Anion channel blockers attenuate delayed neuronal cell death induced by transient forebrain ischemia

2007 ◽  
Vol 85 (7) ◽  
pp. 1427-1435 ◽  
Author(s):  
Hana Inoue ◽  
Hirokazu Ohtaki ◽  
Tomoya Nakamachi ◽  
Seiji Shioda ◽  
Yasunobu Okada
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Anion Channel ◽  
Channel Blockers ◽  
Forebrain Ischemia ◽  
Transient Forebrain Ischemia ◽  
Delayed Neuronal Cell Death

scholarly journals Correlation between Delayed Neuronal Cell Death and Selective Decrease in Phosphatidylinositol 4-Kinase Expression in the CA1 Subfield of the Hippocampus after Transient Forebrain Ischemia

2003 ◽  
Vol 23 (8) ◽  
pp. 962-971 ◽  
Author(s):  
Yudai Furuta ◽  
Takashi Uehara ◽  
Yasuyuki Nomura
Keyword(s):  
Cell Death ◽  
Ischemia Reperfusion ◽  
Neuronal Cell Death ◽  
Neuroblastoma Cells ◽  
Neuronal Cell ◽  
Mrna Levels ◽  
Forebrain Ischemia ◽  
Transient Forebrain Ischemia ◽  
Phosphatidylinositol 4 ◽  
Delayed Neuronal Cell Death

Transient forebrain ischemia induces a delayed neuronal death in the CA1 area of the hippocampus. However, the mechanism leading to this phenomenon has yet to be established. The authors used an mRNA differential-display method to isolate genes for which mRNA levels change only in the hippocampus during ischemia/reperfusion. They succeeded in identifying the product of one down-regulated gene as phosphatidylinositol 4-kinase (PI 4-K). Compared with control levels, PI 4-K mRNA expression in the hippocampus, but not the cerebral cortex, was significantly decreased by 30% and about 80% 1 and 7 days after ischemia/reperfusion, respectively. Interestingly, PI 4-K and PI bisphosphate levels were selectively decreased in the CA1 region, but not other regions, whereas TUNEL-positive cells could be detected 3 days after ischemia. Consistent with these results, PI 4-K expression was suppressed by hypoxia in SK-N-MC neuroblastoma cells before loss of cell viability. Overexpression of wild-type PI 4-K, but not the kinase-negative mutant of PI 4-K (K1789A), recovered the loss of viability induced by hypoxia. These findings strongly suggest that a prior decrease in PI 4-K and PI bisphosphate levels caused by brain ischemia/hypoxia is partly involved in delayed neuronal cell death.

Late-onset lipid peroxidation and neuronal cell death following transient forebrain ischemia in rat brain

1997 ◽  
Vol 772 (1-2) ◽  
pp. 37-44 ◽  
Author(s):  
Yoichi Kondo ◽  
Masato Asanuma ◽  
Sakiko Nishibayashi ◽  
Emi Iwata ◽  
Norio Ogawa
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Rat Brain ◽  
Late Onset ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Forebrain Ischemia ◽  
Transient Forebrain Ischemia

scholarly journals Prostaglandin E2 Type 1 Receptors Contribute to Neuronal Apoptosis after Transient Forebrain Ischemia

2013 ◽  
Vol 33 (8) ◽  
pp. 1207-1214 ◽  
Author(s):  
Munehisa Shimamura ◽  
Ping Zhou ◽  
Barbara Casolla ◽  
Liping Qian ◽  
Carmen Capone ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Apoptosis ◽  
Ischemia Reperfusion ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Prostaglandin E ◽  
Pathophysiological Mechanism ◽  
Forebrain Ischemia ◽  
Transient Forebrain Ischemia

Cyclooxygenase-2-derived prostaglandin E2 (PGE2) contributes to excitotoxic and ischemic neuronal cell death by engaging neuronal PGE2 type 1 receptors (EP1R). Our previous studies have shown that EP1R signaling resulted in disturbances of intracellular Ca2 + homeostasis and suppression of the pro-survival protein kinase AKT. The aim of this study was to investigate whether these pathophysiological mechanism have a role in the neuronal cell death after transient forebrain ischemia. Mice were subjected to ischemia/reperfusion by bilateral common carotid artery occlusion. Hippocampal cornu ammonis area 1 (CA1) neuronal cell death was determined 5 days after reperfusion. Animals treated with the EP1R antagonist SC51089 or EP1R-deficient mice (EP1 –/–) showed significantly less neuronal injury as compared to vehicle-treated wild-type controls. Benefits of EP1R blockage were still evident 14 days after injury. Better neuronal survival was correlated with reduced neuronal caspase-3 activity and decreased nuclear translocation of the apoptosis-inducing factor. Neuroprotection could be reverted by intracerebroventricular administration of the phosphoinositide 3-kinase inhibitor LY294002 and was not further increased by the calcineurin inhibitor FK506. These data implicate EP1R in postischemic neuronal apoptosis possibly by facilitating AKT inhibition.

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