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

摘要

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 4h. All rats were killed at 24 or 72h 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 24h, 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 72h, 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.