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 induc ible heat shock protein), HO-1 (heme oxygenase-1, HSP32) and HSP47 (a colla gen chaperone) stress proteins were induced in the same focal regions of ra t brain following experimental subarachnoid hemorrhage (SAH). The next obje ctive was to determine whether anti-oxidants prevented the stress gene expr ession in the focal regions. Lysed blood (150 mu l) was injected into the s ubarachnoid space of adult, female Sprague-Dawley rats via the cisterna mag na. Animals were sacrificed 24 h later. Immunocytochemistry showed focal re gions of stress gene induction in most animals (13/21), HSP70 and HO-1 prot eins being expressed in neurons, microglia and astrocytes and HSP47 being e xpressed in microglia. Go-induction of the same three stress proteins was o bserved in focal areas in the striatum and cerebellum as well. In the 13 an imals with focal regions of stress gene induction there were 8.1 +/- 1.8 fo ci in cortex, 5.5 +/- 0.9 foci in striatum, rind 11.7 +/- 7.3 foci in cereb ellum in the brain of each animal. The focal regions of stress gene inducti on varied in size from 200 mu m to 7 mm in diameter. Systemic administratio n 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 tre ated animals (0/15) with focal areas of stress gene induction compared to n on-drug (13/21) treated animals following the cisternal lysed blood injecti ons (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. (C) 1999 Elsevier Science B.V. All rights reserved.