Greater stress protein expression enhanced by combined prostaglandin A sub(1) and lithium in a rat model of focal ischemia

Aim: To investigate the effects of lithium (Li) and prostaglandin A sub(1) (PGA sub(1)) on the expression of heat shock factor 1 (HSF-1), heat shock proteins (HSP), and apoptosis protease activating factor-1 (Apaf-1) induced by permanent focal ischemia in rats. Methods: The rats were pretreated with a subcutaneous (sc) injection of Li for 2 d or a single intracerebral ventricle (icv) administration of PGA sub(1) for 15 min before ischemic insult, or a combination of Li (sc, 1 mEqkg, 2 d) and PGA sub(1) (icv, 15 min prior to ischemic insult). Brain ischemia was induced by the permanent middle cerebral artery occlusion (pMCAO). Twenty-four hours after the occlusion, the expression of HSF-1, HSP, andApaf-1 in the ischemic striatum were examined with Western blot analysis. Results: The expression of HSF-1, heme oxygenase-1 (HO-1), HSP90 alpha , and Apaf-1 were significantly increased, but the expression of HSP90 beta was significantly decreased 24 h after the pMCAO. PGA sub(1) and Li and their combination significantly enhanced the ischemia-induced elevation in the levels of HSF-1, HO-1, and HSP90 alpha , and recovered HSP90 beta expression, but decreased Apaf-1 levels in the ischemic striatum. Conclusion: The present study demonstrates that PGA sub(1) and Li have synergistic effects on the enhancement of the expression of HSP, suggesting that the synergistic effects of PGA1 and Li in the rat model of permanent focal cerebral ischemia may be mediated by the enhancement expression of HSP expression and the downregulation of Apaf-1. Our studies suggest that combined PGA sub(1) and Li may have potential clinical value for the treatment of stroke.