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Ischemic Brain Injury (ischemic + brain_injury)
Selected AbstractsQuantitative EEG Asymmetry Correlates with Clinical Severity in Unilateral Sturge-Weber SyndromeEPILEPSIA, Issue 1 2007Laura A. Hatfield Summary:,Purpose: Sturge-Weber syndrome (SWS) is a neurocutaneous disorder with vascular malformations of the skin, brain, and eye. SWS results in ischemic brain injury, seizures, and neurologic deficits. We hypothesized that a decrease in quantitative EEG (qEEG) power, on the affected side, correlates with clinical severity in subjects with SWS. Methods: Fourteen subjects had 16-channel scalp EEG recordings. Data were analyzed using fast Fourier transform and calculation of power asymmetry. Blinded investigators assigned scores for clinical neurological status and qualitative assessment of MRI and EEG asymmetry. Results: The majority of subjects demonstrated lower total power on the affected side, usually involving all four frequency bands (delta, theta, alpha, and beta). qEEG asymmetry correlated strongly with neurologic clinical severity scores and MRI asymmetry scores. qEEG data generally agreed with the MRI evidence of regional brain involvement. In MRI-qEEG comparisons that did not agree, decreased power on qEEG in a brain region not affected on MRI was more likely to occur in subjects with more severe neurologic deficits. Conclusions: qEEG provides an objective measure of EEG asymmetry that correlates with clinical status and brain asymmetry seen on MRI. These findings support the conclusion that qEEG reflects the degree and extent of brain involvement and dysfunction in SWS. qEEG may potentially be a useful tool for early diagnosis and monitoring of disease progression in SWS. qEEG may prove useful, in severely affected individuals with SWS, for determining regions of brain dysfunction. [source] Subtoxic N -methyl- D -aspartate delayed neuronal death in ischemic brain injury through TrkB receptor- and calmodulin-mediated PI-3K/Akt pathway activationHIPPOCAMPUS, Issue 7 2007Jing Xu Abstract Previous studies have shown that subtoxic NMDA moderated the neuronal survival in vitro and vivo. We performed this experiment to clarify the precise mechanism underlie subtoxic NMDA delayed neuronal death in ischemic brain injury. We found that pretreatment of NMDA (100 mg/kg) increased the number of the surviving CA1 pyramidal cells of hippocampus at 5 days of reperfusion. This dose of NMDA could also enhance Akt activation after ischemia/reperfusion (I/R). Here, we examined the possible mechanism that NMDA induced Akt activation. On the one hand, we found NMDA receptor-mediated Akt activation was associated with increased expression of BDNF (brain-derived neurotrophic factor) and activation of its high-affinity receptor TrkB after I/R in the hippocampus CA1 region, which could be held down by TrkB receptor antagonist K252a. On the other hand, we found that NMDA enhanced the binding of Ca2+ -dependent calmodulin (CaM) to p85 (the regulation subunit of PI-3K), which led to the activation of Akt. W-13, an active CaM inhibitor, prevented the combination of CaM and p85 and subsequent Akt activation. Furthermore, NMDA receptor-mediated Akt activation was reversed by combined treatment with LY294002, the specific blockade of PI-3K. Taken together, our results suggested that subtoxic NMDA exerts the neuroprotective effect via activation of prosurvival PI-3K/Akt pathway against ischemic brain injury, and BDNF-TrkB signaling and Ca2+ -dependent CaM cascade might contribute to NMDA induced activation of PI-3K/Akt pathway. © 2007 Wiley-Liss, Inc. [source] Human neural stem cell transplantation attenuates apoptosis and improves neurological functions after cerebral ischemia in ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2009P. ZHANG Background: Neuroprotection is a major therapeutic approach for ischemic brain injury. We investigated the neuroprotective effects induced by transplantation of human embryonic neural stem cells (NSCs) into the cortical penumbra 24 h after focal cerebral ischemia. Methods: NSCs were prepared from human embryonic brains obtained at 8 weeks of gestation. Focal cerebral ischemia was induced in adult rats by permanent occlusion of the middle cerebral artery. Animals were randomly divided into two groups: NSCs-grafted group and medium-grafted group (control). Infarct size was assessed 28 days after transplantation by hematoxylin and eosin staining. Neurological severity scores were evaluated before ischemia and at 1, 7, 14, and 28 days after transplantation. