INDOMETHACIN ATTENUATES EARLY INCREASES IN INDUCIBLE HEAT-SHOCK-PROTEIN-70 AFTER CEREBRAL ISCHEMIA REPERFUSION IN PIGLETS/

Indomethacin-sensitive mechanisms involved in inducible heat shock pro tein 70 (iHSP 70) synthesis were investigated at 6 h after global cere bral ischemia in parietal cortex and hippocampus. In anesthetized pigl ets, increased intracranial pressure was used to produce 5 or 10 min o f cerebral ischemia. Brain regions were sampled for immunoblot analysi s, immunohistochemistry and morphology. Immunoblots revealed different ial expression of iHSP 70 in untreated brains. Cerebellum contained su bstantial amounts of iHSP 70 while lower levels were present in pariet al cortex and hippocampus. Detectable increases in iHSP 70 were observ ed at 2 h after ischemia in parietal cortex and hippocampus. Using imm unoblot data, calculation of percent change from control at 6 h after ischemia revealed significant (p < 0.05) increases in iHSP 70 of 111 /- 39% ((x) over bar +/- sem) (n = 6) in parietal cortex and 195 +/- 6 9% (n = 8) in hippocampus. Increased iHSP 70 immunoreactivity occurred primarily in the granular/subgranular area of the dentate gyrus 6 h a fter ischemia. Histological staining revealed little cellular injury a t 6 h after ischemia in the granular/subgranular region injury whereas the CA3 region, which lacked iHSP 70 staining, displayed modest cellu lar injury. Cellular injury was also observed in cortical layers II/II I and VI. At 6 h after ischemia, indomethacin pretreatment (5 mg/kg, i .v.) attenuated the iHSP 70 increases in parietal cortex and hippocamp us (7 +/- 30% and 89 +/- 30%, respectively n = 5; p < 0.05 compared to ischemia). Also, the increase in iHSP 70 immunoreactivity and appeara nce of cellular injury were not detected with indomethacin pretreatmen t. Thus, prior administration of indomethacin is associated with atten uation of ischemia-induced increases in iHSP 70 and cellular injury. ( C) 1998 Elsevier Science B.V.