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Transient Global Ischemia (transient + global_ischemia)
Selected AbstractsDoes 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] An ultrastructural study of cell death in the CA1 pyramidal field of the hippocapmus in rats submitted to transient global ischemia followed by reperfusionJOURNAL OF ANATOMY, Issue 5 2007Aline De Souza Pagnussat Abstract In the course of ischemia and reperfusion a disruption of release and uptake of excitatory neurotransmitters occurs. This excitotoxicity triggers delayed cell death, a process closely related to mitochondrial physiology and one that shows both apoptotic and necrotic features. The aim of the present study was to use electron microscopy to characterize the cell death of pyramidal cells from the CA1 field of the hippocampus after 10 min of transient global ischemia followed by short reperfusion periods. For this study 25 adult male Wistar rats were used, divided into six groups: 10 min of ischemia, 3, 6, 12 and 24 h of reperfusion and an untouched group. Transient forebrain ischemia was produced using the 4-vessel occlusion method. The pyramidal cells of the CA1 field from rat hippocampus submitted to ischemia exhibited intracellular alterations consistent with a process of degeneration, with varied intensities according to the reperfusion period and bearing both apoptotic and necrotic features. Gradual neuronal and glial modifications allowed for the classification of the degenerative process into three stages: initial, intermediate and final were found. With 3 and 6 h of reperfusion, slight and moderate morphological alterations were seen, such as organelle and cytoplasm edema. Within 12 h of reperfusion, there was an apparent recovery and more ,intact' cells could be identified, while 24 h after the event neuronal damage was more severe and cells with disrupted membranes and cell debris were identified. Necrotic-like neurons were found together with some apoptotic bodies with 24 h of reperfusion. Present results support the view that cell death in the CA1 field of rat hippocampus submitted to 10 min of global transient ischemia and early reperfusion times includes both apoptotic and necrotic features, a process referred to as parapoptosis. [source] Zn2+ mediates ischemia-induced impairment of the ubiquitin-proteasome system in the rat hippocampusJOURNAL OF NEUROCHEMISTRY, Issue 5 2009Min Chen Abstract Deposition of ubiquitinated protein aggregates is a hallmark of neurodegeneration in both acute neural injuries, such as stroke, and chronic conditions, such as Parkinson's disease, but the underlying mechanisms are poorly understood. In the present study, we examined the role of Zn2+ in ischemia-induced impairment of the ubiquitin-proteasome system in the CA1 region of rat hippocampus after transient global ischemia. We found that scavenging endogenous Zn2+ reduced ischemia-induced ubiquitin conjugation and free ubiquitin depletion. Furthermore, exposure to zinc chloride increased ubiquitination and inhibited proteasomal enzyme activity in cultured hippocampal neurons in a concentration- and time-dependent manner. Further studies of the underlying mechanisms showed that Zn2+ -induced ubiquitination required p38 activation. These findings indicate that alterations in Zn2+ homeostasis impair the protein degradation pathway. [source] Regulatory proteins of eukaryotic initiation factor 2-alpha subunit (eIF2,) phosphatase, under ischemic reperfusion and toleranceJOURNAL OF NEUROCHEMISTRY, Issue 4 2007Lidia García-Bonilla Abstract Phosphorylation of the , subunit of eukaryotic translation initiation factor 2 (eIF2,), which is one of the substrates of protein phosphatase 1 (PP1), occurs rapidly during the first minutes of post-ischemic reperfusion after an episode of cerebral ischemia. In the present work, two experimental models of transient global ischemia and ischemic tolerance (IT) were used to study PP1 interacting/regulatory proteins following ischemic reperfusion. For that purpose we utilized PP1 purified by microcystin chromatography, as well as 2D DIGE of PP1, and PP1, immunoprecipitates. The highest levels of phosphorylated eIF2, found after 30 min reperfusion in rats without IT, correlated with increased levels in PP1 immunoprecipitates of the inhibitor DARPP32 as well as GRP78 and HSC70 proteins. After 4 h reperfusion, the levels of these proteins in PP1c complexes had returned to control values, in parallel to a significant decrease in eIF2, phosphorylated levels. IT that promoted a decrease in eIF2, phosphorylated levels after 30 min reperfusion induced the association of GADD34 with PP1c, while prevented that of DARPP32, GRP78, and HSC70. Different levels of HSC70 and DARPP32 associated with PP1, and PP1, isoforms, whereas GRP78 was only detected in PP1, immunoprecipitates. Here we suggest that PP1, through different signaling complexes with their interacting proteins, may modulate the eIF2, phosphorylation/dephosphorylation during reperfusion after a transient global ischemia in the rat brain. Of particular interest is the potential role of GADD34/PP1c complexes after tolerance acquisition. [source] Increases in tumor necrosis factor-, following