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Cerebral Ischemia (cerebral + ischemia)
Kinds of Cerebral Ischemia Selected AbstractsInduction of Oxidative DNA Damage in the Peri-Infarct Region After Permanent Focal Cerebral IschemiaJOURNAL OF NEUROCHEMISTRY, Issue 4 2000Tetsuya Nagayama Abstract: To address the role of oxidative DNA damage in focal cerebral ischemia lacking reperfusion, we investigated DNA base and strand damage in a rat model of permanent middle cerebral artery occlusion (MCAO). Contents of 8-hydroxyl-2,-deoxyguanosine (8-OHdG) and apurinic/apyrimidinic abasic sites (AP sites), hallmarks of oxidative DNA damage, were quantitatively measured in nuclear DNA extracts from brains obtained 4-72 h after MCAO. DNA single- and double-strand breaks were detected on coronal brain sections using in situ DNA polymerase I-mediated biotin-dATP nick-translation (PANT) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), respectively. Levels of 8-OHdG and AP sites were markedly elevated 16-72 h following MCAO in the frontal cortex, representing the peri-infarct region, but levels did not significantly change within the ischemic core regions of the caudateputamen and parietal cortex. PANT- and TUNEL-positive cells began to be detectable 4-8 h following MCAO in the caudate-putamen and parietal cortex and reached maximal levels at 72 h. PANT- and TUNEL-positive cells were also detected 16-72 h after MCAO in the lateral frontal cortex within the infarct border, where many cells also showed colocalization of DNA single-strand breaks and DNA fragmentation. In contrast, levels of PANT-positive cells alone were transiently increased (16 h after MCAO) in the medial frontal cortex, an area distant from the infarct zone. These data suggest that within peri-infarct brain regions, oxidative injury to nuclear DNA in the form of base and strand damage may be a significant and contributory cause of secondary expansion of brain damage following permanent focal ischemia. [source] Inflammatory and Hemodynamic Changes in the Cerebral Microcirculation of Aged Rats after Global Cerebral Ischemia and ReperfusionMICROCIRCULATION, Issue 4 2008Leslie Ritter ABSTRACT Effects of aging on inflammation and blood flow in the brain are unclear. Young (three to six months) and aged (19,22 months) male Brown Norway Fisher rats were used to compare (i) leukocyte function in nonischemic conditions and (ii) leukocyte function and hemodynamic changes after ischemia-reperfusion (I-R). In nonischemic studies, polymorphonuclear (PMN) CD11b expression and reactive oxygen species (ROS) production were measured with flow cytometry and PMN chemotaxis was measured with a Boyden chamber (+/-fMLP). In I-R studies, ischemia was induced by bilateral carotid artery occlusion and hypotension (20 minutes). During early reperfusion (30 minutes), leukocyte adhesion and rolling and blood-shear rates were measured using fluorescence microscopy. During late reperfusion (48 hours), mortality, neurological function, and leukocyte infiltration were measured. Stimulated PMN chemotaxis was increased in nonischemic aged rats (p < 0.05). In early reperfusion, there was a significant increase in leukocyte rolling and adhesion in the cerebral microcirculation and a significant decrease in shear rate in aged rats, compared to the young (p < 0.05). During late reperfusion, neurologic function was worse in aged vs. young rats (p < 0.05). These findings suggest that increased intravascular PMN adhesion and vascular dysfunction may contribute to poor neurologic outcome after cerebral I-R in the aged brain. [source] Occlusion of the Middle Cerebral Artery: a New Method of Focal Cerebral Ischemia in RatsANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005E. Cam The study in Wistar rats attempted to improve the occlusion technique of the middle cerebral artery (MCA) as a precise method for initiating stroke. In a first part it was necessary to study the exact anatomy of blood vessels of the brain in seven rats of 170-410 g body weight by corrosion cast. The lengths and diameters of defined locations of the blood vessels were measured. The temporary as well as the permanent methods were refined or replaced. The first one was completed in main training the physiological blood flow after temporary occlusion, while the permanent occlusion was performed by positioning a silicone cap in the MCA. A filament guide was introduced from the common carotid artery (CCA) via internal carotid artery (ICA) to guide the silicon cap at the branch of the MCA. Histological sections of the brain of rats showed 24 h after the permanent occlusion a reproducible infarct in the brain. This area corresponded very well with the supply of the MCA. The new occlusion method with a silicon cap was compared with the occlusion methods of CCA route and external carotid artery (ECA) route. The total infarct volume was significantly larger in the CCA route and ECA route groups than in the silicon cap group (means: CCA route 261 mm3; ECA route 191 mm3 vs. 128 mm3 silicon cap group; P < 0,05). It could be demonstrated that the new silicon cap occlusion technique imitates the pathological situation of a cerebral infarct in man. Moreover it is less invasive for the animals and more precise and reproducible regarding the infarcted area in comparison to the other occlusion methods. Based on anatomical measurements of the blood vessels the described silicon cap method can be recommended for rats of a body weight between 340,370 g. [source] Neuroprotective Effects of N -Alkyl-1,2,4-oxadiazolidine-3,5-diones and Their Corresponding Synthetic Intermediates N -Alkylhydroxylamines and N -1-Alkyl-3-carbonyl-1-hydroxyureas against in,vitro Cerebral IschemiaCHEMMEDCHEM, Issue 1 2010Alain, Cesar Biraboneye Abstract Herein we report the synthesis and neuroprotective effects of new N -alkyl-1,2,4-oxadiazolidine-3,5-diones and their corresponding synthetic intermediates, N -alkylhydroxylamines and N -1-alkyl-3-carbonyl-1-hydroxyureas, in an in,vitro model of ischemia. We found five analogues that protect HT22 cells from death in the concentration range of 1,5,,M. Because