01-01

In order to investigate the clinical characteristics of cerebral arteriosclerosis in diabetic subjects, brain MRI studies were conducted in diabetic patients and healthy subjects. The subjects were 93 diabetic patients without symptoms and signs of cerebral infarction (49 males and 44 females) with a mean age of 59 years and 73 healthy subjects (43 males and 30 females) with a mean age of 57 years. The MRI studies were performed on a General Electric 1.5-T signa system. The spin-echo technique (T2-weighted image) was used with a pulse repetition time (TR) of 2,500 msec and echo time (TE) of 80 msec. The quantitative evaluation of cerebral infarction was assessed using personal computer and image-scanner. By MRI, the incidence of cerebral infarction in diabetic patients was significantly higher than that in healthy subjects (30.1% vs. 13.7%, respectively, p<0.05). The mean age of the diabetic patients with cerebral infarctions was higher than that of those without cerebral infarctions. Hypertension and diabetic nephropathy were present more frequently in the subjects with cerebral infarctions. These data suggest that it is important to delay the onset and slow the progression of cerebral infarction in diabetic patients by strict blood glucose control and management of blood pressure. (author)

Motricidade reflexa na morte cerebral The reflex activity in the brain death

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Wilson L. Sanvito

1972-03-01

Full Text Available O diagnóstico de morte cerebral está baseado em critérios clínicos, eletrencefalográficos e angiográficos. Do ponto de vista clínico deve ser evidenciado o seguinte quadro: coma profundo, midríase paralítica bilateral, ausência de reação a qualquer estímulo externo, apnéia, arreflexia superficial e profunda. Do ponto de vista eletrencefalográfico são necessários dois registros, separados por um intervalo de 24 horas, evidenciando traçados iselétricos. No presente trabalho são estudados 15 pacientes com morte cerebral comprovada do ponto de vista clínico e eletrencefalográfico. Em 8 pacientes havia persistência de atividade reflexa durante a fase de morte cerebral (reflexos profundos e/ou superficiais. Fenômenos de automatismos medulares também foram verificados em 3 pacientes.The diagnosis of brain death is based in clinical, electroencephalographic and angiographic data. The criteria for diagnosis of brain death are: deep coma with unreceptivity and unresponsiveness, no movements or breathing (the patient's respiration must be maintained artificially, bilateral dilated and fixed pupils, absence of corneal reflexes, no response to caloric test, absence of deep tendon reflexes and of the superficial abdominal and plantar reflexes, isoelectric EEG maintained for twenty-four hours. The purpose of this study was to observe the natural clinical courses of 15 patients with brain death, specially the data concerning the deep and superficial reflexes. From 15 patients fulfilling the criteria of brain death, 8 maintained spinal reflexes up to the time of cardiac arrest; in five of these patients the superficial abdominal reflexes were present and the reflexes of spinal automatism could be elicited. These results show that the absence of deep and superficial reflexes can't be considered as essencial for the diagnosis of brain death.

A comparative study: use of a Brain-computer Interface (BCI) device by people with cerebral palsy in interaction with computers.

Science.gov (United States)

Heidrich, Regina O; Jensen, Emely; Rebelo, Francisco; Oliveira, Tiago

2015-01-01

This article presents a comparative study among people with cerebral palsy and healthy controls, of various ages, using a Brain-computer Interface (BCI) device. The research is qualitative in its approach. Researchers worked with Observational Case Studies. People with cerebral palsy and healthy controls were evaluated in Portugal and in Brazil. The study aimed to develop a study for product evaluation in order to perceive whether people with cerebral palsy could interact with the computer and compare whether their performance is similar to that of healthy controls when using the Brain-computer Interface. Ultimately, it was found that there are no significant differences between people with cerebral palsy in the two countries, as well as between populations without cerebral palsy (healthy controls).

Diffuse brain calcification after radiation therapy in infantile cerebral malignant glioma

International Nuclear Information System (INIS)

Hondo, Hiroaki; Tanaka, Ryuichi; Yamada, Nobuhisa; Takeda, Norio

1987-01-01

We reported a case of infantile cerebral malignant glioma, which showed extensive intracranial calcification following radiation therapy, and reviewed the literature. A 4-month-old female infant was admitted to our hospital because of vomiting, enlargement of the head and convulsive seizures. Computerized tomography (CT) scans demonstrated a heterogeneously contrast-enhanced mass in the right temporo-parieto-occipital region and marked obstructive hydrocephalus. Subsequent to ventriculo-peritoneal shunt, biopsy was performed. The surgical specimen revealed anaplastic glioma. She then underwent whole brain irradiation with 1800 rads before subtotal removal and 3000 rads postoperatively. Calcification was first identified in the right frontal region and left basal ganglia 2.5 months after radiation therapy. At the age of 14 months, CT scans demonstrated extensive intracranial calcification in the cerebral hemispheres, basal ganglias, thalami, pons and cerebellum. A biopsy specimen of the frontal lobe revealed calcospherites of various sizes within and beside the walls of small vessels, but no tumor cells were observed. Cranial radiation therapy is a standard modality for treatment of children with neoplasm in the central nervous system. Since, however this therapy possibly causes long-term complications on the developing brain, it is important to plan radiation therapy for the brain tumor carefully. (author)

Clinical and neuroimaging profile of congenital brain malformations in children with spastic cerebral palsy

International Nuclear Information System (INIS)

Kulak, W.; Okurowska-Zawada, B.; Sobaniec, W.; Goscik, M.; Olenski, J.

2008-01-01

Purpose: Analysis of the incidence of congenital brain malformations in children with spastic cerebral palsy (CP) in a hospital based study. Material and Methods: The present study included 74 boys and 56 girls with spastic tetraplegia, diplegia, and hemiplegia CP. Magnetic resonance imaging MRI findings were analyzed in children with CP. Results: Significant abnormalities relevant to the CP were evident on MRI in 124 (95.3%) subjects. Periventicular leukomalacia (PVL) was detected more frequently in children with spastic diplegia than in patients with tetraplegia or hemiplegia. Cerebral atrophy was found more often in the tetraplegic group compared to the diplegic patients. Porencephalic cysts were detected more often in children with spastic hemiplegia. Congenital brain anomalies were evident in 15 (10.7%) children with spastic CP. Brain malformations included: schizencephaly (5), agenesis corpus callosum (4), polymicrogyria (2), holoprosencephaly (2) and lissencephaly (2). Intractable epilepsy and mental retardation were observed more often in children with brain anomalies. Twelve patients with congenital brain malformations were born at term and three born at preterm. Conclusions: Neuroimaging results in children with CP may help determine the etiology and make better prognosis of CP. (authors)

A novel bioactivity of andrographolide from Andrographis paniculata on cerebral ischemia/reperfusion-induced brain injury through induction of cerebral endothelial cell apoptosis.

Science.gov (United States)

Yen, Ting-Lin; Hsu, Wen-Hsien; Huang, Steven Kuan-Hua; Lu, Wan-Jung; Chang, Chao-Chien; Lien, Li-Ming; Hsiao, George; Sheu, Joen-Rong; Lin, Kuan-Hung

2013-09-01

Andrographolide, extracted from the leaves of Andrographis paniculata (Burm. f.) Nees (Acanthaceae), is a labdane diterpene lactone. It is widely reported to possess anti-inflammatory and antitumorigenic activities. Cerebral endothelial cells (CECs) play a crucial role in supporting the integrity and the function of the blood-brain barrier (BBB). However, no data are available concerning the effects of andrographolide in CECs. The aim of this study was to examine the detailed mechanisms of andrographolide on CECs. This study investigated a novel bioactivity of andrographolide on cerebral ischemia/reperfusion-induced brain injury. CECs were treated with andrographolide (20-100 µΜ) for the indicated times (0-24 h). After the reactions, cell survival rate and cytotoxicity were tested by the MTT assay and the lactate dehydrogenase (LDH) test, respectively. Western blotting was used to detect caspase-3 expression. In addition, analysis of cell cycle and apoptosis using PI staining and annexin V-FITC/PI labeling, respectively, was performed by flow cytometry. We also investigated the effect of andrographolide on middle cerebral artery occlusion (MCAO)/reperfusion-induced brain injury in a rat model. In the present study, we found that andrographolide (50-100 µΜ) markedly inhibited CEC growth according to an MTT assay and caused CEC damage according to a LDH test. Our data also revealed that andrographolide (50 µM) induced CEC apoptosis and caspase-3 activation as respectively detected by PI/annexin-V double staining and western blotting. Moreover, andrographolide arrested the CEC cell cycle at the G0/G1 phase by PI staining. In addition, andrographolide (5 mg/kg) caused deterioration of MCAO/reperfusion-induced brain injury in a rat model. These data suggest that andrographolide may disrupt BBB integrity, thereby deteriorating MCAO/reperfusion-induced brain injury, which are, in part, associated with its capacity to arrest cell-cycle and induce CEC

In vivo imaging of brain ischemia using an oxygen-dependent degradative fusion protein probe.

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Youshi Fujita

Full Text Available Within the ischemic penumbra, blood flow is sufficiently reduced that it results in hypoxia severe enough to arrest physiological function. Nevertheless, it has been shown that cells present within this region can be rescued and resuscitated by restoring perfusion and through other protective therapies. Thus, the early detection of the ischemic penumbra can be exploited to improve outcomes after focal ischemia. Hypoxia-inducible factor (HIF-1 is a transcription factor induced by a reduction in molecular oxygen levels. Although the role of HIF-1 in the ischemic penumbra remains unknown, there is a strong correlation between areas with HIF-1 activity and the ischemic penumbra. We recently developed a near-infrared fluorescently labeled-fusion protein, POH-N, with an oxygen-dependent degradation property identical to the alpha subunit of HIF-1. Here, we conduct in vivo imaging of HIF-active regions using POH-N in ischemic brains after transient focal cerebral ischemia induced using the intraluminal middle cerebral artery occlusion technique in mice. The results demonstrate that POH-N enables the in vivo monitoring and ex vivo detection of HIF-1-active regions after ischemic brain injury and suggest its potential in imaging and drug delivery to HIF-1-active areas in ischemic brains.

Plasmalemmal Vesicle Associated Protein-1 (PV-1 is a marker of blood-brain barrier disruption in rodent models

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Ali Zarina S

2008-02-01

Full Text Available Abstract Background Plasmalemmal vesicle associated protein-1 (PV-1 is selectively expressed in human brain microvascular endothelial cells derived from clinical specimens of primary and secondary malignant brain tumors, cerebral ischemia, and other central nervous system (CNS diseases associated with blood-brain barrier breakdown. In this study, we characterize the murine CNS expression pattern of PV-1 to determine whether localized PV-1 induction is conserved across species and disease state. Results We demonstrate that PV-1 is selectively upregulated in mouse blood vessels recruited by brain tumor xenografts at the RNA and protein levels, but is not detected in non-neoplastic brain. Additionally, PV-1 is induced in a mouse model of acute ischemia. Expression is confined to the cerebovasculature within the region of infarct and is temporally regulated. Conclusion Our results confirm that PV-1 is preferentially induced in the endothelium of mouse brain tumors and acute ischemic brain tissue and corresponds to blood-brain barrier disruption in a fashion analogous to human patients. Characterization of PV-1 expression in mouse brain is the first step towards development of rodent models for testing anti-edema and anti-angiogenesis therapeutic strategies based on this molecule.

The correlation of insulin resistance with the cerebral injury and stress reaction in patients with traumatic brain injury

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Zhan Lan

2017-04-01

Full Text Available Objective: To study the correlation of insulin resistance with the cerebral injury and stress reaction in patients with traumatic brain injury (TBI. Methods: 78 patients who were diagnosed with acute traumatic brain injury in our hospital between May 2014 and August 2016 were selected as the TBI group, and 90 healthy volunteers who received physical examination during the same period were selected as the control group. The peripheral blood was collected to detect glucose, insulin and nerve injury marker molecules, stress hormones as well as oxidative stress reaction products, and the insulin resistance index (HOMA-IR was calculated. Results: The HOMA-IR index of TBI group was significantly higher than that of control group (P<0.05; serum neuron-specific enolase (NSE, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1, S100β, myelin basic protein (MBP, glucagon, growth hormone, cortisol, malondialdehyde (MDA and 8-hydroxy-deoxyguanosine (8-OHdGlevels of TBI group were significantly higher than those of control group (P<0.05; serum NSE, UCH-L1, S100β, MBP, glucagon, growth hormone, cortisol, MDA and 8-OHdG levels of patients with high HOMA-IR were significantly higher than those of patients with low HOMA-IR (P<0.05. Conclusion: The insulin resistance increases significantly in patients with traumatic brain injury, and is closely related to the degree of cerebral injury and stress reaction.

Differences in fatty acid composition between cerebral brain lobes in juvenile pigs after fish oil feeding

NARCIS (Netherlands)

Dullemeijer, Carla; Zock, Peter L.; Coronel, Ruben; den Ruijter, Hester M.; Katan, Martijn B.; Brummer, Robert-Jan M.; Kok, Frans J.; Beekman, Jet; Brouwer, Ingeborg A.

2008-01-01

Very long-chain n-3 PUFA from fish are suggested to play a role in the development of the brain. Fish oil feeding results in higher proportions of n-3 PUFA in the brains of newborn piglets. However, the effect of fish oil on the fatty acid composition of specific cerebral brain lobes in juvenile

Cerebral atrophic and degenerative changes following various cerebral diseases, (1)

International Nuclear Information System (INIS)

Kino, Masao; Anno, Izumi; Yano, Yuhiko; Anno, Yasuro.

1980-01-01

Patients having cerebral atrophic and degenerative changes following hypoglycemia, cerebral contusion, or cerebral hypoxia including cerebrovascular disorders were reported. Description was made as to cerebral changes visualized on CT images and clinical courses of a patient who revived 10 minutes after heart stoppage during neurosurgery, a newborn with asphyxia, a patient with hypoglycemia, a patient who suffered from asphyxia by an accident 10 years before, a patient with carbon monoxide poisoning at an acute stage, a patient who had carbon monoxide poisoning 10 years before, a patient with diffuse cerebral ischemic changes, a patient with cerebral edema around metastatic tumor, a patient with respiration brain, a patient with neurological sequelae after cerebral contusion, a patient who had an operation to excise right parietal lobe artery malformation, and a patient who was shooted by a machine gun and had a lead in the brain for 34 years. (Tsunoda, M.)

Tunicamycin-induced unfolded protein response in the developing mouse brain

International Nuclear Information System (INIS)

Wang, Haiping; Wang, Xin; Ke, Zun-Ji; Comer, Ashley L.; Xu, Mei; Frank, Jacqueline A.; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

2015-01-01

Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident by the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific

Tunicamycin-induced unfolded protein response in the developing mouse brain

Energy Technology Data Exchange (ETDEWEB)

Wang, Haiping; Wang, Xin [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Ke, Zun-Ji [Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203 (China); Comer, Ashley L.; Xu, Mei; Frank, Jacqueline A. [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Zhang, Zhuo; Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Luo, Jia, E-mail: jialuo888@uky.edu [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States)

2015-03-15

Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident by the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific.

Regional gray matter growth, sexual dimorphism, and cerebral asymmetry in the neonatal brain.

Science.gov (United States)

Gilmore, John H; Lin, Weili; Prastawa, Marcel W; Looney, Christopher B; Vetsa, Y Sampath K; Knickmeyer, Rebecca C; Evans, Dianne D; Smith, J Keith; Hamer, Robert M; Lieberman, Jeffrey A; Gerig, Guido

2007-02-07

Although there has been recent interest in the study of childhood and adolescent brain development, very little is known about normal brain development in the first few months of life. In older children, there are regional differences in cortical gray matter development, whereas cortical gray and white matter growth after birth has not been studied to a great extent. The adult human brain is also characterized by cerebral asymmetries and sexual dimorphisms, although very little is known about how these asymmetries and dimorphisms develop. We used magnetic resonance imaging and an automatic segmentation methodology to study brain structure in 74 neonates in the first few weeks after birth. We found robust cortical gray matter growth compared with white matter growth, with occipital regions growing much faster than prefrontal regions. Sexual dimorphism is present at birth, with males having larger total brain cortical gray and white matter volumes than females. In contrast to adults and older children, the left hemisphere is larger than the right hemisphere, and the normal pattern of fronto-occipital asymmetry described in older children and adults is not present. Regional differences in cortical gray matter growth are likely related to differential maturation of sensory and motor systems compared with prefrontal executive function after birth. These findings also indicate that whereas some adult patterns of sexual dimorphism and cerebral asymmetries are present at birth, others develop after birth.

Thyroid Hormone Economy in the Perinatal Mouse Brain: Implications for Cerebral Cortex Development.

Science.gov (United States)

Bárez-López, Soledad; Obregon, Maria Jesus; Bernal, Juan; Guadaño-Ferraz, Ana

2018-05-01

Thyroid hormones (THs, T4 and the transcriptionally active hormone T3) play an essential role in neurodevelopment; however, the mechanisms underlying T3 brain delivery during mice fetal development are not well known. This work has explored the sources of brain T3 during mice fetal development using biochemical, anatomical, and molecular approaches. The findings revealed that during late gestation, a large amount of fetal brain T4 is of maternal origin. Also, in the developing mouse brain, fetal T3 content is regulated through the conversion of T4 into T3 by type-2 deiodinase (D2) activity, which is present from earlier prenatal stages. Additionally, D2 activity was found to be essential to mediate expression of T3-dependent genes in the cerebral cortex, and also necessary to generate the transient cerebral cortex hyperthyroidism present in mice lacking the TH transporter Monocarboxylate transporter 8. Notably, the gene encoding for D2 (Dio2) was mainly expressed at the blood-cerebrospinal fluid barrier (BCSFB). Overall, these data signify that T4 deiodinated by D2 may be the only source of T3 during neocortical development. We therefore propose that D2 activity at the BCSFB converts the T4 transported across the choroid plexus into T3, thus supplying the brain with active hormone to maintain TH homeostasis.

Regional cerebral blood flow in psychiatry: The resting and activated brains of schizophrenic patients

International Nuclear Information System (INIS)

Gur, R.E.

1984-01-01

The investigation of regional brain functioning in schizophrenia has been based on behavioral techniques. Although results are sometimes inconsistent, the behavioral observations suggest left hemispheric dysfunction and left hemispheric overreaction. Recent developments in neuroimaging technology make possible major refinements in assessing regional brain function. Both anatomical and physiological information now be used to study regional brain development in psychiatric disorders. This chapter describes the application of one method - the xenon-133 technique for measuring regional cerebral blood flow (rCBF) - in studying the resting and activated brains of schizoprenic patients

NADPH Oxidase Activity in Cerebral Arterioles Is a Key Mediator of Cerebral Small Vessel Disease-Implications for Prevention.

Science.gov (United States)

McCarty, Mark F

2015-04-15

Cerebral small vessel disease (SVD), a common feature of brain aging, is characterized by lacunar infarcts, microbleeds, leukoaraiosis, and a leaky blood-brain barrier. Functionally, it is associated with cognitive decline, dementia, depression, gait abnormalities, and increased risk for stroke. Cerebral arterioles in this syndrome tend to hypertrophy and lose their capacity for adaptive vasodilation. Rodent studies strongly suggest that activation of Nox2-dependent NADPH oxidase activity is a crucial driver of these structural and functional derangements of cerebral arterioles, in part owing to impairment of endothelial nitric oxide synthase (eNOS) activity. This oxidative stress may also contribute to the breakdown of the blood-brain barrier seen in SVD. Hypertension, aging, metabolic syndrome, smoking, hyperglycemia, and elevated homocysteine may promote activation of NADPH oxidase in cerebral arterioles. Inhibition of NADPH oxidase with phycocyanobilin from spirulina, as well as high-dose statin therapy, may have potential for prevention and control of SVD, and high-potassium diets merit study in this regard. Measures which support effective eNOS activity in other ways-exercise training, supplemental citrulline, certain dietary flavonoids (as in cocoa and green tea), and capsaicin, may also improve the function of cerebral arterioles. Asian epidemiology suggests that increased protein intakes may decrease risk for SVD; conceivably, arginine and/or cysteine-which boosts tissue glutathione synthesis, and can be administered as N-acetylcysteine-mediate this benefit. Ameliorating the risk factors for SVD-including hypertension, metabolic syndrome, hyperglycemia, smoking, and elevated homocysteine-also may help to prevent and control this syndrome, although few clinical trials have addressed this issue to date.

Detection of cerebral atrophy in type- II diabetes mellitus by magnetic resonance imaging of brain

International Nuclear Information System (INIS)

Khan, G.; Khan, N.; Aziz, A.

2010-01-01

Background: Diabetes is a metabolic disorder that affects many systems in the body. Cerebral atrophy is one of the complications of diabetes and research is on going to find out its aetiopathological factors. The main aim of the study was to determine the frequency of cerebral atrophy in type-II diabetes mellitus using magnetic resonance imaging of the brain. Methods: One hundred diabetic patients (Random blood sugar >126 mg/dl) were recruited in this study after the informed consent from every patient. Duration of diabetes was five years and more in all the patients as determined by their glycosylated haemoglobin which was >6 in all the patients. All the patients were undergone MRI of brain using 1.5 Tesla power magnetic resonance imaging machine of Picker Company. Evan's index, a specific parameter for measurement of cerebral atrophy was calculated on MR images and was used in this study. Results: In male group the frequency of cerebral atrophy was 22 (47%) and in female group it was found to be 23 (43%). When we study the overall population the frequency was found to be 45 (45%). The results are well in concordance with the previous data published on this issue. Conclusions: Cerebral atrophy, a complication of long standing diabetes is quite frequent in our population and is well diagnosed by MRI. (author)

Changes in cerebral blood flow and psychometric indicators in veterans with early forms of chronic brain ischemia

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Vasilenko Т.М.

2015-09-01

Full Text Available The goal is to study the cerebral blood flow and psychometric characteristics in veterans of Afghanistan with early forms of chronic brain ischemia. Material and Methods. The study included 74 veterans of the Afghan war aged from 45 to 55 years: group 1, 28 people with NPNKM; Group 2-28 patients with circulatory encephalopathy stage 1; group 3-18 healthy persons. Doppler examination of cerebral vessels was carried out on the unit «Smart-lite». Reactive and personal anxiety of patients was assessed using the scale of Spielberger, evaluation of the quality of life through the test SAN. Determining the level of neuroticism and psychoticism was conducted by the scale of neuroticism and psy-choticism. Results: The study of cerebral blood flow in the Afghan war veterans showed signs of insolvency of carotid and carotid-basilar anastomoses, hypoperfusion phenomenon with the depletion of autoregulation, violation of the outflow of venous blood at the level of the microvasculature, accompanied by cerebral arteries spasm. More than 40% of patients with early forms of chronic brain ischemia had high personal anxiety, low levels of well-being and activity, with maximum expression of dyscirculatory hypoxia. Conclusion. Readaptation of veterans of Afghanistan is accompanied by the changes in psychometric performance and the formation of the earliest forms of brain chronic ischemia associated with inadequate hemodynamics providing increased functional activity of the brain and the inefficiency of compensatory-adaptive reactions.

Protective effect of grifolin against brain injury in an acute cerebral ...

African Journals Online (AJOL)

Purpose: To evaluate the protective effects of grifolin against brain injury in an acute cerebral ischemia rat model. Methods: Rats were assigned to five groups: control, negative control, and grifolin (50, 100, and 200 mg/kg, p.o.) treated groups, which received the drug for 2 weeks. All the animals were sacrificed at the end of ...

Cerebral microcirculation during experimental normovolaemic anaemia

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Judith eBellapart

2016-02-01

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

Cerebral ischemia is exacerbated by extracellular nicotinamide phosphoribosyltransferase via a non-enzymatic mechanism.

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Bing Zhao

Full Text Available Intracellular nicotinamide phosphoribosyltransferase (iNAMPT in neuron has been known as a protective factor against cerebral ischemia through its enzymatic activity, but the role of central extracellular NAMPT (eNAMPT is not clear. Here we show that eNAMPT protein level was elevated in the ischemic rat brain after middle-cerebral-artery occlusion (MCAO and reperfusion, which can be traced to at least in part from blood circulation. Administration of recombinant NAMPT protein exacerbated MCAO-induced neuronal injury in rat brain, while exacerbated oxygen-glucose-deprivation (OGD induced neuronal injury only in neuron-glial mixed culture, but not in neuron culture. In the mixed culture, NAMPT protein promoted TNF-α release in a time- and concentration-dependent fashion, while TNF-α neutralizing antibody protected OGD-induced, NAMPT-enhanced neuronal injury. Importantly, H247A mutant of NAMPT with essentially no enzymatic activity exerted similar effects on ischemic neuronal injury and TNF-α release as the wild type protein. Thus, eNAMPT is an injurious and inflammatory factor in cerebral ischemia and aggravates ischemic neuronal injury by triggering TNF-α release from glia cells, via a mechanism not related to NAMPT enzymatic activity.

Cerebral microbleeds in a neonatal rat model.

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Brianna Carusillo Theriault

Full Text Available In adult humans, cerebral microbleeds play important roles in neurodegenerative diseases but in neonates, the consequences of cerebral microbleeds are unknown. In rats, a single pro-angiogenic stimulus in utero predisposes to cerebral microbleeds after birth at term, a time when late oligodendrocyte progenitors (pre-oligodendrocytes dominate in the rat brain. We hypothesized that two independent pro-angiogenic stimuli in utero would be associated with a high likelihood of perinatal microbleeds that would be severely damaging to white matter.Pregnant Wistar rats were subjected to intrauterine ischemia (IUI and low-dose maternal lipopolysaccharide (mLPS at embryonic day (E 19. Pups were born vaginally or abdominally at E21-22. Brains were evaluated for angiogenic markers, microhemorrhages, myelination and axonal development. Neurological function was assessed out to 6 weeks.mRNA (Vegf, Cd31, Mmp2, Mmp9, Timp1, Timp2 and protein (CD31, MMP2, MMP9 for angiogenic markers, in situ proteolytic activity, and collagen IV immunoreactivity were altered, consistent with an angiogenic response. Vaginally delivered pups exposed to prenatal IUI+mLPS had spontaneous cerebral microbleeds, abnormal neurological function, and dysmorphic, hypomyelinated white matter and axonopathy. Pups exposed to the same pro-angiogenic stimuli in utero but delivered abdominally had minimal cerebral microbleeds, preserved myelination and axonal development, and neurological function similar to naïve controls.In rats, pro-angiogenic stimuli in utero can predispose to vascular fragility and lead to cerebral microbleeds. The study of microbleeds in the neonatal rat brain at full gestation may give insights into the consequences of microbleeds in human preterm infants during critical periods of white matter development.

Enhanced cerebral uptake of receptor ligands by modulation of P-glycoprotein function in the blood-brain barrier

NARCIS (Netherlands)

Doze, P; Van Waarde, A; Elsinga, P H; Hendrikse, N H; Vaalburg, W

Low cerebral uptake of some therapeutic drugs can be enhanced by modulation of P-glycoprotein (P-gp), an ATP-driven drug efflux pump at the blood-brain barrier (BBB). We investigated the possibility of increasing cerebral uptake of the beta-adrenergic ligands S-1'-[(18)F]-fluorocarazolol (FCAR) and

Real-time changes in brain tissue oxygen during endovascular treatment of cerebral vasospasm

DEFF Research Database (Denmark)

Rasmussen, Rune; Bache, Søren; Stavngaard, Trine

2015-01-01

pressure (PtiO₂) in target parenchyma. However, during the intervention, dangerously low levels of brain tissue oxygen, leading to cerebral infarction, may occur. Thus, no clinical improvement was seen in two of the patients and a dramatic worsening was observed in the third patient. Because the decrease...... minute-by-minute changes in brain tissue oxygen during balloon angioplasty and intraarterial administration of vasodilators in three patients.Our results confirm that endovascular intervention is capable of not only resolving angiographic vasospasm, but also of normalizing values of brain tissue oxygen...... in brain tissue oxygen was seen after administration of vasopressor agents, this may be a contributing factor....

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

International Nuclear Information System (INIS)

van Duinen, S.G.; Castano, E.M.; Prelli, F.; Bots, G.T.A.B.; Luyendijk, W.; Frangione, B.

1987-01-01

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 β-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 the leptomeningeal vessels of one patient who clinically had no signs of dementia. The protein had a molecular weight of ∼ 4000 and its partial amino acid sequence to position 21 showed homology to the β-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 β-protein in brain tissue seems to be related to a spectrum of diseases involving vascular syndromes, progressive dementia, or both

Racking the brain: Detection of cerebral edema on postmortem computed tomography compared with forensic autopsy

Energy Technology Data Exchange (ETDEWEB)

Berger, Nicole [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Institute of Diagnostic and Interventional Radiology, University Hospital of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Ampanozi, Garyfalia; Schweitzer, Wolf; Ross, Steffen G.; Gascho, Dominic [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Ruder, Thomas D. [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Institute of Diagnostic, Interventional and Pediatric Radiology, University Hospital of Bern, Freiburgstrasse, 3010 Bern (Switzerland); Thali, Michael J. [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Flach, Patricia M., E-mail: patricia.flach@irm.uzh.ch [Institute of Forensic Medicine, Virtopsy, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Institute of Diagnostic and Interventional Radiology, University Hospital of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland)

2015-04-15

Graphical abstract: -- Highlights: •Postmortem swelling of the brain is a typical finding on PMCT and occurs concomitant with potential antemortem or agonal brain edema. •Cerebral edema despite normal postmortem swelling is indicated by narrowed temporal horns and symmetrical herniation of the cerebral tonsils on PMCT. •Cases with intoxication or asphyxia demonstrated higher deviations of the attenuation between white and gray matter (>20 Hounsfield Units) and a ratio >1.58 between the gray and white matter. •The Hounsfield measurements of the white and gray matter help to determine the cause of death in cases of intoxication or asphyxia. -- Abstract: Purpose: The purpose of this study was to compare postmortem computed tomography with forensic autopsy regarding their diagnostic reliability of differentiating between pre-existing cerebral edema and physiological postmortem brain swelling. Materials and methods: The study collective included a total of 109 cases (n = 109/200, 83 male, 26 female, mean age: 53.2 years) and were retrospectively evaluated for the following parameters (as related to the distinct age groups and causes of death): tonsillar herniation, the width of the outer and inner cerebrospinal fluid spaces and the radiodensity measurements (in Hounsfield Units) of the gray and white matter. The results were compared with the findings of subsequent autopsies as the gold standard for diagnosing cerebral edema. p-Values <0.05 were considered statistically significant. Results: Cerebellar edema (despite normal postmortem swelling) can be reliably assessed using postmortem computed tomography and is indicated by narrowed temporal horns and symmetrical herniation of the cerebellar tonsils (p < 0.001). There was a significant difference (p < 0.001) between intoxication (or asphyxia) and all other causes of death; the former causes demonstrated higher deviations of the attenuation between white and gray matter (>20 Hounsfield Units), and the gray to

Racking the brain: Detection of cerebral edema on postmortem computed tomography compared with forensic autopsy

International Nuclear Information System (INIS)

Berger, Nicole; Ampanozi, Garyfalia; Schweitzer, Wolf; Ross, Steffen G.; Gascho, Dominic; Ruder, Thomas D.; Thali, Michael J.; Flach, Patricia M.

2015-01-01

Graphical abstract: -- Highlights: •Postmortem swelling of the brain is a typical finding on PMCT and occurs concomitant with potential antemortem or agonal brain edema. •Cerebral edema despite normal postmortem swelling is indicated by narrowed temporal horns and symmetrical herniation of the cerebral tonsils on PMCT. •Cases with intoxication or asphyxia demonstrated higher deviations of the attenuation between white and gray matter (>20 Hounsfield Units) and a ratio >1.58 between the gray and white matter. •The Hounsfield measurements of the white and gray matter help to determine the cause of death in cases of intoxication or asphyxia. -- Abstract: Purpose: The purpose of this study was to compare postmortem computed tomography with forensic autopsy regarding their diagnostic reliability of differentiating between pre-existing cerebral edema and physiological postmortem brain swelling. Materials and methods: The study collective included a total of 109 cases (n = 109/200, 83 male, 26 female, mean age: 53.2 years) and were retrospectively evaluated for the following parameters (as related to the distinct age groups and causes of death): tonsillar herniation, the width of the outer and inner cerebrospinal fluid spaces and the radiodensity measurements (in Hounsfield Units) of the gray and white matter. The results were compared with the findings of subsequent autopsies as the gold standard for diagnosing cerebral edema. p-Values <0.05 were considered statistically significant. Results: Cerebellar edema (despite normal postmortem swelling) can be reliably assessed using postmortem computed tomography and is indicated by narrowed temporal horns and symmetrical herniation of the cerebellar tonsils (p < 0.001). There was a significant difference (p < 0.001) between intoxication (or asphyxia) and all other causes of death; the former causes demonstrated higher deviations of the attenuation between white and gray matter (>20 Hounsfield Units), and the gray to

Analysis of Regional Cerebral Blood Flow Using 99mTc-HMPAO Brain SPECT in Senile Dementia of Alzheimer Type

International Nuclear Information System (INIS)

Lee, Myung Hae; Lee, Myung Chul; Koh, Chang Soon; Roh, Jae Kyu; Woo, Chong In

1988-01-01

99m Tc-HMPAO brain SPECT studies were performed in 11 patients with Alzheimer's disease, 7 patients with psychological depression and 12 normal controls. Changes of regional cerebral blood flow was semiquantitatively analyzed and the results were as follows. 1) In 11 patients with Alzheimer's disease, significant reduction of regional cerebral blood flow was found In both temporoparietal areas. 2) Relative perfusion between cerebral hemispheres was rather symmetrical in patient with Alzheimer's disease. 3) All patients with depression showed normal SPECT findings. As for conclusion, 99m Tc-HMPAO brain SPECT seemed to be a valuable method for clinical assessment and management of patients with Alzheimer's disease.

Regional cerebral blood flow and brain atrophy in senile dementia of Alzheimer type (SDAT)

International Nuclear Information System (INIS)

Okada, Kazunori; Kobayashi, Shoutai; Yamaguchi, Shuhei; Kitani, Mituhiro; Tsunematsu, Tokugoro

1987-01-01

To investigate the relationship between the reduction of cerebal blood flow and brain atrophy in SDAT, these were measured in 13 cases of senile dementia of Alzheimer type, and compared to 15 cases of multi-infarct Dementia, 39 cases of lacunar infarction without dementia (non-demented CVD group) and 69 cases of aged normal control. Brain atrophy was evaluated by two-dimensional method on CT film by digitizer and regional cerebral blood flow (rCBF) was measured by 133 Xe inhalation method. The degree of brain atrophy in SDAT was almost similar of that of MID. But it was more severe than that of non-demented group. MID showed the lowest rCBF among these groups. SDAT showed significantly lower rCBF than that of aged control, but rCBF in SDAT was equal to that of lacunar stroke without dementia. Focal reduction of cerebral blood flow in bilateral fronto-parietal and left occipital regions were observed in SDAT. Verbal intelligence score (Hasegawa's score) correlated with rCBF and brain atrophy index in MID, and a tendency of correlation between rCBF and brain atrophy in MID was also observed. However, there was no correlation among those indices in SDAT. These findings suggest that the loss of brain substance dose not correspond to the reduction of rCBF in SDAT and simultaneous measurement of rCBF and brain atrophy was useful to differ SDAT from MID. (author)

Nanomedicine in cerebral palsy

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Balakrishnan B

2013-11-01

Full Text Available Bindu Balakrishnan,1 Elizabeth Nance,1 Michael V Johnston,2 Rangaramanujam Kannan,3 Sujatha Kannan1 1Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University; Baltimore, MD, USA; 2Department of Neurology and Pediatrics, Kennedy Krieger Institute, Baltimore, MD, USA; 3Department of Ophthalmology, Center for Nanomedicine, Johns Hopkins University, Baltimore, MD, USA Abstract: Cerebral palsy is a chronic childhood disorder that can have diverse etiologies. Injury to the developing brain that occurs either in utero or soon after birth can result in the motor, sensory, and cognitive deficits seen in cerebral palsy. Although the etiologies for cerebral palsy are variable, neuroinflammation plays a key role in the pathophysiology of the brain injury irrespective of the etiology. Currently, there is no effective cure for cerebral palsy. Nanomedicine offers a new frontier in the development of therapies for prevention and treatment of brain injury resulting in cerebral palsy. Nanomaterials such as dendrimers provide opportunities for the targeted delivery of multiple drugs that can mitigate several pathways involved in injury and can be delivered specifically to the cells that are responsible for neuroinflammation and injury. These materials also offer the opportunity to deliver agents that would promote repair and regeneration in the brain, resulting not only in attenuation of injury, but also enabling normal growth. In this review, the current advances in nanotechnology for treatment of brain injury are discussed with specific relevance to cerebral palsy. Future directions that would facilitate clinical translation in neonates and children are also addressed. Keywords: dendrimer, cerebral palsy, neuroinflammation, nanoparticle, neonatal brain injury, G4OH-PAMAM

Role of cerebral blood volume changes in brain specific-gravity measurements

International Nuclear Information System (INIS)

Picozzi, P.; Todd, N.V.; Crockard, A.H.

