Indomethacin attenuates early increases in inducible heat shock protein 70 after cerebral ischemia/reperfusion in piglets.
Indomethacin-sensitive mechanisms involved in inducible heat shock protein 70 (iHSP 70) synthesis were investigated at 6 h after global cerebral ischemia in parietal cortex and hippocampus. In anesthetized piglets, increased intracranial pressure was used to produce 5 or 10 min of cerebral ischemia. Brain regions were sampled for immunoblot analysis, immunohistochemistry and morphology. Immunoblots revealed differential expression of iHSP 70 in untreated brains. Cerebellum contained substantial amounts of iHSP 70 while lower levels were present in parietal cortex and hippocampus. Detectable increases in iHSP 70 were observed at 2 h after ischemia in parietal cortex and hippocampus. Using immunoblot 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 +/- sem) (n = 6) in parietal cortex and 195 +/- 69% (n = 8) in hippocampus. Increased iHSP 70 immunoreactivity occurred primarily in the granular/subgranular area of the dentate gyrus 6 h after ischemia. Histological staining revealed little cellular injury at 6 h after ischemia in the granular/subgranular region injury whereas the CA3 region, which lacked iHSP 70 staining, displayed modest cellular injury. Cellular injury was also observed in cortical layers II/III and VI. At 6 h after ischemia, indomethacin pretreatment (5 mg/kg, i.v.) attenuated the iHSP 70 increases in parietal cortex and hippocampus (7 +/- 30% and 89 +/- 30%, respectively n = 5; p < 0.05 compared to ischemia). Also, the increase in iHSP 70 immunoreactivity and appearance of cellular injury were not detected with indomethacin pretreatment. Thus, prior administration of indomethacin is associated with attenuation of ischemia-induced increases in iHSP 70 and cellular injury.
Beasley
T C
TC
Department of Neurobiology and Anatomy, Bowman Gray School of Medicine Wake Forest University, Winston-Salem, NC 27157-1083, USA.
Bari
F
F
Thore
C
C
Thrikawala
N
N
Louis
T
T
Busija
D
D
D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D013552:Swine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006360:Heat-Shock Proteins; D007213:Indomethacin