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and immunohistochemical analysis of Bcl-2 and Bax were performed at 7, 14, and 28 days after transplantation. Results: Physiological parameters of the two groups were comparable, but not significantly different. NSC transplantation significantly improved neurological function (P<0.05) but did not reduce the infarct size significantly (P>0.05). Compared with the control, NSC transplantation significantly reduced the number of TUNEL- and Bax-positive cells in the penumbra at 7 days. Interestingly, the number of Bcl-2-positive cells in the penumbra after NSC transplantation was significantly higher than that after medium transplantation (P<0.05). Conclusions: The results indicate that NSC transplantation has anti-apoptotic activity and can improve the neurological function; these effects are mediated by the up-regulation of Bcl-2 expression in the penumbra. [source] Intracerebral monitoring in comatose patients treated with hypothermia after a cardiac arrestACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2009J. NORDMARK Background: Induced mild hypothermia (32,34 °C) has proven to reduce ischemic brain injury and improve outcome after a cardiac arrest (CA). The aim of this investigation was to study the occurrence of increased intracranial pressure (ICP) and neurochemical metabolic changes indicating cerebral ischemia, after CA and cardiopulmonary resuscitation (CPR), when induced hypothermia was applied. Methods: ICP, brain chemistry and brain temperature were monitored during induced hypothermia and re-warming in four adult unconscious patients with restoration of spontaneous circulation after CA and CPR. Results: ICP was occasionally above 20 mmHg. Neurochemical changes indicating cerebral ischemia (increased lactate/pyruvate ratio) and excitoxicity (increased glutamate) were found after CA, and signs of ischemia were also observed during the re-warming phase. A biphasic increase in glycerol was seen, which may have been a result of both membrane degradation and overspill from the general circulation. Conclusions: Intracerebral microdialysis and ICP monitoring may be used in selected patients not requiring anticoagulants and PCI to obtain information regarding the common disturbances of intracranial dynamics after CA. The results of this study underline the importance of inducing hypothermia quickly after CA and emphasize the need for developing tools for guidance of the re-warming. [source] Neuroprotection by baicalein in ischemic brain injury involves PTEN/AKT pathwayJOURNAL OF NEUROCHEMISTRY, Issue 6 2010Chao Liu J. Neurochem. (2010) 112, 1500,1512. Abstract Recently more evidences support baicalein (Bai) is neuroprotective in models of ischemic stroke. This study was conducted to determine the molecular mechanisms involved in this effect. Either permanent or transient (2 h) middle cerebral artery occlusion (MCAO) was induced in rats in this study. Permanent MCAO led to larger infarct volumes in contrast to transient MCAO. Only in transient MCAO, Bai administration significantly reduced infarct size. Baicalein also markedly reduced apoptosis in the penumbra of transient MCAO rats. Additionally, oxygen and glucose deprivation (OGD) was used to mimic ischemic insult in primary cultured cortical neurons. A rapid increase in the intracellular reactive oxygen species level and nitrotyrosine formation induced by OGD was counteracted by Bai, which is parallel with attenuated cell injury. The reduction of phosphorylation Akt and glycogen synthase kinase-3, (GSK3,) induced by OGD was restored by Bai, which was associated with preserved levels of phosphorylation of PTEN, the phophatase that negatively regulates Akt. As a consequence, Bcl-2/Bcl-xL-associated death protein phosphorylation was increased and the protein level of Bcl-2 in motochondria was maintained, which subsequently antagonize cytochrome c released