Quantitative evaluation of the neuroprotective effects of hypothermia ranging from 34°C to 31°C on brain ischemia in gerbils and determination of the mechanism of neuroprotection

Objective: The present study was designed to determine whether the predominant factor responsible for neuroprotection of hypothermia ranging from 31 to 34°C is prolongation of onset of ischemic depolarization or suppression of neuronal injury during ischemic depolarization and to quantitatively determine the neuroprotective effects of hypothermia of 34°C and 31°C. Design: Prospective animal study. Setting: A university research laboratory. Subjects: Eighty-nine gerbils. Interventions: Bilateral common carotid arteries were occluded for 3-20 mins. The brain temperature was set at 37°C, 34°C, or 31 °C before and during ischemic depolarization. Measurements and Main Results: DC potentials were measured in the CA1 region, where histologic evaluation was performed 7 days later. Onset times of ischemic depolarization were 1.3 ± 0.2, 1.6 ± 0.4, and 2.4 ± 0.7 mins at 37°C, 34°C, and 31 °C, respectively. The logistic regression curve demonstrated a close relationship between duration of ischemic depolarization and neuronal damage and showed a rightward shift by lowering the brain temperature. In the 37°C, 34°C, and 31°C groups, the durations of ischemic depolarization causing 50% neuronal damage were estimated to be 8.0, 14.2, and 26.0 mins, respectively, and the ischemia times causing 50% neuronal damage were estimated to be 4.9, 8.1, and 14.2 mins, respectively. Conclusions: The onset of ischemic depolarization was prolonged in the 34°C and 31°C groups by only 0.3 and 1.1 mins, respectively, compared with that in the 37°C group. Most of the neuroprotection by hypothermia was attributed to the suppression of neuronal injury during ischemic depolarization, suggesting that hypothermia has neuroprotective effects if it is initiated during the ischemic depolarization period. The results also indicate that the neuroprotective effect at 31°C is about three times greater than that at 34°C and that neuronal cells can withstand 2.9 times longer duration of ischemia at 31°C than at 37°C.