members of the MAP kinase family are known to be key players in nerve cell survival and death, we characterized the role of these kinases in the neuroprotective mechanisms of the newly synthesized analogues. The results indicate that these compounds provide neuroprotection through distinct mechanisms of action. [source] Neuroprotective effects of a combination of dexmedetomidine and hypothermia after incomplete cerebral ischemia in ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2010K. SATO Background: Dexmedetomidine and hypothermia are known to reduce neuronal injury following cerebral ischemia. We examined whether a combination of dexmedetomidine and hypothermia reduces brain injury after transient forebrain ischemia in rats to a greater extent than either treatment alone. Methods: Thirty-eight male Sprague,Dawley rats were anesthetized with fentanyl and nitrous oxide in oxygen. Four groups were tested: group C (saline 1 ml/kg, temporal muscle temperature 37.5 °C); group H (saline 1 ml/kg, 35.0 °C); group D (dexmedetomidine 100 ,g/kg, 37.5 °C); and group DH (dexmedetomidine 100 ,g/kg, 35.0 °C). Dexmedetomidine or saline was administered intraperitoneally 30 min before ischemia. Cerebral ischemia was produced by right carotid artery ligation with hemorrhagic hypotension (mean arterial pressure 40 mmHg) for 20 min. Neurologic outcome was evaluated at 24, 48, and 72 h after ischemia. Histopathology was evaluated in the caudate and hippocampus at 72 h after ischemia. Results: Neurologic outcome was significantly better in the group DH than the group C (P<0.05), whereas it was similar between the group DH and the groups D or H. Survival rate of the hippocampal CA1 neurons was significantly greater in groups D, H, and DH than group C (P<0.05). Histopathologic injury in the caudate section was significantly less in groups H and DH than group C (P<0.05). Conclusion: The combination of dexmedetomidine and hypothermia improved short-term neurologic outcome compared with the control group, whereas the combination therapy provided comparable neuroprotection with either of the two therapies alone. [source] Effects of sevoflurane on cognitive deficit, motor function, and histopathology after cerebral ischemia in ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2009E. EBERSPÄCHER Background: The volatile anesthetic sevoflurane exhibits neuroprotective properties when assessed for motor function and histopathology after cerebral ischemia in rats. Damage of hippocampal neurons after ischemia relates to a number of cognitive deficits that are not revealed by testing animals for motor function. Therefore, the present study evaluates cognitive and behavioral function as well as hippocampal damage in rats subjected to cerebral ischemia under sevoflurane compared with fentanyl/nitrous oxide (N2O)/O2 anesthesia. Methods: Thirty-four rats were trained for 10 days using a hole-board test to detect changes in cognitive and behavioral function. Rats were randomly assigned to the following groups: (A) sham/fentanyl/N2O/O2 (n=7); (B) ischemia/fentanyl/N2O/O2 (n=10); (C) sham/2.0 vol% sevoflurane in O2/air (n=7); and (D) ischemia/2.0 vol% sevoflurane in O2/air (n=10). Cerebral ischemia was produced by unilateral common carotid artery occlusion combined with hemorrhagic hypotension (mean arterial blood pressure 40 mmHg for 45 min). Temperature, arterial blood gases, and pH were maintained constant. Cerebral blood flow was measured using laser-Doppler flowmetry. After surgery, cognitive and behavioral function was re-evaluated for 10 days. On day 11, the brains were removed for histopathologic evaluation (hematoxylin/eosin-staining). Results: Cognitive testing revealed deficits in declarative and working memory in ischemic rats anesthetized with fentanyl/N2O. Rats anesthetized with sevoflurane during ischemia showed a significantly better outcome. Hippocampal damage was significantly worse with fentanyl/N2O. Conclusion: The present data add to previous investigations showing that sevoflurane prevents a deficit in cognitive function and histopathological damage induced by cerebral ischemia in rats. [source] Enhanced proliferation of progenitor cells in the subventricular zone and limited neuronal production in the striatum and neocortex of adult macaque monkeys after global cerebral ischemia,JOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2005Anton B. Tonchev Abstract Cerebral ischemia in adult rodent models increases the proliferation of endogenous neural progenitor cells residing in the subventricular zone along the anterior horn of the lateral ventricle (SVZa) and induces neurogenesis in the postischemic striatum and cortex. Whether the adult primate brain preserves a similar ability in response to an ischemic insult is uncertain. We used the DNA synthesis indicator bromodeoxyuridine (BrdU) to label newly generated cells in adult macaque monkeys and show here that the proliferation of cells with a progenitor phenotype (double positive for BrdU and the markers Musashi1, Nestin, and ,III-tubulin) in SVZa increased during the second week after a 20-min transient global brain ischemia. Subsequent progenitor migration seemed restricted to the rostral migratory stream toward the olfactory bulb and ischemia increased the proportion of adult-generated cells retaining their location in SVZa with a progenitor phenotype. Despite the lack of evidence for progenitor cell migration toward the postischemic striatum or prefrontal neocortex, a small but sustained proportion of BrdU-labeled cells expressed features of postmitotic neurons (positive for the protein NeuN and the transcription factors Tbr1 and Islet1) in these two regions for at least 79 days after ischemia. Taken together, our data suggest an enhanced neurogenic response in the adult primate telencephalon after a cerebral ischemic insult. © 2005 Wiley-Liss, Inc. [source] In-vivo visualization of phagocytotic cells in rat brains after transient ischemia by USPIONMR IN BIOMEDICINE, Issue 4 2002M. Rausch Abstract Cerebral ischemia provokes tissue damage by two major patho-physiological mechanisms. Direct cell necrosis