Induction of heat shock protein 70 in the rat brain following intracisternal infusion of autologous blood: evaluation of acute neuronal damage

Object. Investigation into a potential treatment for the acute period follo wing onset of spontaneous subarachnoid hemorrhage (SAH) is hampered by the lack of a standardized experimental model. For that purpose the authors ela borated on a small-animal model in which computer-controlled intracisternal blood infusion is used and investigated whether this model can reliably re produce acute neuronal injury after SAH. Methods. Whole autologous blood (blood-infused group) or isotonic saline (c ontrol group) was infused into the cisterna magna or olfactory cistern of r ats. The infusions decreased exponentially during a 5-minute period. Throug hout the infusion period, intracranial pressure (ICP) was monitored. Neuron al injury was quantified by observing tissue immunoreactivity to a 70-kD he at shock protein (HSP\70) and comparing this with the tissue's reaction to hematoxylin and eosin staining. On Days 1, 3, and 5, the CA i, CA3, and den tate gyrus regions of the hippocampus were analyzed, respectively. During saline infusion ICP increased within seconds beyond 80 mm Hg and aft erward decreased in accordance with the infusion rate. During the infusion of blood, the same initial pressure peak was found, but the ICP remained in creased beyond this pressure level throughout the 5-minute infusion period. The HSP70 immunoreactivity in the saline-infused group was found only on D ay 1 in the CA1 region and the dentate gyms, but not in the CA3. After inje ction of whole blood, there was HSP70-positive staining in the CA1, CA3, an d dentate gyrus regions throughout the observation period. Conclusions. The controlled cisternal infusion of blood caused neuronal inj ury that resembled that of previous experimental models that produce SAH by rupture of intracranial vessels with endovascular techniques. Unlike those experiments, the intracisternal infusion technique presented by the author s provides more standardized bleeding with regard to ICP, the volume of sub arachnoid blood. and the extent of acute cellular injury.