1985-01-01

Cerebral blood volume (CBV) was calculated in gerbils from specific-gravity (SG) changes between normal and saline-perfused brains. Furthermore, changes in CBV were investigated during ischemia using carbon-14-labeled dextran (MW 70,000) as an intravascular marker. Both data were used to evaluate the possible error due to a change in CBV on the measurement of ischemic brain edema by the SG method. The methodological error found was 0.0004 for a 100% CBV change. This error is insignificant, being less than the standard deviation in the SG measured for the gerbil cortex. Thus, CBV changes are not responsible for the SG variations observed during the first phase of ischemia. These variations are better explained as an increase of brain water content during ischemia

Identification of proteins in hyperglycemia and stroke animal models.

Science.gov (United States)

Sung, Jin-Hee; Shah, Fawad-Ali; Gim, Sang-Ah; Koh, Phil-Ok

2016-01-01

Stroke is a major cause of disability and death in adults. Diabetes mellitus is a metabolic disorder that strongly increases the risk of severe vascular diseases. This study compared changes in proteins of the cerebral cortex during ischemic brain injury between nondiabetic and diabetic animals. Adult male rats were injected with streptozotocin (40 mg/kg) via the intraperitoneal route to induce diabetes and underwent surgical middle cerebral artery occlusion (MCAO) 4 wk after streptozotocin treatment. Cerebral cortex tissues were collected 24 h after MCAO and cerebral cortex proteins were analyzed by two-dimensional gel electrophoresis and mass spectrometry. Several proteins were identified as differentially expressed between nondiabetic and diabetic animals. Among the identified proteins, we focused on the following metabolism-related enzymes: isocitrate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, adenosylhomocysteinase, pyruvate kinase, and glucose-6-phosphate isomerase (neuroleukin). Expression of these proteins was decreased in animals that underwent MCAO. Moreover, protein expression was reduced to a greater extent in diabetic animals than in nondiabetic animals. Reverse transcription-polymerase chain reaction analysis confirmed that the diabetic condition exacerbates the decrease in expression of metabolism-related proteins after MCAO. These results suggest that the diabetic condition may exacerbate brain damage during focal cerebral ischemia through the downregulation of metabolism-related proteins. Copyright © 2016 Elsevier Inc. All rights reserved.

Correlations between regional cerebral blood flow and age-related brain atrophy: a quantitative study with computed tomography and the xenon-133 inhalation method

International Nuclear Information System (INIS)

Yamaguchi, T.; Hatazawa, J.; Kubota, K.; Abe, Y.; Fujiwara, T.; Matsuzawa, T.

1983-01-01

One hundred and two subjects (40 men and 62 women) neither having a history of neurologic deficits nor showing organic lesions on computed tomographic examination of the brain were studied. Ages of the subjects ranged from 26 to 81 years. Regional cerebral blood flow was measured by the xenon-133 inhalation method, and the volume percentage of brain with respect to the cranial cavity (craniocerebral index) was calculated by means of computer programs. Regional cerebral blood flow was computed as the fast component of two-compartmental analysis and as the initial slope index value. The percentage of each subject's craniocerebral index in relation to the standard for subjects with non-atrophied brains (brain volume index) was calculated as the indicator of brain atrophy. Both the mean brain fast component values and the mean brain initial slope index values correlated closely with the brain volume index in the elderly. Low cerebral blood flow values coincided with loss of brain substance in the final stage of age-related brain atrophy, but not in the intermediate stage

Hereditary protein S deficiency presenting with cerebral sinus thrombosis in an adolescent girl

NARCIS (Netherlands)

Koelman, J. H.; Bakker, C. M.; Plandsoen, W. C.; Peeters, F. L.; Barth, P. G.

1992-01-01

A 14-year-old girl, on oral contraceptives for 3 months, presented with cerebral sinus thrombosis. Investigation revealed underlying hereditary protein S deficiency. This uncommon cause of cerebral sinus thrombosis and the possible association with oral contraceptives are discussed

Functional MR imaging using sensory and motor task in brain tumors and other focal cerebral lesions

International Nuclear Information System (INIS)

Ok, Chul Su; Lim, Myung Kwan; Yu, Ki Bong; Kim, Hyung Jin; Suh, Chang Hae

2002-01-01

To determine the usefulness of the functional MRI (fMRI) using motor and sensory stimuli in patients with brain tumors of focal cerebral lesions. This study involved five patients with brain tumors (n=2) or cerebral lesions (cysticercosis (n=1), arteriovenous malformation (n=1), focal infarction (n=1) and seven normal controls. For MR examinations a 1.5T scanner was used, and during motor or sensory stimulation, the EPI BOLD technique was employed. For image postprocessing an SPM program was utilized. In volunteers, contralateral sensori-motor cortices were activated by both motor and sensory stimuli, while supplementary motor cortices were activated by motor stimuli and other sensory cortices by sensory stimuli. Preoperative evaluation of the relationship between lesions and important sensory and motor areas was possible, and subsequent surgery was thus successful, involving no severe complications. Activation of ipsilateral or other areas occurred in patients with destruction of a major sensory and/or motor area, suggesting compensatory reorganization. fMRI could be a useful supportive method for determining the best approach to surgery treatment in patients with brain tumors or focal cerebral lesions

Neuroprotective effects of NAP against excitotoxic brain damage in the newborn mice: implications for cerebral palsy.

Science.gov (United States)

Sokolowska, P; Passemard, S; Mok, A; Schwendimann, L; Gozes, I; Gressens, P

2011-01-26

Activity-dependent neuroprotective protein (ADNP) was shown to be essential for embryogenesis and brain development while NAP, an active motif of ADNP, is neuroprotective in a broad range of neurodegenerative disorders. In the present study, we examined the protective potential of ADNP/NAP in a mouse model of excitotoxic brain lesion mimicking brain damage associated with cerebral palsy. We demonstrated that NAP had a potent neuroprotective effect against ibotenate-induced excitotoxic damage in the cortical plate and the white matter of P5 mice, and moderate against brain lesions of P0 mice. In contrast, endogenous ADNP appears not to be involved in the response to excitotoxic challenge in the studied model. Our findings further show that NAP reduced the number of apoptotic neurons through activation of PI-3K/Akt pathway in the cortical plate or both PI-3K/Akt and MAPK/MEK1 kinases in the white matter. In addition, NAP prevented ibotenate-induced loss of pre-oligodendrocytes without affecting the number of astrocytes or activated microglia around the site of injection. These findings indicate that protective actions of NAP are mediated by triggering transduction pathways that are crucial for neuronal and oligodendroglial survival, thus, NAP might be a promising therapeutic agent for treating developing brain damage. © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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.

Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial

DEFF Research Database (Denmark)

Plomgaard, Anne M.; Alderliesten, Thomas; Austin, Topun

2017-01-01

Background The randomized clinical trial, SafeBoosC II, examined the effect of monitoring of cerebral oxygenation by near-infrared spectroscopy combined with a guideline on treatment when cerebral oxygenation was out of the target range. Data on cerebral oxygenation was collected in both the inte......Background The randomized clinical trial, SafeBoosC II, examined the effect of monitoring of cerebral oxygenation by near-infrared spectroscopy combined with a guideline on treatment when cerebral oxygenation was out of the target range. Data on cerebral oxygenation was collected in both......, and the biomarkers of brain injury from birth till term equivalent age that was collected as secondary and explorative outcomes in the SafeBoosC II trial. Methods Cerebral oxygenation was continuously monitored during the first 72h of life in 166 extremely preterm infants. Cranial ultrasound was performed at day 1...

Evaluation of the effects of rehabilitation exercise on cerebral infarction with 99Tcm-ECD SPECT brain imaging

International Nuclear Information System (INIS)

Jiang Ningyi; Lu Xianping; Liu Xingguang; Xiao Xiuhong; Xu Jianxing

2003-01-01

Objective: To investigate the therapeutic effects of motor therapy on hemiplegia with SPECT brain perfusion imaging. Methods: The study population consisted of 59 patients with cerebral infarction, and all patients were treated with motor therapy. Among them, 30 cases were assigned to undertake single bridging exercise and 29 cases passive exercise. SPECT brain perfusion imaging was performed before and after motor therapy under the same condition, and the regional cerebral blood flow (rCBF) changes were compared and analysed with visual and semi-quantitative methods; in addition, the relationship between rCBF changes and scores of Fugl-Meyer or Barthel index were also analysed. Results: After motor therapy, various degrees of radioactivity increase were compared with the pretreatment radioactivity hypoperfusion in patients with cerebral infarction, and showed that motor therapy could evidently improve rCBF of regional hypoperfusion. The posttreatment rCBF was higher than the pretreatment level (P<0.01), and the rCBF of group of single bridging was higher than that of passive exercise group. And the changes of rCBF were all significant after motor therapy. In addition, the variation of the rCBF after motor therapy was positively correlated with the variation of Fugl-Meyer and Barthel score. Conclusions: SPECT brain perfusion imaging can serve as a useful method for evaluating the effectiveness of motor therapy in cerebral infarction rehabilitation. The single bridging exercise and the passive exercise are both beneficial to brain rehabilitation, but the former improves the rCBF in lesions better than the later does

Quantitative evaluation of regional cerebral blood flow by visual stimulation in 99mTc-HMPAO brain SPECT

International Nuclear Information System (INIS)

Juh, R. H.; Suh, T. S.; Chung, Y. A.

2002-01-01

The purpose of this study is to investigate the effects of visual activation and quantitative analysis of regional cerebral blood flow. Visual activation was known to increase regional cerebral blood flow in the visual cortex in occipital lobe. We evaluated that change in the distribution of 99mTc-HMPAO (Hexamethyl propylene amine oxime) to reflect in regional cerebral blood flow. The six volunteers were injected with 925 MBq (mean ages: 26.75 years, n=6, 3men, 3women) underwent MRI and 99mTc- HMPAO SPECT during a rest state with closed eyes and visual stimulated with 8 Hz LED. We delineate the region of interest and calculated the mean count per voxel in each of the fifteen slices to quantitative analysis. The ROI to whole brain ratio and regional index was calculated pixel to pixel subtraction visual non-activation image from visual activation image and constructed brain map using a statistical parameter map (SPM99). The mean regional cerebral blood flow was increased due to visual stimulation. The increase rate of the mean regional cerebral blood flow which of the activation region in primary visual cortex of occipital lobe was 32.50±5.67%. The significant activation sites using a statistical parameter of brain constructed a rendering image and image fusion with SPECT and MRI. Visual activation was revealed significant increase through quantitative analysis in visual cortex. Activation region was certified in Talairach coordinate and primary visual cortex (Ba17),visual association area (Ba18,19) of Brodmann

Quantitative evaluation of regional cerebral blood flow by visual stimulation in 99mTc- HMPAO brain SPECT

International Nuclear Information System (INIS)

Juh, Ra Hyeong; Suh, Tae Suk; Kwark, Chul Eun; Choe, Bo Young; Lee, Hyoung Koo; Chung, Yong An; Kim, Sung Hoon; Chung, Soo Kyo

2002-01-01

The purpose of this study is to investigate the effects of visual activation and quantitative analysis of regional cerebral blood flow. Visual activation was known to increase regional cerebral blood flow in the visual cortex in occipital lobe. We evaluated that change in the distribution of '9 9m Tc-HMPAO (Hexamethyl propylene amine oxime) to reflect in regional cerebral blood flow. The six volunteers were injected with 925 MBq (mean ages: 26.75 years, n=6, 3men, 3women) underwent MRI and 99m Tc-HMPAO SPECT during a rest state with closed eyes and visual stimulated with 8 Hz LED. We delineate the region of interest and calculated the mean count per voxel in each of the fifteen slices to quantitative analysis. The ROI to whole brain ratio and regional index was calculated pixel to pixel subtraction visual non-activation image from visual activation image and constructed brain map using a statistical parameter map(SPM99). The mean regional cerebral blood flow was increased due to visual stimulation. The increase rate of the mean regional cerebral blood flow which of the activation region in primary visual cortex of occipital lobe was 32.50±5.67%. The significant activation sites using a statistical parameter of brain constructed a rendering image and image fusion with SPECT and MRI. Visual activation was revealed significant increase through quantitative analysis in visual cortex. Activation region was certified in Talairach coordinate and primary visual cortex (Ba17),visual association area (Ba18,19) of Brodmann

Regional distribution of serotonin transporter protein in postmortem human brain

International Nuclear Information System (INIS)

Kish, Stephen J.; Furukawa, Yoshiaki; Chang Lijan; Tong Junchao; Ginovart, Nathalie; Wilson, Alan; Houle, Sylvain; Meyer, Jeffrey H.

2005-01-01

Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met

Regional distribution of serotonin transporter protein in postmortem human brain

Energy Technology Data Exchange (ETDEWEB)

Kish, Stephen J. [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)]. E-mail: Stephen_Kish@CAMH.net; Furukawa, Yoshiaki [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Chang Lijan [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Tong Junchao [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Ginovart, Nathalie [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Wilson, Alan [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Houle, Sylvain [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Meyer, Jeffrey H. [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

2005-02-01

Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met.

Split-brain reveals separate but equal self-recognition in the two cerebral hemispheres.

Science.gov (United States)

Uddin, Lucina Q; Rayman, Jan; Zaidel, Eran

2005-09-01

To assess the ability of the disconnected cerebral hemispheres to recognize images of the self, a split-brain patient (an individual who underwent complete cerebral commissurotomy to relieve intractable epilepsy) was tested using morphed self-face images presented to one visual hemifield (projecting to one hemisphere) at a time while making "self/other" judgments. The performance of the right and left hemispheres of this patient as assessed by a signal detection method was not significantly different, though a measure of bias did reveal hemispheric differences. The right and left hemispheres of this patient independently and equally possessed the ability to self-recognize, but only the right hemisphere could successfully recognize familiar others. This supports a modular concept of self-recognition and other-recognition, separately present in each cerebral hemisphere.

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

Science.gov (United States)

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

2013-03-01

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

Studies on so-called redistribution phenomenon of cerebral blood flow imaging

International Nuclear Information System (INIS)

Oba, Hiroshi

1989-01-01

To elucidate the relationship between so-called redistribution phenomenon and metabolism or viability of the brain tissue, a new quantitative triple-radionuclide autoradiography was developed, whereby making it possible to compare both late images and reditribution of IMP with cerebral metabolism in experimentally induced unilateral ischemic brain tissue of rats. Iodine-123 IMP and I-125 IMP were used as tracers for early and late imaging, and H-3 amino acid mixture or H-3 H-2 deoxyglucose as a tracer for protein synthesis or glucose metabolism imaging. There was no significant relationship between redistribution index and protein synthesis or glucose metabolism. Protein synthesis was remarkably decreased in the affected hemisphere regardless of redistribution index values. Although the redistribution indices showed a gentle peak at approximately 34 μ mol/100 g/ min of glucose metabolism, there was no obvious relationship between either late images or redistribution index images and glucose metabolism images. Redistribution indices showed a maximum value at approximately 40 to 50 ml/100 g/min of cerebral blood flow. Reverse redistribution was observed with 160 ml/100 g/min or more of flow. Thin layer chromatographic findings were similar in the affected and non-affected resions, suggesting redistribution of a lipophilic IMP metabolite of p-iodoamphetamine in the affected region. In vitro autoradiography revealed no significant reduction in binding ability of IMP to the affected ischemic cortex. In a computer simulation study for brain activity curve, brain activity at 150 min was found to be almost constant at more than 25 ml/100 g/min of flow. IMP redistribution was unlikely to reflect directly either brain metabolism or function, and both blood flow partition coefficient and blood flow values were independently responsible for cerebral kinetics of IMP. (N.K.)

A reduced cerebral metabolic ratio in exercise reflects metabolism and not accumulation of lactate within the human brain

DEFF Research Database (Denmark)

Dalsgaard, Mads K; Quistorff, Bjørn; Danielsen, Else R

2003-01-01

During maximal exercise lactate taken up by the human brain contributes to reduce the cerebral metabolic ratio, O(2)/(glucose + 1/2 lactate), but it is not known whether the lactate is metabolized or if it accumulates in a distribution volume. In one experiment the cerebral arterio-venous differe......During maximal exercise lactate taken up by the human brain contributes to reduce the cerebral metabolic ratio, O(2)/(glucose + 1/2 lactate), but it is not known whether the lactate is metabolized or if it accumulates in a distribution volume. In one experiment the cerebral arterio......-venous differences (AV) for O(2), glucose (glc) and lactate (lac) were evaluated in nine healthy subjects at rest and during and after exercise to exhaustion. The cerebrospinal fluid (CSF) was drained through a lumbar puncture immediately after exercise, while control values were obtained from six other healthy.......0 to 0.9 +/- 0.1 mM (P ratio from 6.0 +/- 0.3 to 2.8 +/- 0.2 (P

NADPH Oxidase Activity in Cerebral Arterioles Is a Key Mediator of Cerebral Small Vessel Disease—Implications for Prevention

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Mark F. McCarty

2015-04-01

Full Text Available Cerebral small vessel disease (SVD, a common feature of brain aging, is characterized by lacunar infarcts, microbleeds, leukoaraiosis, and a leaky blood-brain barrier. Functionally, it is associated with cognitive decline, dementia, depression, gait abnormalities, and increased risk for stroke. Cerebral arterioles in this syndrome tend to hypertrophy and lose their capacity for adaptive vasodilation. Rodent studies strongly suggest that activation of Nox2-dependent NADPH oxidase activity is a crucial driver of these structural and functional derangements of cerebral arterioles, in part owing to impairment of endothelial nitric oxide synthase (eNOS activity. This oxidative stress may also contribute to the breakdown of the blood-brain barrier seen in SVD. Hypertension, aging, metabolic syndrome, smoking, hyperglycemia, and elevated homocysteine may promote activation of NADPH oxidase in cerebral arterioles. Inhibition of NADPH oxidase with phycocyanobilin from spirulina, as well as high-dose statin therapy, may have potential for prevention and control of SVD, and high-potassium diets merit study in this regard. Measures which support effective eNOS activity in other ways—exercise training, supplemental citrulline, certain dietary flavonoids (as in cocoa and green tea, and capsaicin, may also improve the function of cerebral arterioles. Asian epidemiology suggests that increased protein intakes may decrease risk for SVD; conceivably, arginine and/or cysteine—which boosts tissue glutathione synthesis, and can be administered as N-acetylcysteine—mediate this benefit. Ameliorating the risk factors for SVD—including hypertension, metabolic syndrome, hyperglycemia, smoking, and elevated homocysteine—also may help to prevent and control this syndrome, although few clinical trials have addressed this issue to date.

Pathological review of late cerebral radionecrosis

International Nuclear Information System (INIS)

Yoshii, Yoshihiko

2008-01-01

Late cerebral radionecrosis may be considered to be a specific chronic inflammatory response, although it is unknown whether the initial damage by brain irradiation is to an endothelial cell or a glial cell. I discuss the pathological specificity of late cerebral radionecrosis by studying the published literature and a case that I experienced. In late cerebral radionecrosis, there are typical coagulation necrosis areas containing fibrinoid necrosis with occlusion of the lumina and poorly active inflammatory areas with many inflammatory ghost cells, focal perivascular lymphocytes, hyalinized vessels, and telangiectatic vascularization near and in the necrotic tissue, and more active inflammatory areas formed as a partial rim of the reactive zone by perivascular lymphocytes, much vascularization, and glial fibrillary acidic protein (GFAP)-positive astrocytes at the corticomedullary border adjacent to necrotic tissue in the white matter. It is difficult to believe that coagulation necrosis occurs without first disordering the vascular endothelial cells because fibrinoid necrosis is a main feature and a diffusely multiple lesion in late cerebral radionecrosis. Because various histological findings do develop, progress, and extend sporadically at different areas and times in the irradiated field of the brain for a long time after radiation, uncontrolled chronic inflammation containing various cytokine secretions may also play a key role in progression of this radionecrosis. Evaluation of the mechanism of the development/aggravation of late cerebral radionecrosis requires a further study for abnormal cytokine secretions and aberrant inflammatory reactions. (author)

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

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

2018-07-01

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

Structure-guided identification of a family of dual receptor-binding PfEMP1 that is associated with cerebral malaria

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Lennartz, Frank; Adams, Yvonne; Bengtsson, Anja

2017-01-01

Cerebral malaria is a deadly outcome of infection by Plasmodium falciparum, occurring when parasite-infected erythrocytes accumulate in the brain. These erythrocytes display parasite proteins of the PfEMP1 family that bind various endothelial receptors. Despite the importance of cerebral malaria...

Age-dependent changes in the total protein concentrations in the ...

African Journals Online (AJOL)

related changes in total protein concentrations in ten regions of the pig brain and hypophyses from birth to 36 months of age. Age-related changes in protein concentrations in all the brain regions except the pons and cerebral cortex were not ...

[Cerebral protection].

Science.gov (United States)

Cattaneo, A D

1993-09-01

Cerebral protection means prevention of cerebral neuronal damage. Severe brain damage extinguishes the very "human" functions such as speech, consciousness, intellectual capacity, and emotional integrity. Many pathologic conditions may inflict injuries to the brain, therefore the protection and salvage of cerebral neuronal function must be the top priorities in the care of critically ill patients. Brain tissue has unusually high energy requirements, its stores of energy metabolites are small and, as a result, the brain is totally dependent on a continuous supply of substrates and oxygen, via the circulation. In complete global ischemia (cardiac arrest) reperfusion is characterized by an immediate reactive hyperemia followed within 20-30 min by a delayed hypoperfusion state. It has been postulated that the latter contributes to the ultimate neurologic outcome. In focal ischemia (stroke) the primary focus of necrosis is encircled by an area (ischemic penumbra) that is underperfused and contains neurotoxic substances such as free radicals, prostaglandins, calcium, and excitatory neurotransmitters. The variety of therapeutic effort that have addressed the question of protecting the brain reflects their limited success. 1) Barbiturates. After an initial enthusiastic endorsement by many clinicians and years of vigorous controversy, it can now be unequivocally stated that there is no place for barbiturate therapy following resuscitation from cardiac arrest. One presumed explanation for this negative statement is that cerebral metabolic suppression by barbiturates (and other anesthetics) is impossible in the absence of an active EEG. Conversely, in the event of incomplete ischemia EEG activity in usually present (albeit altered) and metabolic suppression and hence possibly protection can be induced with barbiturates. Indeed, most of the animal studies led to a number of recommendations for barbiturate therapy in man for incomplete ischemia. 2) Isoflurane. From a cerebral

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

Science.gov (United States)

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

2016-01-01

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

Analysis of Regional Cerebral Blood Flow Using {sup 99m}Tc-HMPAO Brain SPECT in Senile Dementia of Alzheimer Type

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Lee, Myung Hae; Lee, Myung Chul; Koh, Chang Soon; Roh, Jae Kyu; Woo, Chong In [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1988-03-15

{sup 99m}Tc-HMPAO brain SPECT studies were performed in 11 patients with Alzheimer's disease, 7 patients with psychological depression and 12 normal controls. Changes of regional cerebral blood flow was semiquantitatively analyzed and the results were as follows. 1) In 11 patients with Alzheimer's disease, significant reduction of regional cerebral blood flow was found In both temporoparietal areas. 2) Relative perfusion between cerebral hemispheres was rather symmetrical in patient with Alzheimer's disease. 3) All patients with depression showed normal SPECT findings. As for conclusion, {sup 99m}Tc-HMPAO brain SPECT seemed to be a valuable method for clinical assessment and management of patients with Alzheimer's disease.

Cell-penetrating anti-GFAP VHH and corresponding fluorescent fusion protein VHH-GFP spontaneously cross the blood-brain barrier and specifically recognize astrocytes: application to brain imaging.

Science.gov (United States)

Li, Tengfei; Bourgeois, Jean-Pierre; Celli, Susanna; Glacial, Fabienne; Le Sourd, Anne-Marie; Mecheri, Salah; Weksler, Babette; Romero, Ignacio; Couraud, Pierre-Olivier; Rougeon, François; Lafaye, Pierre

2012-10-01

Antibodies normally do not cross the blood-brain barrier (BBB) and cannot bind an intracellular cerebral antigen. We demonstrate here for the first time that a new class of antibodies can cross the BBB without treatment. Camelids produce native homodimeric heavy-chain antibodies, the paratope being composed of a single-variable domain called VHH. Here, we used recombinant VHH directed against human glial fibrillary acidic protein (GFAP), a specific marker of astrocytes. Only basic VHHs (e.g., pI=9.4) were able to cross the BBB in vitro (7.8 vs. 0% for VHH with pI=7.7). By intracarotid and intravenous injections into live mice, we showed that these basic VHHs are able to cross the BBB in vivo, diffuse into the brain tissue, penetrate into astrocytes, and specifically label GFAP. To analyze their ability to be used as a specific transporter, we then expressed a recombinant fusion protein VHH-green fluorescent protein (GFP). These "fluobodies" specifically labeled GFAP on murine brain sections, and a basic variant (pI=9.3) of the fusion protein VHH-GFP was able to cross the BBB and to label astrocytes in vivo. The potential of VHHs as diagnostic or therapeutic agents in the central nervous system now deserves attention.

Selected Gray Matter Volumes and Gender but Not Basal Ganglia nor Cerebellum Gyri Discriminate Left Versus Right Cerebral Hemispheres: Multivariate Analyses in human Brains at 3T.

Science.gov (United States)

Roldan-Valadez, Ernesto; Suarez-May, Marcela A; Favila, Rafael; Aguilar-Castañeda, Erika; Rios, Camilo

2015-07-01

Interest in the lateralization of the human brain is evident through a multidisciplinary number of scientific studies. Understanding volumetric brain asymmetries allows the distinction between normal development stages and behavior, as well as brain diseases. We aimed to evaluate volumetric asymmetries in order to select the best gyri able to classify right- versus left cerebral hemispheres. A cross-sectional study performed in 47 right-handed young-adults healthy volunteers. SPM-based software performed brain segmentation, automatic labeling and volumetric analyses for 54 regions involving the cerebral lobes, basal ganglia and cerebellum from each cerebral hemisphere. Multivariate discriminant analysis (DA) allowed the assembling of a predictive model. DA revealed one discriminant function that significantly differentiated left vs. right cerebral hemispheres: Wilks' λ = 0.008, χ(2) (9) = 238.837, P brain gyri are able to accurately classify left vs. right cerebral hemispheres by using a multivariate approach; the selected regions correspond to key brain areas involved in attention, internal thought, vision and language; our findings favored the concept that lateralization has been evolutionary favored by mental processes increasing cognitive efficiency and brain capacity. © 2015 Wiley Periodicals, Inc.

Effects of the duration of hyperlipidemia on cerebral lipids, vessels and neurons in rats.

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Yang, Weichun; Shi, He; Zhang, Jianfen; Shen, Ziyi; Zhou, Guangyu; Hu, Minyu

2017-01-31

The present study was designed to investigate the effects of hyperlipidemia on the cerebral lipids, vessels and neurons of rats, and to provide experimental evidence for subsequent intervention. One hundred adult SD rats, half of which were male and half of which were female, were randomly divided into five groups on the basis of serum total cholesterol (TC) levels. Four groups were fed a hypercholesterolemic diet (rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil - this is also called a CCT diet) for periods of 1 week, 2 weeks, 3 weeks and 4 weeks, respectively. A control group was included. The levels of serum lipids, cerebral lipids, free fatty acids (FFA), interleukin-6 (IL-6), interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), oxidized low density lipoprotein (ox-LDL), A-beta precursor proteins (APP), amyloid beta (Aβ), glial fibrillary acidic protein (GFAP) and tight junction protein Claudin-5 were measured after the experiment. The pathologic changes and apoptosis of the rat brains were evaluated. Compared with the control group, after 1 week of a CCT diet, the levels of serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and brain triglycerides had increased by 2.40, 1.29 and 1.75 and 0.3 times, respectively. The serum high density lipoprotein cholesterol (HDL-C) had decreased by 0.74 times (P neurons, had increased (P neurons had increased (P neuronal apoptosis in the rat brains, and they all were negatively correlated with Claudin-5 (P neurons by causing the secretion of TNF-α and IL-1 in the brains of rats. In the metabolic procession, brain tissue was shown to generate FFA that aggravated the biosynthesis of ox-LDL. With the extension of the duration of hyperlipidemia, high levels of cerebral TC and LDL-C were shown to aggravate the deposition of Aβ, induce the secretion of VEGF, reduce the expression of tight

Enhanced phosphorylation of cyclic AMP response element binding protein in Brain of mice following repetitive hypoxic exposure

International Nuclear Information System (INIS)

Gao Yanan; Gao Ge; Long Caixia; Han Song; Zu Pengyu; Fang Li; Li Junfa

2006-01-01

Cerebral ischemic/hypoxic preconditioning (I/HPC) is a phenomenon of endogenous protection that renders Brain tolerant to sustained ischemia/hypoxia. This profound protection induced by I/HPC makes it an attractive target for developing potential clinical therapeutic approaches. However, the molecular mechanism of I/HPC is unclear. Cyclic AMP (cAMP) response element binding protein (CREB), a selective nuclear transcriptional factor, plays a key role in the neuronal functions. Phosphorylation of CREB on Ser-133 may facilitate its transcriptional activity in response to various stresses. In the current study, we observed the changes in CREB phosphorylation (Ser-133) and protein expression in Brain of auto-hypoxia-induced HPC mice by using Western blot analysis. We found that the levels of phosphorylated CREB (Ser-133), but not protein expression of CREB, increased significantly (p < 0.05) in the hippocampus and the frontal cortex of mice after repetitive hypoxic exposure (H2-H4, n = 6 for each group), when compared to that of the normoxic (H0, n = 6) or hypoxic exposure once group (H1, n = 6). In addition, a significant enhancement (p < 0.05) of CREB phosphorylation (Ser-133) could also be found in the nuclear extracts from the whole hippocampus of hypoxic preconditioned mice (H2-H4, n = 6 for each group). These results suggest that the phosphorylation of CREB might be involved in the development of cerebral hypoxic preconditioning

Alpha-MSH decreases core and brain temperature during global cerebral ischemia in rats

DEFF Research Database (Denmark)

Spulber, S.; Moldovan, Mihai; Oprica, M.

2005-01-01

-vessel occlusion forebrain ischemia on core temperature (CT) and brain temperature (BT), respectively. After 10 min cerebral ischemia, BT was lower in alpha-MSH- than in saline-injected animals. After 10 min reperfusion, both CT and BT were lower than the corresponding pre-ischemic levels after injection of alpha...

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

Science.gov (United States)

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

2017-04-01

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

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

Science.gov (United States)

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.

User’s Emotions and Usability Study of a Brain-Computer Interface Applied to People with Cerebral Palsy

Directory of Open Access Journals (Sweden)

Alejandro Rafael García Ramírez

2018-02-01

Full Text Available People with motor and communication disorders face serious challenges in interacting with computers. To enhance this functionality, new human-computer interfaces are being studied. In this work, a brain-computer interface based on the Emotiv Epoc is used to analyze human-computer interactions in cases of cerebral palsy. The Phrase-Composer software was developed to interact with the brain-computer interface. A system usability evaluation was carried out with the participation of three specialists from The Fundação Catarinense de Educação especial (FCEE and four cerebral palsy volunteers. Even though the System Usability Scale (SUS score was acceptable, several challenges remain. Raw electroencephalography (EEG data were also analyzed in order to assess the user’s emotions during their interaction with the communication device. This study brings new evidences about human-computer interaction related to individuals with cerebral palsy.

Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice.

Science.gov (United States)

Cahill, Lindsay S; Gazdzinski, Lisa M; Tsui, Albert Ky; Zhou, Yu-Qing; Portnoy, Sharon; Liu, Elaine; Mazer, C David; Hare, Gregory Mt; Kassner, Andrea; Sled, John G

2017-03-01

Cerebral ischemia is a significant source of morbidity in children with sickle cell anemia; however, the mechanism of injury is poorly understood. Increased cerebral blood flow and low hemoglobin levels in children with sickle cell anemia are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia may be an important factor contributing to subsequent morbidity. To better understand the pathophysiology of brain injury, brain physiology and morphology were characterized in a transgenic mouse model, the Townes sickle cell model. Relative to age-matched controls, sickle cell anemia mice demonstrated: (1) decreased brain tissue pO 2 and increased expression of hypoxia signaling protein in the perivascular regions of the cerebral cortex; (2) elevated basal cerebral blood flow , consistent with adaptation to anemia-induced tissue hypoxia; (3) significant reduction in cerebrovascular blood flow reactivity to a hypercapnic challenge; (4) increased diameter of the carotid artery; and (5) significant volume changes in white and gray matter regions in the brain, as assessed by ex vivo magnetic resonance imaging. Collectively, these findings support the hypothesis that brain tissue hypoxia contributes to adaptive physiological and anatomic changes in Townes sickle cell mice. These findings may help define the pathophysiology for stroke in children with sickle cell anemia.

Evaluation of fetal brain development by magnetic resonance imaging. Subependymal germinal matrix layer and cerebral ventricle

International Nuclear Information System (INIS)

Kinoshita, Yoshimasa; Yokota, Akira; Okudera, Toshio

1999-01-01

Three dimensional data of brain from the formalin-fixed fetuses were collected without isolation, by the 4.7 tesla super high magnetic field MRI and the developmental process of the cerebral parenchyma was studied by 3D images. Subjects were 13 fetal brain and MRI was performed using 3D-steady-state free precession sequence. The isolated brain is very soft and fragile and is deformed by its weight at the imaging. However 3D-MRI can be obtained without isolation, and the deformation is remarkably small. The subependymal germinal matrix layer did not be observed in 7 weeks-old fetus, appeared at 9 weeks-old and increased gradually. Then it rapidly reduced from 28 weeks-old. The volume calculated, from 3D-MRI, increased rapidly from 9 weeks-old to 23 weeks-old, and reached the maximum (2.346 mm 3 ) at 23 weeks-old. The relation between fetal ages and volume of cerebral ventricle also showed similar pattern. This method will be useful to examine the development of the fetal brain without any damage. (K.H.)

Andrographolide stimulates p38 mitogen-activated protein kinase-nuclear factor erythroid-2-related factor 2-heme oxygenase 1 signaling in primary cerebral endothelial cells for definite protection against ischemic stroke in rats.

Science.gov (United States)

Yen, Ting-Lin; Chen, Ray-Jade; Jayakumar, Thanasekaran; Lu, Wan-Jung; Hsieh, Cheng-Ying; Hsu, Ming-Jen; Yang, Chih-Hao; Chang, Chao-Chien; Lin, Yen-Kuang; Lin, Kuan-Hung; Sheu, Joen-Rong

2016-04-01

Stroke pathogenesis involves complex oxidative stress-related pathways. The nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) pathways have been considered molecular targets in pharmacologic intervention for ischemic diseases. Andrographolide, a labdane diterpene, has received increasing attention in recent years because of its various pharmacologic activities. We determined that andrographolide modulates the mitogen-activated protein kinase (MAPK)-Nrf2-HO-1 signaling cascade in primary cerebral endothelial cells (CECs) to provide positive protection against middle cerebral artery occlusion (MCAO)-induced ischemic stroke in rats. In the present study, andrographolide (10 μM) increased HO-1 protein and messenger RNA expressions, Nrf2 phosphorylation, and nuclear translocation in CECs, and these activities were disrupted by a p38 MAPK inhibitor, SB203580, but not by the extracellular signal-regulated kinase inhibitor PD98059 or c-Jun amino-terminal kinase inhibitor SP600125. Similar results were observed in confocal microscopy analysis. Moreover, andrographolide-induced Nrf2 and HO-1 protein expressions were significantly inhibited by Nrf2 small interfering RNA. Moreover, HO-1 knockdown attenuated the protective effect of andrographolide against oxygen-glucose deprivation-induced CEC death. Andrographolide (0.1 mg/kg) significantly suppressed free radical formation, blood-brain barrier disruption, and brain infarction in MCAO-insulted rats, and these effects were reversed by the HO-1 inhibitor zinc protoporphyrin IX. The mechanism is attributable to HO-1 activation, as directly evidenced by andrographolide-induced pronounced HO-1 expression in brain tissues, which was highly localized in the cerebral capillary. In conclusion, andrographolide increased Nrf2-HO-1 expression through p38 MAPK regulation, confirming that it provides protection against MCAO-induced brain injury. These findings provide strong evidence that andrographolide could

Lactate Receptor Sites Link Neurotransmission, Neurovascular Coupling, and Brain Energy Metabolism

DEFF Research Database (Denmark)

Lauritzen, Knut H; Morland, Cecilie; Puchades, Maja

2013-01-01

The G-protein-coupled lactate receptor, GPR81 (HCA1), is known to promote lipid storage in adipocytes by downregulating cAMP levels. Here, we show that GPR81 is also present in the mammalian brain, including regions of the cerebral neocortex and hippocampus, where it can be activated by physiolog......The G-protein-coupled lactate receptor, GPR81 (HCA1), is known to promote lipid storage in adipocytes by downregulating cAMP levels. Here, we show that GPR81 is also present in the mammalian brain, including regions of the cerebral neocortex and hippocampus, where it can be activated...

