INDUCTION OF HSP70 IN RAT-BRAIN FOLLOWING SUBARACHNOID HEMORRHAGE PRODUCED BY ENDOVASCULAR PERFORATION

Current experimental research on subarachnoid hemorrhage (SAH) has bee n limited by the lack of a small-animal model that physiologically res embles SAH and consistently demonstrates acute and delayed cellular in jury. Recently, a model for inducing SAH by endovascular perforation o f the internal carotid artery has been developed in the rat. This mode l physiologically resembles SAH. However, little histological data det ailing cellular injury after SAH are available in this or other models . Using immunocytochemistry, the authors investigated the induction of the 70-kD heat shock protein, HSP70, a sensitive marker for cellular stress or injury in the brain, 1 and 5 days following endovascular SAH . The authors also used the conventional histological techniques of cr esyl violet and hematoxylin and eosin staining to investigate cellular damage 1 and 5 days after the endovascular SAH. One day following the SAH, HSP70 was induced in all six animals examined in multiple anatom ical regions, including the basal forebrain, thalamus, neocortex, stri atum, and hippocampus. This HSP70 induction was observed in multiple v ascular distributions bilaterally. Immunostaining with HSP70 occurred primarily in neurons but also was observed in glia and endothelium. Fi ve days after the SAH, a similar but more intense pattern of HSP70 imm unostaining was observed in all eight animals examined. Specifically, HSP70 immunoreactivity was observed in at least one region of the hipp ocampus more often at 5 days (six of eight animals) than at 1 day (one of six animals, p < 0.05, one-tailed Fisher's exact test). No HSP70 i mmunostaining was observed in control animals at 1 day or at 5 days. C onventional histology demonstrated foci of ischemic neuronal damage an d cellular necrosis; however, HSP70 immunocytochemistry detailed cellu lar injury far better than conventional histology in all animals teste d at both 1 day and 5 days. Our results demonstrate that HSP70 is indu ced in multiple regions and cell types 1 day and 5 days following endo vascular SAH. Because ischemia is a known inducer of stress genes, the authors propose that acute and delayed ischemia are the processes res ponsible for the induction of HSP70 that was observed at 1 day and 5 d ays, respectively. Investigation of HSP70 induction following endovasc ular SAH may also serve as the basis for a new, inexpensive animal mod el to assess potential therapeutic interventions.