Protection of the rat brain from hypothermic circulatory arrest injury by a chipmunk protein.

OBJECTIVES: The study objectives were to test the hypothesis that special protein exists in hibernating chipmunk albumin and whether this protein has a neuroprotective effect in Sprague-Dawley rats during deep hypothermia circulatory arrest.

METHODS: Forty chipmunks were allocated into a hibernation group and an active group (20 chipmunks in each group). Special protein was detected and isolated from hibernating chipmunk albumin. Forty Sprague-Dawley rats were randomly divided into a sham group, deep hypothermia circulatory arrest group, special protein group, and naloxone group (10 rats in each group). Special protein that was detected and collected from hibernating chipmunks were injected in rats in the special protein group for 3 consecutive days before operation, and naloxone was given at the same time in the naloxone group. Rats were subjected to cardiopulmonary bypass and 60-minute deep hypothermia circulatory arrest. Tumor necrosis factor-α and interleukin-6 levels were detected. Animals received neurologic testing. Relative protein expression, malondialdehyde, and superoxide dismutase of hippocampus were detected. The brain was fixed for histopathologic assessment.

RESULTS: The rats that received special protein displayed ischemic tolerance after deep hypothermia circulatory arrest. The neuroprotective effect could be reversed by naloxone. The inflammation response was attenuated in the special protein group (P < .008, compared with the deep hypothermia circulatory arrest and naloxone groups). The mature brain-derived neurotrophic factor and SIRT1 levels were higher in the special protein group (P < .01, compared with the deep hypothermia circulatory arrest and naloxone groups). Histopathologic assessment showed that the injury in the special protein group was attenuated (pathological score, P < .05; surviving hippocampal CA1 neurons, P < .01; TUNEL-positive neurons, P < .01; compared with deep hypothermia circulatory arrest and naloxone groups). Intravenous injection of special protein significantly improved neurologic recovery.

CONCLUSIONS: We found that a specific protein existed in hibernating chipmunk albumin and could play an important neuroprotective role in rats.