title: Protective effect of mild-induced hypothermia against moderate traumatic brain injury in rats involved in necroptotic and apoptotic pathways.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  HT treatment significantly reduced RIPK-1 upregulation, which may inhibit necroptosis and apoptosis pathways after moderate TBI.
authors.affiliation: a Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience of Chinese People's Armed Police Forces (PAP) , Neurosurgical and Neurological Hospital of PAP , Tianjin , PR China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Zhang
authors.affiliation: a Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience of Chinese People's Armed Police Forces (PAP) , Neurosurgical and Neurological Hospital of PAP , Tianjin , PR China.
authors.forename: Shi-Xiang
authors.initials: SX
authors.lastname: Cheng
authors.affiliation: a Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience of Chinese People's Armed Police Forces (PAP) , Neurosurgical and Neurological Hospital of PAP , Tianjin , PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Tu
authors.affiliation: a Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience of Chinese People's Armed Police Forces (PAP) , Neurosurgical and Neurological Hospital of PAP , Tianjin , PR China.
authors.forename: Sai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: a Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience of Chinese People's Armed Police Forces (PAP) , Neurosurgical and Neurological Hospital of PAP , Tianjin , PR China.
authors.forename: Shi-Ke
authors.initials: SK
authors.lastname: Hou
authors.affiliation: a Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience of Chinese People's Armed Police Forces (PAP) , Neurosurgical and Neurological Hospital of PAP , Tianjin , PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D000070642:Brain Injuries, Traumatic / Q000150:complications* / Q000628:therapy*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D007036:Hypothermia, Induced; D008297:Male; D009336:Necrosis / Q000209:etiology / Q000378:metabolism; D009460:Neurologic Examination; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C505535:Fadd protein, rat; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D014409:Tumor Necrosis Factor-alpha; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D017346:Protein Serine-Threonine Kinases; C586536:RIPK1 protein, rat; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D020169:Caspases
keywords: RIPK-1; Traumatic brain injury; apoptosis; hypothermia; necroptosis