is induced by diminished access of neurons and glia to essential nutrients such as glucose and oxygen leading to energy failure. A second factor of cellular loss is related to the activation of immune-competent cells within and around the primary infarct. While granulocytes and presumably monocytes are linked to the no-reflow phenomenon, activated microglia cells and monocytes can release cytotoxic substrates, which cause delayed cell death. As a consequence the infarct volume will increase, despite restoration of cerebral perfusion. In the past, visualization of immune competent cells was only possible by histological analysis of post-mortem tissue. However, contrast agents based on small particles of iron oxide are known to accumulate in organs rich in cells with phagocytotic function. These particles can be tracked in vivo by MRI methods based on their relaxation properties. In the present study, the spatio-temporal distribution of USPIO particles was monitored in a rat model of transient cerebral infarction using T1 - and T2 -weighted MRI sequences. USPIO were detected in vessels at 24,h after administration. At later time points specific accumulation of USPIO was observed within the infarcted hemisphere, with maximal signal enhancement on day 2. Their detectability based on T1 -contrast disappeared between day 4 and day 7. Immuno-histochemically (IHC) stains confirmed the presence of macrophages, presumably blood-derived monocytes within areas of T1 signal enhancement. Direct visualization of iron-burdened macrophages by IHC was only possible later than day 3 after occlusion. Copyright © 2002 John Wiley & Sons, Ltd. [source] Delayed treatment with a p53 inhibitor enhances recovery in stroke brain,ANNALS OF NEUROLOGY, Issue 5 2009Yu Luo PhD Objective Cerebral ischemia can activate endogenous reparative processes, such as proliferation of endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ). Most of these new cells die shortly after injury. The purpose of this study was to examine a novel strategy for treatment of stroke at 1 week after injury by enhancing the survival of ischemia-induced endogenous NPCs in SVZ. Methods Adult rats were subjected to a 90-minutes middle cerebral artery occlusion. A p53 inhibitor pifithrin-, (PFT-,) was administered to stroke rats from days 6 to 9 after middle cerebral artery occlusion. Locomotor behavior was measured using an activity chamber. Proliferation, survival, migration, and differentiation of endogenous NPCs were examined using quantitative reverse transcription polymerase chain reaction, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, and immunohistochemistry. Results PFT-, enhanced functional recovery as assessed by a significant increase in multiple behavioral measurements. Delayed PFT-, treatment had no effect on the cell death processes in the lesioned cortical region. However, it enhanced the survival of SVZ progenitor cells, and promoted their proliferation and migration. PFT-, inhibited the expression of a p53-dependent proapoptotic gene, termed PUMA (p53-upregulated modulator of apoptosis), within the SVZ of stroke animals. The enhancement of survival/proliferation of NPCs was further found in SVZ neurospheres in tissue culture. PFT-, dose-dependently increased the number and size of new neurosphere formation. Interpretation Delayed treatment with a p53 inhibitor PFT-, is able to modify stroke-induced endogenous neurogenesis and improve the functional recovery in stroke animals. Ann Neurol 2009;65:520,530 [source] Impact of early surgery after aneurysmal subarachnoid haemorrhageACTA NEUROLOGICA SCANDINAVICA, Issue 2 2009M. Van Der Jagt Objectives,,, To investigate the effect of early aneurysm surgery (<72 h) on outcome in patients with subarachnoid haemorrhage (SAH). Materials and methods,,, We studied two consecutive series of patients with aneurysmal SAH [postponed surgery (PS) cohort, n = 118, 1989,1992: surgery was planned on day 12 and early surgery (ES) cohort, n = 85, 1996,1998: ES was performed only in patients with Glasgow Coma Scale (GCS) >13]. We used multivariable logistic regression analysis to assess outcome at 3 months. Results,,, Favourable outcome (Glasgow Outcome Scale 4 or 5) was similar in both cohorts. Cerebral ischemia occurred significantly more often in the ES cohort. The occurrence of rebleeds was similar in both cohorts. External cerebrospinal fluid (CSF) drainage was performed more often in the ES cohort (51% vs 19%). Patients with cisternal sum score (CSS) of subarachnoid blood <15 on admission [adjusted odds ratio (OR) for favourable outcome: 6.4, 95% confidence interval (CI) 1.0,39.8] and patients with both CSS <15 and GCS > 12 on admission benefited from the strategy including ES (OR 10.5, 95% CI 1.1,99.4). Conclusions,,, Our results support the widely adopted practice of ES in good-grade SAH patients. [source] Delta2 -Specific Opioid Receptor Agonist and Hibernating Woodchuck Plasma Fraction Provide Ischemic NeuroprotectionACADEMIC EMERGENCY MEDICINE, Issue 3 2008Meera Govindaswami PhD Abstract Objectives:, The authors present evidence that the , opioid receptor agonist Deltorphin-Dvariant (Delt-Dvar) and hibernating woodchuck plasma (HWP), but not summer-active woodchuck plasma (SAWP), can provide significant neuroprotection from focal ischemia in mice by a mechanism that relies in part on reducing nitric oxide (NO) release in ischemic tissue. Methods:, Cerebral ischemia was produced in wild-type and NO synthase,deficient (NOS,/,) mice by transient, 1-hour middle cerebral artery occlusion (MCAO). Behavioral deficits were determined at 22 hours and infarct volume was assessed at 24 hours after MCAO. Mice were treated with saline or Delt-Dvar at 2.0 and 4.0 mg/kg, or 200 ,L of HWP or SAWP. NOS,/, mice were treated with either saline or Delt-Dvar at 4.0 mg/kg. NO release was determined using an N9 microglial cell line pretreated with ,- or ,-specific opioids and HWP or SAWP prior to activation with lipopolysaccharide and interferon-,. Nitrate in the medium was measured as an indicator of NO production. Results:, Infusion of Delt-Dvar or HWP (but not