in cytosol. LY294002 blocked the increase in phospho-AKT evoked by Bai and abolished the associated protective effect. Together, these findings provide evidence that Bai protects neurons against ischemia injury and this neuroprotective effect involves PI3K/Akt and PTEN pathway. [source] Antiapoptotic and antiautophagic effects of glial cell line-derived neurotrophic factor and hepatocyte growth factor after transient middle cerebral artery occlusion in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 10 2010Jingwei Shang Abstract Glial cell line-derived neurotrophic factor (GDNF) and hepatocyte growth factor (HGF) are strong neurotrophic factors, which function as antiapoptotic factors. However, the neuroprotective effect of GDNF and HGF in ameliorating ischemic brain injury via an antiautophagic effect has not been examined. Therefore, we investigated GDNF and HGF for changes of infarct size and antiapoptotic and antiautophagic effects after transient middle cerebral artery occlusion (tMCAO) in rats. For the estimation of ischemic brain injury, the infarct size was calculated at 24 hr after tMCAO by HE staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) was performed for evaluating the antiapoptotic effect. Western blot analysis of microtubule-associated protein 1 light chain 3 (LC3) and immunofluorescence analysis of LC3 and phosphorylated mTOR/Ser2448 (p-mTOR) were performed for evaluating the antiautophagic effect. GDNF and HGF significantly reduced infarct size after cerebral ischemia. The amounts of LC3-I plus LC3-II (relative to ,-tubulin) were significantly increased after tMCAO, and GDNF and HGF significantly decreased them. GDNF and HGF significantly increased p-mTOR-positive cells. GDNF and HGF significantly decreased the numbers of TUNEL-, LC3-, and LC3/TUNEL double-positive cells. LC3/TUNEL double-positive cells accounted for about 34.3% of LC3 plus TUNEL-positive cells. This study suggests that the protective effects of GDNF and HGF were greatly associated with not only the antiapoptotic but also the antiautophagic effects; maybe two types of cell death can occur in the same cell at the same time, and GDNF and HGF are capable of ameliorating these two pathways. © 2010 Wiley-Liss, Inc. [source] 9-Cis-retinoic acid reduces ischemic brain injury in rodents via bone morphogenetic proteinJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2009Hui Shen Abstract Retinoic acid (RA), a biologically active derivative of vitamin A, has protective effects against damage caused by H2O2 or oxygen-glucose deprivation in mesangial and PC12 cells. In cultured human osteosarcoma cells, RA enhances the expression of bone morphogenetic protein-7 (BMP7), a trophic factor that reduces ischemia- or neurotoxin-mediated neurodegeneration in vivo. The purpose of this study is to examine whether RA reduces ischemic brain injury through a BMP7 mechanism. We found that intracerebroventricular administration of 9-cis-retinoic acid (9cRA) enhanced BMP7 mRNA expression, detected by RT-PCR, in rat cerebral cortex at 24 hr after injection. Rats were also subjected to transient focal ischemia induced by ligation of the middle cerebral artery (MCA) at 1 day after 9cRA injection. Pretreatment with 9cRA increased locomotor activity and attenuated neurological deficits 2 days after MCA ligation. 9cRA also reduced cerebral infarction and TUNEL labeling. These protective responses were antagonized by the BMP antagonist noggin given 1 day after 9cRA injection. Taken together, our data suggest that 9cRA has protective effects against ischemia-induced injury, and these effects involve BMPs. © 2008 Wiley-Liss, Inc. [source] Protective effects of melatonin in ischemic brain injuryJOURNAL OF PINEAL RESEARCH, Issue 4 2000Salvatore Cuzzocrea Recent studies have demonstrated that melatonin is a scavenger of oxyradicals and peroxynitrite and an inhibitor of nitric oxide (NO) production. NO, peroxynitrite (formed from NO and superoxide anion), and poly (ADP-Ribose) synthetase (PARS) have been implicated as mediators of neuronal damage following focal ischemia. In the present study, we have investigated the effects of melatonin treatment in Mongolian gerbils subjected to cerebral ischemia. Treatment of gerbils with