Neuroprotection of hypothermia against neuronal death in rat hippocampus through inhibiting the increased assembly of GluR6-PSD95-MLK3 signaling module induced by cerebral ischemia/reperfusion

Hippocampus ◽  
2008 ◽  
Vol 18 (4) ◽  
pp. 386-397 ◽  
Author(s):  
Wei-Wei Hu ◽  
Yang Du ◽  
Chong Li ◽  
Yuan-Jian Song ◽  
Guang-Yi Zhang
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Death ◽  
Ischemia Reperfusion ◽  
Rat Hippocampus ◽  
Cerebral Ischemia Reperfusion

Abstract T P84: Neuroprotective Effect of Probenecid in a Rat Model of Transient Global Cerebral Ischemia-Reperfusion

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Rui-li Wei ◽  
Yan Xu ◽  
Jing-ye Wang ◽  
Ben-yan Luo
Keyword(s):  
Cerebral Ischemia ◽  
Protective Effect ◽  
Neuronal Death ◽  
Ischemia Reperfusion ◽  
Cerebral Injury ◽  
Therapeutic Drug ◽  
Ca1 Region ◽  
Cerebral Ischemia Reperfusion ◽  
Hippocampal Ca1

Background and Purpose: Probenecid (PROB) has been used for decades to treat gouty arthritis with few side effects and recent studies revealed that it is also a specific inhibitor of pannexin-1 channel. Panx1 channel was activated by ischemic injury and inhibition of the panx1 channel maybe efficacious in stroke treatment. However, the role of PROB in cerebral ischemia /reperfusion (I/R) injury remains unclear. The aim of this study was to investigate the role of PROB in the transient global cerebral I/R injury in rats and its protective mechanisms. Methods: Twenty minutes of transient global cerebral I/R was induced using the four-vessel occlusion (4-VO) method in rats. PROB was given in the different dose, time and administration routes to verify its neuroprotective effects. Neuronal death in the hippocampal CA1 region was observed using H & E staining 7 days after ischemia. Molecular mechanisms of activation of calpain-cathepsin pathway and inflammatory cells by I/R injury were also investigated. Results: Treatment with PROB (0.1, 1 and 10 mg/kg ) 10 min before ischemia protected against I/R-induced hippocampal CA1 neuronal death significantly, and 1 mg/kg has best protective effect. Post-insult treatment 2h after reperfusion also protected against neuronal death and prolonged use for continuous 7 days could improve its protective effects compared to the single use 6h after reperfusion.Furthermore,oral administration also had protective effect. Cathepsin B expression was inceased significantly in CA-1 region after ischemia and PROB treatment could inhibit its expression. Expression of both calpain-1 and hsp70 at 1d ,2d and 3d after reperfusion were upregulated, whereas the expression of calpain-1 was inhibited and hsp70 was strengthened by pre-treatment with PROB. Prolonged PROB treatment suppressed the activation of microglia and astrocytes, reduced the number of microglia in CA1 region. Conclusions: Our study indicates that PROB protects against transient global cerebral I/R injury administrated before ischemia and even 6h after reperfusion by reducing calpain-1 expression , inhibiting lysosomal rupture and the activation of the glia, which suggests RPOB may be a promising therapeutic drug for clinical treatment of ischemic cerebral injury.

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