SAWP) decreased infarct volume and improved behavioral deficits following 1 hour of MCAO and 24 hours of reperfusion. In NOS,/, mice, endothelial NOS+/+ is required to provide Delt-Dvar,induced neuroprotection. Delt-Dvar and HWP dose-dependently decreased NO release in cell culture, while SAWP and other ,- and ,-specific opioids did not. Conclusions:, Delt-Dvar and HWP, but not SAWP, are effective neuroprotectant agents in a mouse model of transient MCAO. In cell culture, the mechanism of this ischemic neuroprotection may rely in part on their ability to block NO release. [source] Calpain cleavage of collapsin response mediator proteins in ischemic mouse brainEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2007Susan X. Jiang Abstract Collapsin response mediator proteins (CRMPs) are important brain-specific proteins with distinct functions in modulating growth cone collapse and axonal guidance during brain development. Our previous studies have shown that calpain cleaves CRMP3 in the adult mouse brain during cerebral ischemia [S.T. Hou et al. (2006) J. Neurosci., 26, 2241,2249]. Here, the expression of all CRMP family members (1,5) was examined in mouse brains that were subjected to middle cerebral artery occlusion. Among the five CRMPs, the expressions of CRMP1, CRMP3 and CRMP5 were the most abundant in the cerebral cortex and all CRMPs were targeted for cleavage by ischemia-activated calpain. Sub-cellular fractionation analysis showed that cleavage of CRMPs by calpain occurred not only in the cytoplasm but also in the synaptosomes isolated from ischemic brains. Moreover, synaptosomal CRMPs appeared to be at least one-fold more sensitive to cleavage compared with those isolated from the cytosolic fraction in an in-vitro experiment, suggesting that synaptosomal CRMPs are critical targets during cerebral ischemia-induced neuronal injury. Finally, the expression of all CRMPs was colocalized with TUNEL-positive neurons in the ischemic mouse brain, which further supports the notion that CRMPs may play an important role in neuronal death following cerebral ischemia. Collectively, these studies demonstrated that CRMPs are targets of calpains during cerebral ischemia and they also highlighted an important potential role that CRMPs may play in modulating ischemic neuronal death. [source] Dietary phytoestrogens improve stroke outcome after transient focal cerebral ischemia in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006María C. Burguete Abstract As phytoestrogens are postulated as being neuroprotectants, we assessed the hypothesis that dietary isoflavone-type phytoestrogens are neuroprotective against ischemic stroke. Transient focal cerebral ischemia (90 min) was induced by middle cerebral artery occlusion (MCAO) following the intraluminal thread technique, both in rats fed with soy-based diet and in rats fed with isoflavone-free diet. Cerebro-cortical laser-Doppler flow (cortical perfusion, CP), arterial blood pressure, core temperature, PaO2, PaCO2, pH and glycemia were measured before, during and after MCAO. Neurological examination and infarct volume measurements were carried out 3 days after the ischemic insult. Dietary isoflavones (both glycosides and aglycones) were measured by high-performance liquide chromatography. Neither pre-ischemic, intra-ischemic nor post-ischemic CP values were significantly different between the soy-based diet and the isoflavone-free diet groups. Animals fed with the soy-based diet showed an infarct volume of 122 ± 20.2 mm3 (19 ± 3.3% of the whole ipsilateral hemisphere volume). In animals fed with the isoflavone-free diet the mean infarct volume was significantly higher, 191 ± 26.7 mm3 (28 ± 4.1%, P < 0.05). Neurological examination revealed significantly higher impairment in the isoflavone-free diet group compared with the soy-based diet group (3.3 ± 0.5 vs. 1.9 ± 0.5, P < 0.05). These results demonstrate that dietary isoflavones improve stroke outcome after transient focal cerebral ischemia in such a way that a higher dietary isoflavone content results in a lower infarct volume and a better neurological status. [source] Differential responses to NMDA receptor activation in rat hippocampal interneurons and pyramidal cells may underlie enhanced pyramidal cell vulnerabilityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2005E. Avignone Abstract Hippocampal interneurons are generally more resistant than pyramidal cells to excitotoxic insults. Because NMDA receptors play a crucial role in neurodegeneration, we have compared the response to exogenous NMDA in CA1 pyramidal cells and interneurons of the stratum oriens using combined whole-cell patch-clamp recording and ratiometric Ca2+ imaging. In voltage-clamp, current-clamp or in nominally Mg2+ -free medium, NMDA (10 µm; 3,5 min exposure in the presence of tetrodotoxin) induced a markedly larger inward current and Ca2+ rise in pyramidal cells than in interneurons. Pyramidal cells also showed a more pronounced voltage dependence in their response to NMDA. We hypothesized that this enhanced response to NMDA receptor activation in pyramidal cells could underlie their increased vulnerability to excitotoxicity. Using loss of dye as an indicator of degenerative membrane disruption, interneurons tolerated continuous exposure to a high concentration of NMDA (30 µm) for longer periods than pyramidal cells. This acute neurodegeneration in pyramidal cells was independent of intracellular Ca2+, because high intracellular BAPTA (20 mm) did not prolong survival time. Thus, a plausible explanation for the enhanced sensitivity of pyramidal neurons to excitotoxic insults associated with cerebral ischemia is their greater response to NMDA receptor activation, which may reflect differences in NMDA receptor expression and/or subunit composition. [source] On the Future of Reanimatology,ACADEMIC EMERGENCY MEDICINE, Issue 1 2000Peter Safar MD Abstract: This article is adapted from a presentation given at the 1999 SAEM annual meeting by Dr. Peter Safar. Dr. Safar has been involved in resuscitation research for 44 years, and is a distinguished professor and past initiating chairman of the