Intraischemic Modest Hypothermia Does Not Prevent Onset of Locomotor Inactivity After Transient Forebrain Ischemia in Rats.

Although modest hypothermia of 35°C has been demonstrated to provide histological neuroprotection in a rodent model of cerebral ischemia, the long-term behavioral outcome is still not clear. This study was designed to investigate whether modest hypothermia of 35°C provides sustained histological and behavioral neuroprotection following transient forebrain ischemia in rats. Male Sprague-Dawley rats were randomly assigned to one of three groups: sham, control, and modest hypothermia group. Each group contained eight rats. Ten-minute transient forebrain ischemia was produced by bilateral carotid artery occlusion plus hemorrhagic hypotension (mean arterial pressure = 40 mmHg). The hypothermic group was cooled to 35°C in preischemic period, and the cooling was continued for 1 hour postischemia. To evaluate behavioral outcome, spontaneous alternation behavior and locomotor activity were assessed using Y-maze test on a weekly basis. The rats were sacrificed after 28 days, and the number of intact neurons per 1 mm in the hippocampal CA1 subfield was counted microscopically. There was significant difference between the control [19(24.5)/mm: median (interquartile range)] and hypothermia groups [116(24)/mm; p < 0.01] in the intact CA1 neuron count. In the control and modest hypothermia groups, the locomotor activities were gradually decreased, and reached significantly lower levels in comparison with the sham group at 14 days postischemia. This study indicates that intraischemic modest hypothermia provided long-term histological neuroprotection, but did not reverse the onset of locomotor inactivity in a rat transient forebrain ischemia model.