transient global cerebral ischemia do not contribute to neuron death in mouse hippocampusJOURNAL OF NEUROCHEMISTRY, Issue 6 2005Yuki Murakami Abstract The actions of tumor necrosis factor-, (TNF-,) produced by resident brain cells and bone marrow-derived cells in brain following a transient global ischemia were evaluated. In wild-type mice (C57Bl/6J) following 20 min ischemia with bilateral common carotid artery occlusion (BCCAo), TNF-, mRNA expression levels in the hippocampus were significantly increased at 3 h and 36 h and exhibited a biphasic expression pattern. There were no hippocampal TNF-, mRNA expression levels at early time points in either wild-type mice bone marrow transplanted (BMT)-chimeric-TNF-, gene-deficient (T/W) or TNF-, gene-deficient mice BMT-TNF-, gene-deficient mice (T/T), although TNF-, mRNA levels were detectable in T/W BMT mice at 36 h. Histopathological findings showed no intergroup differences between wild-type and TNF-, gene-deficient mice at 4 and 7 days after transient ischemia. In addition, nuclear factor-,B (NF-,B) was activated within 12 h after global cerebral ischemia, but electrophoretic mobility shift assays (EMSA) showed no intergroup differences between wild type and TNF-, gene-deficient mice. In summary, early hippocampal TNF-, mRNA expression may not be related to bone marrow-derived cells, and secondary TNF-, expression as early as 36 h after ischemia probably resulted mainly from endogenous brain cells and possibly a few bone marrow-derived cells. Although we cannot exclude the possibility of the TNF-, contribution to the physiologic changes of hippocampus after transient global ischemia, these results indicate that TNF-, does not influence the morphological changes of the hippocampal neurons under our study condition. [source] Increased phosphorylation and redistribution of NMDA receptors between synaptic lipid rafts and post-synaptic densities following transient global ischemia in the rat brainJOURNAL OF NEUROCHEMISTRY, Issue 1 2005Shintaro Besshoh Abstract Ischemia results in increased phosphorylation of NMDA receptors. To investigate the possible role of lipid rafts in this increase, lipid rafts and post-synaptic densities (PSDs) were isolated by the extraction of rat brain synaptosomes with Triton X-100 followed by sucrose density gradient centrifugation. Lipid rafts accounted for the majority of PSD-95, whereas SAP102 was predominantly located in PSDs. Between 50 and 60% of NMDA receptors were associated with lipid rafts. Greater than 85,90% of Src and Fyn were present in lipid rafts, whereas Pyk2 was mainly associated with PSDs. Lipid rafts and PSDs were isolated from animals subjected to 15 min of global ischemia followed by 6 h of recovery. Ischemia did not affect the yield, density, flotillin-1 or cholesterol content of lipid rafts. Following ischemia, the phosphorylation of NR1 by protein kinase C and tyrosine phosphorylation of NR2A and NR2B was increased in both lipid rafts and PSDs, with a greater increase in tyrosine phosphorylation occurring in the raft fraction. Following ischemia, NR1, NR2A and NR2B levels were elevated in PSDs and reduced in lipid rafts. The findings are consistent with a model involving close interaction between lipid rafts and PSDs and a role for lipid rafts in ischemia-induced signaling pathways. [source] Modulation of ERK and JNK activity by transient forebrain ischemia in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2006Deborah A. Shackelford Abstract The mitogen-activated protein (MAP) kinase families of ERK and JNK participate in numerous intracellular signaling pathways and are abundantly expressed in the CNS. Activation of ERK and JNK during reperfusion of ischemic tissue is implicated in promoting cell death, insofar as inhibition of either pathway reduces neuronal cell death. However, ERK or JNK activation provides protection in other neuronal injury models. In this study, we monitored the concurrent modulation of ERK and JNK activity in the hippocampus, neocortex, and striatum during ischemia and immediately upon reperfusion in a rat model of transient global ischemia. All three regions incur a similar reduction in blood flow during occlusion but show different extents and temporal patterns of injury following reperfusion. ERK and JNK were active in the normal rat forebrain, and phosphorylation was reduced by ischemia. Upon reperfusion, ERK was rapidly activated in the hippocampus, neocortex, and striatum, whereas JNK phosphorylation increased in the hippocampus and striatum but not in the neocortex. The response of JNK vs. ERK more closely reflects the susceptibility of these regions. JNK1 was the predominant phosphorylated isoform. A minor pool of phosphorylated JNK3 increased above the control level after reperfusion in hippocampal but not in neocortical particulate fractions. In addition, a novel 32,35-kDa c-Jun kinase activity was detected in the hippocampus, neocortex, and striatum. The results show that ERK and JNK activities are rapidly, but not identically, modulated by ischemia and reperfusion and indicate that the MAP kinase pathways contribute to regulating the response to acute CNS injury. © 2006 Wiley-Liss, Inc. [source] | ||||||||||