Cerebral gumma mimicking a brain tumor in a human immunodeficiency virus-negative patient: A case report

International Nuclear Information System (INIS)

Baek, Hye Jin; Kim, Woo Jin

2013-01-01

Syphilis has a broad spectrum of clinical manifestations, and the cerebral gumma is a kind of neurosyphilis which is rare and can be cured by appropriate antibiotic treatments. However, in clinical practices, diagnosis of cerebral syphilitic gumma is often difficult because imaging and laboratory findings revealed elusive results. Herein, we present a rare case of neurosyphilis presenting as cerebral gumma confirmed by histopathological examination, and positive serologic and cerebrospinal fluid analyses. This case report suggests that cerebral gumma should be considered as possible diagnosis for human immunodeficiency virus-negative patients with space-occupying lesion of the brain. And this case also provides importance of clinical suspicions in diagnosing neurosyphilis because syphilis serology is not routinely tested on patients with neurologic symptoms.

Cerebral gumma mimicking a brain tumor in a human immunodeficiency virus-negative patient: A case report

Energy Technology Data Exchange (ETDEWEB)

Baek, Hye Jin; Kim, Woo Jin [Haeundae Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

2013-09-15

Syphilis has a broad spectrum of clinical manifestations, and the cerebral gumma is a kind of neurosyphilis which is rare and can be cured by appropriate antibiotic treatments. However, in clinical practices, diagnosis of cerebral syphilitic gumma is often difficult because imaging and laboratory findings revealed elusive results. Herein, we present a rare case of neurosyphilis presenting as cerebral gumma confirmed by histopathological examination, and positive serologic and cerebrospinal fluid analyses. This case report suggests that cerebral gumma should be considered as possible diagnosis for human immunodeficiency virus-negative patients with space-occupying lesion of the brain. And this case also provides importance of clinical suspicions in diagnosing neurosyphilis because syphilis serology is not routinely tested on patients with neurologic symptoms.

Cerebral oxygenation in contusioned vs. nonlesioned brain tissue: monitoring of PtiO2 with Licox and Paratrend.

Science.gov (United States)

Sarrafzadeh, A S; Kiening, K L; Bardt, T F; Schneider, G H; Unterberg, A W; Lanksch, W R

1998-01-01

Brain tissue PO2 in severely head injured patients was monitored in parallel with two different PO2-microsensors (Licox and Paratrend). Three different locations of sensor placement were chosen: (1) both catheters into non lesioned tissue (n = 3), (2) both catheters into contusioned tissue (n = 2), and (3) one catheter (Licox) into pericontusional versus one catheter (Paratrend) into non lesioned brain tissue (n = 2). Mean duration of PtiO2-monitoring with both microsensors in parallel was 68.1 hours. Brain tissue PO2 varied when measured in lesioned and nonlesioned tissue. In non lesioned tissue both catheters closely correlated (delta Licox/Paratrend: mean PtiO2 delta lesioned/non lesioned: mean PtiO2: 10.3 mm Hg). In contusioned brain tissue PtiO2 was always below the "hypoxic threshold" of 10 mm Hg, independent of the type of microsensor used. During a critical reduction in cerebral perfusion pressure (PO2, only increased PtiO2 when measured in pericontusional and nonlesioned brain. To recognize critical episodes of hypoxia or ischemia, PtiO2-monitoring of cerebral oxygenation is recommended in nonlesioned brain tissue.

Upregulation of neuronal zinc finger protein A20 expression is required for electroacupuncture to attenuate the cerebral inflammatory injury mediated by the nuclear factor-kB signaling pathway in cerebral ischemia/reperfusion rats.

Science.gov (United States)

Zhan, Jian; Qin, Wenyi; Zhang, Ying; Jiang, Jing; Ma, Hongmei; Li, Qiongli; Luo, Yong

2016-10-03

Zinc finger protein A20 (tumor necrosis factor alpha-induced protein 3) functions as a potent negative feedback inhibitor of the nuclear factor-kB (NF-kB) signaling. It exerts these effects by interrupting the activation of IkB kinase beta (IKKβ), the most critical kinase in upstream of NF-kB, and thereby controlling inflammatory homeostasis. We reported previously that electroacupuncture (EA) could effectively suppress IKKβ activation. However, the mechanism underlying these effects was unclear. Therefore, the current study further explored the effects of EA on A20 expression in rat brain and investigated the possible mechanism of A20 in anti-neuroinflammation mediated by EA using transient middle cerebral artery occlusion (MCAO) rats. Rats were treated with EA at the "Baihui (GV20)," "Hegu (L14)," and "Taichong (Liv3)" acupoints once a day starting 2 h after focal cerebral ischemia. The spatiotemporal expression of A20, neurobehavioral scores, infarction volumes, cytokine levels, glial cell activation, and the NF-kB signaling were assessed at the indicated time points. A20 gene interference (overexpression and silencing) was used to investigate the role of A20 in mediating the neuroprotective effects of EA and in regulating the interaction between neuronal and glial cells by suppressing neuronal NF-kB signaling during cerebral ischemia/reperfusion-induced neuroinflammation. EA treatment increased A20 expression with an earlier peak and longer lasting upregulation. The upregulated A20 protein was predominantly located in neurons in the cortical zone of the ischemia/reperfusion. Furthermore, neuronal A20 cell counts were positively correlated with neurobehavioral scores but negatively correlated with infarct volume, the accumulation of pro-inflammatory cytokines, and glial cell activation. Moreover, the effects of EA on improving the neurological outcome and suppressing neuroinflammation in the brain were reversed by A20 silencing. Finally, A20 silencing also

Are we there yet? Evaluating commercial grade brain-computer interface for control of computer applications by individuals with cerebral palsy.

Science.gov (United States)

Taherian, Sarvnaz; Selitskiy, Dmitry; Pau, James; Claire Davies, T

2017-02-01

Using a commercial electroencephalography (EEG)-based brain-computer interface (BCI), the training and testing protocol for six individuals with spastic quadriplegic cerebral palsy (GMFCS and MACS IV and V) was evaluated. A customised, gamified training paradigm was employed. Over three weeks, the participants spent two sessions exploring the system, and up to six sessions playing the game which focussed on EEG feedback of left and right arm motor imagery. The participants showed variable inconclusive results in the ability to produce two distinct EEG patterns. Participant performance was influenced by physical illness, motivation, fatigue and concentration. The results from this case study highlight the infancy of BCIs as a form of assistive technology for people with cerebral palsy. Existing commercial BCIs are not designed according to the needs of end-users. Implications for Rehabilitation Mood, fatigue, physical illness and motivation influence the usability of a brain-computer interface. Commercial brain-computer interfaces are not designed for practical assistive technology use for people with cerebral palsy. Practical brain-computer interface assistive technologies may need to be flexible to suit individual needs.

Nimodipine Effects on Cerebral Microvessels and Sciatic Nerve in Aging Rats

NARCIS (Netherlands)

de Jong, Giena; Jansen, Arthur; Horvath, E.; Gispen, W.H.; Luiten, P.G.M.

1992-01-01

At the ultrastructural level different anomalies of the cerebral microvasculature were encountered in the brains of aged rats. These aberrations can either be attributed to degeneration processes or to the perivascular deposition of, e.g., collagen fibrils and other, unidentified, proteinous debris.

Adrenergic-induced enhancement of brain barrier system permeability to small nonelectrolytes: choroid plexus versus cerebral capillaries

International Nuclear Information System (INIS)

Murphy, V.A.; Johanson, C.E.

1985-01-01

Acute hypertension induced by adrenergic agents opens up the blood-CSF barrier (choroid plexus) to nonelectrolyte and protein tracers. Sprague-Dawley adult rats anesthetized with ketamine were given an intravenous bolus of either epinephrine (10 micrograms/kg), phenylephrine (100 micrograms/kg), isoproterenol (10 micrograms/kg), or D,L-amphetamine (2 mg/kg). Tracers were injected simultaneously with test agents, and the animals killed 10 min later. Epinephrine raised MABP by 57 mm Hg, to a peak pressure of 160 mm Hg; and it increased the volume of distribution (Vd) of urea, mannitol, and 125 I-bovine serum albumin in CSF by 1.5-, 2.7-, and 30-fold, respectively. There was enhanced uptake by lateral and fourth ventricle choroid plexuses, cerebral cortex, cerebellum, medulla, and thalamus. Phenylephrine also elevated MABP to 160 mm Hg, but it increased permeation of tracers into CSF (and several brain regions) to a lesser extent than epinephrine, attributable to protective vasoconstriction associated with alpha-agonist activity. Ratio analysis of Vd data provides evidence that augmented permeation of nonelectrolyte tracers in acute hypertension occurs predominantly by diffusion rather than vesicular transport. It is postulated that elevated MABP distends the central cores of choroid plexus villi and cerebral capillaries, with resultant stretching and opening of tight junctions in both barrier systems; with less hindrance to diffusion, urea and mannitol are cleared at rates closer to free diffusion. Neither isoproterenol (decreased MABP by 40 mm Hg) nor amphetamine (did not alter MABP) significantly opened the choroid plexus or blood-brain barrier to tracers

Quantitative evaluation of regional cerebral blood flow by visual stimulation in {sup 99m}Tc- HMPAO brain SPECT

Energy Technology Data Exchange (ETDEWEB)

Juh, Ra Hyeong; Suh, Tae Suk; Kwark, Chul Eun; Choe, Bo Young; Lee, Hyoung Koo; Chung, Yong An; Kim, Sung Hoon; Chung, Soo Kyo [College of Medicine, The Catholic Univ. of Seoul, Seoul (Korea, Republic of)

2002-06-01

The purpose of this study is to investigate the effects of visual activation and quantitative analysis of regional cerebral blood flow. Visual activation was known to increase regional cerebral blood flow in the visual cortex in occipital lobe. We evaluated that change in the distribution of '9{sup 9m}Tc-HMPAO (Hexamethyl propylene amine oxime) to reflect in regional cerebral blood flow. The six volunteers were injected with 925 MBq (mean ages: 26.75 years, n=6, 3men, 3women) underwent MRI and {sup 99m}Tc-HMPAO SPECT during a rest state with closed eyes and visual stimulated with 8 Hz LED. We delineate the region of interest and calculated the mean count per voxel in each of the fifteen slices to quantitative analysis. The ROI to whole brain ratio and regional index was calculated pixel to pixel subtraction visual non-activation image from visual activation image and constructed brain map using a statistical parameter map(SPM99). The mean regional cerebral blood flow was increased due to visual stimulation. The increase rate of the mean regional cerebral blood flow which of the activation region in primary visual cortex of occipital lobe was 32.50{+-}5.67%. The significant activation sites using a statistical parameter of brain constructed a rendering image and image fusion with SPECT and MRI. Visual activation was revealed significant increase through quantitative analysis in visual cortex. Activation region was certified in Talairach coordinate and primary visual cortex (Ba17),visual association area (Ba18,19) of Brodmann.

Quantitative evaluation of regional cerebral blood flow by visual stimulation in {sup 99m}Tc-HMPAO brain SPECT

Energy Technology Data Exchange (ETDEWEB)

Juh, R. H.; Suh, T. S.; Chung, Y. A. [The Catholic Univ., of Korea, Seoul (Korea, Republic of)

2002-07-01

The purpose of this study is to investigate the effects of visual activation and quantitative analysis of regional cerebral blood flow. Visual activation was known to increase regional cerebral blood flow in the visual cortex in occipital lobe. We evaluated that change in the distribution of 99mTc-HMPAO (Hexamethyl propylene amine oxime) to reflect in regional cerebral blood flow. The six volunteers were injected with 925 MBq (mean ages: 26.75 years, n=6, 3men, 3women) underwent MRI and 99mTc- HMPAO SPECT during a rest state with closed eyes and visual stimulated with 8 Hz LED. We delineate the region of interest and calculated the mean count per voxel in each of the fifteen slices to quantitative analysis. The ROI to whole brain ratio and regional index was calculated pixel to pixel subtraction visual non-activation image from visual activation image and constructed brain map using a statistical parameter map (SPM99). The mean regional cerebral blood flow was increased due to visual stimulation. The increase rate of the mean regional cerebral blood flow which of the activation region in primary visual cortex of occipital lobe was 32.50{+-}5.67%. The significant activation sites using a statistical parameter of brain constructed a rendering image and image fusion with SPECT and MRI. Visual activation was revealed significant increase through quantitative analysis in visual cortex. Activation region was certified in Talairach coordinate and primary visual cortex (Ba17),visual association area (Ba18,19) of Brodmann.

Brain imaging and brain function

International Nuclear Information System (INIS)

Sokoloff, L.

1985-01-01

This book is a survey of the applications of imaging studies of regional cerebral blood flow and metabolism to the investigation of neurological and psychiatric disorders. Contributors review imaging techniques and strategies for measuring regional cerebral blood flow and metabolism, for mapping functional neural systems, and for imaging normal brain functions. They then examine the applications of brain imaging techniques to the study of such neurological and psychiatric disorders as: cerebral ischemia; convulsive disorders; cerebral tumors; Huntington's disease; Alzheimer's disease; depression and other mood disorders. A state-of-the-art report on magnetic resonance imaging of the brain and central nervous system rounds out the book's coverage

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

Science.gov (United States)

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

2015-01-01

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

Hemopexin induces neuroprotection in the rat subjected to focal cerebral ischemia

OpenAIRE

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

2013-01-01

Background 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. Results I...

Peripherally applied synthetic peptide isoAsp7-Aβ(1-42) triggers cerebral β-amyloidosis.

Science.gov (United States)

Kozin, S A; Cheglakov, I B; Ovsepyan, A A; Telegin, G B; Tsvetkov, P O; Lisitsa, A V; Makarov, A A

2013-10-01

Intracerebral and intraperitoneal inoculation with β-amyloid-rich brain extracts originating from patients with Alzheimer's disease as well as intracerebral injection of aggregates composed of synthetic Aβ can induce cerebral β-amyloidosis, and associated cognitive dysfunctions in susceptible animal hosts. We have found that repetitive intravenous administration of 100 μg of synthetic peptide corresponding to isoAsp7-containing Aβ(1-42), an abundant age-dependent Aβ isoform present both in the pathological brain and in synthetic Aβ preparations, robustly accelerates formation of classic dense-core congophilic amyloid plaques in the brain of β-amyloid precursor protein transgenic mice. Our findings indicate this peptide as an inductive agent of cerebral β-amyloidosis in vivo.

Evaluation of cerebral blood flow, cerebral metabolism and cerebral function by magnetic resonance imaging

International Nuclear Information System (INIS)

Tanaka, Chuzo; Higuchi, Toshihiro; Umeda, Masahiro; Naruse, Shoji; Horikawa, Yoshiharu; Ueda, Satoshi; Furuya, Seiichi.

1995-01-01

The magnetic resonance (MR) method has the unique potentiality of detecting cerebral metabolites, cerebral blood flow and brain functions in a noninvasive fashion. We have developed several MR techniques to detect these cerebral parameters with the use of clinical MRI scanners. By modifying the MR spectroscopy (MRS) technique, both 31 P- and 1 H-MRS data can be obtained from multiple, localized regions (multi-voxel method) of the brain, and the distribution of each metabolite in the brain can be readily visualized by metabolite mapping. The use of diffusion weighted images (DWI) permits visualization of the anisotropy of water diffusion in white matter, and based on the difference of diffusion coefficiency, the differential diagnosis between epidermoid tumor and arachnoid cyst can be made. By employing dynamic-MRI (Dyn-MRI) with Gd-DTPA administration, it is possible to examine the difference in blood circulation between brain tumor tissue and normal tissue, as well as among different types of brain tumors. By using magnetization transfer contrast (MTC) imaging, it has become possible to detect brain tumors, and with a small dose of Gd-DTPA, to visualize the vascular system. Functional MRI (fMRI) visualizes the activated brain by using conventional gradient echo technique on conventional MRI scanners. This method has the unique characteristic of detecting a brain function with high spatial and temporal resolution by using the intrinsic substance. Moreover, the localization of motor and sensory areas was detected by noninvasive means within few minutes. The fMRI procedure will be used in the future to analyze the higher and complex brain functions. In conclusion, multi-modality MR is a powerful technique that is useful for investigating the pathogenesis of many diseases, and provides a noninvasive analytic modality for studying brain function. (author)

Multiplex Brain Proteomic Analysis Revealed the Molecular Therapeutic Effects of Buyang Huanwu Decoction on Cerebral Ischemic Stroke Mice.

Directory of Open Access Journals (Sweden)

Hong-Jhang Chen

Full Text Available Stroke is the second-leading cause of death worldwide, and tissue plasminogen activator (TPA is the only drug used for a limited group of stroke patients in the acute phase. Buyang Huanwu Decoction (BHD, a traditional Chinese medicine prescription, has long been used for improving neurological functional recovery in stroke. In this study, we characterized the therapeutic effect of TPA and BHD in a cerebral ischemia/reperfusion (CIR injury mouse model using multiplex proteomics approach. After the iTRAQ-based proteomics analysis, 1310 proteins were identified from the mouse brain with <1% false discovery rate. Among them, 877 quantitative proteins, 10.26% (90/877, 1.71% (15/877, and 2.62% (23/877 of the proteins was significantly changed in the CIR, BHD treatment, and TPA treatment, respectively. Functional categorization analysis showed that BHD treatment preserved the integrity of the blood-brain barrier (BBB (Alb, Fga, and Trf, suppressed excitotoxicity (Grm5, Gnai, and Gdi, and enhanced energy metabolism (Bdh, thereby revealing its multiple effects on ischemic stroke mice. Moreover, the neurogenesis marker doublecortin was upregulated, and the activity of glycogen synthase kinase 3 (GSK-3 and Tau was inhibited, which represented the neuroprotective effects. However, TPA treatment deteriorated BBB breakdown. This study highlights the potential of BHD in clinical applications for ischemic stroke.

Unilateral cerebral polymicrogyria with ipsilateral cerebral hemiatrophy

Energy Technology Data Exchange (ETDEWEB)

Hayakawa, Katsumi [Department of Radiology, Kyoto City Hospital, 1-2 Higashi-Takada-cho, Mibu, Nakagyo-ku, 604-8845 Kyoto (Japan); Kanda, Toyoko; Yamori, Yuriko [Department of Pediatric Neurology, St. Joseph Hospital for Handicapped Children, 603-8323 Kyoto (Japan)

2002-10-01

We evaluated six children in whom MR imaging showed unilateral cerebral polymicrogyria associated with ipsilateral cerebral atrophy and ipsilateral brain stem atrophy. The aim of this study was to clarify whether this disorder based on neuroimaging constitutes a new homogeneous clinical entity. The subjects were six children whose ages at the time of MR imaging ranged from 8 months to 11 years. Their clinical and MR features were analyzed. All of the children were born between 38 and 42 weeks gestation, without any significant perinatal events. Spastic hemiplegia and epilepsy were observed in all of the patients, and mental retardation was observed in four. The MR findings included unilateral cerebral polymicrogyria associated with ipsilateral cerebral hemiatrophy and ipsilateral brain stem atrophy in all patients. The ipsilateral sylvian fissure was hypoplastic in four patients. These patients showed relatively homogeneous clinical and neuroimaging features. Although the additional clinical features varied according to the site and the extent affected by the polymicrogyria, this disorder could constitute a new relatively homogeneous clinical entity. (orig.)

Unilateral cerebral polymicrogyria with ipsilateral cerebral hemiatrophy

International Nuclear Information System (INIS)

Hayakawa, Katsumi; Kanda, Toyoko; Yamori, Yuriko

2002-01-01

We evaluated six children in whom MR imaging showed unilateral cerebral polymicrogyria associated with ipsilateral cerebral atrophy and ipsilateral brain stem atrophy. The aim of this study was to clarify whether this disorder based on neuroimaging constitutes a new homogeneous clinical entity. The subjects were six children whose ages at the time of MR imaging ranged from 8 months to 11 years. Their clinical and MR features were analyzed. All of the children were born between 38 and 42 weeks gestation, without any significant perinatal events. Spastic hemiplegia and epilepsy were observed in all of the patients, and mental retardation was observed in four. The MR findings included unilateral cerebral polymicrogyria associated with ipsilateral cerebral hemiatrophy and ipsilateral brain stem atrophy in all patients. The ipsilateral sylvian fissure was hypoplastic in four patients. These patients showed relatively homogeneous clinical and neuroimaging features. Although the additional clinical features varied according to the site and the extent affected by the polymicrogyria, this disorder could constitute a new relatively homogeneous clinical entity. (orig.)

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

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

2004-09-15

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

Tetrahydrobiopterin in antenatal brain hypoxia-ischemia-induced motor impairments and cerebral palsy.

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Vasquez-Vivar, Jeannette; Shi, Zhongjie; Luo, Kehuan; Thirugnanam, Karthikeyan; Tan, Sidhartha

2017-10-01

Antenatal brain hypoxia-ischemia, which occurs in cerebral palsy, is considered a significant cause of motor impairments in children. The mechanisms by which antenatal hypoxia-ischemia causes brain injury and motor deficits still need to be elucidated. Tetrahydrobiopterin is an important enzyme cofactor that is necessary to produce neurotransmitters and to maintain the redox status of the brain. A genetic deficiency of this cofactor from mutations of biosynthetic or recycling enzymes is a well-recognized factor in the development of childhood neurological disorders characterized by motor impairments, developmental delay, and encephalopathy. Experimental hypoxia-ischemia causes a decline in the availability of tetrahydrobiopterin in the immature brain. This decline coincides with the loss of brain function, suggesting this occurrence contributes to neuronal dysfunction and motor impairments. One possible mechanism linking tetrahydrobiopterin deficiency, hypoxia-ischemia, and neuronal injury is oxidative injury. Evidence of the central role of the developmental biology of tetrahydrobiopterin in response to hypoxic ischemic brain injury, especially the development of motor deficits, is discussed. Copyright © 2017. Published by Elsevier B.V.

Computerized tomography of the brain and associated risk factors in 240 patients iwth reversible cerebral ischemic attacks (RIAs)

International Nuclear Information System (INIS)

Bozzao, L.; Fantozzi, L.M.; Carolei, A.; Pappata, S.; Vesentini, G.; Allori, L.; Rasura, M.; Fieschi, C.

1985-01-01

The frequency and distribution of focal low density cerebral ischemic lesions in RIA patients with regard to factors as age at onset, number and temporal profile of the reversible cerebral ischemic events on admission, presence of associated medical conditions such as hypertension and diabetes mellitus, have been investigated with computerized tomography of the brain. (author). 7 refs.; 1 tab

Blood-brain barrier transport and protein binding of flumazenil and iomazenil in the rat: implications for neuroreceptor studies

DEFF Research Database (Denmark)

Videbaek, C; Ott, P; Paulson, O B

1999-01-01

of blood-brain barrier permeability for two benzodiazepine antagonists were performed in 44 rats by the double-indicator technique. Cerebral blood flow was measured by intracarotid Xe-injection. The apparent permeability-surface product (PSapp) was measured while CBF or bolus composition was changed......The calculated fraction of receptor ligands available for blood-brain barrier passage in vivo (f(avail)) may differ from in vitro (f(eq)) measurements. This study evaluates the protein-ligand interaction for iomazenil and flumazenil in rats by comparing f(eq) and f(avail). Repeated measurements......(avail) and f(eq) as well as the effect of CBF on PSapp can be caused by capillary heterogeneity....

Cerebral hemodynamic changes of mild traumatic brain injury at the acute stage.

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Hardik Doshi

Full Text Available Mild traumatic brain injury (mTBI is a significant public health care burden in the United States. However, we lack a detailed understanding of the pathophysiology following mTBI and its relation to symptoms and recovery. With advanced magnetic resonance imaging (MRI, we can investigate brain perfusion and oxygenation in regions known to be implicated in symptoms, including cortical gray matter and subcortical structures. In this study, we assessed 14 mTBI patients and 18 controls with susceptibility weighted imaging and mapping (SWIM for blood oxygenation quantification. In addition to SWIM, 7 patients and 12 controls had cerebral perfusion measured with arterial spin labeling (ASL. We found increases in regional cerebral blood flow (CBF in the left striatum, and in frontal and occipital lobes in patients as compared to controls (p = 0.01, 0.03, 0.03 respectively. We also found decreases in venous susceptibility, indicating increases in venous oxygenation, in the left thalamostriate vein and right basal vein of Rosenthal (p = 0.04 in both. mTBI patients had significantly lower delayed recall scores on the standardized assessment of concussion, but neither susceptibility nor CBF measures were found to correlate with symptoms as assessed by neuropsychological testing. The increased CBF combined with increased venous oxygenation suggests an increase in cerebral blood flow that exceeds the oxygen demand of the tissue, in contrast to the regional hypoxia seen in more severe TBI. This may represent a neuroprotective response following mTBI, which warrants further investigation.

MRI findings of acute cerebral swelling and brain edema in the acute stage

International Nuclear Information System (INIS)

Oki, Hideo; Ueda, Shin; Matsumoto, Keizo; Kashihara, Michiharu; Furuichi, Masashi.

1988-01-01

We report two cases, one of acute cerebral swelling and the other with a major stroke, whose MRI has shown very interesting findings. Case 1, a 32-year-old male, was admitted to our service because of a lowering of his consciousness immediately after a head injury. On admission, the patient was semicomatous (E 1 M 2 V 1 , with anisocoria (R > L). His plain skull X-ray was normal. A CT scan, however, demonstrated right isodensity hemispheric swelling associated with a subarachnoid hemorrhage in the right Sylvian fissure. A right carotid angiogram showed no vascular disorders. MR imaging of the spin density demonstrated a hyperintensitive thickening of the gray matter in the whole right hemisphere. Case 2, a 58-year-old female, was admitted because of a sudden onset of loss of consciousness, with right hemiparesis and dysarthria. On admission, her consciousness was semicomatous (E 1 M 3 V 1 ), and it deteriorated to a deep coma 1 hour later. A CT scan demonstrated a diffuse left hemispheric low density, with a finding of hemorrhagic infarction in the basal ganglia. MR imaging of the spin density showed a hyperintensitive thickening of the gray matter resembling that of Case 1. The findings of the spin-echo images of our two cases showed a hyperintensitive thickening of the gray matter in both. The hyperintensity and thickening of the gray matter apparently indicated a sort of hyperemia and brain edema. These findings led us to suspect that the hyperemia associated with acute cerebral swelling and ischemic brain edema of our two cases originated in the gray matter, although it has been considered that the pathogenesis of acute cerebral swelling is not known and that brain edema, especially vasogenic edema, will mostly develop in the white matter rather than in the gray matter. (author)

Post Traumatic Cerebral Oedema in Severe Head Injury is Related to Intracranial Pressure and Cerebral Perfusion Pressure but not to Cerebral Compliance

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U Nujaimin

2009-07-01

Full Text Available This was a prospective cohort study, carried out in the Neuro Intensive Care Unit, Department of Neurosciences, Hospital Universiti Sains Malaysia, Kubang Kerian Kelantan. The study was approved by the local ethics committee and was conducted between November 2005 and September 2007 with a total of 30 patients included in the study. In our study, univariate analysis showed a statistically significant relationship between mean intracranial pressure (ICP as well as cerebral perfusion pressure (CPP with both states of basal cistern and the degree of diffuse injury and oedema based on the Marshall classification system. The ICP was higher while CPP and compliance were lower whenever the basal cisterns were effaced in cases of cerebral oedema with Marshall III and IV. In comparison, the study revealed lower ICP, higher mean CPP and better mean cerebral compliance if the basal cisterns were opened or the post operative CT brain scan showed Marshall I and II. These findings suggested the surgical evacuation of clots to reduce the mass volume and restoration of brain anatomy may reduce vascular engorgement and cerebral oedema, therefore preventing intracranial hypertension, and improving cerebral perfusion pressure and cerebral compliance. Nevertheless the study did not find any significant relationship between midline shifts and mean ICP, CPP or cerebral compliance even though lower ICP, higher CPP and compliance were frequently observed when the midline shift was less than 0.5 cm. As the majority of our patients had multiple and diffuse brain injuries, the absence of midline shift did not necessarily mean lower ICP as the pathology was bilateral and even when after excluding the multiple lesions, the result remained insignificant. We assumed that the CT brain scan obtained after evacuation of the mass lesion to assess the state basal cistern and classify the diffuse oedema may prognosticate the intracranial pressure and cerebral perfusion pressure

Aquaporin-4 inhibition mediates piroxicam-induced neuroprotection against focal cerebral ischemia/reperfusion injury in rodents.

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Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana; Yavagal, Dileep R

2013-01-01

Aquaporin-4(AQP4) is an abundant water channel protein in brain that regulates water transport to maintain homeostasis. Cerebral edema resulting from AQP4 over expression is considered to be one of the major determinants for progressive neuronal insult during cerebral ischemia. Although, both upregulation and downregulation of AQP4 expression is associated with brain pathology, over expression of AQP4 is one of the chief contributors of water imbalance in brain during ischemic pathology. We have found that Piroxicam binds to AQP4 with optimal binding energy value. Thus, we hypothesized that Piroxicam is neuroprotective in the rodent cerebral ischemic model by mitigating cerebral edema via AQP4 regulation. Rats were treated with Piroxicam OR placebo at 30 min prior, 2 h post and 4 h post 60 minutes of MCAO followed by 24 hour reperfusion. Rats were evaluated for neurological deficits and motor function just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, biochemical analysis, RT-PCR and western blot experiments. Piroxicam pretreatment thirty minutes prior to ischemia and four hour post reperfusion afforded neuroprotection as evident through significant reduction in cerebral infarct volume, improvement in motor behavior, neurological deficit and reduction in brain edema. Furthermore, ischemia induced surge in levels of nitrite and malondialdehyde were also found to be significantly reduced in ischemic brain regions in treated animals. This neuroprotection was found to be associated with inhibition of acid mediated rise in intracellular calcium levels and also downregulated AQP4 expression. Findings of the present study provide significant evidence that Piroxicam acts as a potent AQP4 regulator and renders neuroprotection in focal cerebral ischemia. Piroxicam could be clinically exploited for the treatment of brain stroke along with other anti-stroke therapeutics in future.

Cerebral volumes, neuronal integrity and brain inflammation measured by MRI in patients receiving PI monotherapy or triple therapy.

Science.gov (United States)

Valero, Ignacio Pérez; Baeza, Alicia Gonzalez; Hernandez-Tamames, Juan Antonio; Monge, Susana; Arnalich, Francisco; Arribas, Jose Ramon

2014-01-01

Penetration of protease inhibitors (PI) in the central nervous system (CNS) is limited. Therefore, there are concerns about the capacity of PI monotherapy (MT) to control HIV in CNS and preserve brain integrity. Exploratory case-control study designed to compare neuronal integrity and brain inflammation in HIV-suppressed patients (>2 years) with and without neurocognitive impairment (NI), treated with MT or triple therapy (TT), 3-Tesla cerebral magnetic resonance image (MRI) and spectroscopy (MRS) were used to evaluate neuronal integrity (volume of cerebral structures and MRS levels of N-acetyl-aspartate (NAA)) and brain inflammation (MRS levels of myo-inositol (MI) and choline (CHO)). MRS biomarkers were measured in 4 voxels located in basal ganglia, frontal (2) and parietal lobes. A comprehensive battery of tests (14 tests - 7 domains) was used to diagnose neurocognitive impairment (1). We included 18 neurocognitively impaired patients (MT: 10, TT: 8) and 21 without NI (MT: 9; TT: 12, Table 1). Subset of patients with NI: cerebral volumes and MRS biomarkers were mostly similar between MT and TT with exception of the right cingulate nucleolus volume (MT: 8854±1851 vs TT: 10482±1107 mm(3); p<0.04), CHO levels in basal ganglia (MT: 0.44±0.05 vs TT: 0.37±0.03 MMOL/L; p<0.01) and the NAA levels in parietal lobe (MT: 1.49±0.12 vs 1.70±0.13 MMOL/L; p<0.01). Subset of patients without NI: cerebral volumes and MRS biomarkers were mostly similar between MT and TT with exception of MI levels in frontal lobe (MT: 1.20±0.36 vs 0.81±0.25 MMOL/L; p=0.01). We did not find significant differences in cerebral volumes or MRS biomarkers in most areas of the brain. However, we found higher levels of inflammation and neuronal damage in some brain areas of patients who received MT. This observation has to be taken into caution while we could not adjust our results by potential confounders. Further investigation is needed to confirm these preliminary results.

Brain sweet brain: importance of sugars for the cerebral microenvironment and tumor development Cérebro doce cérebro: importância dos açúcares para o microambiente cerebral e o desenvolvimento tumoral

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Thereza Quirico-Santos

2010-10-01

Full Text Available The extracellular matrix (ECM in the brain tissue is a complex network of glycoproteins and proteoglycans that fills the intercellular space serving as scaffolding to provide structural framework for the tissue and regulate the behavior of cells via specific receptors - integrins. There is enormous structural diversity among proteoglycans due to variation in the core protein, the number of glycosaminoglycans chains, the extent and position of sulfation. The lectican family of proteoglycans interacts with growth factors, hyaluronan and tenascin forming a complex structure that regulates neuronal plasticity and ion homeostasis around highly active neurons. In this review, we will discuss the latest insights into the roles of brain glycoproteins as modulators of cell adhesion, migration, neurite outgrowth and glial tumor invasion.A matriz extracelular (ECM no tecido cerebral é formada por uma rede complexa de glicoproteínas e proteoglicanas que preenchem o espaço intercelular participando como estrutura de sustentação do arcabouço tecidual regulando a função celular por interações com receptores específicos - as integrinas. Existe enorme diversidade estrutural entre as proteoglicanas, devido à variação na proteína central (core, à quantidade de cadeias de glicosaminoglicanas, ao grau e posição de grupamentos sulfato na molécula. As proteoglicanas lecticanas interagem com fatores de crescimento, com hialuronana e tenascina formando uma estrutura complexa regulando a homeostase de íons e a plasticidade neuronal. Neste artigo de revisão serão apresentados dados relevantes da literatura sobre o papel das glicoproteínas no microambiente do tecido cerebral, como moduladores da neuritogênese, da adesão, migração celular e invasividade de células tumorais de origem glial.

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

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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.

