Effect of Post-Traumatic Mild Hypothermia on Hippocampal Cell Death after Traumatic Brain Injury in Rats

In this investigation, we evaluated the effect of post-traumatic mild hypothermia on cell death in the hippocampus after fluid percussion traumatic brain injury (TBI) in rats. Adult male Sprague-Dawley rats were randomly divided into three groups (n = 40/group): TBI with hypothermia treatment (32°C), TBI with normothermia (37°C), and sham injury. The TBI model was induced by a fluid percussion TBI device. Mild hypothermia (32°C) was achieved by partial immersion in a water bath (0°C) under general anesthesia for 4 h. All rats were killed at 24 or 72 h after TBI. The ipsilateral hippocampal CA1 in all rats were analyzed by hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling (TUNEL), and 4′,6-diamidino-2-phenylindole (DAPI) staining for determining cell death. Caspase-3 expression was examined by reverse transcription—polymerase chain reaction (RT-PCR) and Western blotting. At 24 h, based on TUNEL and DAPI results, the cell death index was 28.80 ± 2.60% and 32.10 ± 1.40% in the normothermia TBI group, while reaching only 14.30 ± 2.70% and 18.40 ± 2.10% in the hypothermic TBI group (p < 0.01). Based on RT-PCR and Western blotting results, the expression of caspase-3 was 210.20 ± 5.30% and 170.30 ± 4.80% in the normothermic TBI group, while reaching only 165.10 ± 3.70% and 130.60 ± 4.10% in the hypothermic TBI group (p < 0.05). At 72 h, based on TUNEL and DAPI results, the cell death index was 20.80 ± 2.50% and 25.50 ± 1.80% in the normothermic TBI group, while reaching only 10.20 ± 2.60% and 15.50 ± 2.10% in the hypothermic TBI group (p < 0.01). Based on RT-PCR and Western blotting results, the expression of caspase-3 was 186.20 ± 6.20% and 142.30 ± 5.10% in the normothermic TBI group, versus only 152.10 ± 3.60% and 120.60 ± 3.90% in the hypothermic TBI group (p < 0.05). Based on our findings, we conclude that post-traumatic hypothermia significantly attenuates cell death within the hippocampus following fluid percussion injury. Taken together with other studies, these observations support the premise that post-traumatic mild hypothermia can provide cerebral protection for patients with TBI.