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Transient Forebrain Ischemia (transient + forebrain_ischemia)
Selected AbstractsLipid Alterations in Transient Forebrain IschemiaJOURNAL OF NEUROCHEMISTRY, Issue 6 2000Possible New Mechanisms of CDP-Choline Neuroprotection Abstract: We have previously demonstrated that cytidine5,-diphosphocholine (CDP-choline or citicoline) attenuated arachidonicacid (ArAc) release and provided significant protection for the vulnerablehippocampal CA1 neurons of the cornu ammonis after transientforebrain ischemia of gerbil. ArAc is released by the activation ofphospholipases and the alteration of phosphatidylcholine (PtdCho) synthesis.Released ArAc is metabolized by cyclooxygenases/lipoxygenases to formeicosanoids and reactive oxygen species (ROS). ROS contribute to neurotoxicitythrough generation of lipid peroxides and the cytotoxic byproducts4-hydroxynonenal and acrolein. ArAc can also stimulate sphingomyelinase toproduce ceramide, a potent pro-apoptotic agent. In the present study, weexamined the changes and effect of CDP-choline on ceramide and phospholipidsincluding PtdCho, phosphatidylethanolamine (PtdEtn), phosphatidylinositol(PtdIns), phosphatidylserine (PtdSer), sphingomyelin, and cardiolipin (anexclusive inner mitochondrial membrane lipid essential for electron transport)following ischemia/1-day reperfusion. Our studies indicated significantdecreases in total PtdCho, PtdIns, PtdSer, sphingomyelin, and cardiolipin andloss of ArAc from PtdEtn in gerbil hippocampus after 10-min forebrainischemia/1-day reperfusion. CDP-choline (500 mg/kg i.p. immediately afterischemia and at 3-h reperfusion) significantly restored the PtdCho,sphingomyelin, and cardiolipin levels as well as the ArAc content of PtdChoand PtdEtn but did not affect PtdIns and PtdSer. These data suggest multiplebeneficial effects of CDP-choline: (1) stabilizing the cell membrane byrestoring PtdCho and sphingomyelin (prominent components of outer cellmembrane), (2) attenuating the release of ArAc and limiting its oxidativemetabolism, and (3) restoring cardiolipin levels. [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] Transient forebrain ischemia modulates focal adhesion kinase (FAK)-mediated signal transduction in gerbil hippocampusJOURNAL OF NEUROCHEMISTRY, Issue 2003M. Ziemka-Na Focal adhesion kinase (FAK) is thought to play a major role in conveying survival signals from extracellular matrix (ECM). Phosphorylated FAK may interact with other nonreceptor kinases such as Src, and adaptor molecule Cas, perhaps providing a pathway by which ECM may regulate cell viability. In the present study the expression and tyrosine phosphorylation of FAK, Src and Cas after 5 min of global ischemia were investigated. The primary activation/phosphorylation of FAK, observed during first 6 h after ischemic injury, was followed by its profound down-regulation. At 72 h of reperfusion the level of phosphorylated FAK decrease to about 50% of the control. The decrease of FAK phosphorylation coincides with its proteolytic degradation. Cleavage of FAK coincided temporally with the loss of Src and Cas. Ischemia-induced proteolytic processing of the investigated proteins may lead to the interruption of ECM-derived signals and compromise neuronal survival. Acknowledgements:, Sponsored by SCSR 4P05A 08619 and Med. Res. Ctr. [source] Astrocyte targeted overexpression of Hsp72 or SOD2 reduces neuronal vulnerability to forebrain ischemiaGLIA, Issue 9 2010Lijun Xu Abstract Brief forebrain ischemia is a model of the delayed hippocampal neuronal loss seen in patients following cardiac arrest and resuscitation. Previous studies demonstrated that selective dysfunction of hippocampal CA1 subregion astrocytes occurs hours to days before delayed neuronal death. In this study we tested the strategy of directing protection to astrocytes to protect neighboring neurons from forebrain ischemia. Two well-studied protective proteins, heat shock protein 72 (Hsp72) or superoxide dismutase 2 (SOD2), were genetically targeted for expression in astrocytes using the astrocyte-specific human glial fibrillary acidic protein (GFAP) promoter. The expression constructs were injected stereotacticly immediately above the hippocampal CA1 region on one side of the rat brain two days prior to forebrain ischemia. Cell type specific expression was confirmed by double label immunohistochemistry. When the expression constructs were injected two days before transient forebrain ischemia, the loss of CA1 hippocampal neurons observed seven days later was significantly reduced on the injected side compared with controls. This neuroprotection was associated with significantly better preservation of astrocyte glutamate transporter-1 immunoreactivity at 5-h reperfusion and reduced oxidative stress. Improving the resistance of astrocytes to ischemic stress by targeting either the cytosolic or mitochondrial compartment was thus associated with preservation of CA1 neurons following forebrain ischemia. Targeting astrocytes is a promising strategy for neuronal preservation following cardiac arrest and resuscitation. © 2010 Wiley-Liss, Inc. [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] The combined neuroprotective effects of lidocaine and dexmedetomidine after transient forebrain ischemia in ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2009T. GOYAGI Background: We investigated whether coadministration of lidocaine and dexmedetomidine would reduce brain injury following transient forebrain ischemia in rats to a greater extent than either drug alone. Methods: Adult male Sprague,Dawleyrats were anesthetized with halothane to maintain normocapnia and normoxia. Rats received subcutaneous injection of saline 1 ml/kg, lidocaine 