Expression of glial fibrillar acidic protein in the sensorimotor cortex of the cerebral hemispheres in the modeling of transient ischemia against the background of previous sensitization by brain antigen and immunocorrection

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L. M. Yaremenko

2017-12-01

Full Text Available Aim. In order to analyze the dynamics of expression of glial fibrillar acidic protein in the sensorimotor cortex of the large hemispheres in the simulation of transient ischemia against the background of previous sensitization by brain antigen and immunocorrection. Materials and methods. The study is conducted on 185 male mature white rats from Wistar line weighing 260-290 g, in which the damage of the brain was modulated. The brain for study was taken on the 1st, 3rd, 10th, 30th and 90th days after the start of the experiment. The histological, immunohistochemical, morphometric and statistical methods were used. Results. Observations have shown that sensitization by the brain antigen causes neurodegenerative changes in the sensorimotor cortex and a moderate increase in the number of GFAP+-gliocytes, which is gradually increasing. The discirculatory changes that occurred with PO and BCA against the background of previous sensitization practically do not lead to changes in the number of GFAP+-cells. Against the background of sensitization by brain antigen, brain ischemia leads to an increase in the number of gliocytes that are GFAP labeled. In the affected hemisphere, their number reaches a maximum in the end of the acute period of ischemia, after which it decreases. But even in 3 months after transient vascular lesion, there are almost twice as many as in conditionally intact rats. This can be a factor that will significantly affect the function of brain regions after a vascular accident. The increase in the number of GFAP+-gliocytes in the contralateral hemisphere allows us to speak about a certain systemic response of astrocytic glia after ischemic trauma. An early reaction to increase of the number of labeled astrocytes just a day after ischemic attack suggests that some of this type of gliocytes does not expresses GFAP under normal conditions. The action of Imunofan in MEAs results in a less significant decrease in manifestations of

Induction of complement proteins in a mouse model for cerebral microvascular Aβ deposition

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DeFilippis Kelly

2007-09-01

Full Text Available Abstract The deposition of amyloid β-protein (Aβ in cerebral vasculature, known as cerebral amyloid angiopathy (CAA, is a common pathological feature of Alzheimer's disease and related disorders. In familial forms of CAA single mutations in the Aβ peptide have been linked to the increase of vascular Aβ deposits accompanied by a strong localized activation of glial cells and elevated expression of neuroinflammatory mediators including complement proteins. We have developed human amyloid-β precursor protein transgenic mice harboring two CAA Aβ mutations (Dutch E693Q and Iowa D694N that mimic the prevalent cerebral microvascular Aβ deposition observed in those patients, and the Swedish mutations (K670N/M671L to increase Aβ production. In these Tg-SwDI mice, we have reported predominant fibrillar Aβ along microvessels in the thalamic region and diffuse plaques in cortical region. Concurrently, activated microglia and reactive astrocytes have been detected primarily in association with fibrillar cerebral microvascular Aβ in this model. Here we show that three native complement components in classical and alternative complement pathways, C1q, C3, and C4, are elevated in Tg-SwDI mice in regions rich in fibrillar microvascular Aβ. Immunohistochemical staining of all three proteins was increased in thalamus, hippocampus, and subiculum, but not frontal cortex. Western blot analysis showed significant increases of all three proteins in the thalamic region (with hippocampus as well as the cortical region, except C3 that was below detection level in cortex. Also, in the thalamic region (with hippocampus, C1q and C3 mRNAs were significantly up-regulated. These complement proteins appeared to be expressed largely by activated microglial cells associated with the fibrillar microvascular Aβ deposits. Our findings demonstrate that Tg-SwDI mice exhibit elevated complement protein expression in response to fibrillar vascular Aβ deposition that is

Apparent brain temperature imaging with multi-voxel proton magnetic resonance spectroscopy compared with cerebral blood flow and metabolism imaging on positron emission tomography in patients with unilateral chronic major cerebral artery steno-occlusive disease

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Nanba, Takamasa; Nishimoto, Hideaki; Murakami, Toshiyuki; Fujiwara, Shunrou; Ogasawara, Kuniaki [Iwate Medical University, Department of Neurosurgery, Iwate (Japan); Yoshioka, Yoshichika [Osaka University, Open and Transdisciplinary Research Initiatives, Osaka (Japan); Sasaki, Makoto; Uwano, Ikuko [Iwate Medical University, Institute for Biomedical Science, Iwate (Japan); Terasaki, Kazunori [Iwate Medical University, Cyclotron Research Center, Iwate (Japan)

2017-09-15

The purpose of the present study was to determine whether apparent brain temperature imaging using multi-voxel proton magnetic resonance (MR) spectroscopy correlates with cerebral blood flow (CBF) and metabolism imaging in the deep white matter of patients with unilateral chronic major cerebral artery steno-occlusive disease. Apparent brain temperature and CBF and metabolism imaging were measured using proton MR spectroscopy and {sup 15}O-positron emission tomography (PET), respectively, in 35 patients. A set of regions of interest (ROIs) of 5 x 5 voxels was placed on an MR image so that the voxel row at each edge was located in the deep white matter of the centrum semiovale in each cerebral hemisphere. PET images were co-registered with MR images with these ROIs and were re-sliced automatically using image analysis software. In 175 voxel pairs located in the deep white matter, the brain temperature difference (affected hemisphere - contralateral hemisphere: ΔBT) was correlated with cerebral blood volume (CBV) (r = 0.570) and oxygen extraction fraction (OEF) ratios (affected hemisphere/contralateral hemisphere) (r = 0.641). We excluded voxels that contained ischemic lesions or cerebrospinal fluid and calculated the mean values of voxel pairs in each patient. The mean ΔBT was correlated with the mean CBF (r = - 0.376), mean CBV (r = 0.702), and mean OEF ratio (r = 0.774). Apparent brain temperature imaging using multi-voxel proton MR spectroscopy was correlated with CBF and metabolism imaging in the deep white matter of patients with unilateral major cerebral artery steno-occlusive disease. (orig.)

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

Science.gov (United States)

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:…

Effect of ephedrine and phenylephrine on brain oxygenation and microcirculation in anaesthetised patients with cerebral tumours

DEFF Research Database (Denmark)

Koch, Klaus Ulrik; Tietze, Anna; Aanerud, Joel

2017-01-01

extraction fraction. Surgery is initiated after MRI/PET measurements and subdural intracranial pressure is measured. ETHICS AND DISSEMINATION: This study was approved by the Central Denmark Region Committee on Health Research Ethics (12 June 2015; 1-10-72-116-15). Results will be disseminated via peer......INTRODUCTION: During brain tumour surgery, vasopressor drugs are commonly administered to increase mean arterial blood pressure with the aim of maintaining sufficient cerebral perfusion pressure. Studies of the commonly used vasopressors show that brain oxygen saturation is reduced after......, anaesthetised patients will be randomised to receive either phenylephrine or ephedrine infusion until mean arterial blood pressure increases to above 60 mm Hg or 20% above baseline. Twenty-four patients were allocated to MRI and another 24 patients to PET examination. MRI measurements include cerebral blood...

Diagnosis and Management of Combined Central Diabetes Insipidus and Cerebral Salt Wasting Syndrome After Traumatic Brain Injury.

Science.gov (United States)

Wu, Xuehai; Zhou, Xiaolan; Gao, Liang; Wu, Xing; Fei, Li; Mao, Ying; Hu, Jin; Zhou, Liangfu

2016-04-01

Combined central diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury (TBI) is rare, is characterized by massive polyuria leading to severe water and electrolyte disturbances, and usually is associated with very high mortality mainly as a result of delayed diagnosis and improper management. We retrospectively reviewed the clinical presentation, management, and outcomes of 11 patients who developed combined central diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury to define distinctive features for timely diagnosis and proper management. The most typical clinical presentation was massive polyuria (10,000 mL/24 hours or >1000 mL/hour) refractory to vasopressin alone but responsive to vasopressin plus cortisone acetate. Other characteristic presentations included low central venous pressure, high brain natriuretic peptide precursor level without cardiac dysfunction, high 24-hour urine sodium excretion and hypovolemia, and much higher urine than serum osmolarity; normal serum sodium level and urine specific gravity can also be present. Timely and adequate infusion of sodium chloride was key in treatment. Of 11 patients, 5 had a good prognosis 3 months later (Extended Glasgow Outcome Scale score ≥6), 1 had an Extended Glasgow Outcome Scale score of 4, 2 died in the hospital of brain hernia, and 3 developed a vegetative state. For combined diabetes insipidus and cerebral salt wasting syndrome after traumatic brain injury, massive polyuria is a major typical presentation, and intensive monitoring of fluid and sodium status is key for timely diagnosis. To achieve a favorable outcome, proper sodium chloride supplementation and cortisone acetate and vasopressin coadministration are key. Copyright © 2016 Elsevier Inc. All rights reserved.

Pathophysiological studies of experimental brain edema and cerebral ischemia using MRI/S

International Nuclear Information System (INIS)

Naruse, Shoji; Higuchi, Toshihiro; Horikawa, Yoshiharu; Tanaka, Chuzo; Hirakawa, Kimiyoshi

1987-01-01

Pathophysiological changes in experimental brain edema and cerebral ischemia were examined by the in vivo 1 H- and 31 P-NMR method. Two types of experimental brain edema were induced in rats by cold injury and by triethyltin (TET) intoxication. Experimental cerebral ischemia was induced in rats by the four-vessel occlusion method. During the course of these pathological conditions, the 1 H-MRIs and 31 P-NMR spectra were measured sequentially with a single NMR spectrometer (4.8 tesla, 9 cm bore magnet). In the cold-injury edema, high-intensity lesions were detected in the gray and white matters of the injured hemisphere by means of SE images with a long Te 3 hours after the injury. The intensity reached its maximum 16 to 24 hours after the injury, and then returned to normal 7 days later. These high-intensity lesions indicated an increase in the T2 value in the edematous tissue. There were no changes in the 31 P-NMR spectra during the course of edema formation and absorption. In the TET-induced edema, high-intensity lesions were also detected in the bilateral white matter by means of SE images with a long Te from the 3rd day up to the 7th day during the injection of TET. These high-intensity lesions subsided 42 days after the discontinuance of injecting TET. There were no changes in the 31 P-NMR spectra during the whole course of TET-induced edema. In the cerebral ischemia, no remarkable changes in the MRI were detected in either SE or IR images during the ischemic and recirculated periods. However, dynamic changes in the 31 P-NMR spectra were detected during the course of cerebral ischemia. In the pre-ischemic period, the peaks of the ATP, PCr, phosphodiesters (PDE), Pi, and phosphomonoesters (PME) were detected. After the induction of ischemia, the ATP and PCr peaks decreased, while one Pi peak increased rapidly. (J.P.N.)

Pathophysiological studies of experimental brain edema and cerebral ischemia using MRI/S

Energy Technology Data Exchange (ETDEWEB)

Naruse, S; Higuchi, T; Horikawa, Y; Tanaka, C; Hirakawa, K

1987-02-01

Pathophysiological changes in experimental brain edema and cerebral ischemia were examined by the in vivo /sup 1/H- and /sup 31/P-NMR method. Two types of experimental brain edema were induced in rats by cold injury and by triethyltin (TET) intoxication. Experimental cerebral ischemia was induced in rats by the four-vessel occlusion method. During the course of these pathological conditions, the /sup 1/H-MRIs and /sup 31/P-NMR spectra were measured sequentially with a single NMR spectrometer (4.8 tesla, 9 cm bore magnet). In the cold-injury edema, high-intensity lesions were detected in the gray and white matters of the injured hemisphere by means of SE images with a long Te 3 hours after the injury. The intensity reached its maximum 16 to 24 hours after the injury, and then returned to normal 7 days later. These high-intensity lesions indicated an increase in the T2 value in the edematous tissue. There were no changes in the /sup 31/P-NMR spectra during the course of edema formation and absorption. In the TET-induced edema, high-intensity lesions were also detected in the bilateral white matter by means of SE images with a long Te from the 3rd day up to the 7th day during the injection of TET. These high-intensity lesions subsided 42 days after the discontinuance of injecting TET. There were no changes in the /sup 31/P-NMR spectra during the whole course of TET-induced edema. In the cerebral ischemia, no remarkable changes in the MRI were detected in either SE or IR images during the ischemic and recirculated periods. However, dynamic changes in the /sup 31/P-NMR spectra were detected during the course of cerebral ischemia. In the pre-ischemic period, the peaks of the ATP, PCr, phosphodiesters (PDE), Pi, and phosphomonoesters (PME) were detected. After the induction of ischemia, the ATP and PCr peaks decreased, while one Pi peak increased rapidly.

Protein metabolism in the rat cerebral cortex in vivo and in vitro as affected by the acquisition enhancing drug piracetam

NARCIS (Netherlands)

Nickolson, V.J.; Wolthuis, O.L.

1976-01-01

The effect of Piracetam on rat cerebral protein metabolism in vivo and in vitro was studied. It was found that the drug stimulates the uptake of labelled leucine by cerebral cortex slices, has no effect on the incorporation of leucine into cerebral protein, neither in slices nor in vivo, but

The blood-brain barrier fatty acid transport protein 1 (FATP1/SLC27A1) supplies docosahexaenoic acid to the brain, and insulin facilitates transport.

Science.gov (United States)

Ochiai, Yusuke; Uchida, Yasuo; Ohtsuki, Sumio; Tachikawa, Masanori; Aizawa, Sanshiro; Terasaki, Tetsuya

2017-05-01

We purposed to clarify the contribution of fatty acid transport protein 1 (FATP1/SLC 27A1) to the supply of docosahexaenoic acid (DHA) to the brain across the blood-brain barrier in this study. Transport experiments showed that the uptake rate of [ 14 C]-DHA in human FATP1-expressing HEK293 cells was significantly greater than that in empty vector-transfected (mock) HEK293 cells. The steady-state intracellular DHA concentration was nearly 2-fold smaller in FATP1-expressing than in mock cells, suggesting that FATP1 works as not only an influx, but also an efflux transporter for DHA. [ 14 C]-DHA uptake by a human cerebral microvascular endothelial cell line (hCMEC/D3) increased in a time-dependent manner, and was inhibited by unlabeled DHA and a known FATP1 substrate, oleic acid. Knock-down of FATP1 in hCMEC/D3 cells with specific siRNA showed that FATP1-mediated uptake accounts for 59.2-73.0% of total [ 14 C]-DHA uptake by the cells. Insulin treatment for 30 min induced translocation of FATP1 protein to the plasma membrane in hCMEC/D3 cells and enhanced [ 14 C]-DHA uptake. Immunohistochemical analysis of mouse brain sections showed that FATP1 protein is preferentially localized at the basal membrane of brain microvessel endothelial cells. We found that two neuroprotective substances, taurine and biotin, in addition to DHA, undergo FATP1-mediated efflux. Overall, our results suggest that FATP1 localized at the basal membrane of brain microvessels contributes to the transport of DHA, taurine and biotin into the brain, and insulin rapidly increases DHA supply to the brain by promoting translocation of FATP1 to the membrane. Read the Editorial Comment for this article on page 324. © 2016 International Society for Neurochemistry.

Maintained exercise-enhanced brain executive function related to cerebral lactate metabolism in men

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Hashimoto, Takeshi; Tsukamoto, Hayato; Takenaka, Saki

2018-01-01

. Fourteen healthy, male subjects performed 2 HIIE protocols separated by 60 min of rest. Blood samples were obtained from the right internal jugular venous bulb and from the brachial artery to determine differences across the brain for lactate (a-v difflactate), glucose (diffglucose), oxygen (diffoxygen......High-intensity interval exercise (HIIE) improves cerebral executive function (EF), but the improvement in EF is attenuated after repeated HIIE, perhaps because of lower lactate availability for the brain. This investigation examined whether improved EF after exercise relates to brain lactate uptake......), and brain-derived neurotrophic factor (BDNF; diffBDNF). EF was evaluated by the color-word Stroop task. The first HIIE improved EF for 40 min, whereas the second HIIE improved EF only immediately after exercise. The a-v diffglucose was unchanged, whereas the a-v diffBDNF increased similarly after both HIIEs...

Brain SPECT by intraarterial infusion of 99mTc-HMPAO for assessing the cerebral distribution of carotid artery infusions in patient with brain tumor

International Nuclear Information System (INIS)

Kosuda, Shigeru; Kusano, Shoichi; Aoki, Shigeki

1993-01-01

In order to assess the cerebral distribution of intracarotid chemotherapy, 17 postoperative patients with brain tumor underwent brain SPECT obtrained by intraarterial infusion of 18.5 MBq of 99m Tc-d,l,-hexamethylpropyleneamine oxime ( 99m Tc-HMPAO). Injection methods were continuous (5.0 ml/min) or pulsatile infusion with supra- or infraophthalmic catheterization. The findings obtained by brain SPECT were frequently different from those of angiography and/or DSA. In supraophthalmic catheterization with continuous infusion, only 2 of 10 studies (20%) had homogeneous distribution and 5 of them (50%) had maldistribution of 99m Tc-HMPAO which appears in association with laminar flow effect. The remaining 3 studies showed localized distribution (two: tumor localization, one: healthy brain localization). On the other hand, all of 5 studies with pulsatile infusion had homogeneous distribution of 99m Tc-HMPAO. In infraophthalmic catheterization, all but one of 5 studies had homogeneous distribution with continuous infusion. These results suggest that pulsatile infusion may be effective in eliminating maldistribution of 99m Tc-HMPAO in supraophthalmic catheterization. In conclusion, we are convinced that 99m Tc-HMPAO is a useful intraarterial agent for assessing cerebral distribution of intracarotid chemotherpay. (author)

Blood-brain barrier transport and protein binding of flumazenil and iomazenil in the rat: implications for neuroreceptor studies

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Videbaek, C; Ott, P; Paulson, O B

1999-01-01

The calculated fraction of receptor ligands available for blood-brain barrier passage in vivo (f(avail)) may differ from in vitro (f(eq)) measurements. This study evaluates the protein-ligand interaction for iomazenil and flumazenil in rats by comparing f(eq) and f(avail). Repeated measurements...... of blood-brain barrier permeability for two benzodiazepine antagonists were performed in 44 rats by the double-indicator technique. Cerebral blood flow was measured by intracarotid Xe-injection. The apparent permeability-surface product (PSapp) was measured while CBF or bolus composition was changed...... and flumazenil increased significantly by 89% and 161% after relative CBF increases of 259% and 201%, respectively. The results demonstrate that application of f(eq) in neuroreceptor studies underestimates the plasma input function to the brain. Model simulations render possible that the differences between f...

The application of microfocal radiography to neuroanatomy and neuropathology research, and its relation to cerebral magnification angiography and brain scan interpretation. Chapter 3

International Nuclear Information System (INIS)

Saunders, R.L. de C.H.

1980-01-01

Microfocal radiography is used to study post mortem, the microcirculatory and neuronal organization of the normal and diseased brain, as well as to interpret the images obtained clinically by the new techniques of cerebral magnification angiography and X-ray brain scanning. An outline of the basic technique underlying CT scanning and magnification radiography of the living human brain is given to facilitate the understanding of why microfocal radiography is central to magnification radiography and complementary to CT scanning. Microangiography, one of the microfocal radiographic techniques, is discussed at length in relation to the microvasculature of the human cerebral cortex, the vasculature of the subcortical or medullary white matter, the microvascular patterns of the central grey matter and internal capsule, the vascular patterns of the visual cortex and hippocampus; the application of microangiography to the spinal cord and nerve roots is also discussed. Another microfocal radiographic technique described is cerebral historadiography, i.e. X-ray studies of brain histology, with particular reference to the human hippocampal formation. Finally, the correlation of microfocal X-ray and brain CT scan images is discussed. (U.K.)

Pharmacologic modulation of cerebral metabolic derangement and excitotoxicity in a porcine model of traumatic brain injury and hemorrhagic shock

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Hwabejire, John O; Jin, Guang; Imam, Ayesha M

2013-01-01

Cerebral metabolic derangement and excitotoxicity play critical roles in the evolution of traumatic brain injury (TBI). We have shown previously that treatment with large doses of valproic acid (VPA) decreases the size of brain lesion. The goal of this experiment was to determine whether...

AbetaPP/APLP2 family of Kunitz serine proteinase inhibitors regulate cerebral thrombosis.

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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.

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

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Phillip A Swanson

2016-12-01

Full Text Available 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

Nicotinamide mononucleotide inhibits post-ischemic NAD(+) degradation and dramatically ameliorates brain damage following global cerebral ischemia.

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Park, Ji H; Long, Aaron; Owens, Katrina; Kristian, Tibor

2016-11-01

Nicotinamide adenine dinucleotide (NAD(+)) is an essential cofactor for multiple cellular metabolic reactions and has a central role in energy production. Brain ischemia depletes NAD(+) pools leading to bioenergetics failure and cell death. Nicotinamide mononucleotide (NMN) is utilized by the NAD(+) salvage pathway enzyme, nicotinamide adenylyltransferase (Nmnat) to generate NAD(+). Therefore, we examined whether NMN could protect against ischemic brain damage. Mice were subjected to transient forebrain ischemia and treated with NMN or vehicle at the start of reperfusion or 30min after the ischemic insult. At 2, 4, and 24h of recovery, the proteins poly-ADP-ribosylation (PAR), hippocampal NAD(+) levels, and expression levels of NAD(+) salvage pathway enzymes were determined. Furthermore, animal's neurologic outcome and hippocampal CA1 neuronal death was assessed after six days of reperfusion. NMN (62.5mg/kg) dramatically ameliorated the hippocampal CA1 injury and significantly improved the neurological outcome. Additionally, the post-ischemic NMN treatment prevented the increase in PAR formation and NAD(+) catabolism. Since the NMN administration did not affect animal's temperature, blood gases or regional cerebral blood flow during recovery, the protective effect was not a result of altered reperfusion conditions. These data suggest that administration of NMN at a proper dosage has a strong protective effect against ischemic brain injury. Published by Elsevier Inc.

Detection of misery perfusion in the cerebral hemisphere with chronic unilateral major cerebral artery steno-occlusive disease using crossed cerebellar hypoperfusion: comparison of brain SPECT and PET imaging

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Matsumoto, Yoshiyasu; Ogasawara, Kuniaki; Saito, Hideo; Takahashi, Yoshihiro; Ogasawara, Yasushi; Kobayashi, Masakazu; Ogawa, Akira [Iwate Medical University, Department of Neurosurgery, Morioka (Japan); Iwate Medical University, Cyclotron Research Center, Morioka (Japan); Terasaki, Kazunori [Iwate Medical University, Cyclotron Research Center, Morioka (Japan); Yoshida, Kenji; Beppu, Takaaki; Kubo, Yoshitaka; Fujiwara, Shunrou [Iwate Medical University, Department of Neurosurgery, Morioka (Japan); Tsushima, Eiki [Hirosaki University, Graduate School of Health Sciences, Hirosaki (Japan)

2013-10-15

In patients with unilateral internal carotid or middle cerebral artery (ICA or MCA) occlusive disease, the degree of crossed cerebellar hypoperfusion that is evident within a few months after the onset of stroke may reflect cerebral metabolic rate of oxygen in the affected cerebral hemisphere relative to that in the contralateral cerebral hemisphere. The aim of the present study was to determine whether the ratio of blood flow asymmetry in the cerebellar hemisphere to blood flow asymmetry in the cerebral hemisphere on positron emission tomography (PET) and single photon emission computed tomography (SPECT) correlates with oxygen extraction fraction (OEF) asymmetry in the cerebral hemisphere on PET in patients with chronic unilateral ICA or MCA occlusive disease and whether this blood flow ratio on SPECT detects misery perfusion in the affected cerebral hemisphere in such patients. Brain blood flow and OEF were assessed using {sup 15}O-PET and N-isopropyl-p-[{sup 123}I]iodoamphetamine ({sup 123}I-IMP) SPECT, respectively. All images were anatomically standardized using SPM2. A region of interest (ROI) was automatically placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres using a three-dimensional stereotaxic ROI template, and affected-to-contralateral asymmetry in the MCA territory or contralateral-to-affected asymmetry in the cerebellar hemisphere was calculated. Sixty-three patients with reduced blood flow in the affected cerebral hemisphere on {sup 123}I-IMP SPECT were enrolled in this study. A significant correlation was observed between MCA ROI asymmetry of PET OEF and the ratio of cerebellar hemisphere asymmetry of blood flow to MCA ROI asymmetry of blood flow on PET (r = 0.381, p = 0.0019) or SPECT (r = 0.459, p = 0.0001). The correlation coefficient was higher when reanalyzed in a subgroup of 43 patients undergoing a PET study within 3 months after the last ischemic event (r = 0.541, p = 0.0001 for PET; r = 0.609, p < 0

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

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

2013-07-21

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

What is cerebral small vessel disease?

International Nuclear Information System (INIS)

Onodera, Osamu

2011-01-01

An accumulating amount of evidence suggests that the white matter hyperintensities on T 2 weighted brain magnetic resonance imaging predict an increased risk of dementia and gait disturbance. This state has been proposed as cerebral small vessel disease, including leukoaraiosis, Binswanger's disease, lacunar stroke and cerebral microbleeds. However, the concept of cerebral small vessel disease is still obscure. To understand the cerebral small vessel disease, the precise structure and function of cerebral small vessels must be clarified. Cerebral small vessels include several different arteries which have different anatomical structures and functions. Important functions of the cerebral small vessels are blood-brain barrier and perivasucular drainage of interstitial fluid from the brain parenchyma. Cerebral capillaries and glial endfeet, take an important role for these functions. However, the previous pathological investigations on cerebral small vessels have focused on larger arteries than capillaries. Therefore little is known about the pathology of capillaries in small vessel disease. The recent discoveries of genes which cause the cerebral small vessel disease indicate that the cerebral small vessel diseases are caused by a distinct molecular mechanism. One of the pathological findings in hereditary cerebral small vessel disease is the loss of smooth muscle cells, which is an also well-recognized finding in sporadic cerebral small vessel disease. Since pericytes have similar character with the smooth muscle cells, the pericytes should be investigated in these disorders. In addition, the loss of smooth muscle cells may result in dysfunction of drainage of interstitial fluid from capillaries. The precise correlation between the loss of smooth muscle cells and white matter disease is still unknown. However, the function that is specific to cerebral small vessel may be associated with the pathogenesis of cerebral small vessel disease. (author)

Cerebral vasculitis

International Nuclear Information System (INIS)

Greenan, T.J.; Grossman, R.I.

1990-01-01

This paper reviews retrospectively MR, CT, and angiographic findings in patients with cerebral vasculitis in order to understand the strengths and weaknesses of the various imaging modalities, as well as the spectrum of imaging abnormalities in this disease entity. Studies were retrospectively reviewed in 12 patients with cerebral vasculitis proved by means of angiography and/or brain biopsy

[Expression of c-jun protein after experimental rat brain concussion].

Science.gov (United States)

Wang, Feng; Li, Yong-hong

2010-02-01

To observe e-jun protein expression after rat brain concussion and explore the forensic pathologic markers following brain concussion. Fifty-five rats were randomly divided into brain concussion group and control group. The expression of c-jun protein was observed by immunohistochemistry. There were weak positive expression of c-jun protein in control group. In brain concussion group, however, some neutrons showed positive expression of c-jun protein at 15 min after brain concussion, and reach to the peak at 3 h after brain concussion. The research results suggest that detection of c-jun protein could be a marker to determine brain concussion and estimate injury time after brain concussion.

Middle cerebral artery thrombosis: acute blood-brain barrier consequences

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Dietrich, W.D.; Prado, R.; Watson, B.D.; Nakayama, H.

1988-07-01

The effect of middle cerebral artery (MCA) thrombosis on the integrity of the blood-brain barrier (BBB) was studied in rats using horseradish peroxidase (HRP). Endothelial injury with subsequent platelet thrombosis was produced by means of a rose bengal-sensitized photochemical reaction, facilitated by irradiating the right proximal MCA segment with the focused beam of an argon laser. At 15 minutes following thrombosis formation, diffuse leakage of HRP was observed bilaterally within cortical and subcortical brain areas. Peroxidase extravasation was most dense within the territory of the occluded artery including neocortical areas and dorso-lateral striatum. Contralaterally, a similar distribution was observed but with less intense HRP leakage. Ultrastructural studies demonstrated an increase in permeability to HRP within arterioles, venules and capillaries. At these sites, the vascular endothelium contained HRP-filled pinocytotic vesicles and tubular profiles. Although less intense, bilateral HRP leakage was also observed following MCA stenosis or femoral artery occlusion. Endothelial-platelet interactions at the site of vascular injury may be responsible for releasing substances or neurohumoral factors which contribute to the acute opening of the BBB.

Gene expression in cerebral ischemia: a new approach for neuroprotection.

Science.gov (United States)

Millán, Mónica; Arenillas, Juan

2006-01-01

Cerebral ischemia is one of the strongest stimuli for gene induction in the brain. Hundreds of genes have been found to be induced by brain ischemia. Many genes are involved in neurodestructive functions such as excitotoxicity, inflammatory response and neuronal apoptosis. However, cerebral ischemia is also a powerful reformatting and reprogramming stimulus for the brain through neuroprotective gene expression. Several genes may participate in both cellular responses. Thus, isolation of candidate genes for neuroprotection strategies and interpretation of expression changes have been proven difficult. Nevertheless, many studies are being carried out to improve the knowledge of the gene activation and protein expression following ischemic stroke, as well as in the development of new therapies that modify biochemical, molecular and genetic changes underlying cerebral ischemia. Owing to the complexity of the process involving numerous critical genes expressed differentially in time, space and concentration, ongoing therapeutic efforts should be based on multiple interventions at different levels. By modification of the acute gene expression induced by ischemia or the apoptotic gene program, gene therapy is a promising treatment but is still in a very experimental phase. Some hurdles will have to be overcome before these therapies can be introduced into human clinical stroke trials. Copyright 2006 S. Karger AG, Basel.

Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

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Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

1985-05-01

The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions.

Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

International Nuclear Information System (INIS)

Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

1985-01-01

The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions

Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson's disease

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Zabel Claus

2011-09-01

Full Text Available Abstract Parkinson's disease (PD is histologically well defined by its characteristic degeneration of dopaminergic neurons in the substantia nigra pars compacta. Remarkably, divergent PD-related mutations can generate comparable brain region specific pathologies. This indicates that some intrinsic region-specificity respecting differential neuron vulnerability exists, which codetermines the disease progression. To gain insight into the pathomechanism of PD, we investigated protein expression and protein oxidation patterns of three different brain regions in a PD mouse model, the PINK1 knockout mice (PINK1-KO, in comparison to wild type control mice. The dysfunction of PINK1 presumably affects mitochondrial turnover by disturbing mitochondrial autophagic pathways. The three brain regions investigated are the midbrain, which is the location of substantia nigra; striatum, the major efferent region of substantia nigra; and cerebral cortex, which is more distal to PD pathology. In all three regions, mitochondrial proteins responsible for energy metabolism and membrane potential were significantly altered in the PINK1-KO mice, but with very different region specific accents in terms of up/down-regulations. This suggests that disturbed mitophagy presumably induced by PINK1 knockout has heterogeneous impacts on different brain regions. Specifically, the midbrain tissue seems to be most severely hit by defective mitochondrial turnover, whereas cortex and striatum could compensate for mitophagy nonfunction by feedback stimulation of other catabolic programs. In addition, cerebral cortex tissues showed the mildest level of protein oxidation in both PINK1-KO and wild type mice, indicating either a better oxidative protection or less reactive oxygen species (ROS pressure in this brain region. Ultra-structural histological examination in normal mouse brain revealed higher incidences of mitophagy vacuoles in cerebral cortex than in striatum and substantia

Cerebral hemorrhagic infarction after radiation for pituitary adenoma

International Nuclear Information System (INIS)

Ogaki, Satoko; Suzuki, Masatsune; Shimano, Hitoshi; Toyoshima, Hideo; Sone, Hirohito; Okuda, Yukichi; Yamada, Nobuhiro

2002-01-01

We report a case of cerebral hemorrhagic infarction after radiation for pituitary adenoma. A 55-year-old woman was hospitalized to check for aldosteronism, post-operative pituitary function, and recurrence of thyroid cancer. She had short-term memory disturbance beginning two months prior to admission. Brain MRI showed a T1 and T2 high intensity lesion of her left anterolateral thalamus. Brain MRA revealed a narrowing in her left middle cerebral artery. The abnormal brain lesion was diagnosed as cerebral hemorrhagic infarction. She had received radiation therapy for pituitary adenoma 20 years earlier. It was considered that her cerebral hemorrhagic infarction was caused by radiation therapy. (author)

Assessment of Blood-Brain Barrier Permeability by Dynamic Contrast-Enhanced MRI in Transient Middle Cerebral Artery Occlusion Model after Localized Brain Cooling in Rats

International Nuclear Information System (INIS)

Kim, Eun Soo; Lee, Seung-Koo; Kwon, Mi Jung; Lee, Phil Hye; Ju, Young-Su; Yoon, Dae Young; Kim, Hye Jeong; Lee, Kwan Seop

2016-01-01

The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20℃) infusion group, and localized warm-saline (37℃) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min -1 vs. 0.07 ± 0.02 min -1 , p = 0.661 for K trans ; 0.30 ± 0.05 min -1 vs. 0.37 ± 0.11 min -1 , p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Localized brain cooling (20℃) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37℃) infusion group

Assessment of blood-brain barrier permeability by dynamic contrast-enhanced MRI in transient middle cerebral artery occlusion model after localized brain cooling in rats

International Nuclear Information System (INIS)

Kim, Eun Soo; Lee, Kwan Seop; Kwon, Mi Jung; Ju, Young Su; Lee, Seung Koo; Lee, Phil Hye; Yoon, Dae Young; Kim, Hye Jeong

2016-01-01

The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20 .deg. ) infusion group, and localized warm-saline (37 .deg. ) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min -1 vs. 0.07 ± 0.02 min -1 ,p = 0.661 for K trans ; 0.30 ± 0.05 min -1 vs. 0.37 ± 0.11 min -1 ,p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Localized brain cooling (20 .deg. ) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37 .deg. ) infusion group

Nrdp1 Increases Ischemia Induced Primary Rat Cerebral Cortical Neurons and Pheochromocytoma Cells Apoptosis Via Downregulation of HIF-1α Protein

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Yuan Zhang

2017-09-01

Full Text Available Neuregulin receptor degradation protein-1 (Nrdp1 is an E3 ubiquitin ligase that targets proteins for degradation and regulates cell growth, apoptosis and oxidative stress in various cell types. We have previously shown that Nrdp1 is implicated in ischemic cardiomyocyte death. In this study, we investigated the change of Nrdp1 expression in ischemic neurons and its role in ischemic neuronal injury. Primary rat cerebral cortical neurons and pheochromocytoma (PC12 cells were infected with adenoviral constructs expressing Nrdp1 gene or its siRNA before exposing to oxygen-glucose deprivation (OGD treatment. Our data showed that Nrdp1 was upregulated in ischemic brain tissue 3 h after middle cerebral artery occlusion (MCAO and in OGD-treated neurons. Of note, Nrdp1 overexpression by Ad-Nrdp1 enhanced OGD-induced neuron apoptosis, while knockdown of Nrdp1 with siRNA attenuated this effect, implicating a role of Nrdp1 in ischemic neuron injury. Moreover, Nrdp1 upregulation is accompanied by increased protein ubiquitylation and decreased protein levels of ubiquitin-specific protease 8 (USP8 in OGD-treated neurons, which led to a suppressed interaction between USP8 and HIF-1α and subsequently a reduction in HIF-1α protein accumulation in neurons under OGD conditions. In conclusion, our data support an important role of Nrdp1 upregulation in ischemic neuronal death, and suppressing the interaction between USP8 and HIF-1α and consequently the hypoxic adaptive response of neurons may account for this detrimental effect.

Specific binding of atrial natriuretic factor in brain microvessels

International Nuclear Information System (INIS)

Chabrier, P.E.; Roubert, P.; Braquet, P.

1987-01-01

Cerebral capillaries constitute the blood-brain barrier. Studies of specific receptors (neurotransmitters or hormones) located on this structure can be performed by means of radioligand-binding techniques on isolated brain microvessels. The authors examined on pure bovine cerebral microvessel preparations the binding of atrial natriuretic factor (ANF), using 125 I-labeled ANF. Saturation and competition experiments demonstrated the presence of a single class of ANF-binding sites with high affinity and with a binding capacity of 58 fmol/mg of protein. The binding of 125 I-labeled ANF to brain microvessels is specific, reversible, and time dependent, as is shown by association-dissociation experiments. The demonstration of specific ANF-binding sites on brain microvessels supposes a physiological role of ANF on brain microvasculature. The coexistence of ANF and angiotensin II receptors on this cerebrovascular tissue suggests that the two circulating peptides may act as mutual antagonists in the regulation of brain microcirculation and/or blood-brain barrier function

Cerebral energy metabolism during induced mitochondrial dysfunction

DEFF Research Database (Denmark)

Nielsen, T H; Bindslev, TT; Pedersen, S M

2013-01-01

In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes...... in brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets....

CNS-syndrome. Characterization of rat brain intermediate filaments

International Nuclear Information System (INIS)

Nedzvetskij, V.S.; Busygina, S.G.; Berezin, V.A.; Dvoretskij, A.I.

1990-01-01

A study was made of the effect of ionizing radiation on the content and polypeptide composition of filamentous and soluble glial fibrillary acidic protein (GFAP) in different regions of rat brain. Ionizing radiation was shown to decrease considerably the level of soluble GFAP in cerebral cortex, cerebellum, middle brain and hippocampus. Polypeptide composition of soluble GFAP detected by the immonublot-method was found to be changed considerably in different brain areas of irradiated animals

Brain immune cell composition and functional outcome after cerebral ischemia: Comparison of two mouse strains

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Hyun Ah eKim

2014-11-01

Full Text Available Inflammatory cells may contribute to secondary brain injury following cerebral ischemia. The C57Bl/6 mouse strain is known to exhibit a T helper 1-prone, pro-inflammatory type response to injury, whereas the FVB strain is relatively T helper 2-prone, or anti-inflammatory, in its immune response. We tested whether stroke outcome is more severe in C57Bl/6 than FVB mice. Male mice of each strain underwent sham surgery or 1 h occlusion of the middle cerebral artery followed by 23 h of reperfusion. Despite no difference in infarct size, C57Bl/6 mice displayed markedly greater functional deficits than FVB mice after stroke, as assessed by neurological scoring and hanging wire test. Total numbers of CD45+ leukocytes tended to be larger in the brains of C57Bl/6 than FVB mice after stroke, but there were marked differences in leukocyte composition between the two mouse strains. The inflammatory response in C57Bl/6 mice primarily involved T and B lymphocytes, whereas neutrophils, monocytes and macrophages were more prominent in FVB mice. Our data are consistent with the concept that functional outcome after stroke is dependent on the immune cell composition which develops following ischemic brain injury.

Ischemia - reperfusion induced changes in levels of ion transport proteins in gerbil brain

International Nuclear Information System (INIS)

Lehotsky, J.; Racay, P.; Kaplan, P.; Mezesova, V.; Raeymaekers, L.

