Protective effect of mild-induced hypothermia against moderate traumatic brain injury in rats involved in necroptotic and apoptotic pathways

Abstract

ABSTRACTAim: To investigate the protective effect of hypothermia (HT) on brain injury in moderate traumatic brain injury (TBI) rat models and the potential mechanisms, especially the involvement of RIPK1 in apoptosis and necroptosis.Methods: Adult Sprague-Dawley rats were randomized to four groups: sham+normothermia (sham+NT), sham+hypothermia (sham+HT), moderate TBI+normothermia (TBI+NT) and moderate TBI+hypothermia (TBI+HT). The sham+HT and TBI+HT groups were submitted to 32°C for 6 hours. The regional cerebral blood flow (rCBF) was assessed 24 hours after TBI; 24 and 48 hours after TBI, the modified neurological severity score (mNSS) was assessed. Immediately after behavioural tests, rats were sacrificed to harvest the brain tissues.Results: mNSS scores were lower in the TBI+HT group compared with the TBI+NT group (p < 0.01) and cerebral blood flow was better (p < 0.01). H&E staining of the cortex and ipsilateral hippocampus showed pyknotic and irregularly shaped neurons in TBI+NT rats, which were less frequent in TBI+HT rats. The TBI+NT and TBI+HT groups showed higher TNF-α, TRAIL, FasL, FADD, caspase-3, caspase-8, PARP-1, RIPK-1 and RIPK-3 levels than the sham+NT group (all p < 0.05), but the levels of these proteins were all lower in the TBI+HT group compared with the TBI+NT group (all p < 0.01).Conclusion: HT treatment significantly reduced RIPK-1 upregulation, which may inhibit necroptosis and apoptosis pathways after moderate TBI.