Prolonged but delayed postischemic hypothermia: A long-term outcome study in the rat middle cerebral artery occlusion model

Delayed but prolonged hypothermia persistently decreases cell death and fun ctional deficits after global cerebral ischemia in rodents. Postischemic hy pothermia also reduces infarction after middle cerebral artery occlusion (M CAO) in rat. Because initial neuroprotection is sometimes transient and may not subserve functional recovery, especially on demanding tasks, the autho rs examined whether postischemic cooling would persistently reduce infarcti on and forelimb reaching deficits after MCAO. Male spontaneously hypertensi ve rats were trained to retrieve food pellets in a staircase test that meas ures independent forelimb reaching ability. Later, rats underwent 90 minute s of normothermic MCAO, through a microclip, or sham operation. In some rat s, prolonged cooling (33 degreesC for 24 hours and then 35 degreesC for 24 hours) began 2.5 hours after the onset of ischemia (60 minutes after the st art of reperfusion; n = 17 with subsequently I death) or sham procedures (n = 4), whereas untreated sham(n = 4) and ischemic (n = 16 with subsequently 1 death) rats maintained normothermia. An indwelling abdominal probe conti nually measured core temperature, and an automated fan and water spray syst em was used to produce hypothermia. One month later rats were reassessed in the staircase test over five days and then killed. The contralateral limb impairment in food pellet retrieval was completely prevented by hypothermia (P = 0.0001). Hypothermia reduced an infarct Volume of 67.5 mm(3) after un treated ischemia to 35.8 mm(3) (P < 0.0001). These findings of persistent b enefit encourage the clinical assessment of hypothermia.