Autophagy Inhibitor 3-MA Weakens Neuroprotective Effects of Posttraumatic Brain Injury Moderate Hypothermia.

Abstract

The role of autophagy in moderate hypothermia in posttraumatic brain injury (post-TBI) remains elusive. In this study, we evaluated the protective role of autophagy in post-TBI moderate hypothermia. Adult male Sprague-Dawley rats were randomly divided into 3 groups (n = 36/group): TBI with hypothermia group (sham), TBI with hypothermia and a single intracerebroventricular injection of saline (saline, 5 μL), and TBI with hypothermia and a single intracerebroventricular injection of 3-methyladenine (600 nmol, diluted in 0.9% saline to a final volume of 5 μL). All rats, except those in the behavioral tests, were killed at 24 hours after fluid percussion TBI. Immunohistochemistry staining, western blot, and transmission electron microscopy were performed to assess changes in apoptosis and autophagy after injection of 3-methyladenine. Motor function (beam-walk test) and spatial learning/memory (Morris water maze) were assessed on postoperative days 1-5 and 11-15, respectively. Our results showed downregulation of the expression level of microtubule-associated protein 1 light chain 3 and Beclin-1, aggravation of behavioral outcome, and increase of apoptosis. Our results suggest that the autophagy pathway is involved in the neuroprotective effect of post-TBI hypothermia and negative modulation of apoptosis may be 1 possible mechanism.