1998-01-01

A quantitative Western blotting was used to asses the levels of ion transport proteins in gerbil brain in control and in animals after ischemic-reperfusion injury (IRI). The gene products of plasma membrane Ca 2+ pump (PMCA) were detected in the hippocampus, cerebral cortex and cerebellum. However, they showed a distinct distribution pattern. Inositol 1,4,5-triphosphate (Ins 3 ) receptor and reticular Ca 2+ pump are the most abundant in cerebellum and hippocampus. The IRI leads to a selective decrease in content of PMCA and InsP 3 receptor I isoforms. The levels of α 3 isoform of Na + pump and reticular proteins: Ca 2+ pump and calreticulin remained constant. InsP 3 receptor and organellar Ca 2+ (SERCA) are the most abundant in cerebellum and hippocampus. Ischemia and reperfusion up to 10 days leads to a signal decrease of PMCA immuno-signal. We suppose that alteration of number of ion transport proteins, can contribute to changes which participate or follow the delayed death of neurons in hippocampus. (authors)

Klotho upregulation contributes to the neuroprotection of ligustilide against cerebral ischemic injury in mice.

Science.gov (United States)

Long, Fang-Yi; Shi, Meng-Qi; Zhou, Hong-Jing; Liu, Dong-Ling; Sang, Na; Du, Jun-Rong

2018-02-05

Klotho, an aging-suppressor gene, encodes a protein that potentially acts as a neuroprotective factor. Our previous studies showed that ligustilide minimizes the cognitive dysfunction and brain damage induced by cerebral ischemia; however, the underlying mechanisms remain unclear. This study aims to investigate whether klotho is involved in the protective effects of ligustilide against cerebral ischemic injury in mice. Cerebral ischemia was induced by bilateral common carotid arterial occlusion. Neurobehavioral tests as well as Nissl and Fluoro-Jade B staining were used to evaluate the protective effects of ligustilide in cerebral ischemia, and Western blotting and ELISA approaches were used to investigate the underlying mechanisms. Administration of ligustilide prevented the development of neurological deficits and reduced neuronal loss in the hippocampal CA1 region and the caudate putamen after cerebral ischemia. The protective effects were associated with inhibition of the RIG-I/NF-κB p65 and Akt/FoxO1 pathways and with prevention of inflammation and oxidative stress in the brain. Further, downregulation of klotho could attenuate the neuroprotection of ligustilide against cerebral ischemic injury. Ligustilide exerted neuroprotective effects in mice after cerebral ischemia by regulating anti-inflammatory and anti-oxidant signaling pathways. Furthermore, klotho upregulation contributes to the neuroprotection of LIG against cerebral ischemic injury. These results indicated that ligustilide may be a promising therapeutic agent for the treatment of cerebral ischemia. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of hypoxia on cerebral blood flow regulation during rest and exercise : role of cerebral oxygen delivery on performance

OpenAIRE

Fan, J.-L.

2014-01-01

Adequate supply of oxygen to the brain is critical for maintaining normal brain function. Severe hypoxia, such as that experienced during high altitude ascent, presents a unique challenge to brain oxygen (O2) supply. During high-intensity exercise, hyperventilation-induced hypocapnia leads to cerebral vasoconstriction, followed by reductions in cerebral blood flow (CBF), oxygen delivery (DO2), and tissue oxygenation. This reduced O2 supply to the brain could potentially account for the reduce...

Neuroprotective effects of SMADs in a rat model of cerebral ischemia/reperfusion

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Fang-fang Liu

2015-01-01

Full Text Available Previous studies have shown that up-regulation of transforming growth factor β1 results in neuroprotective effects. However, the role of the transforming growth factor β1 downstream molecule, SMAD2/3, following ischemia/reperfusion remains unclear. Here, we investigated the neuroprotective effects of SMAD2/3 by analyzing the relationships between SMAD2/3 expression and cell apoptosis and inflammation in the brain of a rat model of cerebral ischemia/reperfusion. Levels of SMAD2/3 mRNA were up-regulated in the ischemic penumbra 6 hours after cerebral ischemia/reperfusion, reached a peak after 72 hours and were then decreased at 7 days. Phosphorylated SMAD2/3 protein levels at the aforementioned time points were consistent with the mRNA levels. Over-expression of SMAD3 in the brains of the ischemia/reperfusion model rats via delivery of an adeno-associated virus containing the SMAD3 gene could reduce tumor necrosis factor-α and interleukin-1β mRNA levels, down-regulate expression of the pro-apoptotic gene, capase-3, and up-regulate expression of the anti-apoptotic protein, Bcl-2. The SMAD3 protein level was negatively correlated with cell apoptosis. These findings indicate that SMAD3 exhibits neuroprotective effects on the brain after ischemia/reperfusion through anti-inflammatory and anti-apoptotic pathways.

[Blood-brain barrier part III: therapeutic approaches to cross the blood-brain barrier and target the brain].

Science.gov (United States)

Weiss, N; Miller, F; Cazaubon, S; Couraud, P-O

2010-03-01

Over the last few years, the blood-brain barrier has come to be considered as the main limitation for the treatment of neurological diseases caused by inflammatory, tumor or neurodegenerative disorders. In the blood-brain barrier, the close intercellular contact between cerebral endothelial cells due to tight junctions prevents the passive diffusion of hydrophilic components from the bloodstream into the brain. Several specific transport systems (via transporters expressed on cerebral endothelial cells) are implicated in the delivery of nutriments, ions and vitamins to the brain; other transporters expressed on cerebral endothelial cells extrude endogenous substances or xenobiotics, which have crossed the cerebral endothelium, out of the brain and into the bloodstream. Recently, several strategies have been proposed to target the brain, (i) by by-passing the blood-brain barrier by central drug administration, (ii) by increasing permeability of the blood-brain barrier, (iii) by modulating the expression and/or the activity of efflux transporters, (iv) by using the physiological receptor-dependent blood-brain barrier transport, and (v) by creating new viral or chemical vectors to cross the blood-brain barrier. This review focuses on the illustration of these different approaches. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

Opening of the blood-brain barrier before cerebral pathology in mild hyperhomocysteinemia.

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Bryce C Rhodehouse

Full Text Available Hyperhomocysteinemia (HHcy is a risk factor for cognitive impairment. The purpose of this study was to determine the temporal pattern of cerebral pathology in a mouse model of mild HHcy, because understanding this time course provides the basis for understanding the mechanisms involved. C57Bl/6 mice with heterozygous deletion cystathionine β-synthase (cbs (+/-; Het were used as a model of mild HHcy along with their wild-type littermates (cbs (+/+; WT. Mice were 'young' (5.3±0.2 months of age and 'old' (16.6±0.9 months of age. Blood-brain barrier (BBB permeability was quantified from Evans blue and sodium fluorescein extravasation. Microvascular architecture was assessed by z-stack confocal microscopy. Leukoaraiosis was measured from Luxol fast blue stained slides of paraffin brain sections. Inflammation was quantified using standard antibody-based immunohistochemical techniques. Cognitive function was assessed using the Morris water maze. BBB permeability was significantly greater in Het vs. WT mice at all ages (p<0.05. There were no differences in microvascular architecture among the groups. Compared with all other groups, old Het mice had significantly greater leukoaraiosis, inflammation in the fornix, and cognitive impairment (p<0.05. In mild HHcy, increased permeability of the BBB precedes the onset of cerebral pathology. This new paradigm may play a role in the progression of disease in HHcy.

The imaging diagnosis of diffuse brain swelling due to severe brain trauma

International Nuclear Information System (INIS)

Shen Jianqiang; Hu Jiawang

2008-01-01

Objective: To discuss the clinical and pathological characteristics and the imaging types of the diffuse brain swelling due to severe brain trauma. Methods: The clinical data and CT and MR images on 48 cases with diffuse brain swelling due to severe brain trauma were analyzed. Results: Among these 48 cases of the diffuse brain swelling due to severe brain trauma, 33 cases were complicated with brain contusions (including 12 cases brain diffuse axonal injury, 1 case infarct of the right basal ganglion), 31 cases were complicated with hematoma (epidural, subdural or intracerebral), 27 cases were complicated with skull base fracture, and 10 cases were complicated with subarachnoid hematoma. The CT and MR imaging of the diffuse brain swelling included as followed: (1) Symmetrically diffuse brain swelling in both cerebral hemispheres with cerebral ventricles decreased or disappeared, without median line shift. (2)Diffuse brain swelling in one side cerebral hemisphere with cerebral ventricles decreased or disappeared at same side, and median line shift to other side. (3) Subarachnoid hematoma or little subcortex intracerebral hematoma were complicated. (4) The CT value of the cerebral could be equal, lower or higher comparing with normal. Conclusion: The pathological reason of diffuse brain swelling was the brain vessel expanding resulting from hypothalamus and brainstem injured in severe brain trauma. There were four CT and MR imaging findings in diffuse brain swelling. The diffuse brain swelling without hematoma may be caused by ischemical reperfusion injury. (authors)

AβPP/APLP2 Family of Kunitz Serine Proteinase Inhibitors Regulate Cerebral Thrombosis

Science.gov (United States)

Xu, Feng; Previti, Mary Lou; Nieman, Marvin T.; Davis, Judianne; Schmaier, Alvin H.; Van Nostrand, William E.

2009-01-01

The amyloid β-protein precursor (AβPP) is best recognized as the precursor to the Aβ peptide that accumulates in the brains of patients with Alzheimer’s disease, but less is known about its physiological functions. Isoforms of AβPP 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 AβPP regulates cerebral thrombosis in vivo (Xu et al., 2005 Proc. Natl. Acad. Sci. USA 102:18135–18140; Xu et al. 2007 Stroke 38:2598–2601). Amyloid precursor like protein-2 (APLP2), a closely related homolog to AβPP, 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 AβPP and APLP2 both inhibit the plasma clotting in vitro. In a carotid artery thrombosis model both AβPP−/− and APLP2−/− mice exhibit similar significantly shorter times to vessel occlusion compared with wild-type mice indicating a pro-thrombotic phenotype. Similarly, in an experimental model of intracerebral hemorrhage both AβPP−/− and APLP2−/− mice produce significantly smaller hematomas with reduced brain hemoglobin content compared with wild-type mice. Together, these results indicate that AβPP and APLP2 share overlapping anticoagulant functions with regard to regulating thrombosis after cerebral vascular injury. PMID:19403832

Imaging of Neuronal Activity in Awake Mice by Measurements of Flavoprotein Autofluorescence Corrected for Cerebral Blood Flow.

Science.gov (United States)

Takahashi, Manami; Urushihata, Takuya; Takuwa, Hiroyuki; Sakata, Kazumi; Takado, Yuhei; Shimizu, Eiji; Suhara, Tetsuya; Higuchi, Makoto; Ito, Hiroshi

2017-01-01

Green fluorescence imaging (e.g., flavoprotein autofluorescence imaging, FAI) can be used to measure neuronal activity and oxygen metabolism in living brains without expressing fluorescence proteins. It is useful for understanding the mechanism of various brain functions and their abnormalities in age-related brain diseases. However, hemoglobin in cerebral blood vessels absorbs green fluorescence, hampering accurate assessments of brain function in animal models with cerebral blood vessel dysfunctions and subsequent cerebral blood flow (CBF) alterations. In the present study, we developed a new method to correct FAI signals for hemoglobin-dependent green fluorescence reductions by simultaneous measurements of green fluorescence and intrinsic optical signals. Intrinsic optical imaging enabled evaluations of light absorption and scatters by hemoglobin, which could then be applied to corrections of green fluorescence intensities. Using this method, enhanced flavoprotein autofluorescence by sensory stimuli was successfully detected in the brains of awake mice, despite increases of CBF, and hemoglobin interference. Moreover, flavoprotein autofluorescence could be properly quantified in a resting state and during sensory stimulation by a CO 2 inhalation challenge, which modified vascular responses without overtly affecting neuronal activities. The flavoprotein autofluorescence signal data obtained here were in good agreement with the previous findings from a condition with drug-induced blockade of cerebral vasodilation, justifying the current assaying methodology. Application of this technology to studies on animal models of brain diseases with possible changes of CBF, including age-related neurological disorders, would provide better understanding of the mechanisms of neurovascular coupling in pathological circumstances.

Cerebral circulation and metabolism in the patients with higher brain dysfunction caused by chronic minor traumatic brain injury. A study by the positron emission tomography in twenty subjects with normal MRI findings

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Kabasawa, Hidehiro; Ogawa, Tetsuo; Iida, Akihiko; Matsubara, Michitaka [Nagoya City Rehabilitation and Sports Center (Japan)

2002-06-01

Many individuals are affected on their higher brain functions, such as intelligence, memory, and attention, even after minor traumatic brain injury (MTBI). Although higher brain dysfunction is based on impairment of the cerebral circulation and metabolism, the precise relationship between them remains unknown. This study was undertaken to investigate the relationship between the cerebral circulation or cerebral metabolism and higher brain dysfunction. Twenty subjects with higher brain dysfunction caused by chronic MTBI were studied. They had no abnormal MRI findings. The full-scale intelligence quotient (FIQ) were quantitatively evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the subjects were classified into the normal group and the impaired group. Concurrent with the evaluation of FIQ, positron emission tomography (PET) was performed by the steady state method with {sup 15}O gases inhalation. Regional cerebral blood flow (rCBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO{sub 2}) were calculated in the bilateral frontal, parietal, temporal, and occipital lobe. First, of all twenty subjects, we investigated rCBF, OEF and CMRO{sub 2} in all regions. Then we compared rCBF, OEF, and CMRO{sub 2} between the normal group and the impaired group based on FIQ score. We also studied the change of FIQ score of 13 subjects 9.3 months after the first evaluation. In addition, we investigated the change of rCBF, OEF and CMRO{sub 2} along with the improvement of FIQ score. Although rCBF and OEF of all subjects were within the normal range in all regions, CMRO{sub 2} of more than half of subjects was under the lower normal limit in all regions except in the right occipital lobe, showing the presence of ''relative luxury perfusion''. Comparison of rCBF, OEF and CMRO{sub 2} between normal group and impaired group revealed that CMRO{sub 2} of the impaired group was significantly lower than that of the

Cerebral circulation and metabolism in the patients with higher brain dysfunction caused by chronic minor traumatic brain injury. A study by the positron emission tomography in twenty subjects with normal MRI findings

International Nuclear Information System (INIS)

Kabasawa, Hidehiro; Ogawa, Tetsuo; Iida, Akihiko; Matsubara, Michitaka

2002-01-01

Many individuals are affected on their higher brain functions, such as intelligence, memory, and attention, even after minor traumatic brain injury (MTBI). Although higher brain dysfunction is based on impairment of the cerebral circulation and metabolism, the precise relationship between them remains unknown. This study was undertaken to investigate the relationship between the cerebral circulation or cerebral metabolism and higher brain dysfunction. Twenty subjects with higher brain dysfunction caused by chronic MTBI were studied. They had no abnormal MRI findings. The full-scale intelligence quotient (FIQ) were quantitatively evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the subjects were classified into the normal group and the impaired group. Concurrent with the evaluation of FIQ, positron emission tomography (PET) was performed by the steady state method with 15 O gases inhalation. Regional cerebral blood flow (rCBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) were calculated in the bilateral frontal, parietal, temporal, and occipital lobe. First, of all twenty subjects, we investigated rCBF, OEF and CMRO 2 in all regions. Then we compared rCBF, OEF, and CMRO 2 between the normal group and the impaired group based on FIQ score. We also studied the change of FIQ score of 13 subjects 9.3 months after the first evaluation. In addition, we investigated the change of rCBF, OEF and CMRO 2 along with the improvement of FIQ score. Although rCBF and OEF of all subjects were within the normal range in all regions, CMRO 2 of more than half of subjects was under the lower normal limit in all regions except in the right occipital lobe, showing the presence of ''relative luxury perfusion''. Comparison of rCBF, OEF and CMRO 2 between normal group and impaired group revealed that CMRO 2 of the impaired group was significantly lower than that of the normal group in the bilateral frontal, temporal, and occipital

Cerebral toksoplasmose primaert diagnosticeret som tumor

DEFF Research Database (Denmark)

Cortsen, M E; Skøt, J; Skriver, E B

1992-01-01

Three cases of cerebral toxoplasmosis as the presenting manifestation of AIDS are reported. The initial diagnoses were brain tumors because of the cerebral mass lesions which resembled glioblastoma. In the light of the increasing occurrence of AIDS, attention is drawn to cerebral toxoplasmosis...

Cystatin C Has a Dual Role in Post-Traumatic Brain Injury Recovery

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Marina Martinez-Vargas

2014-04-01

Full Text Available Cathepsin B is one of the major lysosomal cysteine proteases involved in neuronal protein catabolism. This cathepsin is released after traumatic injury and increases neuronal death; however, release of cystatin C, a cathepsin inhibitor, appears to be a self-protective brain response. Here we describe the effect of cystatin C intracerebroventricular administration in rats prior to inducing a traumatic brain injury. We observed that cystatin C injection caused a dual response in post-traumatic brain injury recovery: higher doses (350 fmoles increased bleeding and mortality, whereas lower doses (3.5 to 35 fmoles decreased bleeding, neuronal damage and mortality. We also analyzed the expression of cathepsin B and cystatin C in the brains of control rats and of rats after a traumatic brain injury. Cathepsin B was detected in the brain stem, cerebellum, hippocampus and cerebral cortex of control rats. Cystatin C was localized to the choroid plexus, brain stem and cerebellum of control rats. Twenty-four hours after traumatic brain injury, we observed changes in both the expression and localization of both proteins in the cerebral cortex, hippocampus and brain stem. An early increase and intralysosomal expression of cystatin C after brain injury was associated with reduced neuronal damage.

Microsurgery Simulator of Cerebral Aneurysm Clipping with Interactive Cerebral Deformation Featuring a Virtual Arachnoid.

Science.gov (United States)

Shono, Naoyuki; Kin, Taichi; Nomura, Seiji; Miyawaki, Satoru; Saito, Toki; Imai, Hideaki; Nakatomi, Hirofumi; Oyama, Hiroshi; Saito, Nobuhito

2018-05-01

A virtual reality simulator for aneurysmal clipping surgery is an attractive research target for neurosurgeons. Brain deformation is one of the most important functionalities necessary for an accurate clipping simulator and is vastly affected by the status of the supporting tissue, such as the arachnoid membrane. However, no virtual reality simulator implementing the supporting tissue of the brain has yet been developed. To develop a virtual reality clipping simulator possessing interactive brain deforming capability closely dependent on arachnoid dissection and apply it to clinical cases. Three-dimensional computer graphics models of cerebral tissue and surrounding structures were extracted from medical images. We developed a new method for modifiable cerebral tissue complex deformation by incorporating a nonmedical image-derived virtual arachnoid/trabecula in a process called multitissue integrated interactive deformation (MTIID). MTIID made it possible for cerebral tissue complexes to selectively deform at the site of dissection. Simulations for 8 cases of actual clipping surgery were performed before surgery and evaluated for their usefulness in surgical approach planning. Preoperatively, each operative field was precisely reproduced and visualized with the virtual brain retraction defined by users. The clear visualization of the optimal approach to treating the aneurysm via an appropriate arachnoid incision was possible with MTIID. A virtual clipping simulator mainly focusing on supporting tissues and less on physical properties seemed to be useful in the surgical simulation of cerebral aneurysm clipping. To our knowledge, this article is the first to report brain deformation based on supporting tissues.

Rapamycin preconditioning attenuates transient focal cerebral ischemia/reperfusion injury in mice.

Science.gov (United States)

Yin, Lele; Ye, Shasha; Chen, Zhen; Zeng, Yaoying

2012-12-01

Rapamycin, an mTOR inhibitor and immunosuppressive agent in clinic, has protective effects on traumatic brain injury and neurodegenerative diseases. But, its effects on transient focal ischemia/reperfusion disease are not very clear. In this study, we examined the effects of rapamycin preconditioning on mice treated with middle cerebral artery occlusion/reperfusion operation (MCAO/R). We found that the rapamycin preconditioning by intrahippocampal injection 20 hr before MCAO/R significantly improved the survival rate and longevity of mice. It also decreased the neurological deficit score, infracted areas and brain edema. In addition, rapamycin preconditioning decreased the production of NF-κB, TNF-α, and Bax, but not Bcl-2, an antiapoptotic protein in the ischemic area. From these results, we may conclude that rapamycin preconditioning attenuate transient focal cerebral ischemia/reperfusion injury and inhibits apoptosis induced by MCAO/R in mice.

Recirculation usually precedes malignant edema in middle cerebral artery infarcts

DEFF Research Database (Denmark)

Nielsen, T H; Ståhl, N; Schalén, W

2012-01-01

In patients with large middle cerebral artery (MCA) infarcts, maximum brain swelling leading to cerebral herniation and death usually occurs 2-5 days after onset of stroke. The study aimed at exploring the pattern of compounds related to cerebral energy metabolism in infarcted brain tissue....

Effects of acetazolamide on cerebral blood flow and brain tissue oxygenation

DEFF Research Database (Denmark)

Lassen, N A; Friberg, L; Kastrup, J

1987-01-01

Oral administration of 1 g of acetazolamide to 8 normal subjects studied at sea level and in normoxia caused an acute increase in cerebral blood flow (CBF). During the subsequent prolonged oral treatment with 1 g of acetazolamide daily, CBF returned to normal within 2 days. The alveolar CO2 tension...... decreased gradually to 70% of the control value, indicating hyperventilation. At sea level hyperventilation will not increase brain oxygenation significantly in normal man, as the arterial oxygen content only increases minimally, while CBF is unchanged. At high altitude the beneficial effects...... of acetazolamide on the symptoms of acute mountain sickness may well be due to an improved oxygen supply to the brain, as hyperventilation will, at the low ambient PO2, cause a significant increase of the arterial oxygen content, while CBF presumably is unaffected by the drug. During hypoxia at high altitude...

Preparation of Amyloid Fibrils Seeded from Brain and Meninges.

Science.gov (United States)

Scherpelz, Kathryn P; Lu, Jun-Xia; Tycko, Robert; Meredith, Stephen C

2016-01-01

Seeding of amyloid fibrils into fresh solutions of the same peptide or protein in disaggregated form leads to the formation of replicate fibrils, with close structural similarity or identity to the original fibrillar seeds. Here we describe procedures for isolating fibrils composed mainly of β-amyloid (Aβ) from human brain and from leptomeninges, a source of cerebral blood vessels, for investigating Alzheimer's disease and cerebral amyloid angiopathy. We also describe methods for seeding isotopically labeled, disaggregated Aβ peptide solutions for study using solid-state NMR and other techniques. These methods should be applicable to other types of amyloid fibrils, to Aβ fibrils from mice or other species, tissues other than brain, and to some non-fibrillar aggregates. These procedures allow for the examination of authentic amyloid fibrils and other protein aggregates from biological tissues without the need for labeling the tissue.

Pharmacokinetic Study of Piracetam in Focal Cerebral Ischemic Rats.

Science.gov (United States)

Paliwal, Pankaj; Dash, Debabrata; Krishnamurthy, Sairam

2018-04-01

Cerebral ischemia affects hepatic enzymes and brain permeability extensively. Piracetam was investigated up to phase III of clinical trials and there is lack of data on brain penetration in cerebral ischemic condition. Thus, knowledge of the pharmacokinetics and brain penetration of piracetam during ischemic condition would aid to improve pharmacotherapeutics in ischemic stroke. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h in male Wistar rats followed by reperfusion. After 24 h of middle cerebral artery occlusion or 22 h of reperfusion, piracetam was administered for pharmacokinetic, brain penetration, and pharmacological experiments. In pharmacokinetic study, blood samples were collected at different time points after 200-mg/kg (oral) and 75-mg/kg (intravenous) administration of piracetam through right external jugular vein cannulation. In brain penetration study, the cerebrospinal fluid, systemic blood, portal blood, and brain samples were collected at pre-designated time points after 200-mg/kg oral administration of piracetam. In a separate experiment, the pharmacological effect of the single oral dose of piracetam in middle cerebral artery occlusion was assessed at a dose of 200 mg/kg. All the pharmacokinetic parameters of piracetam including area under curve (AUC 0-24 ), maximum plasma concentration (C max ), time to reach the maximum plasma concentration (t max ), elimination half-life (t 1/2 ), volume of distribution (V z ), total body clearance, mean residence time, and bioavailability were found to be similar in ischemic stroke condition except for brain penetration. Piracetam exposure (AUC 0-2 ) in brain and CSF were found to be 2.4- and 3.1-fold higher, respectively, in ischemic stroke compared to control rats. Piracetam significantly reduced infarct volume by 35.77% caused by middle cerebral artery occlusion. There was no change in the pharmacokinetic parameters of piracetam in the ischemic stroke model except for

Mapping synaptic pathology within cerebral cortical circuits in subjects with schizophrenia

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Robert Sweet

2010-06-01

Full Text Available Converging lines of evidence indicate that schizophrenia is characterized by impairments of synaptic machinery within cerebral cortical circuits. Efforts to localize these alterations in brain tissue from subjects with schizophrenia have frequently been limited to the quantification of structures that are non-selectively identified (e.g. dendritic spines labeled in Golgi preparations, axon boutons labeled with synaptophysin, or to quantification of proteins using methods unable to resolve relevant cellular compartments. Multiple label fluorescence confocal microscopy represents a means to circumvent many of these limitations, by concurrently extracting information regarding the number, morphology, and relative protein content of synaptic structures. An important adaptation required for studies of human disease is coupling this approach to stereologic methods for systematic random sampling of relevant brain regions. In this review article we consider the application of multiple label fluorescence confocal microscopy to the mapping of synaptic alterations in subjects with schizophrenia and describe the application of a novel, readily automated, iterative intensity/morphological segmentation algorithm for the extraction of information regarding synaptic structure number, size, and relative protein level from tissue sections obtained using unbiased stereological principles of sampling. In this context, we provide examples of the examination of pre- and post-synaptic structures within excitatory and inhibitory circuits of the cerebral cortex.

Serial neuroradiological studies in focal cerebritis

International Nuclear Information System (INIS)

Hatta, S.; Mochizuki, H.; Kuru, Y.; Miwa, H.; Kondo, T.; Mori, H.; Mizuno, Y.

1994-01-01

We report serial neuroradiological studies in a patient with focal cerebritis in the head of the left caudate nucleus. On the day after the onset of symptoms, CT showed an ill-defined low density lesion. The lack of contrast enhancement appeared to be the most important finding for differentiating focal cerebritis from an encapsulated brain abscess or a tumour. MRI two days later revealed the centre of the lesion to be of slightly low intensity on T1-weighted inversion recovery (IR) images and very low intensity on T2-weighted spin echo images, which appeared to correspond to the early cerebritis stage of experimentally induced cerebritis and brain abscess. Ten days after the onset of symptoms, CT revealed a thin ring of enhancement in the head of the caudate nucleus, and a similar small ring was seen in the hypothalamus 16 days after the onset, corresponding to the late cerebritis stage. MRI nine days later revealed ill-defined high signal lesions within the involved area on the T1-weighted IR images. To our knowledge, this is the first published MRI documentation of the early cerebritis stage developing into an encapsulated brain abscess. The mechanisms underlying of these radiographic changes are discussed. (orig.)

On cerebral celebrity and reality TV: subjectivity in times of brain scans and psychotainment.

Science.gov (United States)

De Vos, Jan

2009-01-01

The philosopher Daniel Dennett developed a theory of consciousness in which he replaces the so-called Cartesian theater with conceptions such as "fame in the brain" and "cerebral celebrity." The paradox of this is that Dennett unwittingly reintroduces the metaphors of the stage and the screen. The use of this trope is pursued in this essay in order to juxtapose Dennett's theory with reality TV and celebrity culture. This will allow us to sketch out late-modern subjectivity in times of brains scans and "psychotainment." Drawing on Walter Benjamin, Giorgi Agamben, Slavoj Žižek, and others, a plea is made for a materialism of the zero-level of subjectivity.

Cerebral microdialysis and PtiO2 to decide unilateral decompressive craniectomy after brain gunshot

Directory of Open Access Journals (Sweden)

Boret Henry

2012-01-01

Full Text Available Decompressive craniectomy (DC following brain injury can induce complications (hemorrhage, infection, and hygroma. It is then considered as a last-tier therapy, and can be deleteriously delayed. Focal neuromonitoring (microdialysis and PtiO2 can help clinicians to decide bedside to perform DC in case of intracranial pressure (ICP around 20 to 25 mmHg despite maximal medical treatment. This was the case of a hunter, brain injured by gunshot. DC was performed at day 6, because of unstable ICP, ischemic trend of PtiO2, and decreased cerebral glucose but normal lactate/pyruvate ratio. His evolution was good despite left hemiplegia due to initial injury.

Structures and Interactions of Proteins in the Brain

DEFF Research Database (Denmark)

Nielsen, Lau Dalby

The protein low density lipoprotein receptor related protein 1 (LRP1) plays multiple roles in the biology of amyloid β peptide (Aβ) and Alzheimer’s disease. LRP1 is very important for clearance of Aβ both in the brain and by facilitating Aβ export over the blood brain barrier. In spite of the app......The protein low density lipoprotein receptor related protein 1 (LRP1) plays multiple roles in the biology of amyloid β peptide (Aβ) and Alzheimer’s disease. LRP1 is very important for clearance of Aβ both in the brain and by facilitating Aβ export over the blood brain barrier. In spite...... coding for Arc protein has been domesticated from the same branch of genes that has given rise to retroviruses. We show that even despite the large evolutional distance between Arc and retroviruses. Despite large evolutionary distance Arc still self-assemble into higher order structures that resembles...

Training model for cerebral aneurysm clipping

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Hiroshi Tenjin, M.D., Ph.D.

2017-12-01

Full Text Available Clipping of cerebral aneurysms is still an important skill in neurosurgery. We have made a training model for the clipping of cerebral aneurysms. The concepts for the model were 1: training model for beginners, 2: three dimensional manipulation using an operating microscope, 3: the aneurysm model is to be perfused by simulated blood causing premature rupture. The correct relationship between each tissue, and softness of the brain and vessels were characteristics of the model. The skull, brain, arteries, and veins were made using a 3D printer with data from DICOM. The brain and vessels were made from polyvinyl alcohol (PVA. One training course was held and this model was useful for training of cerebral aneurysm surgery for young neurosurgeons.

Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria.

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Julie Bachmann

2014-04-01

Full Text Available Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria.

Total protein and cholesterol concentrations in brain regions of male ...

African Journals Online (AJOL)

The results showed similarities (P>0.05) between the treatments in total protein concentrations in the cerebral cortex, medulla, hypothalamus, amygdala, mesencephalon and hippocampus. Total protein concentrations however differed significantly between diets (P<0.05) in the cerebellum and pons varoli with the lowest ...

Oxygen-Glucose Deprivation Induces G2/M Cell Cycle Arrest in Brain Pericytes Associated with ERK Inactivation.

Science.gov (United States)

Wei, Wenjie; Yu, Zhiyuan; Xie, Minjie; Wang, Wei; Luo, Xiang

2017-01-01

Growing evidence has revealed that brain pericytes are multifunctional and contribute to the pathogenesis of a number of neurological disorders. However, the role of pericytes in cerebral ischemia, and especially the pathophysiological alterations in pericytes, remains unclear. In the present study, our aim was to determine whether the proliferation of pericytes is affected by cerebral ischemia and, if so, to identify the underlying mechanism(s). Cultured brain pericytes subjected to oxygen-glucose deprivation (OGD) were used as our model of cerebral ischemia; the protein expression levels of cyclin D1, cyclin E, cdk4, and cyclin B1 were determined by Western blot analysis, and cell cycle analysis was assessed by flow cytometry. The OGD treatment reduced the brain pericyte proliferation by causing G2/M phase arrest and downregulating the protein levels of cyclin D1, cyclin E, cdk4, and cyclin B1. Further studies demonstrated a simultaneous decrease in the activity of extracellular regulated protein kinases (ERK), suggesting a critical role of the ERK signaling cascade in the inhibition of OGD-induced pericyte proliferation. We suggest that OGD inhibition of the proliferation of brain pericytes is associated with the inactivation of the ERK signaling pathway, which arrests them in the G2/M phase.

Beneficial Effect of HHI-Ⅰ(活血化瘀注射液Ⅰ号)on Cerebral Microcirculation,Blood-Brain Barrier in Rats and Anti-hypoxic Activity in Mice

Institute of Scientific and Technical Information of China (English)

赵连根; 吴咸中; 伍孝先

2009-01-01

Objective:To investigate the effect of HHI-Ⅰ(活血化瘀注射液Ⅰ号) on the cerebral microcirculation,the blood-brain barrier permeability in rats and anti-hypoxic activity in mice.Methods:(1) The blood microcirculation of the brain in rats was investigated by laser Doppler flowmetry with the probes laid on the cerebral pia mater or inserted into the brain parenchyma.(2) The protective action of HHI-Ⅰagainst the brain microcirculation disturbance induced by intravenous injection of high-molecular dextran(10%,9 mL/kg)...

Electroacupuncture ameliorates post-stroke learning and memory through minimizing ultrastructural brain damage and inhibiting the expression of MMP-2 and MMP-9 in cerebral ischemia-reperfusion injured rats.

Science.gov (United States)

Lin, Ruhui; Yu, Kunqiang; Li, Xiaojie; Tao, Jing; Lin, Yukun; Zhao, Congkuai; Li, Chunyan; Chen, Li-Dian

2016-07-01

The aim of the present study was to investigate the potential neuroprotective effects of electroacupuncture (EA) in the treatment of cerebral ischemia/reperfusion (I/R) injury, and to elucidate the association between this neuroprotective effect and brain ultrastructure and expression of matrix metalloproteinase (MMP)‑2 and 9. Rats underwent focal cerebral I/R injury by arterial ligation and received in vivo therapeutic EA at the Baihui (DU20) and Shenting (DU24) acupoints. The therapeutic efficacy was then evaluated following the surgery. The results of the current study demonstrated that EA treatment significantly ameliorated neurological deficits and reduced cerebral infarct volume compared with I/R injured rats. Furthermore, EA improved the learning and memory ability of rats following I/R injury, inhibited blood brain barrier breakdown and reduced neuronal damage in the ischemic penumbra. Furthermore, EA attenuated ultrastructural changes in the brain tissue following ischemia and inhibited MMP‑2/MMP‑9 expression in cerebral I/R injured rats. The results suggest that EA ameliorates anatomical deterioration, and learning and memory deficits in rats with cerebral I/R injury.

Brain mitochondrial function in a murine model of cerebral malaria and the therapeutic effects of rhEPO

DEFF Research Database (Denmark)

Karlsson, Michael; Hempel, Casper; Sjövall, Fredrik

2013-01-01

and no connection between disease severity and mitochondrial respiratory function. Treatment with rhEPO similarly had no effect on respiratory function. Thus cerebral metabolic dysfunction in CM does not seem to be directly linked to altered mitochondrial respiratory capacity as analyzed in brain homogenates ex...

Improvement of Neuroenergetics by Hypertonic Lactate Therapy in Patients with Traumatic Brain Injury Is Dependent on Baseline Cerebral Lactate/Pyruvate Ratio

KAUST Repository

Quintard, Hervé

2015-09-30

Energy dysfunction is associated with worse prognosis after traumatic brain injury (TBI). Recent data suggest that hypertonic sodium lactate infusion (HL) improves energy metabolism after TBI. Here, we specifically examined whether the efficacy of HL (3h infusion, 30-40 μmol/kg/min) in improving brain energetics (using cerebral microdialysis [CMD] glucose as a main therapeutic end-point) was dependent on baseline cerebral metabolic state (assessed by CMD lactate/pyruvate ratio [LPR]) and cerebral blood flow (CBF, measured with perfusion computed tomography [PCT]). Using a prospective cohort of 24 severe TBI patients, we found CMD glucose increase during HL was significant only in the subgroup of patients with elevated CMD LPR >25 (n = 13; +0.13 [95% confidence interval (CI) 0.08-0.19] mmol/L, p < 0.001; vs. +0.04 [-0.05-0.13] in those with normal LPR, p = 0.33, mixed-effects model). In contrast, CMD glucose increase was independent from baseline CBF (coefficient +0.13 [0.04-0.21] mmol/L when global CBF was <32.5 mL/100 g/min vs. +0.09 [0.04-0.14] mmol/L at normal CBF, both p < 0.005) and systemic glucose. Our data suggest that improvement of brain energetics upon HL seems predominantly dependent on baseline cerebral metabolic state and support the concept that CMD LPR - rather than CBF - could be used as a diagnostic indication for systemic lactate supplementation following TBI. Copyright © 2016 Mary Ann Liebert, Inc.