Department of Anesthesiology and Critical Care Medicine at the University of Pittsburgh. He is the founder and director of the Safar Center for Resuscitation Research at the University of Pittsburgh, and has been the research mentor of many critical care and emergency medicine research fellows. Here he presents a brief history of past accomplishments, recent findings, and future potentials for resuscitation research. Additional advances in resuscitation, from acute terminal states and clinical death, will build upon the lessons learned from the history of reanimatology, including optimal delivery by emergency medical services of already documented cardiopulmonary cerebral resuscitation, basic-advanced,prolonged life support, and future scientific breakthroughs. Current controversies, such as how to best educate the public in life-supporting first aid, how to restore normotensive spontaneous circulation after cardiac arrest, how to rapidly induce mild hypothermia for cerebral protection, and how to minimize secondary insult after cerebral ischemia, are discussed, and must be resolved if advances are to be made. Dr. Safar also summarizes future technologies already under preliminary investigation, such as ultra-advanced life support for reversing prolonged cardiac arrest, extending the "golden hour" of shock tolerance, and suspended animation for delayed resuscitation. [source] Does rat global transient cerebral ischemia serve as an appropriate model to study emotional disturbances?FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2004Guy Bernard Bantsiele Abstract We used two validated psychopharmacological methods, the forced swimming test (FST 20 min and 5 min) and the elevated plus-maze (EPM), to quantify depression-like and anxiety-like behavior induced by transient global cerebral ischemia in the rat. We also validated use of these methods for the study of antidepressant (imipramine) and anti-anxiety drugs (diazepam). Twelve days after surgery to provoke transient global ischemia, spontaneous motor activity was 40% higher in ischemic rats than in sham-operated controls. Duration of immobility during the FST 20 min and 5 min was 28 and 30% shorter, respectively, than in controls. Treatment with imipramine (3 × 30 mg/kg i.p.) induced a significantly shorter duration of immobility during the FST 5 min, but with no difference between ischemia and control rats. The EPM demonstrated that ischemia did not induce any change in the six behavior parameters measured. Diazepam (1.5 mg/kg i.p.) induced significant anxiolytic effects which were similar in ischemic and sham-operated animals. Both tests failed to demonstrate perturbed performance but conversely, these findings did disclose the sensitivity of ischemia-exposed rats to the action of imipramine and diazepam, demonstrating the usefulness of these tests as psychopharmocological tools for evaluating the effect of psychotropics in the ischemic rat. [source] Activation of CysLT receptors induces astrocyte proliferation and death after oxygen,glucose deprivationGLIA, Issue 1 2008Xiao-Jia Huang Abstract We recently found that 5-lipoxygenase (5-LOX) is activated to produce cysteinyl leukotrienes (CysLTs), and CysLTs may cause neuronal injury and astrocytosis through activation of CysLT1 and CysLT2 receptors in the brain after focal cerebral ischemia. However, the property of astrocyte responses to in vitro ischemic injury is not clear; whether 5-LOX, CysLTs, and their receptors are also involved in the responses of ischemic astrocytes remains unknown. In the present study, we performed oxygen-glucose deprivation (OGD) followed by recovery to induce ischemic-like injury in the cultured rat astrocytes. We found that 1-h OGD did not injure astrocytes (sub-lethal OGD) but induced astrocyte proliferation 48 and 72 h after recovery; whereas 4-h OGD moderately injured the cells (moderate OGD) and led to death 24,72 h after recovery. Inhibition of phospholipase A2 and 5-LOX attenuated both the proliferation and death. Sub-lethal and moderate OGD enhanced the production of CysLTs that was inhibited by 5-LOX inhibitors. Sub-lethal OGD increased the expressions of CysLT1 receptor mRNA and protein, while moderate OGD induced the expression of CysLT2 receptor mRNA. Exogenously applied leukotriene D4 (LTD4) induced astrocyte proliferation at 1,10 nM and astrocyte death at 100,1,000 nM. The CysLT1 receptor antagonist montelukast attenuated astrocyte proliferation, the CysLT2 receptor antagonist BAY cysLT2 reversed astrocyte death, and the dual CysLT receptor antagonist BAY u9773 exhibited both effects. In addition, LTD4 (100 nM) increased the expression of CysLT2 receptor mRNA. Thus, in vitro ischemia activates astrocyte 5-LOX to produce CysLTs, and CysLTs result in CysLT1 receptor-mediated proliferation and CysLT2 receptor-mediated death. © 2007 Wiley-Liss, Inc. [source] Proteomic identification of an upregulated isoform of annexin A3 in the rat brain following reversible cerebral ischemiaGLIA, Issue 16 2007Heike Junker Abstract We used proteomics to identify regulated proteins following cerebral ischemia in a rat model. Young rats were subjected to reversible middle cerebral artery (MCA) occlusion and proteins were extracted from the peri-infarcted and the corresponding contralateral area at days 3 and 14 postischemia. Proteins were analyzed by two-dimensional polyacrylamide gel electrophoresis followed by mass spectrometry. We report for the first time that an isoform of annexin A3 (ANXA3) was among the upregulated proteins in the postischemic rat brain. The results were confirmed by real-time PCR and by western blotting. Double- and triple-immunostaining with neuronal and microglia/macrophagic markers demonstrated that ANXA3 is produced by resting microglia in control tissue and by activated microglial/macrophage cells in the infarcted area. 3D-images of the infarcted area suggest that ANXA3 is associated with a phagocytic phenotype. Our study identifies ANXA3 as a novel marker of brain microglia, which should be of substantial value in future studies of microglial cells and its role in the postischemic brain. © 2007 