Anti-oxidants prevent focal rat brain injury as assessed by induction of heat shock proteins (HSP70, HO-1/HSP32, HSP47) following subarachnoid injections of lysed blood.
The initial aim of this study was to determine if the HSP70 (the main inducible heat shock protein), HO-1 (heme oxygenase-1, HSP32) and HSP47 (a collagen chaperone) stress proteins were induced in the same focal regions of rat brain following experimental subarachnoid hemorrhage (SAH). The next objective was to determine whether anti-oxidants prevented the stress gene expression in the focal regions. Lysed blood (150 microliter) was injected into the subarachnoid space of adult, female Sprague-Dawley rats via the cisterna magna. Animals were sacrificed 24 h later. Immunocytochemistry showed focal regions of stress gene induction in most animals (13/21), HSP70 and HO-1 proteins being expressed in neurons, microglia and astrocytes and HSP47 being expressed in microglia. Co-induction of the same three stress proteins was observed in focal areas in the striatum and cerebellum as well. In the 13 animals with focal regions of stress gene induction there were 8.1+/-1.8 foci in cortex, 5.5+/-0.9 foci in striatum, and 11.7+/-7.3 foci in cerebellum in the brain of each animal. The focal regions of stress gene induction varied in size from 200 micrometer to 7 mm in diameter. Systemic administration of the tirilazad-like anti-oxidants U101033E (n=8) and U74389G (n=7) completely blocked stress protein induction in focal brain regions normally produced by cisternal injections of lysed blood. There were fewer drug treated animals (0/15) with focal areas of stress gene induction compared to non-drug (13/21) treated animals following the cisternal lysed blood injections (p<0.01 using Fisher's probability test). This study shows that anti-oxidants prevent focal regions of injury as assessed by heat shock protein expression in a rat model of SAH.
Department of Neurology (V127), University of California at San Francisco, and Department of Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA.
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002560:Cerebrovascular Circulation; D002561:Cerebrovascular Disorders / Q000503:physiopathology; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D050958:HSP47 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051547:Heme Oxygenase-1; D006461:Hemolysis / Q000502:physiology; D020287:In Situ Nick-End Labeling; D009457:Neuroglia / Q000737:chemistry / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D010105:Oxygenases; D010108:Oxyhemoglobins / Q000494:pharmacology; D011281:Pregnatrienes / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*
D000975:Antioxidants; D050958:HSP47 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D010108:Oxyhemoglobins; D011281:Pregnatrienes; D011743:Pyrimidines; D011759:Pyrrolidines; C494662:Serpinh1 protein, rat; C101923:U 101033E; C074965:U 74389F; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C491523:Hmox1 protein, rat