Differential role of nitric oxide pathway and heat shock protein in preconditioning and lipopolysaccharide-induced brain ischemic tolerance

The purposes of this study were to investigate the role of nitric oxide (NO ), nitric oxide synthase (NOS), and 70 kDa heat shock protein in brain isch emic tolerance induced by ischemic preconditioning and lipopolysaccharide. Focal cerebral ischemia was induced in rats by intraluminal middle cerebral artery occlusion. Infarct volume was significantly reduced (1) in rats sub jected to 3 min ischemia 72 h prior to 60 min ischemia; (2) in rats adminis tered lipopolysaccharide (0.5 mg/kg; i.p.) 72 h prior to 60 min ischemia co mpared with controls. The beneficial effect of ischemic preconditioning was unchanged despite prior administration of nitro-L-arginine methyl ester (L -NAME), a NOS inhibitor. Conversely, the protective effect of lipopolysacch aride was nullified by L-NAME. Using immunohistochemical techniques, we obs erved that (1) ischemic preconditioning but not lipopolysaccharide induces the expression of 70 kDa heat shock protein in cerebral cortex and (2) lipo polysaccharide induces early increased expression of endothelial NOS in cer ebral brood vessels. The results suggest that (1) endothelium-derived NO pl ays a role of a trigger in the brain tolerance induced by lipopolysaccharid e, and (2) 70 kDa heat shock protein is involved in the protection afforded by ischemic preconditioning but not by lipopolysaccharide. (C) 2000 Elsevi er Science B.V. All rights reserved.