melatonin (10 mg kg,1, 30 min before reperfusion and 1, 2, and 6 hr after reperfusion) reduced the formation of post-ischemic brain edema, evaluated by water content. Melatonin also attenuated the increase in the brain levels malondialdehyde (MDA) and the increase in the hippocampus of myeloperoxidase (MPO) caused by cerebral ischemia. Positive staining for nitrotyrosine was found in the hippocampus of Mongolian gerbils subjected to cerebral ischemia. Hippocampus tissue sections, from Mongolian gerbils subjected to cerebral ischemia, also showed positive staining for PARS. The degrees of staining for nitrotyrosine and for PARS were markedly reduced in tissue sections obtained from animals that received melatonin. Melatonin treatment increased survival and reduced hyperactivity linked to neurodegeneration induced by cerebral ischemia and reperfusion. Histological observations of the pyramidal layer of CA-1 showed a reduction of neuronal loss in animals that received melatonin. These results show that melatonin improves brain injury induced by transient cerebral ischemia. [source] Assessment of the effect of 2-chloroadenosine in normal rat brain using spin-labeled MRI measurement of perfusionMAGNETIC RESONANCE IN MEDICINE, Issue 5 2001Patrick M. Kochanek Abstract Adenosine analogs such as 2-chloroadenosine are potent cerebrovasodilators. Spin-labeled MRI was used to investigate the spatial distribution, dose-response, and timing of the effect of 2-chloroadenosine on cerebral blood flow (CBF) after intraparenchymal injection into rat brain. Sprague-Dawley rats (N = 10) were injected with 2-chloroadenosine at doses of 0.3, 6.0, or 12 nmoles, or saline vehicle (2,4 ,L). CBF was serially quantified in a slice through the injection site in a circular (3.6 mm diameter) region of interest (ROI) around the injection and in ipsilateral hemispheric ROIs at ,90 min and ,180 min. Marked 3.77- and 3.93-fold increases in CBF (vs. vehicle) were seen in the circular ROI at ,90 min and ,180 min after 12-nmol injection, respectively. Similarly, 2.92- and 2.78-fold increases in hemispheric CBF were observed at ,90 min and ,180 min, respectively, after injection of 12 nmoles. Linear dose-response relationships were observed at both times after injection in both ROIs (all P < 0.01). Spin-labeling MRI assessment revealed that parenchymal injection of 2-chloroadenosine produces potent, dose-dependent, and sustained vasodilation over large areas of brain. This treatment and imaging paradigm should facilitate investigation of the effect of CBF promotion in models of traumatic and ischemic brain injury. Magn Reson Med 45:924,929, 2001. © 2001 Wiley-Liss, Inc. [source] Endothelial progenitor cell transplantation improves long-term stroke outcome in miceANNALS OF NEUROLOGY, Issue 4 2010Yongfeng Fan PhD Objective Endothelial progenitor cells (EPCs) play an important role in tissue repairing and regeneration in ischemic organs, including the brain. However, the cause of EPC migration and the function of EPCs after ischemia are unclear. In this study, we demonstrated the effects of EPCs on ischemic brain injury in a mouse model of transient middle cerebral artery occlusion (tMCAO). Methods Circulating human EPCs were characterized with immunofluorescent staining and flow cytometry. EPCs (1 × 106) were injected into nude mice after 1 hour of tMCAO. Histological analysis and behavioral tests were performed from day 0 to 28 days after tMCAO. Results EPCs were detected in ischemic brain regions 24 hours after tMCAO. EPC transplantation significantly reduced ischemic infarct volume at 3 days after tMCAO compared with control animals (p < 0.05). CXCR4 was expressed in the majority of EPCs, and stromal-derived factor-1 (SDF-1) induced EPC migration, which was blocked by pretreated EPCs with AMD3100 in vitro. SDF-1 was upregulated in ischemic brain. Compared with control animals, injecting AMD3100-pretreated EPCs resulted in a larger infarct volume 3 days after tMCAO, suggesting that SDF-1,mediated signaling was involved in EPC-mediated neuroprotection. In addition, EPC transplantation reduced mouse cortex atrophy 4 weeks after tMCAO and improved neurobehavioral outcomes (p < 0.05). EPC injection potently increased angiogenesis in the