Enhancement Of Neuroprotection And Heat Shock Protein Induction By Combined Prostaglandin A₁ And Lithium In Rodent Models Of Permanent Focal Cerebral Ischemia

Aim: To investigate the neuroprotective effects of prostaglandin A₁ (PGA₁) and Lithuim (Li) and their combination, and the relationships between its neuroprotection and the expression of heat shock proteins (HSPs) in rat models of permanent focal cerebral ischemia; and whether CHOP/GADD153 was involved in their neuroprotection.Methods: Permanent middle cerebral artery occlusion (pMCAO) model was induced by using intraluminal filament technique in rats. PGA₁ (16.5-33nmol) was injected intracerebroventricularly (icv) 15min before the onset of ischemia; Rats pretreated with subcutaneous injection of Li (lmEq/kg) was injected subcutaneously for two days before ischemic insult. Twenty-four hours after the occlusion, the neuroprotections of PGA₁, Li and their combination were analyzed by scoring neurological deficits, assessing brain infarction volume with 2,3,5-triphenyl tetrazolium chloride (TTC), determining the brain water content. Western blot was employed to determine alternations in HO-1/ HSP32, HSP70, GRP78, HSP90α, β and CHOP/GADD153 levels in ischemic striatum 24hr after the occlusion; and immunohistochemistry was employed to detect alternations in the expression of GRP78 24hr after the occlusion.Results: Neurological deficits, infract areas and brain water content were significantly reduced in rats treated with PGA₁ (33nmol) or Li plus PGA₁ (33nmol); Li, PGA₁ or Li plus PGA₁ could significantly reduce infract areas and brain water content. The expression of HO-1, HSP70, GRP78 and HSP90α was significantly...