The beneficial effect of mild hypothermia in a rat model of repeated thromboembolic insults

The post-thrombotic brain has recently been reported to have an enhanced vulnerability to a second embolic insult. Although postischemic hypothermia is neuroprotective in global and focal ischemia models, the effect of mild hypothermia on outcome after thromboembolic insults has not been evaluated. This study therefore determined whether brain hypothermia (33°C) was neuroprotective against repeated thromboembolic insults. Photochemically induced non-occlusive common carotid artery thrombosis (CCAT) leading to platelet embolization to the brain was induced in anesthetized rats (n=35). Thirty minutes after CCAT, brain temperature was maintained at normothermic (37°C) or hypothermic (33°C) levels for 4 h followed by a slow rewarming period (1.5 h). Three days later, rats underwent a secondary CCAT insult under normothermic conditions and were allowed to survive for an additional 3 days prior to perfusion fixation and quantitative histopathological assessment. Compared to normothermic animals, mild hypothermia after the first embolic insult produced a significant reduction (P>0.05) in overall infarct volume. Hypothermia reduced total infarct volume from 7.55±2.32 mm3 (mean ± SEM) in normothermic rats to 2.56±0.88 mm3 in hypothermic animals undergoing repeated insults. Histopathological analysis also demonstrated less evidence for focal hemorrhage in the cooled groups. These data demonstrate that mild hypothermia is protective in a thromboembolic stroke model. In addition, post-thrombotic hypothermia decreases the histopathological vulnerability of the post-thrombotic brain to secondary embolic insults. These findings may be important in the prevention of stroke in patients at risk.