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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Global cerebral ischemia leads to selective neuronal damage in the CA1 sector of the hippocampus and in the striatum. This ischemia leads to a deficit in spatial learning and memory in the water maze. The results of earlier studies that have examined the relationship between neuronal damage and the deficit in the water maze were not clear-cut. It has been observed that neuroprotection reduces both the deficit in the water maze and the neuronal damage. The present study therefore approached the relationship between the neuronal damage and the deficit in the water maze by pharmacological means. Global cerebral ischemia was induced in male Wistar rats by four-vessel occlusion for 20 min. Ischemic rats were then treated with the noncompetitive non-NMDA receptor antagonist GYKI 52466 (30 mg/kg), the radical scavenger LY 231617 (20 mg/kg), the inhibitor of protein kinase C staurosporine (0.1 mg/kg), or solvent. Treatment with GYKI 52466 or LY 231617 reduced the deficit in spatial learning by limiting the increase in swim distance due to ischemia. In addition, LY 231617 reduced the deficit in spatial memory as demonstrated by minimizing the ischemia-induced reduction in time spent in the quadrant of the former platform position during the probe trial. Staurosporine had no influence on the ischemia-induced behavioural changes. Histological examination revealed neuronal damage in the hippocampus and in the striatum in all of the ischemic rats. However, treatment with GYKI 52466 or LY 231617 reduced the hippocampal damage. Correlation analysis demonstrated a correlation between hippocampal damage and total swim distance (r = 0.88, P < 0.001). No correlation was found between hippocampal damage and quadrant time of the probe trial (r = -0.24, p > 0.1). No correlation was observed between striatal damage and either total swim distance of the escape trials (r = 0.28. p > 0.1) or quadrant time of the probe trial (r = -0.08, p > 0.6). It is concluded that a correlation exists between hippocampal damage and the deficit in spatial learning following global cerebral ischemia.
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PMID:Correlation between hippocampal neuronal damage and spatial learning deficit due to global ischemia. 913 Mar 3

Oxidative stress is believed to play an important role in neuronal cell death associated with several neurodegenerative diseases (e.g., Alzheimer disease, Parkinson disease, and cerebral ischemia). Neuronal cell death might be one of the crucial mediators of these diseases. The transcription factor NF-kappaB is well-known for its roles in preventing apoptotic cell death. Data indicated that NF-kappaB activation by pre-conditioning is part of a general brain tolerance program. Here we show that pre-conditioning leading to NF-kappaB activation also protects against oxidative insults generated by Fe2+ ions. Protection was accompanied by a long-lasting (more than 24 h) NF-kappaB activation. Using this paradigm of oxidative insult, we analyzed the effect of hypericin, one of the active principles of St. John's Wort. Hypericin alone was able to induce short-time activation of NF-kappaB, which declined to basal levels after 24 h. Cell death was induced by hypericin at a concentration of 10 microM. A profound synergistic action in inducing apoptosis was detected in co-treatment of hypericin together with FeSO4. In contrast, hypericin in low concentrations was able to partly prevent cell death induced by amyloid-beta-peptide (Abeta). Hypericin (10 microM) synergistically enhanced Abeta neurotoxicity. Since hypericin is a described inhibitor of protein kinase C, we compared its action to staurosporine, another natural neuronal death-promoting PKC inhibitor. Staurosporine induced cell death and activates NF-kappaB. Molecular inhibition of NF-kappaB activation with a transdominant negative IkappaB-alpha protected against staurosporine-induced cell death. In summary, the data describe NF-kappaB in the same primary neuronal culture as stimulus-dependent, anti-apoptotic, or pro-apoptotic factor.
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PMID:Stimulus-dependent activation of NF-kappaB specifies apoptosis or neuroprotection in cerebellar granule cells. 1262 8

Caspase 3 activation has been linked to the acute neurotoxic effects of central nervous system damage, as in traumatic brain injury or cerebral ischaemia, and also to the early events leading to long-term neurodegeneration, as in Alzheimer's disease. However, the precise mechanisms activating caspase 3 in neuronal injury are unclear. RhoB is a member of the Rho GTPase family that is dramatically induced by cerebral ischaemia or neurotrauma, both in preclinical models and clinically. In the current study, we tested the hypothesis that RhoB might directly modulate caspase 3 activity and apoptotic or necrotic responses in neurons. Over-expression of RhoB in the NG108-15 neuronal cell line or in cultured corticohippocampal neurons elevated caspase 3 activity without inducing overt toxicity. Cultured corticohippocampal neurons from RhoB knockout mice did not show any differences in sensitivity to a necrotic stimulus - acute calcium ionophore exposure - compared with neurons from wild-type mice. However, corticohippocampal neurons lacking RhoB exhibited a reduction in the degree of DNA fragmentation and caspase 3 activation induced by the apoptotic agent staurosporine, in parallel with increased neuronal survival. Staurosporine induction of caspase 9 activity was also suppressed. RhoB knockout mice showed reduced basal levels of caspase 3 activity in the adult brain. These data directly implicate neuronal RhoB in caspase 3 activation and the initial stages of programmed cell death, and suggest that RhoB may represent an attractive target for therapeutic intervention in conditions involving elevated caspase 3 activity in the central nervous system.
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PMID:Altered apoptotic responses in neurons lacking RhoB GTPase. 2209 22