Different degrees of hypothermia after experimental stroke: short- and long-term outcome

The neuroprotective role of mild therapeutic hypothermia was established in animal models of cerebral ischemia. Still, several issues, including optimal target temperature, remain unclear. The optimal depth of hypothermia in a rat model of focal cerebral ischemia was investigated.

Eighty-four male Wistar rats (n=84) were subjected to filament occlusion of the middle cerebral artery for 90 minutes. Sixty animals were equally split into 6 groups kept at core temperatures of 37 degrees C, 36 degrees C, 35 degrees C, 34 degrees C, 33 degrees C, and 32 degrees C over a period of 4 hours starting 90 minutes after middle cerebral artery occlusion. Twenty-four hours later, after performing a neuroscore, animals were killed and brains examined for infarct size, edema, and invasion of leukocytes. In the second part, 24 animals (8 per group) were kept at 33 degrees C, 34 degrees C, and 37 degrees C for 4 hours, allowed to survive for 5 days, and underwent additional investigation of transferase dUTP nick-end labeling.

In the first part, one animal in each treatment group and 2 animals in group 37 degrees C died. The infarct size and edema were smaller for 34 degrees C and 33 degrees C compared with all other groups (P<0.05) over 24 hours. These animals also had better functional outcome (P<0.05) with an advantage for 34 degrees C versus 33 degrees C (P<0.05). Leukocyte count was lower for 34 degrees C and 33 degrees C as compared with the 37 degrees C group. Similar results were obtained in the second part of the study with an advantage for 34 degrees C versus 33 degrees C.

Our results suggest that the optimal depth of therapeutic hypothermia in temporary middle cerebral artery occlusion is 34 degrees C.