Asymmetry in the brain influenced the neurological deficits and infarction volume following the middle cerebral artery occlusion in rats

OpenAIRE

Zhang Meizeng; Gao Huanmin

2008-01-01

Abstract Background Paw preference in rats is similar to human handedness, which may result from dominant hemisphere of rat brain. However, given that lateralization is the uniqueness of the humans, many researchers neglect the differences between the left and right hemispheres when selecting the middle cerebral artery occlusion (MCAO) in rats. The aim of this study was to evaluate the effect of ischemia in the dominant hemisphere on neurobehavioral function and on the cerebral infarction vol...

Proteomic Identification of Altered Cerebral Proteins in the Complex Regional Pain Syndrome Animal Model

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Francis Sahngun Nahm

2014-01-01

Full Text Available Background. Complex regional pain syndrome (CRPS is a rare but debilitating pain disorder. Although the exact pathophysiology of CRPS is not fully understood, central and peripheral mechanisms might be involved in the development of this disorder. To reveal the central mechanism of CRPS, we conducted a proteomic analysis of rat cerebrum using the chronic postischemia pain (CPIP model, a novel experimental model of CRPS. Materials and Methods. After generating the CPIP animal model, we performed a proteomic analysis of the rat cerebrum using a multidimensional protein identification technology, and screened the proteins differentially expressed between the CPIP and control groups. Results. A total of 155 proteins were differentially expressed between the CPIP and control groups: 125 increased and 30 decreased; expressions of proteins related to cell signaling, synaptic plasticity, regulation of cell proliferation, and cytoskeletal formation were increased in the CPIP group. However, proenkephalin A, cereblon, and neuroserpin were decreased in CPIP group. Conclusion. Altered expression of cerebral proteins in the CPIP model indicates cerebral involvement in the pathogenesis of CRPS. Further study is required to elucidate the roles of these proteins in the development and maintenance of CRPS.

Proteomic identification of altered cerebral proteins in the complex regional pain syndrome animal model.

Science.gov (United States)

Nahm, Francis Sahngun; Park, Zee-Yong; Nahm, Sang-Soep; Kim, Yong Chul; Lee, Pyung Bok

2014-01-01

Complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder. Although the exact pathophysiology of CRPS is not fully understood, central and peripheral mechanisms might be involved in the development of this disorder. To reveal the central mechanism of CRPS, we conducted a proteomic analysis of rat cerebrum using the chronic postischemia pain (CPIP) model, a novel experimental model of CRPS. After generating the CPIP animal model, we performed a proteomic analysis of the rat cerebrum using a multidimensional protein identification technology, and screened the proteins differentially expressed between the CPIP and control groups. Results. A total of 155 proteins were differentially expressed between the CPIP and control groups: 125 increased and 30 decreased; expressions of proteins related to cell signaling, synaptic plasticity, regulation of cell proliferation, and cytoskeletal formation were increased in the CPIP group. However, proenkephalin A, cereblon, and neuroserpin were decreased in CPIP group. Altered expression of cerebral proteins in the CPIP model indicates cerebral involvement in the pathogenesis of CRPS. Further study is required to elucidate the roles of these proteins in the development and maintenance of CRPS.

Evidence that the EphA2 receptor exacerbates ischemic brain injury.

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John Thundyil

Full Text Available Ephrin (Eph signaling within the central nervous system is known to modulate axon guidance, synaptic plasticity, and to promote long-term potentiation. We investigated the potential involvement of EphA2 receptors in ischemic stroke-induced brain inflammation in a mouse model of focal stroke. Cerebral ischemia was induced in male C57Bl6/J wild-type (WT and EphA2-deficient (EphA2(-/- mice by middle cerebral artery occlusion (MCAO; 60 min, followed by reperfusion (24 or 72 h. Brain infarction was measured using triphenyltetrazolium chloride staining. Neurological deficit scores and brain infarct volumes were significantly less in EphA2(-/- mice compared with WT controls. This protection by EphA2 deletion was associated with a comparative decrease in brain edema, blood-brain barrier damage, MMP-9 expression and leukocyte infiltration, and higher expression levels of the tight junction protein, zona occludens-1. Moreover, EphA2(-/- brains had significantly lower levels of the pro-apoptotic proteins, cleaved caspase-3 and BAX, and higher levels of the anti-apoptotic protein, Bcl-2 as compared to WT group. We confirmed that isolated WT cortical neurons express the EphA2 receptor and its ligands (ephrin-A1-A3. Furthermore, expression of all four proteins was increased in WT primary cortical neurons following 24 h of glucose deprivation, and in the brains of WT mice following stroke. Glucose deprivation induced less cell death in primary neurons from EphA2(-/- compared with WT mice. In conclusion, our data provide the first evidence that the EphA2 receptor directly contributes to blood-brain barrier damage and neuronal death following ischemic stroke.

Early MEK1/2 Inhibition after Global Cerebral Ischemia in Rats Reduces Brain Damage and Improves Outcome by Preventing Delayed Vasoconstrictor Receptor Upregulation

DEFF Research Database (Denmark)

Johansson, Sara Ellinor; Larsen, Stine Schmidt; Povlsen, Gro Klitgaard

2014-01-01

BACKGROUND: Global cerebral ischemia following cardiac arrest is associated with increased cerebral vasoconstriction and decreased cerebral blood flow, contributing to delayed neuronal cell death and neurological detriments in affected patients. We hypothesize that upregulation of contractile ETB...... and 5-HT1B receptors, previously demonstrated in cerebral arteries after experimental global ischemia, are a key mechanism behind insufficient perfusion of the post-ischemic brain, proposing blockade of this receptor upregulation as a novel target for prevention of cerebral hypoperfusion and delayed...... neuronal cell death after global cerebral ischemia. The aim was to characterize the time-course of receptor upregulation and associated neuronal damage after global ischemia and investigate whether treatment with the MEK1/2 inhibitor U0126 can prevent cerebrovascular receptor upregulation and thereby...

Protection by the gross saponins of Tribulus terrestris against cerebral ischemic injury in rats involves the NF-κB pathway

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En-ping Jiang

2011-06-01

Full Text Available The aim of this study was to investigate whether the gross saponins of Tribulus terrestris (GSTT, a traditional Chinese herbal medicine, have neuroprotective effects on rats subjected to middle cerebral artery occlusion (MCAO, through nuclear factor-κB (NF-κB pathway and inflammatory mediators. Cerebral ischemia was produced by MCAO in either untreated (control or GSTT-pretreated rats, and the animals were examined for infarct volume, cerebral edema, neuro-behavioral abnormality and pathological changes. Meanwhile, the expression of NF-κB protein in brain tissue was analyzed on Western blots and the serum levels of TNF-α and IL-1 were determined by ELISA. The experimental results demonstrated that, compared with the control MCAO group, GSTT-pretreated MCAO group had significantly reduced infarct volume, brain edema and neuro-behavioral abnormality, and lesser degree of pathologic changes in the brain, as well as had lower levels of serum TNF-α and IL-1β, and higher levels of brain NF-κB (P<0.05. Furthermore, treatment with an NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC abolished the protective effects of GSTT against MCAO-induced cerebral ischemic injury. These results indicated that GSTT's ability to protect against cerebral ischemic injury was mediated through the NF-κB signaling pathway, and that GSTT may act through inhibition of the production of inflammatory mediators.

Assessment of Blood-Brain Barrier Permeability by Dynamic Contrast-Enhanced MRI in Transient Middle Cerebral Artery Occlusion Model after Localized Brain Cooling in Rats

Energy Technology Data Exchange (ETDEWEB)

Kim, Eun Soo [Department of Radiology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068 (Korea, Republic of); Lee, Seung-Koo [Department of Radiology, Yonsei University College of Medicine, Seoul 03722 (Korea, Republic of); Kwon, Mi Jung [Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068 (Korea, Republic of); Lee, Phil Hye [Department of Neurology, Yonsei University College of Medicine, Seoul 03722 (Korea, Republic of); Ju, Young-Su [Department of Industrial Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068 (Korea, Republic of); Yoon, Dae Young [Department of Radiology, Hallym University Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 05355 (Korea, Republic of); Kim, Hye Jeong [Department of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 07441 (Korea, Republic of); Lee, Kwan Seop [Department of Radiology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068 (Korea, Republic of)

2016-11-01

The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20℃) infusion group, and localized warm-saline (37℃) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min{sup -1} vs. 0.07 ± 0.02 min{sup -1}, p = 0.661 for K{sup trans}; 0.30 ± 0.05 min{sup -1} vs. 0.37 ± 0.11 min{sup -1}, p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Localized brain cooling (20℃) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37℃) infusion group.

Assessment of blood-brain barrier permeability by dynamic contrast-enhanced MRI in transient middle cerebral artery occlusion model after localized brain cooling in rats

Energy Technology Data Exchange (ETDEWEB)

Kim, Eun Soo; Lee, Kwan Seop; Kwon, Mi Jung; Ju, Young Su [Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang (Korea, Republic of); Lee, Seung Koo; Lee, Phil Hye [Yonsei University College of Medicine, Seoul (Korea, Republic of); Yoon, Dae Young [Dept. of Radiology, Hallym University Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul (Korea, Republic of); Kim, Hye Jeong [Dept. of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul (Korea, Republic of)

2016-09-15

The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline (20 .deg. ) infusion group, and localized warm-saline (37 .deg. ) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion 0.09 ± 0.01 min{sup -1} vs. 0.07 ± 0.02 min{sup -1},p = 0.661 for K{sup trans}; 0.30 ± 0.05 min{sup -1} vs. 0.37 ± 0.11 min{sup -1},p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Localized brain cooling (20 .deg. ) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline (37 .deg. ) infusion group.

Imaging of Neuronal Activity in Awake Mice by Measurements of Flavoprotein Autofluorescence Corrected for Cerebral Blood Flow

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Manami Takahashi

2018-01-01

Full Text Available Green fluorescence imaging (e.g., flavoprotein autofluorescence imaging, FAI can be used to measure neuronal activity and oxygen metabolism in living brains without expressing fluorescence proteins. It is useful for understanding the mechanism of various brain functions and their abnormalities in age-related brain diseases. However, hemoglobin in cerebral blood vessels absorbs green fluorescence, hampering accurate assessments of brain function in animal models with cerebral blood vessel dysfunctions and subsequent cerebral blood flow (CBF alterations. In the present study, we developed a new method to correct FAI signals for hemoglobin-dependent green fluorescence reductions by simultaneous measurements of green fluorescence and intrinsic optical signals. Intrinsic optical imaging enabled evaluations of light absorption and scatters by hemoglobin, which could then be applied to corrections of green fluorescence intensities. Using this method, enhanced flavoprotein autofluorescence by sensory stimuli was successfully detected in the brains of awake mice, despite increases of CBF, and hemoglobin interference. Moreover, flavoprotein autofluorescence could be properly quantified in a resting state and during sensory stimulation by a CO2 inhalation challenge, which modified vascular responses without overtly affecting neuronal activities. The flavoprotein autofluorescence signal data obtained here were in good agreement with the previous findings from a condition with drug-induced blockade of cerebral vasodilation, justifying the current assaying methodology. Application of this technology to studies on animal models of brain diseases with possible changes of CBF, including age-related neurological disorders, would provide better understanding of the mechanisms of neurovascular coupling in pathological circumstances.

Cerebral blood flow and metabolism during exercise: implications for fatigue.

Science.gov (United States)

Secher, Neils H; Seifert, Thomas; Van Lieshout, Johannes J

2008-01-01

During exercise: the Kety-Schmidt-determined cerebral blood flow (CBF) does not change because the jugular vein is collapsed in the upright position. In contrast, when CBF is evaluated by (133)Xe clearance, by flow in the internal carotid artery, or by flow velocity in basal cerebral arteries, a approximately 25% increase is detected with a parallel increase in metabolism. During activation, an increase in cerebral O(2) supply is required because there is no capillary recruitment within the brain and increased metabolism becomes dependent on an enhanced gradient for oxygen diffusion. During maximal whole body exercise, however, cerebral oxygenation decreases because of eventual arterial desaturation and marked hyperventilation-related hypocapnia of consequence for CBF. Reduced cerebral oxygenation affects recruitment of motor units, and supplemental O(2) enhances cerebral oxygenation and work capacity without effects on muscle oxygenation. Also, the work of breathing and the increasing temperature of the brain during exercise are of importance for the development of so-called central fatigue. During prolonged exercise, the perceived exertion is related to accumulation of ammonia in the brain, and data support the theory that glycogen depletion in astrocytes limits the ability of the brain to accelerate its metabolism during activation. The release of interleukin-6 from the brain when exercise is prolonged may represent a signaling pathway in matching the metabolic response of the brain. Preliminary data suggest a coupling between the circulatory and metabolic perturbations in the brain during strenuous exercise and the ability of the brain to access slow-twitch muscle fiber populations.

Unilateral traumatic hemorrhage of the basal ganglion and bihemisferic cerebral infarction

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Moscote-Salazar Luis Rafael

2017-09-01

Full Text Available Among the various injuries caused by the cerebral tramatic lesion are traumatic brain contusions. Hemorrhagic contusions of the basal ganglia are unusual. Different injuries such as cranial fractures, epidural hemorrhage, subdural hematoma, subarachnoid hemorrhage among others may be associated with brain contusions. In some cases traumatic brain injury arises. We present a case of a patient with unilateral cerebral contusion associated with bihemispheric cerebral infarction.

MR imaging of cerebral palsy

International Nuclear Information System (INIS)

Saginoya, Toshiyuki; Yamaguchi, Keiichiro; Kuniyoshi, Kazuhide

1996-01-01

We evaluated 35 patients with cerebral palsy on the basis of MR imaging findings in the brain. The types of palsy were spastic quadriplegia (n=11), spastic diplegia (n=9), spastic hemiplegia (n=2), double hemiplegia (n=1), athetosis (n=10) and mixed (n=2). Of all patients, 28 (80%) generated abnormal findings. In spastic quadriplegia, although eight cases revealed severe brain damage, two cases showed no abnormal findings in the brain. One of the three had cervical cord compression caused by atlanto-axial subluxation. In spastic diplegia, the findings were divided according to whether the patient was born at term or preterm. If the patient had been born prematurely, the findings showed periventricular leukomalacia and abnormally high intensity in the posterior limbs of the internal capsule on T2-weighted images. MR imaging in spastic hemiplegia revealed cerebral infarction. In the athetoid type, half of all cases showed either no abnormal findings or slight widening of the lateral ventricle. Three cases showed abnormal signals of the basal ganglia. The reason why athetoid-type palsy did not show severe abnormality is unknown. We believe that MR imaging is a useful diagnostic modality to detect damage in the brain in cerebral palsy and plays an important role in the differentiation of cerebral palsy from the spastic palsy disease. (author)

MR imaging of cerebral palsy

Energy Technology Data Exchange (ETDEWEB)

Saginoya, Toshiyuki [Urasoe General Hospital, Okinawa (Japan); Yamaguchi, Keiichiro; Kuniyoshi, Kazuhide [and others

1996-06-01

We evaluated 35 patients with cerebral palsy on the basis of MR imaging findings in the brain. The types of palsy were spastic quadriplegia (n=11), spastic diplegia (n=9), spastic hemiplegia (n=2), double hemiplegia (n=1), athetosis (n=10) and mixed (n=2). Of all patients, 28 (80%) generated abnormal findings. In spastic quadriplegia, although eight cases revealed severe brain damage, two cases showed no abnormal findings in the brain. One of the three had cervical cord compression caused by atlanto-axial subluxation. In spastic diplegia, the findings were divided according to whether the patient was born at term or preterm. If the patient had been born prematurely, the findings showed periventricular leukomalacia and abnormally high intensity in the posterior limbs of the internal capsule on T2-weighted images. MR imaging in spastic hemiplegia revealed cerebral infarction. In the athetoid type, half of all cases showed either no abnormal findings or slight widening of the lateral ventricle. Three cases showed abnormal signals of the basal ganglia. The reason why athetoid-type palsy did not show severe abnormality is unknown. We believe that MR imaging is a useful diagnostic modality to detect damage in the brain in cerebral palsy and plays an important role in the differentiation of cerebral palsy from the spastic palsy disease. (author)

Memantine mediates neuroprotection via regulating neurovascular unit in a mouse model of focal cerebral ischemia.

Science.gov (United States)

Chen, Zheng-Zhen; Yang, Dan-Dan; Zhao, Zhan; Yan, Hui; Ji, Juan; Sun, Xiu-Lan

2016-04-01

Memantine is a low-moderate affinity and uncompetitive N-methyl-d-aspartate receptor (NMDAR) antagonist, which is also a potential neuroprotectant in acute ischemic stroke for its particular action profiles. The present study was to reveal the mechanisms involved in the neuroprotection of memantine. We used a mouse model of permanent focal cerebral ischemia via middle cerebral artery occlusion to verify our hypothesis. 2,3,5-Triphenyltetrazolium chloride staining was used to compare infarct size. The amount of astrocytes and the somal volume of the microglia cell body were analyzed by immunohistochemistry and stereological estimates. Western blotting was used to determine the protein expressions. Memantine prevented cerebral ischemia-induced brain infarct and neuronal injury, and reduced oxygen-glucose deprivation-induced cortical neuronal apoptosis. Moreover, memantine reduced the amount of the damaged astrocytes and over activated microglia after 24h of ischemia. In the early phase of ischemia, higher production of MMP-9 was observed, and thereby collagen IV was dramatically disrupted. Meanwhile, the post-synaptic density protein 95(PSD-95) was also severely cleavaged. Memantine decreased MMP-9 secretion, prevented the degradation of collagen IV in mouse brain. PSD-95 cleavage was also inhibited by memantine. These results suggested that memantine exerted neuroprotection effects in acute ischemic brain damage, partially via improving the functions of neurovascular unit. Taking all these findings together, we consider that memantine might be a promising protective agent against ischemic stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice

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Grau Georges E

2007-12-01

Full Text Available Abstract Background Microarray analyses allow the identification and assessment of molecular signatures in whole tissues undergoing pathological processes. To better understand cerebral malaria pathogenesis, we investigated intra-cerebral gene-expression profiles in well-defined genetically cerebral malaria-resistant (CM-R and CM-susceptible (CM-S mice, upon infection by Plasmodium berghei ANKA (PbA. We investigated mouse transcriptional responses at early and late stages of infection by use of cDNA microarrays. Results Through a rigorous statistical approach with multiple testing corrections, we showed that PbA significantly altered brain gene expression in CM-R (BALB/c, and in CM-S (CBA/J and C57BL/6 mice, and that 327 genes discriminated between early and late infection stages, between mouse strains, and between CM-R and CM-S mice. We further identified 104, 56, 84 genes with significant differential expression between CM-R and CM-S mice on days 2, 5, and 7 respectively. The analysis of their functional annotation indicates that genes involved in metabolic energy pathways, the inflammatory response, and the neuroprotection/neurotoxicity balance play a major role in cerebral malaria pathogenesis. In addition, our data suggest that cerebral malaria and Alzheimer's disease may share some common mechanisms of pathogenesis, as illustrated by the accumulation of β-amyloid proteins in brains of CM-S mice, but not of CM-R mice. Conclusion Our microarray analysis highlighted marked changes in several molecular pathways in CM-S compared to CM-R mice, particularly at early stages of infection. This study revealed some promising areas for exploration that may both provide new insight into the knowledge of CM pathogenesis and the development of novel therapeutic strategies.

Malignant Hemispheric Cerebral Infarction Associated with Idiopathic Systemic Capillary Leak Syndrome

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Kei Miyata

2013-10-01

Full Text Available Idiopathic systemic capillary leak syndrome (ISCLS is a rare condition that is characterized by unexplained episodic capillary hyperpermeability due to a shift of fluid and protein from the intravascular to the interstitial space. This results in diffuse general swelling, fetal hypovolemic shock, hypoalbuminemia, and hemoconcentration. Although ISCLS rarely induces cerebral infarction, we experienced a patient who deteriorated and was comatose as a result of massive cerebral infarction associated with ISCLS. In this case, severe hypotensive shock, general edema, hemiparesis, and aphasia appeared after serious antecedent gastrointestinal symptoms. Progressive life-threatening ischemic cerebral edema required decompressive hemicraniectomy. The patient experienced another episode of severe hypotension and limb edema that resulted in multiple extremity compartment syndrome. Treatment entailed forearm and calf fasciotomies. Cerebral edema in the ischemic brain progresses rapidly in patients suffering from ISCLS. Strict control of fluid volume resuscitation and aggressive diuretic therapy may be needed during the post-leak phase of fluid remobilization.

Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

Science.gov (United States)

Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S

2018-04-01

Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [ 15 O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.

Neurovascular regulation in the ischemic brain.

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Jackman, Katherine; Iadecola, Costantino

2015-01-10

The brain has high energetic requirements and is therefore highly dependent on adequate cerebral blood supply. To compensate for dangerous fluctuations in cerebral perfusion, the circulation of the brain has evolved intrinsic safeguarding measures. The vascular network of the brain incorporates a high degree of redundancy, allowing the redirection and redistribution of blood flow in the event of vascular occlusion. Furthermore, active responses such as cerebral autoregulation, which acts to maintain constant cerebral blood flow in response to changing blood pressure, and functional hyperemia, which couples blood supply with synaptic activity, allow the brain to maintain adequate cerebral perfusion in the face of varying supply or demand. In the presence of stroke risk factors, such as hypertension and diabetes, these protective processes are impaired and the susceptibility of the brain to ischemic injury is increased. One potential mechanism for the increased injury is that collateral flow arising from the normally perfused brain and supplying blood flow to the ischemic region is suppressed, resulting in more severe ischemia. Approaches to support collateral flow may ameliorate the outcome of focal cerebral ischemia by rescuing cerebral perfusion in potentially viable regions of the ischemic territory.

EAAC1 Gene Deletion Increases Neuronal Death and Blood Brain Barrier Disruption after Transient Cerebral Ischemia in Female Mice

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Bo Young Choi

2014-10-01

Full Text Available EAAC1 is important in modulating brain ischemic tolerance. Mice lacking EAAC1 exhibit increased susceptibility to neuronal oxidative stress in mice after transient cerebral ischemia. EAAC1 was first described as a glutamate transporter but later recognized to also function as a cysteine transporter in neurons. EAAC1-mediated transport of cysteine into neurons contributes to neuronal antioxidant function by providing cysteine substrates for glutathione synthesis. Here we evaluated the effects of EAAC1 gene deletion on hippocampal blood vessel disorganization after transient cerebral ischemia. EAAC1−/− female mice subjected to transient cerebral ischemia by common carotid artery occlusion for 30 min exhibited twice as much hippocampal neuronal death compared to wild-type female mice as well as increased reduction of neuronal glutathione, blood–brain barrier (BBB disruption and vessel disorganization. Pre-treatment of N-acetyl cysteine, a membrane-permeant cysteine prodrug, increased basal glutathione levels in the EAAC1−/− female mice and reduced ischemic neuronal death, BBB disruption and vessel disorganization. These findings suggest that cysteine uptake by EAAC1 is important for neuronal antioxidant function under ischemic conditions.

Cerebral malaria: susceptibility weighted MRI

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Vinit Baliyan

2015-03-01

Full Text Available Cerebral malaria is one of the fatal complications of Plasmodium falciparum infection. Pathogenesis involves cerebral microangiopathy related to microvascular plugging by infected red blood cells. Conventional imaging with MRI and CT do not reveal anything specific in case of cerebral malaria. Susceptibility weighted imaging, a recent advance in the MRI, is very sensitive to microbleeds related to microangiopathy. Histopathological studies in cerebral malaria have revealed microbleeds in brain parenchyma secondary to microangiopathy. Susceptibility weighted imaging, being exquisitely sensitive to microbleeds may provide additional information and improve the diagnostic accuracy of MRI in cerebral malaria.

Neuroprotection of taurine through inhibition of 12/15 lipoxygenase pathway in cerebral ischemia of rats.

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Zhang, Zhe; Yu, Rongbo; Cao, Lei

2017-05-01

Cerebral ischemia exhibits a multiplicity of pathophysiological mechanisms. Taurine (Tau), an endogenous substance, possesses a number of cytoprotective properties. The aim of the present study was to examine the neuroprotective effect of Tau, through affecting 12/15 lipoxygenase (12/15-LOX) signal pathway in an acute permanent middle cerebral artery occlusion (MCAO) model of rats. Sprague-Dawley rats were randomly divided into 3 groups (n = 10), namely the sham-operated group, MCAO group and Tau group. Tau was intraperitoneally administrated immediately after cerebral ischemia. At 24 h after MCAO, neurological function score, brain water content and infarct volume were assessed. The expression of 12/15-lipoxygenase (12/15-LOX), p38 mitogen-activated protein kinase (p38 MAPK), and cytosolic phospholipase A2 (cPLA2) was measured by Western blot. Enzyme-linked immunosorbent assay was used to evaluate the inflammatory factors TNF-α, IL-1β and IL-6 in serum. Compared with MCAO group, taurine significantly improved neurological function and significantly reduced brain water content (p Taurine protected the brain from damage caused by MCAO; this effect may be through down-regulation of 12/15-LOX, p38 MAPK, and cPLA2.

MR findings of cerebral palsy

International Nuclear Information System (INIS)

Yoon, Sang Hum; Chang, Seung Kuk; Cho, Mee Young; Park, Dong Woo; Kim, Jong Deok; Eun, Choong Ki

1994-01-01

To evaluate the MR findings of brain damage in cerebral palised patients and to correlate it with gestational age and the time of damage. A retrospective analysis was performed in 40 patients who underwent MR scanning for evaluation of brain lesion in clinically diagnosed cerebral palsy. Authors classified the patients into two groups as premature and full-term and compared MR findings of the two groups. Abnormal MR findings were noted in 28 cases (70%). Five out of 6 patients who had been born prematurely showed isolate periventricular white matter lesions. Twenty-three out of 34 patients who had been born at full-term showed abnormal MR findings. Of these 23 patients, migration anomalies in 7 patients, isolate periventricular white matter lesions in 3 patients, and other combined periventricular subcortical white matter and deep gray matter lesions in 14 patients were seen. At least, 10 patients(43%) of full term group showed abnormal MRI findings reflecting intrauterine brain damage and all 5 patients of premature group showed isolate periventricular white matter lesions suggesting immaturity of brain. MRI is thought to be very useful in the assessment of brain damage for the patients with cerebral palsy by recognizing the location of the lesion and estimating the time of damage

MR findings of cerebral palsy

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Yoon, Sang Hum; Chang, Seung Kuk; Cho, Mee Young; Park, Dong Woo; Kim, Jong Deok; Eun, Choong Ki [Pusan Paik Hospital, Pusan (Korea, Republic of)

1994-11-15

To evaluate the MR findings of brain damage in cerebral palised patients and to correlate it with gestational age and the time of damage. A retrospective analysis was performed in 40 patients who underwent MR scanning for evaluation of brain lesion in clinically diagnosed cerebral palsy. Authors classified the patients into two groups as premature and full-term and compared MR findings of the two groups. Abnormal MR findings were noted in 28 cases (70%). Five out of 6 patients who had been born prematurely showed isolate periventricular white matter lesions. Twenty-three out of 34 patients who had been born at full-term showed abnormal MR findings. Of these 23 patients, migration anomalies in 7 patients, isolate periventricular white matter lesions in 3 patients, and other combined periventricular subcortical white matter and deep gray matter lesions in 14 patients were seen. At least, 10 patients(43%) of full term group showed abnormal MRI findings reflecting intrauterine brain damage and all 5 patients of premature group showed isolate periventricular white matter lesions suggesting immaturity of brain. MRI is thought to be very useful in the assessment of brain damage for the patients with cerebral palsy by recognizing the location of the lesion and estimating the time of damage.

Cerebral ketone body metabolism.

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Morris, A A M

2005-01-01

Ketone bodies (KBs) are an important source of energy for the brain. During the neonatal period, they are also precursors for the synthesis of lipids (especially cholesterol) and amino acids. The rate of cerebral KB metabolism depends primarily on the concentration in blood; high concentrations occur during fasting and on a high-fat diet. Cerebral KB metabolism is also regulated by the permeability of the blood-brain barrier (BBB), which depends on the abundance of monocarboxylic acid transporters (MCT1). The BBB's permeability to KBs increases with fasting in humans. In rats, permeability increases during the suckling period, but human neonates have not been studied. Monocarboxylic acid transporters are also present in the plasma membranes of neurons and glia but their role in regulating KB metabolism is uncertain. Finally, the rate of cerebral KB metabolism depends on the activities of the relevant enzymes in brain. The activities vary with age in rats, but reliable results are not available for humans. Cerebral KB metabolism in humans differs from that in the rat in several respects. During fasting, for example, KBs supply more of the brain's energy in humans than in the rat. Conversely, KBs are probably used more extensively in the brain of suckling rats than in human neonates. These differences complicate the interpretation of rodent studies. Most patients with inborn errors of ketogenesis develop normally, suggesting that the only essential role for KBs is as an alternative fuel during illness or prolonged fasting. On the other hand, in HMG-CoA lyase deficiency, imaging generally shows asymptomatic white-matter abnormalities. The ability of KBs to act as an alternative fuel explains the effectiveness of the ketogenic diet in GLUT1 deficiency, but its effectiveness in epilepsy remains unexplained.

Brain imaging in psychiatry

International Nuclear Information System (INIS)

Morihisa, J.M.

1984-01-01

This book contains the following five chapters: Positron Emission Tomography (PET) in Psychiatry; Regional Cerebral Blood Flow (CBF) in Psychiatry: Methodological Issues; Regional Cerebral Blood Flow in Psychiatry: Application to Clinical Research; Regional Cerebral Blood Flow in Psychiatry: The Resting and Activated Brains of Schizophrenic Patients; and Brain Electrical Activity Mapping (BEAM) in Psychiatry

CT findings as confirmatory criteria of brain death

International Nuclear Information System (INIS)

Shiogai, Toshiyuki; Takeuchi, Kazuo

1983-01-01

The absence of cerebral circulation and electrocerebral silence have served as an accurate index of irreversible brain death. It is proposed that computed tomography (CT) findings be evaluated as confirmatory criteria of brain death. To this end, CT evaluation of 14 patients satisfying the conventional criteria of brain death was performed. A CT finding of severe compression or dissappearance of the ventricular system, or so called ''brain tamponade'', was seen in 7 (50 %) of the 14 patients. Enhanced contrast CT, especially dynamic CT, usually distinctly reveals the cerebral vessels whenever the cerebral blood flow is preserved; conversely, the lack of enhanced brain structures, even comparing attenuation values, indicates the absence of cerebral blood flow. In 7 (70 %) of 10 patients, however, there was enhanced contrast of vascular brain structures, especially the circle of Willis, major cerebral arteries, choroid plexuses, and venous sinuses. It is suggested that this result is due to the improvement of demonstrability by CT. The usefulness of CT in the confirmation of brain death lies in visualization of the pathological changes associated with a dead brain, such as ''brain tamponade'', and the lack of enhanced contrast indicating the absence of cerebral blood flow. The latter point is still problematic as angiography revealed an extremely low cerebral blood flow in a few cases of ''dead brain'' patients. It is recommended that cerebral blood flow in brain death be evaluated by dynamic CT scanning and correlated with other methods of cerebral blood flow determination (e.g., intravenous digital subtraction angiography). (Author)

CT findings as confirmatory criteria of brain death

Energy Technology Data Exchange (ETDEWEB)

Shiogai, Toshiyuki; Takeuchi, Kazuo (Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine)

1983-12-01

The absence of cerebral circulation and electrocerebral silence have served as an accurate index of irreversible brain death. It is proposed that computed tomography (CT) findings be evaluated as confirmatory criteria of brain death. To this end, CT evaluation of 14 patients satisfying the conventional criteria of brain death was performed. A CT finding of severe compression or dissappearance of the ventricular system, or so called ''brain tamponade'', was seen in 7 (50 %) of the 14 patients. Enhanced contrast CT, especially dynamic CT, usually distinctly reveals the cerebral vessels whenever the cerebral blood flow is preserved; conversely, the lack of enhanced brain structures, even comparing attenuation values, indicates the absence of cerebral blood flow. In 7 (70 %) of 10 patients, however, there was enhanced contrast of vascular brain structures, especially the circle of Willis, major cerebral arteries, choroid plexuses, and venous sinuses. It is suggested that this result is due to the improvement of demonstrability by CT. The usefulness of CT in the confirmation of brain death lies in visualization of the pathological changes associated with a dead brain, such as ''brain tamponade'', and the lack of enhanced contrast indicating the absence of cerebral blood flow. The latter point is still problematic as angiography revealed an extremely low cerebral blood flow in a few cases of ''dead brain'' patients. It is recommended that cerebral blood flow in brain death be evaluated by dynamic CT scanning and correlated with other methods of cerebral blood flow determination (e.g., intravenous digital subtraction angiography).

Time-related sex differences in cerebral hypoperfusion-induced brain injury

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Stanojlović Miloš

2014-01-01

Full Text Available Although the model of cerebral hypoperfusion in rats has been a matter of many investigations over the years, the exact intracellular and biochemical mechanisms that lead to neuron loss and memory decline have not been clearly identified. In the current study, we examined whether cerebral hypoperfusion causes changes in hippocampal protein expression of apoptotic markers in the synaptosomal fraction and neurodegeneration in a time-dependent and sex-specific manner. Adult male and female Wistar rats were divided into two main groups, controls that underwent sham operation, and animals subjected to permanent bilateral occlusion of common carotid arteries. Both male and female rats were killed 3, 7 or 90 days following the insult. The obtained results indicate that the peak of processes that lead to apoptosis occured on postoperative day 7 and that they were more prominent in males, indicating that neuroprotective effects of certain substances (planned for future experiments, should be tested at this time point. [Projekat Ministarstva nauke Republike Srbije, br. 173044 i br. 41014

[Raman spectra of monkey cerebral cortex tissue].

Science.gov (United States)

Zhu, Ji-chun; Guo, Jian-yu; Cai, Wei-ying; Wang, Zu-geng; Sun, Zhen-rong

2010-01-01

Monkey cerebral cortex, an important part in the brain to control action and thought activities, is mainly composed of grey matter and nerve cell. In the present paper, the in situ Raman spectra of the cerebral cortex of the birth, teenage and aged monkeys were achieved for the first time. The results show that the Raman spectra for the different age monkey cerebral cortex exhibit most obvious changes in the regions of 1000-1400 and 2800-3000 cm(-1). With monkey growing up, the relative intensities of the Raman bands at 1313 and 2885 cm(-1) mainly assigned to CH2 chain vibrational mode of lipid become stronger and stronger whereas the relative intensities of the Raman bands at 1338 and 2932 cm(-1) mainly assigned to CH3 chain vibrational mode of protein become weaker and weaker. In addition, the two new Raman bands at 1296 and 2850 cm(-1) are only observed in the aged monkey cerebral cortex, therefore, the two bands can be considered as a character or "marker" to differentiate the caducity degree with monkey growth In order to further explore the changes, the relative intensity ratios of the Raman band at 1313 cm(-1) to that at 1338 cm(-1) and the Raman band at 2885 cm(-1) to that at 2 932 cm(-1), I1313/I1338 and I2885/I2932, which are the lipid-to-protein ratios, are introduced to denote the degree of the lipid content. The results show that the relative intensity ratios increase significantly with monkey growth, namely, the lipid content in the cerebral cortex increases greatly with monkey growth. So, the authors can deduce that the overmuch lipid is an important cause to induce the caducity. Therefore, the results will be a powerful assistance and valuable parameter to study the order of life growth and diagnose diseases.

Proposal for a universal definition of cerebral infarction.

Science.gov (United States)

Saver, Jeffrey L

2008-11-01

Cerebral infarction is a leading cause of disability and death worldwide but has no uniform international definition. Recent diagnostic advances have revised fundamental concepts in cerebral and cardiac ischemia. Cardiologists, already possessed of a nosologic framework distinguishing myocardial infarction from unstable angina on the basis of tissue state, promulgated a new "universal" tissue definition of myocardial infarction incorporating insights afforded by assays of cardiac troponin, a serum biomarker exquisitely sensitive to myocardial injury. Concurrently, vascular neurologists proposed a new tissue, rather than time, criterion to distinguish transient ischemia attack from cerebral infarction, responding to perspectives provided by diffusion MRI and cerebral blood volume CT, imaging biomarkers highly sensitive to neuronal injury. To complete this conceptual realignment, vascular neurology must now advance a clear, uniform, and operationalizable tissue definition of cerebral infarction. This review proposes cerebral infarction be defined as brain or retinal cell death due to prolonged ischemia. This definition categorizes both pannecrosis and neuronal dropout ("complete" and "incomplete" infarcts in classic neuropathologic terminology) as cerebral infarcts. Making the presence of any neuronal or glial cell death essential yields a definition of cerebral infarction that has high relevance to patients, physicians, and policymakers; is more easily applied in clinical practice; fosters action in acute care; harmonizes with myocardial ischemia classification; and focuses diagnostic evaluation on the cause of brain ischemia and the occurrence of end organ injury. The term cerebral infarction should be used when there is evidence of brain or retinal cell death due to cerebral ischemia.