Wiley-Liss, Inc. [source] Thrombin potently enhances swelling-sensitive glutamate efflux from cultured astrocytesGLIA, Issue 9 2007Gerardo Ramos-Mandujano Abstract High concentrations of thrombin (Thr) have been linked to neuronal damage in cerebral ischemia and traumatic brain injury. In the present study we found that Thr markedly enhanced swelling-activated efflux of 3H -glutamate from cultured astrocytes exposed to hyposmotic medium. Thr (0.5,5 U/mL) elicited small 3H -glutamate efflux under isosmotic conditions and increased the hyposmotic glutamate efflux by 5- to 10-fold, the maximum effect being observed at 15% osmolarity reduction. These Thr effects involve its protease activity and are fully mimicked by SFFLRN, the synthetic peptide activating protease-activated receptor-1. Thr potentiation of 3H -glutamate efflux was largely dependent on a Thr-elicited increases in cytosolic Ca2+ (Ca2+i) concentration ([Ca2+]i). Preventing Ca2+i rise by treatment with EGTA-AM or with the phospholipase C blocker U73122 reduced the Thr-increased glutamate efflux by 68%. The protein kinase C blockers Go6976 or chelerythrine reduced the Thr effect by 19%,22%, while Ca/calmodulin blocker W7 caused a 63% inhibition. In addition to this Ca2+ -sensitive pathway, Thr effect on glutamate efflux also involved activation of phosphoinositide-3 kinase (PI3K), since it was reduced by the PI3K inhibitor wortmannin (51% inhibition). Treating cells with EGTA-AM plus wortmannin essentially abolished Thr-dependent glutamate efflux. Thr-activated glutamate release was potently inhibited by the blockers of the volume-sensitive anion permeability pathway, NPPB (IC50 15.8 ,M), DCPIB (IC50 4.2 ,M). These results suggest that Thr may contribute to the excitotoxic neuronal injury by elevating extracellular glutamate release from glial cells. Therefore, this work may aid in search of neuroprotective strategies for treating cerebral ischemia and brain trauma. © 2007 Wiley-Liss, Inc. [source] Intra-Arterial Milrinone for Reversible Cerebral Vasoconstriction SyndromeHEADACHE, Issue 1 2009Manon Bouchard MD Reversible cerebral vasoconstriction syndrome (RCVS) usually presents with recurrent thunderclap headaches and is characterized by multifocal and reversible vasoconstriction of cerebral arteries that can sometimes evolve to severe cerebral ischemia and stroke. We describe the case of a patient who presented with a clinically typical RCVS and developed focal neurological symptoms and signs despite oral treatment with calcium channel blockers. Within hours of neurological deterioration, she was treated with intra-arterial milrinone, a phosphodiesterase inhibitor, which resulted in a rapid and sustained neurological improvement. [source] Association Between Migraine and Headache Attributed to Stroke: A Case,Control StudyHEADACHE, Issue 10 2008Katiuscia Nardi MD Background., Several studies were carried out to investigate the occurrence of headache attributed to acute stroke in patients with a lifetime history of migraine. Methods., In a case,control series of 96 acute stroke patients with a lifetime history of migraine (M+) and 96 stroke patients without (M,), ischemic stroke patients only, without secondary infarction, were selected. The headache attributed to acute ischemic stroke was then analyzed. Results., (M+) patients complained of headache more often than (M,) patients (P < .0001), mainly in the 24 hours before stroke onset (P < .0001). Migraine-like features of headache were recognized in a greater proportion of cases in the (M+) patient group with ischemic stroke (P < .018). A preferential brainstem location of ischemic stroke in (M+) patients emerged compared with (M,) patients (P = .014). Discussion., The high prevalence of headache attributed to stroke in (M+) patients, in a relevant proportion of cases presenting as a sentinel headache, suggests that cerebral ischemia lowers the threshold for head pain more easily in these "susceptible" patients. The most frequent involvement of the brainstem in (M+) patients with ischemic infarction concurs with recent reports that emphasized a greater headache frequency when cerebral infarctions are localized in this structure or deep brain gray matter. [source] Cellular localization of epidermal-type and brain-type fatty acid-binding proteins in adult hippocampus and their response to cerebral ischemiaHIPPOCAMPUS, Issue 7 2010Dexuan Ma Abstract This study aimed at an analysis of expression of epidermal-type and brain-type fatty acid-binding proteins (E-FABP and B-FABP, also called FABP5 and FABP7, respectively) in adult hippocampus and their potential value as neuroprotective factors after ischemic brain damage in monkey model. The immunostaining and Western blotting results show that FABP5 was mainly expressed in neurons, whereas FABP7 was primarily expressed in astrocytes and progenitors of the subgranular zone (SGZ). Interestingly, FABP5 expression in neurons increased in cornu Ammonis 1 (CA1) and remains stable within dentate gyrus (DG) after ischemia; FABP7 expression increased within both CA1 and SGZ. This indicates a potential role for FABP5 and FABP7 in intracellular fatty acid transport within different neural cells. The change in FABP5,7 expression within CA1 and DG of the adult postischemic hippocampus was compatible with previous findings of downregulation in CA1 neurons and upregulation in SGZ progenitor cells after ischemia. Altogether, the present data suggest that polyunsaturated fatty acids, such as docosahexaenoic acid, may act via FABP5 or 7 to regulate adult postischemic hippocampal neuronal antiapoptosis or neurogenesis in primates. © 2009 Wiley-Liss, Inc. [source] Sevoflurane-induced post-conditioning has no beneficial effects on neuroprotection after incomplete cerebral ischemia in ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2010H.