peri-infarction area (p < 0.05). Interpretation We conclude that systemic delivery of EPCs protects the brain against ischemic injury, promotes neurovascular repair, and improves long-term neurobehavioral outcomes. Our data suggest that SDF-1,mediated signaling plays a critical role in EPC-mediated neuroprotection. ANN NEUROL 2010;67:488,497 [source] Age and energy intake interact to modify cell stress pathways and stroke outcomeANNALS OF NEUROLOGY, Issue 1 2010Thiruma V. Arumugam PhD Objective Age and excessive energy intake/obesity are risk factors for cerebrovascular disease, but it is not known if and how these factors affect the extent of brain damage and outcome in ischemic stroke. We therefore determined the interactions of age and energy intake on the outcome of ischemic brain injury, and elucidated the underlying mechanisms. Methods We utilized a novel microchip-based immunoaffinity capillary electrophoresis technology to measure a panel of neurotrophic factors, cytokines, and cellular stress resistance proteins in brain tissue samples from young, middle-aged, and old mice that had been maintained on control or energy-restricted diets prior to middle cerebral artery occlusion and reperfusion. Results Mortality from focal ischemic stroke was increased with advancing age and reduced by an intermittent fasting (IF) diet. Brain damage and functional impairment were reduced by IF in young and middle-aged mice, but not in old mice. The basal and poststroke levels of neurotrophic factors (brain-derived neurotrophic factor and basic fibroblast growth factor), protein chaperones (heat shock protein 70 and glucose regulated protein 78), and the antioxidant enzyme heme oxygenase-1 were decreased, whereas levels of inflammatory cytokines were increased in the cerebral cortex and striatum of old mice compared with younger mice. IF coordinately increased levels of protective proteins and decreased inflammatory cytokines in young, but not in old mice. Interpretation Reduction in dietary energy intake differentially modulates neurotrophic and inflammatory pathways to protect neurons against ischemic injury, and these beneficial effects of IF are compromised during aging, resulting in increased brain damage and poorer functional outcome. ANN NEUROL 2010;67:41,52 [source] Recombinant C1 inhibitor in brain ischemic injury,ANNALS OF NEUROLOGY, Issue 3 2009Raffaella Gesuete BD Objective C1 inhibitor (C1-INH) is an endogenous inhibitor of complement and kinin systems. We have explored the efficacy and the therapeutic window of the recently available human recombinant (rh) C1-INH on ischemic brain injury and investigated its mechanism of action in comparison with that of plasma-derived (pd) C1-INH. Methods rhC1-INH was administered intravenously to C57Bl/6 mice undergoing transient or permanent ischemia, and its protective effects were evaluated by measuring infarct volume and neurodegeneration. The binding profiles of rhC1-INH and pdC1-INH were assessed in vitro using surface plasmon resonance. Their localization in the ischemic brain tissue was determined by immunohistochemistry and confocal analysis. The functional consequences of rhC1-INH and pdC1-INH administration on complement activation were analyzed by enzyme-linked immunosorbent assay on plasma samples. Results rhC1-INH markedly reduced cerebral damage when administered up to 18 hours after transient ischemia and up to 6 hours after permanent ischemia, thus showing a surprisingly wide therapeutic window. In vitro rhC1-INH bound mannose-binding lectin (MBL), a key protein in the lectin complement pathway, with high affinity, whereas pdC1-INH, which has a different glycosylation pattern, did not. In the ischemic brain, rhC1-INH was confined to cerebral vessels, where it colocalized with MBL, whereas pdC1-INH diffused into the brain parenchyma. In addition, rhC1-INH was more active than pdC1-INH in inhibiting MBL-induced complement activation. Interpretation rhC1-INH showed a surprisingly wider time window of efficacy compared with the corresponding plasmatic protein. We propose that the superiority of rhC1-INH is due to its selective binding to MBL, which emerged as a novel target for stroke treatment. Ann Neurol 2009;66:332,342 [source] | |||||||||||||