Multiple small hemorrhagic infarcts in cerebral air embolism: a case report.

Science.gov (United States)

Togo, Masaya; Hoshi, Taku; Matsuoka, Ryosuke; Imai, Yukihiro; Kohara, Nobuo

2017-11-16

Cerebral air embolism is a rare cause of cerebral infarction. In cerebral air embolism, T2 star-weighted imaging shows numerous spotty hypointense signals. Previous reports have suggested that these signals represent air in the brain and are gradually diminished and absorbed. We experienced two cases of cerebral air embolism, and in one of them, we conducted an autopsy. Case 1 was a 76-year-old Japanese man with lung cancer and emphysema. A spasmodic cough induced massive cerebral and cardiac air embolisms and the patient died because of cerebral herniation. T2 star-weighted imaging of brain magnetic resonance imaging showed multiple spotty low signals. Brain autopsy showed numerous spotty hemorrhagic infarcts in the area of T2 star-weighted imaging signals. Case 2 was an 85-year-old Japanese man with emphysema who suffered from acute stroke. Similar spotty T2 star-weighted imaging signals were observed and remained unchanged 2 months after the onset. These findings indicate that T2 star-weighted imaging in cerebral air embolism partially represents micro-hemorrhagic infarction caused by air bubbles that have migrated into the brain.

Quantification of extra-cerebral and cerebral hemoglobin concentrations during physical exercise using time-domain near infrared spectroscopy

OpenAIRE

Auger, Héloïse; Bherer, Louis; Boucher, Étienne; Hoge, Richard; Lesage, Frédéric; Dehaes, Mathieu

2016-01-01

Fitness is known to have beneficial effects on brain anatomy and function. However, the understanding of mechanisms underlying immediate and long-term neurophysiological changes due to exercise is currently incomplete due to the lack of tools to investigate brain function during physical activity. In this study, we used time-domain near infrared spectroscopy (TD-NIRS) to quantify and discriminate extra-cerebral and cerebral hemoglobin concentrations and oxygen saturation (SO2) in young adults...

A study of cerebral circulation in patients on moderate hypothermia therapy

International Nuclear Information System (INIS)

Honda, Mitsuru; Kushida, Tsuyoshi; Nagao, Takeki; Seiki, Yoshikatsu; Shibata, Iekado

2003-01-01

Recently, moderate hypothermia with cooling of the brain to 32-33 deg C has been widely applied to patients with severe brain damage. We evaluated the cerebral circulation of patients treated with moderate hypothermia therapy. In 16 patients with severe brain damage, both Xe-CT and Perfusion CT were performed during moderate hypothermia. The study included 5 head injury patients, 6 anoxic brain patients, 2 subarachnoid hemorrhage patients, 2 cerebral embolization patients and 1 cerebral hemorrhage patient. We measured cerebral blood flow (CBF) values using Xe-CT and mean transit time (MTT) by Perfusion CT and calculated cerebral blood volume (CBV) using an AZ-7000W98 computer system. In 16 patients, moderate hypothermia decreased both CBF (21.4±14.0 ml/100 g/min) and CBV (3.4±2.9 ml/100 g) and increased MTT (9.6±l.9 sec) compared to normal volunteers. However, patients who became brain death during moderate hypothermia maintained high levels of CBF and CBV. Based on the present results, we propose that reduction of CBV and CBF by moderate hypothermia can play important role in protecting brain from damage. (author)

Diffusion-weighted MRI characteristics of the cerebral metastasis to brain boundary predicts patient outcomes

International Nuclear Information System (INIS)

Zakaria, Rasheed; Das, Kumar; Radon, Mark; Bhojak, Maneesh; Rudland, Philip R; Sluming, Vanessa; Jenkinson, Michael D

2014-01-01

Diffusion-weighted MRI (DWI) has been used in neurosurgical practice mainly to distinguish cerebral metastases from abscess and glioma. There is evidence from other solid organ cancers and metastases that DWI may be used as a biomarker of prognosis and treatment response. We therefore investigated DWI characteristics of cerebral metastases and their peritumoral region recorded pre-operatively and related these to patient outcomes. Retrospective analysis of 76 cases operated upon at a single institution with DWI performed pre-operatively at 1.5T. Maps of apparent diffusion coefficient (ADC) were generated using standard protocols. Readings were taken from the tumor, peritumoral region and across the brain-tumor interface. Patient outcomes were overall survival and time to local recurrence. A minimum ADC greater than 919.4 × 10 -6 mm 2 /s within a metastasis predicted longer overall survival regardless of adjuvant therapies. This was not simply due to differences between the types of primary cancer because the effect was observed even in a subgroup of 36 patients with the same primary, non-small cell lung cancer. The change in diffusion across the tumor border and into peritumoral brain was measured by the “ADC transition coefficient” or ATC and this was more strongly predictive than ADC readings alone. Metastases with a sharp change in diffusion across their border (ATC >0.279) showed shorter overall survival compared to those with a more diffuse edge. The ATC was the only imaging measurement which independently predicted overall survival in multivariate analysis (hazard ratio 0.54, 95% CI 0.3 – 0.97, p = 0.04). DWI demonstrates changes in the tumor, across the tumor edge and in the peritumoral region which may not be visible on conventional MRI and this may be useful in predicting patient outcomes for operated cerebral metastases

Global cerebral blood flow changes measured by brain perfusion SPECT immediately after whole brain irradiation

International Nuclear Information System (INIS)

Ohtawa, Nobuyuki; Machida, Kikuo; Honda, Norinari; Hosono, Makoto; Takahashi, Takeo

2003-01-01

Whole brain irradiation (WBI) is still a major treatment option for patients with metastatic brain tumor despite recent advances in chemotherapy and newer techniques of radiation therapy. Cerebral blood flow (CBF) of changes induced by whole brain radiation is not fully investigated, and the aim of the study was to measure CBF changes non-invasively with brain perfusion SPECT to correlate with treatment effect or prognosis. Total of 106 patients underwent WBI during April 1998 to March 2002. Both brain MRI and brain perfusion SPECT could be performed before (less than 1 week before or less than 10 Gy of WBI) and immediately after (between 1 week before and 2 weeks after the completion of WBI) the therapy in 17 of these patients. They, 10 men and 7 women, all had metastatic brain tumor with age range of 45 to 87 (mean of 61.4) years. Tc-99m brain perfusion agent (HMPAO in 4, ECD in 13) was rapidly administered in a 740-MBq dose to measure global and regional CBF according to Matsuda's method, which based on both Patlak plot and Lassens' linearity correction. Brain MRI was used to measure therapeutic response according to World Health Organization (WHO) classification as complete remission (CR), partial response (PR), no change (NC), and progressive disease (PD). Survival period was measured from the completion of WBI. Mean global CBF was 40.6 and 41.5 ml/100 g/min before and immediately after the WBI, respectively. Four patients increased (greater than 10%) their global mean CBF, 10 unchanged (less than 10% increase or decrease), and 3 decreased after the WBI. The WBI achieved CR in none, PR in 8, NC in 6, and PD in 3 on brain MRI. Change in global mean CBF (mean±SD) was significantly larger in PR (4.3±2.0 ml/100 g/min, p=0.002) and in NC (-0.1±4.5) than in PD (-3.9±6.4, P=0.002, P=0.016, respectively). Survival was not significantly (p>0.05) different among the patients with CR (20 weeks), NC (48 weeks), and PD (21 weeks). Change in global CBF and survival was

Relationship between alternation of cerebral blood flow and formation of brain edema around the hematoma after experimental intracerebral hemorrhage

International Nuclear Information System (INIS)

Zhou Jian; Gao Peiyi; Li Xiaoguang

2005-01-01

Objective: To investigate the mechanism of brain edema formation around the hematoma and the relationship between the formation of brain edema and the changes of regional cerebral blood flow after intracerebral hemorrhage (ICH) in rats, and to provide experimental basis for the clinical treatment of ICH . Methods: Seventy male Sprague-Dawley rats were randomly divided into ICH groups and sham-operated groups. ICH was produced by microinjection of 40 ul fresh autologous blood or saline into the right caudatum. Dynamic CT perfusion imaging was performed, and the parameters of regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV), and mean transit time (MTT) around the hematoma were calculated respectively. Then the rats were sacrificed, and the water content, sodium, potassium, and calcium concentrations were measured respectively. The correlative study between the water content and rCBF and rCBV were carried out. Results:The gradient of perihematomal hypoperfusion was revealed on CT perfusion maps in ICH groups. The alternation of rCBF around the hematomas were fluctuated, and rCBF reduction was most pronounced at 1 hour afer ICH, then the rCBF gradually returned, reaching the peaks at 6 hours and 24 hours after ICH, respectively. In the meantime, rCBV reduction around the hematoma was most pronounced at 1 hour after ICH. Then the rCBV gradually increased, and reaching the peak at 24 hours. The water contents were gradually increased in the ipsilateral basal ganglia in the animals sacrificed at 6, 24, and 72 hours. The accumulation of water was at its peak at 24 hours, and remained in the animals sacrificed at the 72 hours. The perihemorrhagic water contents correlated significantly with rCBV surrounding hematomas, r=0.372 (one-tailed), P<0.05. Conclusion: The perihemorrhagic brain edema results from the common effects of the blood-brain-barrier disruption, cytotoxic edema, and the accumulation of osmotically active substances. The r

Further understanding of cerebral autoregulation at the bedside : possible implications for future therapy

NARCIS (Netherlands)

Donnelly, Joseph; Aries, Marcel J.; Czosnyka, Marek

Cerebral autoregulation reflects the ability of the brain to keep the cerebral blood flow (CBF) relatively constant despite changes in cerebral perfusion pressure. It is an intrinsic neuroprotective physiological phenomenon often suggested as part of pathophysiological pathways in brain research.

Post traumatic brain perfusion SPECT analysis using reconstructed ROI maps of radioactive microsphere derived cerebral blood flow and statistical parametric mapping

OpenAIRE

Gonzalez-Brito Manuel; Solano Juan; Sanchez Pablo; Georgiou Michael F; Capille Michael; McGoron Anthony J; Kuluz John W

2008-01-01

Abstract Background Assessment of cerebral blood flow (CBF) by SPECT could be important in the management of patients with severe traumatic brain injury (TBI) because changes in regional CBF can affect outcome by promoting edema formation and intracranial pressure elevation (with cerebral hyperemia), or by causing secondary ischemic injury including post-traumatic stroke. The purpose of this study was to establish an improved method for evaluating regional CBF changes after TBI in piglets. Me...

A radical scavenger edaravone inhibits matrix metalloproteinase-9 upregulation and blood-brain barrier breakdown in a mouse model of prolonged cerebral hypoperfusion.

Science.gov (United States)

Miyamoto, Nobukazu; Pham, Loc-Duyen D; Maki, Takakuni; Liang, Anna C; Arai, Ken

2014-06-24

Matrix metalloproteinase-9 (MMP-9) plays key roles in the brain pathophysiology, especially in blood-brain barrier (BBB) breakdown. Therefore, inhibiting MMP-9 activity may be a promising therapy for protecting brains in cerebrovascular diseases. Here we show that in a mouse prolonged cerebral hypoperfusion model, a clinically proven radical scavenger edaravone suppressed MMP-9 and reduced BBB damage in cerebral white matter. Prolonged cerebral hypoperfusion was induced by bilateral common carotid artery stenosis in male adult C57BL/6J mice (10 weeks old). After 7 days of cerebral hypoperfusion, white matter region (e.g. corpus callosum) exhibited significant BBB leakage, assessed by IgG staining. Correspondingly, immunostaining and western blotting showed that MMP-9 was upregulated in the white matter. Edaravone treatment (3mg/kg, i.p. at days 0 and 3) inhibited both BBB leakage and MMP-9 increase. Under the early phase of cerebral hypoperfusion conditions, oligodendrocyte precursor cells (OPCs) mainly contribute to the MMP-9 increase, but our immunostaining data showed that very little OPCs expressed MMP-9 in the edaravone-treated animals at day 7. Therefore, in vitro studies with primary rat OPCs were conducted to examine whether edaravone would directly suppressed MMP-9 expressions in OPCs. OPC cultures were exposed to sub-lethal CoCl2 for 7 days to induce prolonged chemical hypoxic stress. Prolonged chemical hypoxic stress increased MMP-9 expression in OPCs, and radical scavenging with edaravone (10μM for 7 days) ameliorated the increase. Taken together, our proof-of-concept study demonstrates that radical scavengers may provide a potential therapeutic approach for white matter injury by suppressing BBB damage. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Oxygen, a Key Factor Regulating Cell Behavior during Neurogenesis and Cerebral Diseases.

Science.gov (United States)

Zhang, Kuan; Zhu, Lingling; Fan, Ming

2011-01-01

Oxygen is vital to maintain the normal functions of almost all the organs, especially for brain which is one of the heaviest oxygen consumers in the body. The important roles of oxygen on the brain are not only reflected in the development, but also showed in the pathological processes of many cerebral diseases. In the current review, we summarized the oxygen levels in brain tissues tested by real-time measurements during the embryonic and adult neurogenesis, the cerebral diseases, or in the hyperbaric/hypobaric oxygen environment. Oxygen concentration is low in fetal brain (0.076-7.6 mmHg) and in adult brain (11.4-53.2 mmHg), decreased during stroke, and increased in hyperbaric oxygen environment. In addition, we reviewed the effects of oxygen tensions on the behaviors of neural stem cells (NSCs) in vitro cultures at different oxygen concentration (15.2-152 mmHg) and in vivo niche during different pathological states and in hyperbaric/hypobaric oxygen environment. Moderate hypoxia (22.8-76 mmHg) can promote the proliferation of NSCs and enhance the differentiation of NSCs into the TH-positive neurons. Next, we briefly presented the oxygen-sensitive molecular mechanisms regulating NSCs proliferation and differentiation recently found including the Notch, Bone morphogenetic protein and Wnt pathways. Finally, the future perspectives about the roles of oxygen on brain and NSCs were given.

High dose infusion of activated protein C (rhAPC) fails to improve neuronal damage and cognitive deficit after global cerebral ischemia in rats.

Science.gov (United States)

Brückner, Melanie; Lasarzik, Irina; Jahn-Eimermacher, Antje; Peetz, Dirk; Werner, Christian; Engelhard, Kristin; Thal, Serge C

2013-09-13

Recent studies demonstrated anticoagulatory, antiinflammatory, antiapoptotic, and neuroprotective properties of activated protein C (APC) in rodent models of acute neurodegenerative diseases, suggesting APC as promising broad acting therapeutic agent. Unfortunately, continuous infusion of recombinant human APC (rhAPC) failed to improve brain damage following cardiac arrest in rats. The present study was designed to investigate the neuroprotective effect after global cerebral ischemia (GI) with an optimized infusion protocol. Rats were subjected to bilateral clip occlusion of the common carotid arteries (BCAO) and controlled hemorrhagic hypotension to 40 mm Hg for 14 min and a subsequent 5h-infusion of rhAPC (2mg/kg bolus+6 mg/kg/h continuous IV) or vehicle (0.9% NaCl). The dosage was calculated to maintain plasma hAPC activity at 150%. Cerebral inflammation, apoptosis and neuronal survival was determined at day 10. rhAPC infusion did not influence cortical cerebral perfusion during reperfusion and failed to reduce neuronal cell loss, microglia activation, and caspase 3 activity. Even an optimized rhAPC infusion protocol designed to maintain a high level of APC plasma activity failed to improve the sequels following GI. Despite positive reports about protective effects of APC following, e.g., ischemic stroke, the present study supports the notion that infusion of APC during the early reperfusion phase does not result in sustained neuroprotection and fails to improve outcome after global cerebral ischemia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The prognostic value of cerebral oxygenation and retrograde pressure during carotid endarterectomy

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А. А. Карпенко

2016-08-01

Full Text Available Aim: The study aimed to determine the predictive value of retrograde pressure (RP indicators and cerebral oxygenation in the evaluation of ischemic brain damage during carotid endarterectomy (CEA.Methods: This nonrandomized, prospective pilot study included 87 patients with asymptomatic stenosis greater than 70% who underwent carotid endarterectomy under general anesthesia. Brain tolerance to ischemia was determined by measuring and evaluating RP (∆rSO2 and cerebral oxygenation (rSO2 during a trial clamping of the carotid artery. Depending on the degree of reduction of cerebral oxygenation from the baseline (∆rSO2 during a trial clamping of the carotid artery, patients were divided into 3 groups: the first group (n = 35 - ∆rSO2 <9.9%, the second group (n = 35 - ∆rSO2 from 10 to 19.9%, the third group (n = 14 - ∆rSO2 ≥ 20%. The primary end-point of the study was to obtain the AUC value exceeding 0.70, which could mean a high predictive quality of research methods. Results: There were no perioperative strokes or myocardial infarctions during the study. Average time of carotid artery clamping was 28 (26-30 minutes. 3 patients who received temporary shunts were excluded from the study because of a simultaneous decrease in the rSO2 and ∆rSO2 indicators. It was found out that S-100 and NSE protein concentration in all groups did not significantly differ at different stages (p> 0.05. A temporary shutdown of blood flow in the carotid artery during CEA is accompanied by significant elevation of cerebral damage markers (S100, NSE concentration with their subsequent restoration at 3 days after surgery. ROC - analysis revealed that none of the methods for assessing cerebral ischemic tolerance (RP, ∆rSO2 and rSO2 is precise enough (AUC > 0.7 to predict brain injury during carotid endarterectomy. Satisfactory, but a poor quality (AUC< 0.7 of predicting an increase in the reference values of S-100 protein neuromarkers was demonstrated by

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

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Kristina S Sobotka

Full Text Available 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.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.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.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.

Hyperventilation, cerebral perfusion, and syncope

DEFF Research Database (Denmark)

Immink, R V; Pott, F C; Secher, N H

2014-01-01

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....

Protective effects of taurine in traumatic brain injury via mitochondria and cerebral blood flow.

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Wang, Qin; Fan, Weijia; Cai, Ying; Wu, Qiaoli; Mo, Lidong; Huang, Zhenwu; Huang, Huiling

2016-09-01

In mammalian tissues, taurine is an important natural component and the most abundant free amino acid in the heart, retina, skeletal muscle, brain, and leukocytes. This study is to examine the taurine's protective effects on neuronal ultrastructure, the function of the mitochondrial respiratory chain complex, and on cerebral blood flow (CBF). The model of traumatic brain injury (TBI) was made for SD rats by a fluid percussion device, with taurine (200 mg/kg) administered by tail intravenous injection once daily for 7 days after TBI. It was found that CBF was improved for both left and right brain at 30 min and 7 days post-injury by taurine. Reaction time was prolonged relative to the TBI-only group. Neuronal damage was prevented by 7 days taurine. Mitochondrial electron transport chain complexes I and II showed greater activity with the taurine group. The improvement by taurine of CBF may alleviate edema and elevation in intracranial pressure. Importantly taurine improved the hypercoagulable state.

Assessment of variability in cerebral vasculature for neuro-anatomical surgery planning in rodent brain

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Rangarajan, J. R.; Van Kuyck, K.; Himmelreich, U.; Nuttin, B.; Maes, F.; Suetens, P.

2011-03-01

Clinical and pre-clinical studies show that deep brain stimulation (DBS) of targeted brain regions by neurosurgical techniques ameliorate psychiatric disorder such as anorexia nervosa. Neurosurgical interventions in preclinical rodent brain are mostly accomplished manually with a 2D atlas. Considering both the large number of animals subjected to stereotactic surgical experiments and the associated imaging cost, feasibility of sophisticated pre-operative imaging based surgical path planning and/or robotic guidance is limited. Here, we spatially normalize vasculature information and assess the intra-strain variability in cerebral vasculature for a neurosurgery planning. By co-registering and subsequently building a probabilistic vasculature template in a standard space, we evaluate the risk of a user defined electrode trajectory damaging a blood vessel on its path. The use of such a method may not only be confined to DBS therapy in small animals, but also could be readily applicable to a wide range of stereotactic small animal surgeries like targeted injection of contrast agents and cell labeling applications.

Quantification of extra-cerebral and cerebral hemoglobin concentrations during physical exercise using time-domain near infrared spectroscopy.

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Auger, Héloïse; Bherer, Louis; Boucher, Étienne; Hoge, Richard; Lesage, Frédéric; Dehaes, Mathieu

2016-10-01

Fitness is known to have beneficial effects on brain anatomy and function. However, the understanding of mechanisms underlying immediate and long-term neurophysiological changes due to exercise is currently incomplete due to the lack of tools to investigate brain function during physical activity. In this study, we used time-domain near infrared spectroscopy (TD-NIRS) to quantify and discriminate extra-cerebral and cerebral hemoglobin concentrations and oxygen saturation ( SO 2 ) in young adults at rest and during incremental intensity exercise. In extra-cerebral tissue, an increase in deoxy-hemoglobin ( HbR ) and a decrease in SO 2 were observed while only cerebral HbR increased at high intensity exercise. Results in extra-cerebral tissue are consistent with thermoregulatory mechanisms to dissipate excess heat through skin blood flow, while cerebral changes are in agreement with cerebral blood flow ( CBF ) redistribution mechanisms to meet oxygen demand in activated regions during exercise. No significant difference was observed in oxy- ( HbO 2 ) and total hemoglobin ( HbT ). In addition HbO 2 , HbR and HbT increased with subject's peak power output (equivalent to the maximum oxygen volume consumption; VO 2 peak) supporting previous observations of increased total mass of red blood cells in trained individuals. Our results also revealed known gender differences with higher hemoglobin in men. Our approach in quantifying both extra-cerebral and cerebral absolute hemoglobin during exercise may help to better interpret past and future continuous-wave NIRS studies that are prone to extra-cerebral contamination and allow a better understanding of acute cerebral changes due to physical exercise.

Age-related decline in cerebral blood flow and brain atrophy

International Nuclear Information System (INIS)

Takeda, Shumpei; Matsuzawa, Taiju; Yamada, Kenji

1987-01-01

Using computed tomography, the authors studied brain atrophy during aging in 536 men and 529 women with no neurologic disturbances. They measured cerebrospinal fluid (CSF) space volume and cranial cavity volume above the level of the tentorium cerebelli and calculated a brain atrophy index. CFS space volume strated to increase significantly in the group aged from 45 to 54 years, while the BAI started to increase significantly in the group aged from 35 to 44 years in both men and women. The BAI increased exponentially with the increasing age after 25 years, continuing to increase until 75 years or more in both men and women: log BAI = -0.260 + 0.0150 x age, r = 0.707, n = 493, p < 0.001 in men; log BAI = -0.434 + 0.0162 x age, r = 0.757, n = 504, p < 0.001 in women. Using the xenon-133 inhalation method, the authors studied age-related decline in regional cerebral blood flow (regional initial slope index; rISI) in 197 men and 238 women with no neurologic disturbances, ranging in age from 19 to 88 years. The rISI values in women declined almost linearly with the advancing age from the 50s to the 80s except the 70s. The rISI values in men declined with the advancing age from the 40s to the 60s, but remained unchanged thereafter until the 80s, suggesting the existence of a threshold of rISI values. We estimated the rISI values (probable threshold of brain atrophy), the frequency under which is equivalent to the volume of brain tissues atrophying in a decade, and obtained constant values as about 32 for men and about 37 for women in the 50s, 60s and 70s. If the frequency of rISI values in the brain is distributed according to a Gaussian function and mean of rISI values decreases linearly to the increasing age, then brain tissues having rISI values below the thresholds degenerate almost exponentially with the increasing age, leading to the exponential atrophy of the brain. (J.P.N.)

Age- and Sex-Associated Changes in Cerebral Glucose Metabolism in Normal Healthy Subjects: Statistical Parametric Mapping Analysis of F-18 Fluorodeoxyglucose Brain Positron Emission Tomography

International Nuclear Information System (INIS)

Kim, In-Ju; Kim, Seong-Jang; Kim, Yong-Ki

2009-01-01

Background: The age- and sex-associated changes of brain development are unclear and controversial. Several previous studies showed conflicting results of a specific pattern of cerebral glucose metabolism or no differences of cerebral glucose metabolism in association with normal aging process and sex. Purpose: To investigate the effects of age and sex on changes in cerebral glucose metabolism in healthy subjects using fluorine-18 fluorodeoxyglucose (F-18 FDG) brain positron emission tomography (PET) and statistical parametric mapping (SPM) analysis. Material and Methods: Seventy-eight healthy subjects (32 males, mean age 46.6±18.2 years; 46 females, mean age 40.6±19.8 years) underwent F-18 FDG brain PET. Using SPM, age- and sex-associated changes in cerebral glucose metabolism were investigated. Results: In males, a negative correlation existed in several gray matter areas, including the right temporopolar (Brodmann area [BA] 38), right orbitofrontal (BA 47), left orbitofrontal gyrus (BA 10), left dorsolateral frontal gyrus (BA 8), and left insula (BA 13) areas. A positive relationship existed in the left claustrum and left thalamus. In females, negative changes existed in the left caudate body, left temporopolar area (BA 38), right orbitofrontal gyri (BA 47 and BA 10), and right dorsolateral prefrontal cortex (BA 46). A positive association was demonstrated in the left subthalamic nucleus and the left superior frontal gyrus. In white matter, an age-associated decrease in FDG uptake in males was shown in the left insula, and increased FDG uptake was found in the left corpus callosum. The female group had an age-associated negative correlation of FDG uptake only in the right corpus callosum. Conclusion: Using SPM, we found not only similar areas of brain, but also sex-specific cerebral areas of age-associated changes of FDG uptake

Age- and Sex-Associated Changes in Cerebral Glucose Metabolism in Normal Healthy Subjects: Statistical Parametric Mapping Analysis of F-18 Fluorodeoxyglucose Brain Positron Emission Tomography

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Kim, In-Ju; Kim, Seong-Jang; Kim, Yong-Ki (Dept. of Nuclear Medicine, Pusan National Univ. Hospital, Busan (Korea); Medical Research Institute, Pusan National Univ., Busan (Korea)). e-mail: growthkim@daum.net/growthkim@pusan.ac.kr)

2009-12-15

Background: The age- and sex-associated changes of brain development are unclear and controversial. Several previous studies showed conflicting results of a specific pattern of cerebral glucose metabolism or no differences of cerebral glucose metabolism in association with normal aging process and sex. Purpose: To investigate the effects of age and sex on changes in cerebral glucose metabolism in healthy subjects using fluorine-18 fluorodeoxyglucose (F-18 FDG) brain positron emission tomography (PET) and statistical parametric mapping (SPM) analysis. Material and Methods: Seventy-eight healthy subjects (32 males, mean age 46.6+-18.2 years; 46 females, mean age 40.6+-19.8 years) underwent F-18 FDG brain PET. Using SPM, age- and sex-associated changes in cerebral glucose metabolism were investigated. Results: In males, a negative correlation existed in several gray matter areas, including the right temporopolar (Brodmann area [BA] 38), right orbitofrontal (BA 47), left orbitofrontal gyrus (BA 10), left dorsolateral frontal gyrus (BA 8), and left insula (BA 13) areas. A positive relationship existed in the left claustrum and left thalamus. In females, negative changes existed in the left caudate body, left temporopolar area (BA 38), right orbitofrontal gyri (BA 47 and BA 10), and right dorsolateral prefrontal cortex (BA 46). A positive association was demonstrated in the left subthalamic nucleus and the left superior frontal gyrus. In white matter, an age-associated decrease in FDG uptake in males was shown in the left insula, and increased FDG uptake was found in the left corpus callosum. The female group had an age-associated negative correlation of FDG uptake only in the right corpus callosum. Conclusion: Using SPM, we found not only similar areas of brain, but also sex-specific cerebral areas of age-associated changes of FDG uptake

Efficacy and toxicity of whole brain radiotherapy in patients with multiple cerebral metastases from malignant melanoma

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Hauswald Henrik

2012-08-01

Full Text Available Abstract Background To retrospectively access outcome and toxicity of whole brain radiotherapy (WBRT in patients with multiple brain metastases (BM from malignant melanoma (MM. Patients and methods Results of 87 patients (median age 58 years; 35 female, 52 male treated by WBRT for BM of MM between 2000 and 2011 were reviewed. Total dose applied was either 30 Gy in 10 fractions (n = 56 or 40 Gy in 20 fractions (n = 31. All but 9 patients suffered from extra-cerebral metastases. Prior surgical resection of BM was performed in 18 patients, salvage stereotactic radiosurgery in 13 patients. Results Mean follow-up was 8 months (range, 0–57 months, the 6- and 12-months overall-(OS survival rates were 29.2% and 16.5%, respectively. The median OS was 3.5 months. In cerebral follow-up imaging 6 (11 patients showed a complete (partial remission, while 11 (17 patients had stable disease (intra-cerebral tumor progression. In comparison of total dose, the group treated with 40 Gy in 20 fractions achieved a significant longer OS (p = 0.003, median 3.1 vs. 5.6 months. Furthermore, DS-GPA score (p  Conclusion Treatment of BM from MM with WBRT is tolerated well and some remissions of BM could be achieved. An advantage for higher treatment total doses was seen. However, outcome is non-satisfying, and further improvements in treatment of BM from MM are warranted.

The protective effect of SCR(15-18) on cerebral ischemia-reperfusion injury.

Science.gov (United States)

Li, Shu; Xian, Jinhong; He, Li; Luo, Xue; Tan, Bing; Yang, Yongtao; Liu, Gaoke; Wang, Zhengqing

2011-10-01

Soluble complement receptor type 1 (sCR1), a potent inhibitor of complement activation, has been shown to protect brain cells against cerebral ischemic/reperfusion (CI/R) injury due to its decay-accelerating activity for C3/C5 convertase and co-factor activity for C3b/C4b degradation. However, the effect of short consensus repeats (SCRs) 15-18, one of active domains of sCR1 with high C3b/C4b degradability, has not been demonstrated. Here, we investigated the protective effect of recombinant SCR(15-18) protein in middle cerebral artery occlusion (MCAO)-induced focal CI/R injury. Recombinant SCR(15-18) protein was successfully expressed in Escherichia coli and refolded to its optimal bioactivity. Seventy-five Sprague-Dawley rats were randomly assigned into three groups: sham-operated group, CI/R group, and SCR(15-18)+CI/R group pretreated with 20 mg/kg SCR(15-18) protein. After 2 hours of MCAO and subsequent 24 hours of reperfusion, rats were evaluated for neurological deficits and cerebral infarction. Polymorphonuclear leukocyte accumulation, C3b deposition, and morphological changes in cerebral tissue were also estimated. SCR(15-18) pretreatment induced a 20% reduction of infarct size and an improvement of neurological function with 22·2% decrease of neurological deficit scores. Inhibition of cerebral neutrophils infiltration by SCR(15-18) was indicated from the reduction of myeloperoxidase activity in SCR(15-18)+CI/R rats. Decreased C3b deposition and improved morphological changes were also found in cerebral tissue of SCR(15-18)-treated rats. Our studies suggest a definitive moderately protective effect of SCR(15-18) against CI/R damage and provide preclinical experimental evidence supporting the possibility of using it as a small anti-complement therapeutic agent for CI/R injury therapy.

Intracranial Monitoring after Severe Traumatic Brain Injury

OpenAIRE

Donnelly, Joseph

2018-01-01

Intracranial monitoring after severe traumatic brain injury offers the possibility for early detection and amelioration of physiological insults. In this thesis, I explore cerebral insults due raised intracranial pressure, decreased cerebral perfusion pressure and impaired cerebral pressure reactivity after traumatic brain injury. In chapter 2, the importance of intracranial pressure, cerebral perfusion pressure and pressure reactivity in regulating the cerebral circulation is elucidated ...

Altered Coupling between Motion-Related Activation and Resting-State Brain Activity in the Ipsilesional Sensorimotor Cortex after Cerebral Stroke

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Jianping Hu

2017-07-01

Full Text Available Functional connectivity maps using resting-state functional magnetic resonance imaging (rs-fMRI can closely resemble task fMRI activation patterns, suggesting that resting-state brain activity may predict task-evoked activation or behavioral performance. However, this conclusion was mostly drawn upon a healthy population. It remains unclear whether the predictive ability of resting-state brain activity for task-evoked activation would change under different pathological conditions. This study investigated dynamic changes of coupling between patterns of resting-state functional connectivity (RSFC and motion-related activation in different stages of cerebral stroke. Twenty stroke patients with hand motor function impairment were involved. rs-fMRI and hand motion-related fMRI data were acquired in the acute, subacute, and early chronic stages of cerebral stroke on a 3-T magnetic resonance (MR scanner. Sixteen healthy participants were enrolled as controls. For each subject, an activation map of the affected hand was first created using general linear model analysis on task fMRI data, and then an RSFC map was determined by seeding at the peak region of hand motion activation during the intact hand task. We then measured the extent of coupling between the RSFC maps and motion-related activation maps. Dynamic changes of the coupling between the two fMRI maps were estimated using one-way repeated measures analysis of variance across the three stages. Moreover, imaging parameters were correlated with motor performances. Data analysis showed that there were different coupling patterns between motion-related activation and RSFC maps associating with the affected motor regions during the acute, subacute, and early chronic stages of stroke. Coupling strengths increased as the recovery from stroke progressed. Coupling strengths were correlated with hand motion performance in the acute stage, while coupling recovery was negatively correlated with the recovery

Cerebral carbohydrate cost of physical exertion in humans

DEFF Research Database (Denmark)

Dalsgaard, Mads K; Ogoh, Shigehiko; Dawson, Ellen A

2004-01-01

Above a certain level of cerebral activation the brain increases its uptake of glucose more than that of O(2), i.e., the cerebral metabolic ratio of O(2)/(glucose + 12 lactate) decreases. This study quantified such surplus brain uptake of carbohydrate relative to O(2) in eight healthy males who...... to exhaustion (15.8 +/- 1.7 min; P carbohydrate was not substantiated...... and, consequently, exhaustive exercise involves a brain surplus carbohydrate uptake of a magnitude comparable with its glycogen content....

The maturational theory of brain development and cerebral excitability in the multifactorially inherited manic-depressive psychosis and schizophrenia.

Science.gov (United States)

Saugstad, L F

1994-12-01

An association has been established between the multifactorially inherited rate of physical maturation and the final step in brain development, when some 40% of synapses are eliminated. This may imply that similarly to endocrine disease entities, we have cerebral disease entities at the extremes of the maturational rate continuum. The restriction of prepubertal pruning to excitatory synapses leaving the number of inhibitory ones fairly constant, implies changes in cerebral excitability as a function of rate of maturation (age at puberty). In early maturation there will be an excess in excitatory drive due to prematurely abridged pruning, which compounds a synchronization tendency inherent in excessive synaptic density. Lowering excitatory level with antiepileptics is hypothesized to be a logical treatment in this type of brain dysfunction. In late maturation, a deficit in excitatory drive due to failure to shut down the pruning process associated with a tendency to the breakdown of circuitry and desynchronization, adds to a similar adversity inherent in reduced synaptic density. Raising the excitatory level with convulsants is hypothesized to be the treatment for this type of CNS dysfunction. The maturational theory of Kraepelin's psychoses holds that they are naturally occurring contrasting chemical signaling disorders in the brain at the extremes of the maturational rate continuum: manic depressive psychosis is a disorder of the early maturer and comprises raised cerebral excitability and a raised density of synapses. This is successfully treated with anti-epileptics like sodium valproate and carbamazepin. Schizophrenia is a disorder in late maturation with reduced cerebral excitability and reduced synaptic density. This is accordingly treated with convulsants such as typical and atypical neuroleptics. However, the conventional effective treatments in both disorders act on inhibition only by either lowering or raising inhibitory level. While the neuroleptics

Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

International Nuclear Information System (INIS)

Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

1987-01-01

Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for 82 Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity

Radiopharmaceuticals for brain - SPECT

International Nuclear Information System (INIS)

Moretti, J.L.

1992-01-01

Perfusion tracers for brain SPECT imaging suitable for regional cerebral blood flow measurement and regional cerebral blood volume determination, with respect to their ability to pass the blood-brain-barrier, are described. Problems related t the use of specific radiotracers to map receptors distribution in the brain are also discussed in this lecture. 9 figs, 6 tabs

Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

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Rashedinia, Marzieh; Lari, Parisa [Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Abnous, Khalil, E-mail: Abnouskh@mums.ac.r [Pharmaceutical Research Center, Department of Medicinal Chemistry, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of); Hosseinzadeh, Hossein, E-mail: Hosseinzadehh@mums.ac.ir [Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad (Iran, Islamic Republic of)

2013-10-01

Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased.