10 mg/kg, dexmedetomidine 3 ,g/kg, or lidocaine 10 mg/kg plus dexmedetomidine 3 ,g/kg. Thirty minutes after the drug injection, forebrain ischemia was induced by hemorrhagic hypotension and occlusion of the bilateral carotid arteries, and was confirmed by isoelectric EEG. At the end of 10-min ischemia, rats were reperfused. The same dose of drugs was administered 3, 24, and 48 h after ischemia. Neurological examination was done at 1, 2, and 7 days after ischemia. Seven days after ischemia, the brain was stained with hematoxylin and eosin. We counted ischemic cells in the CA1 hippocampal region, striatum, and cerebral cortex. We also measured extracellular glutamate and norepinephrine concentration in hippocampal CA1 in the four groups. Results: As compared with saline-treated rats, rats receiving dexmedetomidine plus lidocaine showed less than neurological deficit scores at 2 and 7 days after ischemia, and had less ischemic cells in the CA1 region. However, administration of dexmedetomidine plus lidocaine did not alter the area under the glutamate concentration curve and norepinephrine concentration during ischemia in the CA1 region, compared with saline-treated rats. Conclusions: Our results suggest coadministration of lidocaine and dexmedetomidine improves the neurological outcome without alteration of glutamate and norepinephrine concentrations during forebrain ischemia in rats. [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] Differential expression of Musashi1 and nestin in the adult rat hippocampus after ischemiaJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2002Yoshiki Yagita Abstract Both nestin and the neural RNA-binding protein Musashi1 (Msi1) are expressed in neural stem cells in the subventricular zone. Neurogenesis in the hippocampus has received much attention, so we evaluated the expression of Msi1 and nestin in the adult rat hippocampus after transient forebrain ischemia. Both Msi1 and nestin were induced in the reactive astrocytes after ischemia, especially in the CA1 region, until 35 days after ischemia. Induction of both molecules suggested that reactive astrocytes might have immature characteristics. In the subgranular zone (SGZ) of the hippocampal dentate gyrus, Msi1-positive cells formed clusters after ischemia. These cells were labeled by bromodeoxyuridine (BrdU) but did not express glial fibrillary acidic protein. In contrast, very few nestin-positive cells were labeled by BrdU. Our results suggest that neuronal progenitor cells in the SGZ expressed Msi1 but not nestin. © 2002 Wiley-Liss, Inc. [source] Effect of mivazerol, a ,2 -agonist, on striatal norepinephrine concentration during transient forebrain ischemia in rats,ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2008T. KIMURA Background: We have previously reported that mivazerol, a ,2 -agonist, possibly provides neuroprotection against transient forebrain ischemia in rats. This study was designed to investigate the ability of mivazerol to attenuate ischemia-induced increase in striatal norepinephrine concentration after transient forebrain ischemia in rats. Methods: Male Sprague,Dawley rats, anesthetized with halothane, were assigned to one of three groups (n=10 each); control (C, normal saline 1 ml/kg), mivazerol 20 ,g/kg (M20), and 40 ,g/kg (M40) groups. Monitored variables included temporal muscle temperature (maintained at 37.5±0.1 °C), electroencephalogram, systolic/diastolic blood pressure, heart rate, arterial blood gases, and blood glucose concentrations. Thirty minutes after subcutaneous drug administration, forebrain ischemia was induced with hemorrhagic hypotension (systolic arterial pressure: 40,50 mmHg) and bilateral carotid artery occlusion for 10 min, and then the brain was reperfused. Norepinephrine concentration in the interstitial fluids in the striatum was analyzed using in vivo microdialysis in combination with high-performance liquid chromatography. Results: Ischemia resulted in a prompt increase in norepinephrine concentrations in the striatum in all groups. However, there were no significant differences in norepinephrine concentrations in the striatum between the three groups at any period. Conclusions: Our results indicate that mivazerol did not attenuate ischemia-induced increase in striatal norepinephrine concentration. This suggests that the possible neuroprotective property of mivazerol is not related to inhibition of norepinephrine release in the brain. [source] Changes in the proton T2 relaxation times of cerebral water and metabolites during forebrain ischemia in rat at 9.4 TMAGNETIC RESONANCE IN MEDICINE, Issue 6 2003Hao Lei Abstract Proton T2 relaxation times of cerebral water and metabolites were measured before, during, and after transient forebrain ischemia in rat at 9.4 T using localized proton magnetic resonance spectroscopy (1H-MRS) with Hahn echoes formed at different echo times (TEs). It was found that the T2 values of water and N-acetyl aspartate (NAA) methyl, but not total creatine (tCr) methyl, decrease significantly (,10%) during ischemia, and this T2 reduction is reversed by reperfusion. The T2 reduction observed for NAA was most likely caused by the extravascular component of the blood oxygenation level-dependent (BOLD) effect induced by a drastically increased deoxyhemoglobin content during ischemia. The absence of T2 changes for tCr can probably be explained by the fact that the BOLD-related T2 decrease was counterbalanced by the conversion of phosphocreatine (PCr) to creatine (Cr), which has a longer T2 than PCr, during ischemia. The changes in T2 should be taken into account for the quantification of metabolite concentrations during ischemia. Magn Reson Med 49:979,984, 2003. © 2003 Wiley-Liss, Inc. [source] | |||||||||||||