-M. LEE Background: The aim of this study was to investigate whether sevoflurane-induced post-conditioning has a neuroprotective effect against incomplete cerebral ischemia in rats. Methods: After cerebral ischemia by right common carotid artery occlusion in combination with hemorrhagic hypotension (35 mmHg) for 30 min, 1.0 minimum alveolar concentration of sevoflurane was administered for 15 min (Post-C 15, n=8), 30 min (Post-C 30, n=8), or 60 min (Post-C 60, n=8) in rats. Sevoflurane was not administered in control (n=8) and sham control rats (n=8). Neurologic evaluations were performed at 24, 48, and 72 h after ischemia. Degrees of neuronal damage in ischemic hippocampal CA1 and the cortex were assessed by counting eosinophilic neurons, and detection of DNA fragmentation was performed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Results: Neurologic deficit scores in the Post-C 60 group were higher than in the control group at 48 and 72 h post-ischemia (P<0.05). No differences were observed in the percentages of eosinophilic neurons among the control (CA1: 37.3 ± 25.4, cortex: 26.0 ± 8.9), Post-C 15 (CA1: 54.0 ± 21.4, cortex: 30.8 ± 19.9), or Post-C 30 (CA1: 68.4 ± 17.5, cortex: 38.0 ± 11.0) groups in ischemic CA1 and cortices. However, in the Post-C 60 group, the percentages of eosinophilic neurons were higher than in the control group in CA1 and cortices (P<0.05). The percentages of TUNEL-positive cell were similar in the control group and the post-conditioned groups. Conclusion: These findings show that sevoflurane administration after ischemia does not provide neuroprotection in rats subjected to incomplete cerebral ischemia. [source] Effects of xenon on ischemic spinal cord injury in rabbits: a comparison with propofolACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2010Y. YAMAMOTO Background: Xenon has been shown to reduce cellular injury after cerebral ischemia. However, the neuroprotective effects of xenon on ischemic spinal cord are unknown. The authors compared the effects of xenon and propofol on spinal cord injury following spinal cord ischemia in rabbits. Methods: Thirty-two male New Zealand white rabbits were randomly assigned to one of three groups. In the xenon and propofol group, 70% of xenon and 0.8 mg/kg/min of propofol were administered 30 min before an aortic occlusion and maintained until the end of the procedure. The aortic occlusion was performed for 15 min. In the sham group, the aorta was not occluded. After an assessment of the hind limb motor function using the Tarlov score (0=paraplegia, 4=normal) at 48 h after reperfusion, gray and white matter injuries were evaluated based on the number of normal neurons in the anterior spinal cord and the percentage areas of vacuolation in the white matter, respectively. Results: In the xenon and propofol groups, the Tarlov score and the number of normal neurons were significantly lower than those in the sham group, whereas the percentage areas of vacuolation were similar among the three groups. There were no significant differences in Tarlov scores and the number of normal neurons between the xenon and the propofol groups. Conclusion: The results indicated that 70% of xenon has no additional neuroprotective effects on ischemic spinal cord injury in rabbits compared with propofol. [source] Neuroprotective effects of a combination of dexmedetomidine and hypothermia after incomplete cerebral ischemia in ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2010K. SATO Background: Dexmedetomidine and hypothermia are known to reduce neuronal injury following cerebral ischemia. We examined whether a combination of dexmedetomidine and hypothermia reduces brain injury after transient forebrain ischemia in rats to a greater extent than either treatment alone. Methods: Thirty-eight male Sprague,Dawley rats were anesthetized with fentanyl and nitrous oxide in oxygen. Four groups were tested: group C (saline 1 ml/kg, temporal muscle temperature 37.5 °C); group H (saline 1 ml/kg, 35.0 °C); group D (dexmedetomidine 100 ,g/kg, 37.5 °C); and group DH (dexmedetomidine 100 ,g/kg, 35.0 °C). Dexmedetomidine or saline was administered intraperitoneally 30 min before ischemia. Cerebral ischemia was produced by right carotid artery ligation with hemorrhagic hypotension (mean arterial pressure 40 mmHg) for 20 min. Neurologic outcome was evaluated at 24, 48, and 72 h after ischemia. Histopathology was evaluated in the caudate and hippocampus at 72 h after ischemia. Results: Neurologic outcome was significantly better in the group DH than the group C (P<0.05), whereas it was similar between the group DH and the groups D or H. Survival rate of the hippocampal CA1 neurons was significantly greater in groups D, H, and DH than group C (P<0.05). Histopathologic injury in the caudate section was significantly less in groups H and DH than group C (P<0.05). Conclusion: The combination of dexmedetomidine and hypothermia improved short-term neurologic outcome compared with the control group, whereas the combination therapy provided comparable neuroprotection with either of the two therapies alone. [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] Ketamine attenuates post-operative cognitive dysfunction after cardiac surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2009J. A. HUDETZ Background: Post-operative cognitive dysfunction (POCD) commonly occurs after cardiac surgery. Ketamine exerts neuroprotective effects after cerebral ischemia by anti-excitotoxic and anti-inflammatory mechanisms. We hypothesized that ketamine attenuates POCD in patients undergoing cardiac surgery concomitant with an anti-inflammatory effect. Methods: Patients randomly received placebo (0.9% saline; n=26) or an i.v. bolus of ketamine (0.5 mg/kg; n=26) during anesthetic induction. Anesthesia was maintained with isoflurane and fentanyl. A nonsurgical group (n=26) was also included as control. Recent verbal and nonverbal memory and executive functions were assessed before and 1 week after surgery or a 1-week waiting period for the nonsurgical controls. Serum C-reactive protein (CRP) concentrations were determined before surgery and on the first post-operative day. Results: Baseline neurocognitive and depression scores were similar in the placebo, ketamine, and nonsurgical control groups. Cognitive performance after surgery decreased by at least 2 SDs (z -score of 1.96) in 21 patients in the placebo group