Failure of delayed and prolonged hypothermia to favorably affect hemorrhagic stroke in rats

Abstract

Prolonged hypothermia reduces global and focal cerebral ischemic injury in rodents even when delayed for hours. However, it is not known whether hypothermia can reduce injury following intracerebral hemorrhage (ICH). Accordingly, we studied striatal injury and concomitant motor deficits after 2 days of hypothermia, induced 1 h after creation of an ICH by infusion of bacterial collagenase. Rats were first trained to retrieve food pellets in the Montoya staircase task. They were then implanted with core temperature telemetry probes and later subjected to normothermic ICH or sham operation (vehicle injection). Half self-regulated temperature after surgery; others were cooled to 33 °C (24 h) and then 35 °C (24 h). Hypothermia did not affect behavioral scores of sham animals (89.8% of baseline in staircase test) or histology. Untreated (normothermic) ICH rats lost 23.1 mm 3 of tissue at a 1-month survival, which significantly impaired food pellet retrieval (66.0% retrieval) with the contralateral limb (tested on days 21–25). Contrary to our hypothesis, hypothermia failed to lessen either the reaching impairment (62.8%) or the lesion (22.2 mm 3). While other hemorrhagic insults or complications may be improved with hypothermia, our data suggest that it will not salvage tissue that is quickly lost after ICH. We also assessed walking across a horizontal ladder and spontaneous paw usage in a cylinder test at 1–4 weeks after ICH, but neither test was sufficiently sensitive to this mild insult. This indicates that skilled reaching is more severely disrupted than spontaneous paw usage or walking after a striatal hemorrhage.