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Aim:To investigate the effects of lithium(Li)and prostaglandin A_1(PGA_1)on theexpression of heat shock factor 1(HSF- 1),heat shock proteins(HSP),and apoptosisprotease activating factor-1(Apaf-1)induced by permanent focal ischernia in rats.Methods:The rats were pretreated with a subcutaneous(sc)injection of Li for 2 dor a single intracerebral ventricle(icv)administration of PGA_1 for 15 min beforeischemic insult,or a combination ofLi(sc,1 mEq/kg,2 d)and PGA1(icv,15 minprior to ischemic insult).Brain ischemia was induced by the permanent middlecerebral artery occlusion(pMCAO).Twenty-four hours after the occlusion,theexpression of HSF-1,HSE and Apaf-1 in the ischemic striatum were examined withWestern blot analysis.Results:The expression of HSF-1,heme oxygenase-1(HO-1),HSP90α,and Apaf-1 were significantly increased,but the expression ofHSP90β was significantly decreased 24 h after the pMCAO.PGA_1 and Li and theircombination significantly enhanced the ischemia-induced elevation in the levelsof HSF-1,HO-1,and HSP90α,and recovered HSP90β expression,but decreasedApaf-1 levels in the ischemic striatum.Conclusion:The present study demon-strates that PGA_1 and Li have synergistic effects on the enhancement of theexpression of HSP,suggesting that the synergistic effects of PGA_1 and Li in therat model of permanent focal cerebral ischemia may be mediated by the enhance-ment expression of HSP expression and the downregulation of Apaf-1.Our studiessuggest that combined PGA_1 and Li may have potential clinical value for thetreatment of stroke.
Aim: To investigate the effects of lithium (Li) and prostaglandin A_1 (PGA_1) on theexpression of heat shock factor 1 (HSF-1), heat shock proteins (HSP), and apoptosisprotease activating factor-1 (Apaf-1) induced by permanent focal ischernia in rats. Methods: The rats were pretreated with a subcutaneous (sc) injection of Li for 2 dor a single intracerebral ventricle (icv) administration of PGA_1 for 15 min beforeischemic insult, or a combination of Li (sc, 1 mEq / kg, 2 d) and PGA1 (icv, 15 minprior to ischemic insult). Brain ischemia was induced by the permanent middle cerebral artery occlusion (pMCAO). Twenty-four hours after the occlusion, theexpression of HSF- 1, HSE and Apaf- 1 in the ischemic striatum were examined with Western blot analysis. Results: The expression of HSF-1, heme oxygenase-1 (HO-1), HSP90α, and Apaf-1 were significantly increased, but the expression of HSP90β was significantly decreased 24 h after the pMCAO.PGA_1 and Li and theircombination significantly enhanced the ischemia-induced elevation in the l evelsof HSF-1, HO-1, and HSP90α, and recovered HSP90β expression, but decreasedApaf-1 levels in the ischemic striatum. Confluence: The present study demon-strates that PGA_1 and Li have synergistic effects on the enhancement of theexpression of HSP, suggests that the synergistic effects of PGA_1 and Li in therat model of permanent focal cerebral ischemia may be mediated by the enhance-ment expression of HSP expression and the downregulation of Apaf-1.Our studiessuggest that combined PGA_1 and Li may have potential clinical value for thetreatment of stroke.