and only in seven patients in the ketamine group compared with the nonsurgical controls (P<0.001, Fisher's exact test). Cognitive performance was also significantly different between the placebo- and the ketamine-treated groups based on all z -scores (P<0.001, Mann,Whitney U -test). Pre-operative CRP concentrations were similar (P<0.33, Mann,Whitney U -test) in the placebo- and ketamine-treated groups. The post-operative CRP concentration was significantly (P<0.01, Mann,Whitney U -test) lower in the ketamine-treated than in the placebo-treated group. Conclusions: Ketamine attenuates POCD 1 week after cardiac surgery and this effect may be related to the anti-inflammatory action of the drug. [source] The effect of pneumoperitoneum in the steep Trendelenburg position on cerebral oxygenationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2009E. Y. PARK Background: daVinci® robot-assisted laparoscopic radical prostatectomy (RALP) requires pneumoperitoneum in the steep Trendelenburg position, which results in increased intracranial pressure and cerebral blood flow. The aim of this study was to evaluate the effect of pneumoperitoneum in a 30° Trendelenburg position on cerebral oxygenation using regional cerebral oxygen saturation (rSO2). Methods: Thirty-two male patients of ASA I and II physical status without previous episodes of cerebral ischemia or hemorrhage undergoing daVinci® RALP were enrolled. The rSO2 was continuously monitored with near-infrared spectroscopy (INVOS® 5100Ô) during the study period. Measurements were obtained immediately after anesthesia induction (T0; baseline), 5 min after a 30° Trendelenburg position (T1), 5 min after 15 mmHg pneumoperitoneum in a supine position (T2), 30, 60 and 120 min after the pneumoperitoneum in a Trendelenburg position (T3, T4 and T5, respectively) and after desufflation in a supine position (T6). Results: The change in the left and right rSO2 was statistically significant (Left P=0.004 and Right P=0.023). Both the right and the left rSO2 increased significantly during pneumoperitoneum in a Trendelenburg position (from T3 to T5) and at T6 compared with the baseline value at T0. The partial pressure of carbon dioxide (PaCO2) was increased significantly at T2, T3, T5 and T6 compared with the baseline value at T0. Conclusions: During daVinci® RALP, cerebral oxygenation, as assessed by rSO2, increased slightly, which suggests that the procedure did not induce cerebral ischemia. The PaCO2 should be maintained within the normal limit during pneumoperitoneum in a Trendelenburg position in patients undergoing daVinci® RALP because the rSO2 increased in conjunctions with the increase in PaCO2. [source] The association of gingivitis and periodontitis with ischemic strokeJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 5 2004Christof E. Dörfer Abstract Objectives: The aim of this study was to assess the associations of different periodontal parameters with cerebral ischemia. Methods: In a case,control study, 303 consecutive patients with ischemic stroke or transient ischemic attack, and 300 representative population controls received a complete clinical and radiographic dental examination. Patients were examined on average 3 days after ischemia. The individual mean clinical attachment loss measured at four sites per tooth was used as indicator variable for periodontitis. Results: Patients had higher clinical attachment loss than population (p<0.001). After adjustment for age, gender, number of teeth, vascular risk factors and diseases, childhood and adult socioeconomic conditions and lifestyle factors, a mean clinical attachment loss >6 mm had a 7.4 times (95% confidence interval 1.55,15.3) a gingival index >1.2 a 18.3 times (5.84,57.26) and a radiographic bone loss a 3.6 times (1.58,8.28) higher risk of cerebral ischemia than subjects without periodontitis or gingivitis, respectively. Conclusion: Periodontitis is an independent risk factor for cerebral ischemia and acute exacerbation of inflammatory processes in the periodontium might be a trigger for the event of cerebral ischemia. [source] Effects of sevoflurane on cognitive deficit, motor function, and histopathology after cerebral ischemia in ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2009E. EBERSPÄCHER Background: The volatile anesthetic sevoflurane exhibits neuroprotective properties when assessed for motor function and histopathology after cerebral ischemia in rats. Damage of hippocampal neurons after ischemia relates to a number of cognitive deficits that are not revealed by testing animals for motor function. Therefore, the present study evaluates cognitive and behavioral function as well as hippocampal damage in rats subjected to cerebral ischemia under sevoflurane compared with fentanyl/nitrous oxide (N2O)/O2 anesthesia. Methods: Thirty-four rats were trained for 10 days using a hole-board test to detect changes in cognitive and behavioral function. Rats were randomly assigned to the following groups: (A) sham/fentanyl/N2O/O2 (n=7); (B) ischemia/fentanyl/N2O/O2 (n=10); (C) sham/2.0 vol% sevoflurane in O2/air (n=7); and (D) ischemia/2.0 vol% sevoflurane in O2/air (n=10). Cerebral ischemia was produced by unilateral common carotid artery occlusion combined with hemorrhagic hypotension (mean arterial blood pressure 40 mmHg for 45 min). Temperature, arterial blood gases, and pH were maintained constant. Cerebral blood flow was measured using laser-Doppler flowmetry. After surgery, cognitive and behavioral function was re-evaluated for 10 days. On day 11, the brains were removed for histopathologic evaluation (hematoxylin/eosin-staining). Results: Cognitive testing revealed deficits in declarative and working memory in ischemic rats anesthetized with fentanyl/N2O. Rats anesthetized with sevoflurane during ischemia showed a significantly better outcome. Hippocampal damage was significantly worse with fentanyl/N2O. Conclusion: The present data add to previous investigations showing that sevoflurane prevents a deficit in cognitive function and histopathological damage induced by cerebral ischemia in rats. [source] | |||||||||||||||||||||||||||||||