Objective To investigate the effect of graded hypothermia on neuropathologic alterations of neonatal rat brain after exposed to hypoxic-ischemic insult at 37°C

33°C

31°C

and 28°C

respectively

and to observe the effect of hypothermia on 72-kDa heat shock protein (HSP72) expression after hypoxic-ischemic insult. Methods Seven days old Wistar rats were subjected to unilateral common carotid artery ligation followed by exposure to hypoxia in 8% oxygen for 2 hours at 37°C

33°C

31°C

and 28°C

respectively. The brain temperature was monitored indirectly by inserting a mini-thermocouple probe into the temporal muscle during hypoxia. After hypoxia-ischemia their mortality was assessed. Neuronal damage was assessed with HE staining 72 hours after hypoxia. HSP72 expression at 0.5

24

and 72 hours of recovery was immunohistochemically assessed using a monoclonal antibody to HSP72. Results Hypoxia-ischemia caused 10.5% (2/19) of mortality in rat of 37°C group

but no death occurred in 33°C

31°C or 28°C groups. HE staining showed neuropathologic damage was extensive in rats exposed to hypoxia-ischemia at 37°C (more than 80.0%). The incidence of severe brain damage was significantly decreased in 33°C (53.3%) and 31°C groups (44.4%)

and no histologic injury was seen in the 28°C group of rats. Expression of HSP72 was manifest and persistent in the rat brain of 37°C group

but minimum in the rat brain of 28°C group. Conclusion Mild and moderate hypothermia might prevent cerebral visible neuropathologic damage associated with hypoxic-ischemic injury by decreasing stress response.