Hypothermia Modulates Induction of hsp70 and c-jun mRNA in the Rat Brain After Subarachnoid Hemorrhage

Abstract

We investigated expression of hsp70 and c-jun mRNA with in situ hybridization for evaluating hypothermia effect on the brain exposed to subarachnoid hemorrhage (SAH). SAH was induced in Wistar rats with endovascular perforation. Animals were divided arbitrarily into normothermic and hypothermic groups, and they were sacrificed at 3 h or 12 h after SAH. The SAH induced hsp70 and c-jun mRNAs in the cerebral cortex, hippocampus, thalamus, hypothalamus, and caudoputamen. Mild hypothermia depressed hsp70 mRNA expression in the cortex, thalamus, and hippocampus. The c-jun mRNA expression was reduced by hypothermia in the cortex, thalamus, and CA1 of the hippocampus. Based on these findings, we speculate that hypothermia protects the brain exposed to SAH by reducing this stress response. Although it is yet difficult to employ hypothermia in the clinical settings, this study suggests its utility to those patients sustaining severe subarachnoid hemorrhage.

Comparison of three rat models of cerebral vasospasm

“…Only recently have the double-hemorrhage model (30,44) or endovascular puncture model (38) been reported on. Furthermore, most of the studies that used the endovascular puncture model in the rat were employed to investigate the pathophysiology of subarachnoid hemorrhage (22,28) rather than cerebral vasospasm itself (38). We feel that there is an urgent need to compare the rat models of subarachnoid hemorrhage-induced cerebral vasospasm and to establish a guideline for future research.…”

“…Several authors have redesigned the surgical procedure in the endovascular puncture model to control the volume as well as the speed of bleeding into cisterns. They have tried either obliterating the carotid artery (22,47) or decreasing the diameter of the suture used to puncture the artery (39). Although those practices have demonstrated positive results in reducing mortality in studies, the authors pointed out that it can result in cerebral ischemia or decreased blood volume in cisterns (39,40,47).…”

“…A substantial number of studies on subarachnoid hemorrhage-induced cerebral vasospasm have been conducted. They used various species and various methods of inducing experimental subarachnoid hemorrhage such as intracisternal administration of blood (12,19,30,38,39,(43)(44)(45)(46), endovascularly (5,11,22,28,38,44,47) or extravascularly (4,20) puncturing the artery, and blood clot placement around the artery (15). It can be said that existing subarachnoid hemorrhage models of large animals, such as primates and canines, are the preferred models for cerebral vasospasm (31); however, these preferred models are high in cost and often limited in availability due to the difficulties involved in extensive surgery and handling of the subjects when inducing subarachnoid hemorrhage.…”

Subarachnoid Hemorrhage Induces Na+/myo-Inositol Cotransporter in the Rat Brain.

“…9) The ischemia is rather mild and does not result in focal necrosis, but does induce expression of 70-kDa heat-shock protein (hsp70) and immediate early genes. 2,5) This focal ischemia may also cause focal osmolarity change. Increases in focal osmolarity were measured by vapor pressure osmometer 3 to 6 hours after rat middle cerebral artery (MCA) occlusion.…”

“…Details of the procedures are described elsewhere. 2,5) After induction of SAH, the animals SAH Induces SMIT in the Rat Brain were returned to the cages for recovery from anesthesia and allowed free access to food and water. The animals were re-anesthetized deeply with nembutal and sacrificed at 1 hour, 6 hours, 12 hours, 24 hours, or 48 hours after SAH (n ＝ 5 for each time point).…”