Objective To examine peroxisome proliferator-activated receptor(PPAR)isotypes (PPARα,PPARδ/βand PPARγ)expression in rats after cerebral ischemia-reperfusion(I/R)and I/R in combination with pan-PPAR co-agonist,and to explore the effect of altered PPAR expressions in brain injury.Methods Adult male SD rats underwent 2-hour middle cerebral artery occlusion followed by a 22-hour reperfusion(MCAO/R).One hour before the operation,the mice received either vehicle(I/R-group)or bezafibrate(6 mg/kg)treatment(Beza-group).TTC(2,3,5-triphenyhetrazolium)staining was adopted to determine the volume of cerebral infarction.The expressions of PPAR isotypes were characterized by immunohistochemical staining(IHC)and Western blot.Furthermore,the spatial localizations of PPAR isotypes were analyzed with respect to ipsilateral ischemic(core and penumbra)and contralateral nonischemic hemisphere.Results Compared with sham-group,2 h ischemia and 22 h reperfusion caused(1) 44.30%infarct volume in average in ipsilateral hemisphere;(2)Marked increased PPAR expression in all three isotypes evaluated by IHC(t=8.63,9.29,13.62,P:0.000)and Western blot(PPARot by 1.47-fold,PPARδ/β by 3.52-fold,and PPARγ by 2.25-fold;t=8.16,9.24,6.43;P=0.000);(3)Marked increagc in PPAR staining in the ischemia-affected region of the ipsilateral MCA territory,in particular in the ischemic itmnumbra.No detectable increase in number and intensity was observed in the contralateral(nonischemic)hemisphere.The pan-PPAR co-agonists bezafibrate can activate all 3 subtypes of the receptor.Compared with I/R-group,(1)Ischemic size in bezafibrate-group rats was significantly decreased than that in I/R group(20.22±6.18 versus 44.30±4.54,t=7.69,P=0.000).(2)Bezafibrate treatment further increased the alterations of all PPAR expression,which were induced by the exposure of I/R,as determined by IHC(t=7.36,5.64,10.50,and P=0.000)and Western blot(PPARα by 95.45%,PPARS/β by 183.47%,and PPARγ by 224.61%;t=13.02,17.52,13.64,and P=0.000).(3)The PPAR immunoreactive expressions were observed in not only the ipsilateral but the contralateral hemisphere of bezafibrate-group.Conclusions Cerebral I/R injury increases the expression of all three PPAR isotypes and activation of PPAR by pan-PPAR agonist not only reduces ischemic size but further enhances the alteration of PPAR The up-regulation of PPAR expression may represent the compensatory self-protection against brain I/R injury.

Accumulating evidences have demonstrated the beneficial actions of peroxisome proliferator-activated receptor gamma (PPAR gamma) in a variety of animal stroke models. Following middle cerebral artery occlusion (60 min) and 2-24 hr reperfusion in rats, we observed cerebral ischemia/reperfusion (I/R) induced up-regulation of PPAR gamma protein expression and translocation from the cytoplasm into the nucleus in a time-dependent manner. We also found that PPAR gamma agonist rosiglitazone enhanced whereas PPAR gamma antagonist GW9662 inhibited the alteration of PPAR gamma stimulated by I/R, suggesting that the changes of PPAR gamma may result from the activation by endogenous ligands. Moreover, the link between the 12/15-lipoxygenase and the production of activating ligands for PPAR gamma has been proved in various tissues. However, the relation of them in brain tissue has not been identified. We demonstrated that the I/R-induced PPAR gamma alteration was reversed by baicalein, the specific inhibitor of 12/15-lipoxygenase. Baicalein treatment significantly inhibited the up-regulation of PPAR gamma expression and, furthermore, suppressed PPAR gamma nuclear accumulation as well as maintained PPAR gamma cytoplasmic retention. Together, these results suggest that I/R induces both PPAR gamma expression and translocation, probably through the activation by endogenous ligands in a 12/15-lipoxygenase inhibitor-sensitive way.

Summary Novel sulfonated poly(arylene ether ketone)s were prepared directly by aromatic nucleophilic polycondensation of 4,4'-sulfonyldiphenol with various ratios of 4,4'-difluorobenzophenone to 5,5'-carbonylbis(2-fluorobenzenesulfonate) in dimethyl sulfoxide. The resulting polyelectrolytes were characterized by IR, NMR, TGA and DSC. The 10% weight loss temperature of the products is higher than 510°C, and their glass transition temperature is above 260°C. The introduction of 4,4'-sulfonyldiphenol with powerful electron-withdrawing group, -SO 2− , into the main chain of sulfonated poly(arylene ether ketone)s improves the thermal stability against desulfonation. The ion-exchange capacity and swelling of the polyelectrolyte membranes were measured, which are higher than 1.23meq/g and not higher than 20.9%, respectively. The membranes show very good perspectives in polymer electrolyte fuel cell (PEMFC) application.