Proteomic analysis of rat cerebral cortex following subchronic acrolein toxicity

International Nuclear Information System (INIS)

Rashedinia, Marzieh; Lari, Parisa; Abnous, Khalil; Hosseinzadeh, Hossein

2013-01-01

Acrolein, a member of reactive α,β-unsaturated aldehydes, is a major environmental pollutant. Acrolein is also produced endogenously as a toxic by-product of lipid peroxidation. Because of high reactivity, acrolein may mediate oxidative damages to cells and tissues. It has been shown to be involved in a wide variety of pathological states including pulmonary, atherosclerosis and neurodegenerative diseases. In this study we employed proteomics approach to investigate the effects of subchronic oral exposures to 3 mg/kg of acrolein on protein expression profile in the brain of rats. Moreover effects of acrolein on malondialdehyde (MDA) levels and reduced glutathione (GSH) content were investigated. Our results revealed that treatment with acrolein changed levels of several proteins in diverse physiological process including energy metabolism, cell communication and transport, response to stimulus and metabolic process. Interestingly, several differentially over-expressed proteins, including β-synuclein, enolase and calcineurin, are known to be associated with human neurodegenerative diseases. Changes in the levels of some proteins were confirmed by Western blot. Moreover, acrolein increases the level of MDA, as a lipid peroxidation biomarker and decreased GSH concentrations, as a non-enzyme antioxidant in the brain of acrolein treated rats. These findings suggested that acrolein induces the oxidative stress and lipid peroxidation in the brain, and so that may contribute to the pathophysiology of neurological disorders. - Highlights: • Acrolein intoxication increased lipid peroxidation and deplete GSH in rat brain. • Effect of acrolein on protein levels of cerebral cortex was analyzed by 2DE-PAGE. • Levels of a number of proteins with different biological functions were increased

Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

Science.gov (United States)

Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

2015-01-01

Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI.

Cellular consequences of sleep deprivation in the brain.

Science.gov (United States)

Cirelli, Chiara

2006-10-01

Several recent studies have used transcriptomics approaches to characterize the molecular correlates of sleep, waking, and sleep deprivation. This analysis may help in understanding the benefits that sleep brings to the brain at the cellular level. The studies are still limited in number and focus on a few brain regions, but some consistent findings are emerging. Sleep, spontaneous wakefulness, short-term, and long-term sleep deprivation are each associated with the upregulation of hundreds of genes in the cerebral cortex and other brain areas. In fruit flies as well as in mammals, three categories of genes are consistently upregulated during waking and short-term sleep deprivation relative to sleep. They include genes involved in energy metabolism, synaptic potentiation, and the response to cellular stress. In the rat cerebral cortex, transcriptional changes associated with prolonged sleep loss differ significantly from those observed during short-term sleep deprivation. However, it is too early to draw firm conclusions relative to the molecular consequences of sleep deprivation, and more extensive studies using DNA and protein arrays are needed in different species and in different brain regions.

Systematization, distribution and territory of the caudal cerebral artery on the brain's surface of the turkey (Meleagris gallopavo

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Amarílis Díaz de Carvalho

2014-10-01

Full Text Available Thirty Meleagris gallopavo heads with their neck segments were used. Animals were contained and euthanized with the association of mebezonium iodide, embutramide and tetracaine hydrochloride (T 61, Intervet by intravenous injection. The arterial system was rinsed with cold saline solution (15°C, with 5000IU heparin and filled with red-colored latex. The samples were fixed in 20% formaldehyde for seven days. The brains were removed with a segment of cervical spinal cord and after, the dura-mater was removed and the arteries dissected. The cerebral carotid arteries, after the intercarotid anastomosis, were projected around the hypophysis, until they reached the tuber cinereum and divided into their terminal branches, the caudal branch and the rostral branch. The rostral branch was projected rostrolateralwards and gave off, in sequence, two collateral branches, the caudal cerebral and the middle cerebral arteries and the terminal branch was as cerebroethmoidal artery. The caudal cerebral artery of one antimere formed the interhemispheric artery, which gave off dorsal hemispheric branches to the convex surface of both antimeres. Its dorsal tectal mesencephalic branch, of only one antimere, originated the dorsal cerebellar artery. In the interior of the cerebral transverse fissure, after the origin of the dorsal tectal mesencephalic artery, the caudal cerebral artery emitted occipital hemispheric branches, pineal branches and medial hemispheric branches, on both antimeres. The caudal cerebral artery's territory comprehended the entire surface of the dorsal hemioptic lobe, the rostral surface of the cerebellum, the diencephalic structures, the caudal pole and the medial surface of the cerebral hemisphere and in the convex surface, the sagittal eminence except for its most rostral third. Due to the asymmetry found in the caudal cerebral arteries' ramifications, the models were classified into three types and their respective subtypes.

Post traumatic brain perfusion SPECT analysis using reconstructed ROI maps of radioactive microsphere derived cerebral blood flow and statistical parametric mapping

Directory of Open Access Journals (Sweden)

Gonzalez-Brito Manuel

2008-02-01

Full Text Available Abstract Background Assessment of cerebral blood flow (CBF by SPECT could be important in the management of patients with severe traumatic brain injury (TBI because changes in regional CBF can affect outcome by promoting edema formation and intracranial pressure elevation (with cerebral hyperemia, or by causing secondary ischemic injury including post-traumatic stroke. The purpose of this study was to establish an improved method for evaluating regional CBF changes after TBI in piglets. Methods The focal effects of moderate traumatic brain injury (TBI on cerebral blood flow (CBF by SPECT cerebral blood perfusion (CBP imaging in an animal model were investigated by parallelized statistical techniques. Regional CBF was measured by radioactive microspheres and by SPECT 2 hours after injury in sham-operated piglets versus those receiving severe TBI by fluid-percussion injury to the left parietal lobe. Qualitative SPECT CBP accuracy was assessed against reference radioactive microsphere regional CBF measurements by map reconstruction, registration and smoothing. Cerebral hypoperfusion in the test group was identified at the voxel level using statistical parametric mapping (SPM. Results A significant area of hypoperfusion (P Conclusion The suitability of SPM for application to the experimental model and ability to provide insight into CBF changes in response to traumatic injury was validated by the SPECT SPM result of a decrease in CBP at the left parietal region injury area of the test group. Further study and correlation of this characteristic lesion with long-term outcomes and auxiliary diagnostic modalities is critical to developing more effective critical care treatment guidelines and automated medical imaging processing techniques.

Experimental model considerations for the study of protein-energy malnutrition co-existing with ischemic brain injury.

Science.gov (United States)

Prosser-Loose, Erin J; Smith, Shari E; Paterson, Phyllis G

2011-05-01

Protein-energy malnutrition (PEM) affects ~16% of patients at admission for stroke. We previously modeled this in a gerbil global cerebral ischemia model and found that PEM impairs functional outcome and influences mechanisms of ischemic brain injury and recovery. Since this model is no longer reliable, we investigated the utility of the rat 2-vessel occlusion (2-VO) with hypotension model of global ischemia for further study of this clinical problem. Male, Sprague-Dawley rats were exposed to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7d prior to either global ischemia or sham surgery. PEM did not significantly alter the hippocampal CA1 neuron death (p = 0.195 by 2-factor ANOVA) or the increase in dendritic injury caused by exposure to global ischemia. Unexpectedly, however, a strong trend was evident for PEM to decrease the consistency of hippocampal damage, as shown by an increased incidence of unilateral or no hippocampal damage (p=0.069 by chi-square analysis). Although PEM caused significant changes to baseline arterial blood pH, pO(2), pCO(2), and fasting glucose (p0.269). Intra-ischemic tympanic temperature and blood pressure were strictly and equally controlled between ischemic groups. We conclude that co-existing PEM confounded the consistency of hippocampal injury in the 2-VO model. Although the mechanisms responsible were not identified, this model of brain ischemia should not be used for studying this co-morbidity factor. © 2011 Bentham Science Publishers Ltd.

Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.

Science.gov (United States)

Moro, Nobuhiro; Ghavim, Sima; Harris, Neil G; Hovda, David A; Sutton, Richard L

2013-10-16

Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand. © 2013 Elsevier B.V. All rights reserved.

Cerebral edema associated with acute hepatic failure.

OpenAIRE

Fujiwara, Masachika; Watanabe, Akiharu; Yamauchi, Yasuhiko; Hashimoto, Makoto; Nakatsukasa, Harushige; Kobayashi, Michio; Higashi, Toshihiro; Nagashima, Hideo

1985-01-01

The clinicopathological findings of cerebral edema were investigated in patients with acute hepatic failure autopsied at Okayama University Hospital between 1970 and 1980 retrospectively. Nine (64%) of 14 hepatic failure cases were found to have cerebral edema during a post-mortem examination of the brain. Clinical features of the patients with cerebral edema were not significantly different from those of the patients without cerebral edema. However, general convulsions were observed more fre...

The Coupling of Cerebral Metabolic Rate of Glucose and Cerebral Blood Flow In Vivo

DEFF Research Database (Denmark)

Hasselbalch, Steen; Paulson, Olaf Bjarne

2012-01-01

The energy supplied to the brain by metabolic substrate is largely utilized for maintaining synaptic transmission. In this regulation cerebral blood flow and glucose consumption is tightly coupled as well in the resting condition as during activation. Quantification of cerebral blood flow...... not used for aerobic metabolism. Although some of the excess glucose uptake can be explained by lactate production, this phenomenon can still not account for the excess glucose uptake. Thus, more complex metabolic patterns in the brain might be reflected in the excess glucose uptake during activation......, and especially temporal relationships must be taken into account. What triggers the flow increase during functional brain activation is not entirely elucidated. The demand for excess glucose uptake may be important and a possible oxygen deficit in tissue distant from the capillaries is probably of minor...

Cerebral venous angiomas

International Nuclear Information System (INIS)

Agnoli, A.L.; Hildebrandt, G.

1985-01-01

Clinical symptoms and radiological signs in 15 patients with cerebral venous malformations are presented and the diagnostic problems discussed. The circulation time in combination with cerebral malformations and angiomas of the scalp are described. CT findings in cases of venous malformations of the brain stem are evaluated. Spot-like enhancement, as well as sharply demarcated round shaped enhancement are characteristic for venous angiomas. Cavernous angiomas usually present as homogenous or inhomogenous round shaped enhanced areas. (Author)

Cerebral oximetry in preterm infants

DEFF Research Database (Denmark)

Greisen, Gorm; Andresen, Bjørn; Plomgaard, Anne Mette

2016-01-01

Preterm birth constitutes a major cause of death before 5 years of age and it is a major cause of neurodevelopmental impairment across the world. Preterm infants are most unstable during the transition between fetal and newborn life during the first days of life and most brain damage occurs...... in this period. The brain of the preterm infant is accessible for tissue oximetry by near-infrared spectroscopy. Cerebral oximetry has the potential to improve the long-term outcome by helping to tailor the support of respiration and circulation to the individual infant's needs, but the evidence is still lacking....... The goals for research include testing the benefit and harms of cerebral oximetry in large-scale randomized trials, improved definition of the hypoxic threshold, better understanding the effects of intensive care on cerebral oxygenation, as well as improved precision of oximeters and calibration among...

Guideline of procedures 2003 for the gammagraphic study of brain death; Guia de procedimientos 2003 para el estudio gammagrafico de muerte cerebral

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Mora R, R.A. [Instituto Nacional de Pediatria, Mexico D.F. (Mexico)

2003-07-01

The diagnosis of brain death is a clinical diagnosis that is sometimes made with the help of cerebral perfusion scintigraphy. It is important that all physicians be knowledgeable about the clinical requirements for the diagnosis of brain death, especially the need to establish irreversible cessation of all function of the cerebrum and brain stem. Institutions performing scintigraphy for the evaluation of possible brain death should develop clinical guidelines and procedures for the clinical diagnosis that incorporate both clinical evaluations and the integration of ancillary tests such as perfusion scintigraphy. (Author)

In vitro glutathione peroxidase mimicry of ebselen is linked to its oxidation of critical thiols on key cerebral suphydryl proteins - A novel component of its GPx-mimic antioxidant mechanism emerging from its thiol-modulated toxicology and pharmacology.

Science.gov (United States)

Kade, I J; Balogun, B D; Rocha, J B T

2013-10-25

The antioxidant mechanism of ebselen in rats brain is largely linked with its glutathione peroxidase (GPx) rather than its peroxiredoxin mimicry ability. However, the precise molecular dynamics between the GPx-mimicry of ebselen and thiol utilization is yet to be fully clarified and thus still open. Herein, we investigated the influence of dithiothreitol (DTT) on the antioxidant action of ebselen against oxidant-induced cerebral lipid peroxidation and deoxyribose degradation. Furthermore, the critical inhibitory concentrations of ebselen on the activities of sulphydryl enzymes such as cerebral sodium pump, δ-aminolevulinic acid dehydratase (δ-ALAD) and lactate dehydrogenase (LDH) were also investigated. We observe that ebselen (at ≥42 μM) markedly inhibited lipid peroxidation in the presence and absence of DTT, whereas it inhibited deoxyribose degradation only in the presence of DTT. Furthermore, under in vitro conditions, ebselen inhibited the thiol containing enzymes; cerebral sodium pump (at ≥40 μM), δ-ALAD (≥10 μM) and LDH (≥1 μM) which were either prevented or reversed by DTT. However, the inhibition of the activities of these sulphydryl proteins in diabetic animals was prevented by ebselen. Summarily, it is apparent that the effective in vitro inhibitory doses of ebselen on the activity of the sulphydryl proteins are far less than its antioxidant doses. In addition, the presence of DTT is evidently a critical requirement for ebselen to effect its antioxidant action against deoxyribose degeradation and not lipid peroxidation. Consequently, we conclude that ebselen possibly utilizes available thiols on sulphydryl proteins to effect its GPx mimicry antioxidant action against lipid peroxidation in rat brain homogenate. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

CALHM1 deficiency impairs cerebral neuron activity and memory flexibility in mice.

Science.gov (United States)

Vingtdeux, Valérie; Chang, Eric H; Frattini, Stephen A; Zhao, Haitian; Chandakkar, Pallavi; Adrien, Leslie; Strohl, Joshua J; Gibson, Elizabeth L; Ohmoto, Makoto; Matsumoto, Ichiro; Huerta, Patricio T; Marambaud, Philippe

2016-04-12

CALHM1 is a cell surface calcium channel expressed in cerebral neurons. CALHM1 function in the brain remains unknown, but recent results showed that neuronal CALHM1 controls intracellular calcium signaling and cell excitability, two mechanisms required for synaptic function. Here, we describe the generation of Calhm1 knockout (Calhm1(-/-)) mice and investigate CALHM1 role in neuronal and cognitive functions. Structural analysis revealed that Calhm1(-/-) brains had normal regional and cellular architecture, and showed no evidence of neuronal or synaptic loss, indicating that CALHM1 deficiency does not affect brain development or brain integrity in adulthood. However, Calhm1(-/-) mice showed a severe impairment in memory flexibility, assessed in the Morris water maze, and a significant disruption of long-term potentiation without alteration of long-term depression, measured in ex vivo hippocampal slices. Importantly, in primary neurons and hippocampal slices, CALHM1 activation facilitated the phosphorylation of NMDA and AMPA receptors by protein kinase A. Furthermore, neuronal CALHM1 activation potentiated the effect of glutamate on the expression of c-Fos and C/EBPβ, two immediate-early gene markers of neuronal activity. Thus, CALHM1 controls synaptic activity in cerebral neurons and is required for the flexible processing of memory in mice. These results shed light on CALHM1 physiology in the mammalian brain.

Brain alpha- and beta-globin expression after intracerebral hemorrhage

OpenAIRE

He, Yangdong; Hua, Ya; Lee, Jin-Yul; Liu, Wenquan; Keep, Richard F; Wang, Michael M.; Xi, Guohua

2010-01-01

Our recent study has demonstrated that hemoglobin (Hb) is present in cerebral neurons and neuronal Hb is inducible after cerebral ischemia. In the present study, we examined the effects of intracerebral hemorrhage (ICH) on the mRNA levels of the α-globin (HbA) and the β-globin (HbB) components of Hb and Hb protein in the brain in vivo and in vitro. In vivo, male Sprague-Dawley rats received either a needle insertion (sham) or an infusion of autologous whole blood into the basal ganglia and we...

[Acid-base equilibrium and the brain].

Science.gov (United States)

Rabary, O; Boussofara, M; Grimaud, D

1994-01-01

In physiological conditions, the regulation of acid-base balance in brain maintains a noteworthy stability of cerebral pH. During systemic metabolic acid-base imbalances cerebral pH is well controlled as the blood/brain barrier is slowly and poorly permeable to electrolytes (HCO3- and H+). Cerebral pH is regulated by a modulation of the respiratory drive, triggered by the early alterations of interstitial fluid pH, close to medullary chemoreceptors. As blood/brain barrier is highly permeable to Co2, CSF pH is corrected in a few hours, even in case of severe metabolic acidosis and alkalosis. Conversely, during ventilatory acidosis and alkalosis the cerebral pH varies in the same direction and in the same range than blood pH. Therefore, the brain is better protected against metabolic than ventilatory acid-base imbalances. Ventilatory acidosis and alkalosis are able to impair cerebral blood flow and brain activity through interstitial pH alterations. During respiratory acidosis, [HCO3-] increases in extracellular fluids to control cerebral pH by two main ways: a carbonic anhydrase activation at the blood/brain and blood/CSF barriers level and an increase in chloride shift in glial cells (HCO3- exchanged for Cl-). During respiratory alkalosis, [HCO3-] decreases in extracellular fluids by the opposite changes in HCO3- transport and by an increase in lactic acid synthesis by cerebral cells. The treatment of metabolic acidosis with bicarbonates may induce a cerebral acidosis and worsen a cerebral oedema during ketoacidosis. Moderate hypocapnia carried out to treat intracranial hypertension is mainly effective when cerebral blood flow is high and vascular CO2 reactivity maintained. Hypocapnia may restore an altered cerebral blood flow autoregulation. Instrumental hypocapnia requires a control of cerebral perfusion pressure and cerebral arteriovenous difference for oxygen, to select patients for whom this kind of treatment may be of benefit, to choose the optimal level of

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

Science.gov (United States)

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

2014-09-01

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

Cerebral fat embolism

International Nuclear Information System (INIS)

Sakamoto, Toshihisa; Sawada, Yusuke; Yukioka, Tetsuo; Nishide, Kazuyuki; Yoshioka, Toshiharu

1982-01-01

A case of cerebral fat embolism is reported. A 18-year-old patient with multiple bone fractures was in semiconma immediately after an injury. Brain CT showed no brain swelling or intracranial hematoma. Hypoxemia and alcoholemia were noted on admission, which returned to normal without improvement of consciousness level. In addition, respiratory symptoms with positive radiographic changes, tachycardia, pyrexia, sudden drop in hemoglobin level, and sudden thrombocytopenia developed. These symptoms were compatible with Gurd's criteria of systemic fat embolism. Eight days after injury, multiple low density areas appeared on CT and disappeared within the subsequent two weeks, and subdural effusion with cerebral atrophy developed. These CT findings were not considered due to cerebral trauma. Diagnosis of cerebral fat embolism was made. The subdural effusion was drained. Neurologic and pulmonary recoveries took place slowly and one month following the injury the patient became alert and exhibited fully coordinated limb movement. The CT scans of the present case well corresponded with hitherto reported pathological findings. Petechiae in the white matter must have developed on the day of injury, which could not be detected by CT examination. It is suggested that some petechial regions fused to purpuras and then gradually resolved when they were detected as multiple low density areas on CT. CT in the purpuras phase would have shown these lesions as high density areas. These lesions must have healed with formation of tiny scars and blood pigment which were demonstrated as the disappearance of multiple low density areas by CT examination. Cerebral atrophy and subsequent subdural effusion developed as a result of demyelination. The patient took the typical clinical course of cerebral fat embolism and serial CT scans served for its assessment. (author)

Brain metastases from colorectal cancer

DEFF Research Database (Denmark)

Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

2001-01-01

Brain metastases from colorectal cancer are rare. The prognosis for patients with even a single resectable brain metastasis is poor. A case of surgically treated cerebral metastasis from a rectal carcinoma is reported. The brain tumour was radically resected. However, cerebral, as well...... as extracerebral, disease recurred 12 months after diagnosis. Surgical removal of colorectal metastatic brain lesions in selected cases results in a longer survival time....

New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain.

Science.gov (United States)

Venkat, Poornima; Chopp, Michael; Chen, Jieli

2016-06-30

The brain has high metabolic and energy needs and requires continuous cerebral blood flow (CBF), which is facilitated by a tight coupling between neuronal activity, CBF, and metabolism. Upon neuronal activation, there is an increase in energy demand, which is then met by a hemodynamic response that increases CBF. Such regional CBF increase in response to neuronal activation is observed using neuroimaging techniques such as functional magnetic resonance imaging and positron emission tomography. The mechanisms and mediators (eg, nitric oxide, astrocytes, and ion channels) that regulate CBF-metabolism coupling have been extensively studied. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions between the neurons, vascular components, and glial cells in the brain. It is compromised under disease states such as stroke, diabetes, hypertension, dementias, and with aging, all of which trigger a cascade of inflammatory responses that exacerbate brain damage. Hence, tight regulation and maintenance of neurovascular coupling is central for brain homeostasis. This review article also discusses the waste clearance pathways in the brain such as the glymphatic system. The glymphatic system is a functional waste clearance pathway that removes metabolic wastes and neurotoxins from the brain along paravascular channels. Disruption of the glymphatic system burdens the brain with accumulating waste and has been reported in aging as well as several neurological diseases.

The Selfish Brain: Stress and Eating Behavior

Directory of Open Access Journals (Sweden)

Achim ePeters

2011-05-01

Full Text Available The brain occupies a special hierarchical position in human energy metabolism. If cerebral homeostasis is threatened, the brain behaves in a "selfish" manner by competing for energy resources with the body. Here we present a logistic approach, which is based on the principles of supply and demand known from economics. In this "cerebral supply chain" model, the brain constitutes the final consumer. In order to illustrate the operating mode of the cerebral supply chain, we take experimental data which allow to assess the supply, demand and need of the brain under conditions of psychosocial stress. The experimental results show that the brain under conditions of psychosocial stress actively demands energy from the body, in order to cover its increased energy needs. The data demonstrate that the stressed brain uses a mechanism referred to as "cerebral insulin suppression" to limit glucose fluxes into peripheral tissue (muscle, fat and to enhance cerebral glucose supply. Furthermore psychosocial stress elicits a marked increase in eating behavior in the post-stress phase. Subjects ingested more carbohydrates without any preference for sweet ingredients. These experimentally observed changes of cerebral demand, supply and need are integrated into a logistic framework describing the supply chain of the selfish brain.

Cerebral cartography and connectomics.

Science.gov (United States)

Sporns, Olaf

2015-05-19

Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes

Science.gov (United States)

Shimabukuro, Marilia Kimie; Langhi, Larissa Gutman Paranhos; Cordeiro, Ingrid; Brito, José M.; Batista, Claudia Maria de Castro; Mattson, Mark P.; de Mello Coelho, Valeria

2016-01-01

We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN+ LLC. Some cortical NeuN+ neurons, GFAP+ glia limitans astrocytes, Iba-1+ microglia and S100β+ ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes. PMID:27029648

Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes.

Science.gov (United States)

Shimabukuro, Marilia Kimie; Langhi, Larissa Gutman Paranhos; Cordeiro, Ingrid; Brito, José M; Batista, Claudia Maria de Castro; Mattson, Mark P; Mello Coelho, Valeria de

2016-03-31

We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN(+) LLC. Some cortical NeuN(+) neurons, GFAP(+) glia limitans astrocytes, Iba-1(+) microglia and S100β(+) ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes.

Response of rat brain protein synthesis to ethanol and sodium barbital

International Nuclear Information System (INIS)

Tewari, S.; Greenberg, S.A.; Do, K.; Grey, P.A.

1987-01-01

Central nervous system (CNS) depressants such as ethanol and barbiturates under acute or chronic conditions can induce changes in rat brain protein synthesis. While these data demonstrate the individual effects of drugs on protein synthesis, the response of brain protein synthesis to alcohol-drug interactions is not known. The goal of the present study was to determine the individual and combined effects of ethanol and sodium barbital on brain protein synthesis and gain an understanding of the mechanisms by which these alterations in protein synthesis are produced. Specifically, the in vivo and in vitro effects of sodium barbital (one class of barbiturates which is not metabolized by the hepatic tissue) were examined on brain protein synthesis in rats made physically dependent upon ethanol. Using cell free brain polysomal systems isolated from Control, Ethanol and 24 h Ethanol Withdrawn rats, data show that sodium barbital, when intubated intragastrically, inhibited the time dependent incorporation of 14 C) leucine into protein by all three groups of ribosomes. Under these conditions, the Ethanol Withdrawn group displayed the largest inhibition of the 14 C) leucine incorporation into protein when compared to the Control and Ethanol groups. In addition, sodium barbital when added at various concentrations in vitro to the incubation medium inhibited the incorporation of 14 C) leucine into protein by Control and Ethanol polysomes. The inhibitory effects were also obtained following preincubation of ribosomes in the presence of barbital but not cycloheximide. Data suggest that brain protein synthesis, specifically brain polysomes, through interaction with ethanol or barbital are involved in the functional development of tolerance. These interactions may occur through proteins or polypeptide chains or alterations in messenger RNA components associated with the ribosomal units

Magnetization transfer on T2-weighted image : magnetization Transfer ratios in normal brain and cerebral lesions

Energy Technology Data Exchange (ETDEWEB)

Lim, Myung Kwan; Roh, Hong Gee; Suh, Chang Hae; Cho, Young Kook; Kim, Hyung Jin; Kim, Jin Hee; Kim, Sung Tae; Choi, Sung Kyu [Inha Univ. College of Medicine, Incheon (Korea, Republic of)

1998-07-01

To evaluate the magnetization transfer ratio(MTR) of various normal structures and pathologic lesions, as seen on magnetization transfer T2-weighted images (MT+T2WI). Materials and Methods : In ten normal volunteers, T2-weighted images without MT (MT-T2WI) and with MT(MT+T2WI) were obtained. Off-set pulses used in MT+T2WI were 400, 600, 1000, 1500, and 2000Hz. In 60 clinical cases infarction(n=10), brain tumors(n=5), traumatic hematomas(n=5), other hematomas(n=3) vascular malformation(n=2) white matter disease(n=2) normal(n=31) and others(n=2), both MT-T2WI and MT+T2WI images were obtained using an off-set pulse of 600 Hz. In all volunteers and patients, MTR in various normal brain parenchyma and abnormal areas was measured. Results : The MTRs of white and gray matter were 48% and 45% respectively at 400 Hz, 26% and 22% at 600Hz, 12% and 11% of 1000Hz, 10% and 9% 1500HZ, and 9% and 8% at 2000Hz of RF. The MTR of CSF was 43% at 400 Hz of off-resonance RF, while the contrast resolution of T2WI was poor. An off-resonance of 600Hz appeared to be the optimal frequency. In diseased areas,MTRs varied but were usually similar to or lower than those of brain parenchyma. Conclusion : The optimal off-resonance RF on MT+T2WI appears to be 600 Hz for relatively high MTR of brain parenchyma and low MTR of CSF,in which MTRs of white and gray matter were 26% and 22%, respectively, of 600Hz off-set pulse. The MTRs of cerebral lesions varied and further studies of various cerebral lesions are needed.

Cerebral cartography and connectomics

OpenAIRE

Sporns, Olaf

2015-01-01

Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamic...

Cerebral imaging in pediatrics

Energy Technology Data Exchange (ETDEWEB)

Gordon, I [London, Great Ormond Street Hospital for Children (United Kingdom)

1998-06-01

Radioisotope brain imaging has focused mainly on regional cerebral blood flow (rCBF). However the use of ligand which go to specific receptor sites is being introduced in pediatrics, mainly psychiatry. rCBF is potentially available in many institutions, especially with the availability of multi-headed gamma cameras. The use of this technique in pediatrics requires special attention to detail in the manner of data acquisition and handling the child. The interpretation of the rCBF study in a child requires knowledge of normal brain maturation. The major clinical use in pediatrics is epilepsy because of the advances in surgery and the frequency of complex partial seizures. Other indications in pediatric neurology include brain death, acute neurological loss including stroke, language disorders, cerebral palsy, hypertension due to renovascular disease, traumatic brain injury and migraine. There are pediatric physiological conditions in which rCBF has been undertaken, these include anorexia nervosa, autism, Gilles de la Tourette syndrome (GTS) and attention deficit disorder-hyperactivity (ADHD). Research using different ligands to specific receptor sites will also be reviewed in pediatrics.

Cerebral imaging in pediatrics

International Nuclear Information System (INIS)

Gordon, I.

1998-01-01

Radioisotope brain imaging has focused mainly on regional cerebral blood flow (rCBF). However the use of ligand which go to specific receptor sites is being introduced in pediatrics, mainly psychiatry. rCBF is potentially available in many institutions, especially with the availability of multi-headed gamma cameras. The use of this technique in pediatrics requires special attention to detail in the manner of data acquisition and handling the child. The interpretation of the rCBF study in a child requires knowledge of normal brain maturation. The major clinical use in pediatrics is epilepsy because of the advances in surgery and the frequency of complex partial seizures. Other indications in pediatric neurology include brain death, acute neurological loss including stroke, language disorders, cerebral palsy, hypertension due to renovascular disease, traumatic brain injury and migraine. There are pediatric physiological conditions in which rCBF has been undertaken, these include anorexia nervosa, autism, Gilles de la Tourette syndrome (GTS) and attention deficit disorder-hyperactivity (ADHD). Research using different ligands to specific receptor sites will also be reviewed in pediatrics

Systematization, description and territory of the caudal cerebral artery of the brain in broad-snouted Caiman (Caiman latirostris

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Lygia Almeida

2011-09-01

Full Text Available Thirty heads with the neck segment of Caiman latirostris were used. The animals were provided from a creation center called Mister Caiman, under the authorization of the Brazilian Institute of Environment and Renewable Natural Resources (Ibama. Animals were sacrificed according to the slaughtering routine of the abattoir, and the heads were sectioned at the level of the third cervical vertebra. The arterial system was washed with cold saline solution, with drainage through jugular veins. Subsequently, the system was filled with red colored latex injection. Pieces were than fixed in 20% formaldehyde, for seven days. The brains were removed, with a spinal cord segment, the duramater removed and the arteries dissected. At the level of the hypophysis, the internal carotid artery gave off a rostral branch, and a short caudal branch, continuing, naturally, as the caudal cerebral artery. This artery projected laterodorsalwards and, as it overpassed the optic tract, gave off its I (the first central branch. Penetrated in the cerebral transverse fissure, emitting the diencephalic artery and next its II (second central branch. Still inside the fissure, originated occipital hemispheric branches and a pineal branch. Emerged from the cerebral transverse fissure, over the occipital pole of the cerebral hemisphere. Projected rostralwards, sagital to the cerebral longitudinal fissure, as interhemispheric artery. This artery gave off medial and convex hemispheric branches to the respective surfaces of the cerebral hemispheres, anastomosed with its contralateral homologous, forming the common ethmoidal artery. This artery entered the fissure between the olfactory peduncles, emerging ventrally and dividing into ethmoidal arteries, right and left, which progressed towards the nasal cavities, vascularizing them. The territory of the caudal cerebral artery included the most caudal area of the base of the cerebral hemisphere, its convex surface, the olfactory

Cerebral vasculitis associated with Schistosoma mansoni infection

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Camuset Guillaume

2012-09-01

Full Text Available Abstract Background Cerebral involvement in schistosomiasis is not rare, but it is underdiagnosed because of the lack of clinical suspicion and the frequency of asymptomatic forms. Neurologic complications are generally supported by granuloma formation around ectopic eggs which have migrated to the brain. Moreover, vascular lesions and cerebral arteritis have been well documented in histopathological studies. Nevertheless, cerebral vasculitis in later stages of the Schistosoma mansoni infection have not yet been described in living subjects. Case presentation A 28-year-old french woman had a stroke linked with cerebral vasculitis, 6 monthes after returning from Burkina-Faso. At the same time, a S. mansoni disseminated infection was diagnosed. She suffered from a new stroke after undertaking praziquantel therapy, which lead us to associate the S. mansoni infection and cerebral vasculitis. Conclusion This is the first report of such association, since cerebral vasculitis has never been described in later stages of the S. mansoni infection. Although the causal link between the two pathologies could not be proved, we suggest that S. mansoni is able to cause severe vascular damage in cerebral vessels. Schistosomiasis must be investigated in the event of a brain infarct in young people, particularly in patients originating or returning from an endemic area.

MRI assessment of cerebral blood volume in patients with brain infarcts

International Nuclear Information System (INIS)

Wu, R.H.; Bruening, R.; Berchtenbreiter, C.; Weber, J.; Peller, M.; Penzkofer, H.; Reiser, M.; Steiger, H.J.

1998-01-01

MRI perfusion studies have focussed mainly on acute ischaemia and characterisation in ischaemia. Our purpose was to analyse regional brain haemodynamic information in acute, subacute, and chronic ischaemia. We performed 16 examinations of 11 patients on a 1.5 T MR images. Conventional and dynamic contrast-enhanced imaging were employed in all examinations. For the dynamic susceptibility sequences, a bolus (0.2 mmol/kg) of gadopentetate dimeglumine was injected. Reconstructed regional relative cerebral blood volume (rCBV) maps, bolus maps, and conventional images were analysed by consensus reading. In all examinations decreases in rCBV were observed in the lesions. The distribution of regional rCBV in lesions was heterogeneous. The rCBV of the periphery of the lesions was higher than that at their center. There was a correlation between the time since onset and abnormalities on the rCBV map and T2-weighted images (T2WI). In the early stage of acute stroke, the abnormalities tended to be larger on the rCBV than on T2WI. Many patterns of bolus passage were observed in ischaemic regions. rCBV maps provide additional haemodynamic information in patients with brain infarcts. (orig.)

Effects of captopril on cerebral blood flow in normotensive and hypertensive rats

International Nuclear Information System (INIS)

Barry, D.I.; Paulson, O.B.; Jarden, J.O.; Juhler, M.; Graham, D.I.; Strandgaard, S.

1984-01-01

Cerebrovascular effects of the angiotensin converting enzyme inhibitor captopril were examined in normotensive and hypertensive rats. Cerebral blood flow was measured with the intracarotid 133 xenon injection method in halothane-anesthetized animals. The blood-brain barrier permeability of captopril (determined with an integral-uptake method) was negligible, the permeability-surface area product in most brain regions being 1 X 10(-5) cm3/g per second, that is, three to four times lower than that of sodium ion. When administered into the cerebral ventricles to bypass the blood-brain barrier, captopril had no effect on cerebral blood flow: furthermore, cerebral blood flow autoregulation (studied by raising and lowering blood pressure) was identical to that in controls. In contrast, when given intravenously, captopril had a marked effect on cerebral blood flow autoregulation--both the lower and upper limits of autoregulation being shifted to a lower pressure (by about 20 to 30 and 50 to 60 mm Hg, respectively), and the autoregulatory range was shortened by about 40 mm Hg. This effect may be ascribed to inhibition of converting enzyme in the cerebral blood vessels rather than within the brain

Post traumatic brain perfusion SPECT analysis using reconstructed ROI maps of radioactive microsphere derived cerebral blood flow and statistical parametric mapping.

Science.gov (United States)

McGoron, Anthony J; Capille, Michael; Georgiou, Michael F; Sanchez, Pablo; Solano, Juan; Gonzalez-Brito, Manuel; Kuluz, John W

2008-02-29

Assessment of cerebral blood flow (CBF) by SPECT could be important in the management of patients with severe traumatic brain injury (TBI) because changes in regional CBF can affect outcome by promoting edema formation and intracranial pressure elevation (with cerebral hyperemia), or by causing secondary ischemic injury including post-traumatic stroke. The purpose of this study was to establish an improved method for evaluating regional CBF changes after TBI in piglets. The focal effects of moderate traumatic brain injury (TBI) on cerebral blood flow (CBF) by SPECT cerebral blood perfusion (CBP) imaging in an animal model were investigated by parallelized statistical techniques. Regional CBF was measured by radioactive microspheres and by SPECT 2 hours after injury in sham-operated piglets versus those receiving severe TBI by fluid-percussion injury to the left parietal lobe. Qualitative SPECT CBP accuracy was assessed against reference radioactive microsphere regional CBF measurements by map reconstruction, registration and smoothing. Cerebral hypoperfusion in the test group was identified at the voxel level using statistical parametric mapping (SPM). A significant area of hypoperfusion (P TBI. Statistical mapping of the reference microsphere CBF data confirms a focal decrease found with SPECT and SPM. The suitability of SPM for application to the experimental model and ability to provide insight into CBF changes in response to traumatic injury was validated by the SPECT SPM result of a decrease in CBP at the left parietal region injury area of the test group. Further study and correlation of this characteristic lesion with long-term outcomes and auxiliary diagnostic modalities is critical to developing more effective critical care treatment guidelines and automated medical imaging processing techniques.

A visual description of the dissection of the cerebral surface vasculature and associated meninges and the choroid plexus from rat brain.