title: Mild Hypothermia Promotes Pericontusion Neuronal Sprouting via Suppressing Suppressor of Cytokine Signaling 3 Expression after Moderate Traumatic Brain Injury.
abstract: Mild therapeutic hypothermia is a candidate for the treatment of traumatic brain injury (TBI). However, the role of mild hypothermia in neuronal sprouting after TBI remains obscure. We used a fluid percussion injury (FPI) model to assess the effect of mild hypothermia on pericontusion neuronal sprouting after TBI in rats. Male Sprague-Dawley rats underwent FPI or sham surgery, followed by mild hypothermia treatment (33°C) or normothermia treatment (37°C) for 3 h. All the rats were euthanized at 7 days after FPI. Neuronal sprouting that was confirmed by an increase in growth associated protein-43 (GAP-43) expression was evaluated using immunofluorescence and Western blot assays. The expression levels of several intrinsic and extrinsic sprouting-associated genes such as neurite outgrowth inhibitor A (NogoA), phosphatase and tensin homolog (PTEN), and suppressor of cytokine signaling 3 (SOCS3) were analyzed by quantitative real-time polymerase chain reaction (RT-PCR). Our results revealed that mild hypothermia significantly increased the expression level of GAP-43 and dramatically suppressed the expression level of interleukin-6 (IL-6) and SOCS3 at 7 days after FPI in the ipsilateral cortex compared with that of the normothermia TBI group. These data suggest that post-traumatic mild hypothermia promotes pericontusion neuronal sprouting after TBI. Moreover, the mechanism of hypothermia-induced neuronal sprouting might be partially associated with decreased levels of SOCS3.
authors.affiliation: 1 Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai Institute of Head Trauma, Shanghai, People's Republic of China .
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Zhao
authors.affiliation: 1 Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai Institute of Head Trauma, Shanghai, People's Republic of China .
authors.forename: Chuan-Fang
authors.initials: CF
authors.lastname: Wang
authors.affiliation: 2 Department of Neurosurgery, Shenzhen Second People's Hospital, Shenzhen University , Shenzhen, Guangdong, People's Republic of China .
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Li
authors.affiliation: 1 Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai Institute of Head Trauma, Shanghai, People's Republic of China .
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.affiliation: 1 Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai Institute of Head Trauma, Shanghai, People's Republic of China .
authors.forename: Qi-Lin
authors.initials: QL
authors.lastname: Tang
authors.affiliation: 1 Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai Institute of Head Trauma, Shanghai, People's Republic of China .
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Feng
authors.affiliation: 1 Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai Institute of Head Trauma, Shanghai, People's Republic of China .
authors.forename: Qing
authors.initials: Q
authors.lastname: Mao
authors.affiliation: 1 Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai Institute of Head Trauma, Shanghai, People's Republic of China .
authors.forename: Guo-Yi
authors.initials: GY
authors.lastname: Gao
authors.affiliation: 1 Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai Institute of Head Trauma, Shanghai, People's Republic of China .
authors.forename: Ji-Yao
authors.initials: JY
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000070624:Brain Contusion / Q000378:metabolism / Q000628:therapy; D000070642:Brain Injuries, Traumatic / Q000378:metabolism* / Q000628:therapy*; D002540:Cerebral Cortex / Q000378:metabolism*; D004195:Disease Models, Animal; D019922:GAP-43 Protein / Q000378:metabolism*; D007036:Hypothermia, Induced / Q000379:methods*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D000070798:Nogo Proteins / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000378:metabolism*
chemical_list: D019922:GAP-43 Protein; D015850:Interleukin-6; D000070798:Nogo Proteins; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat
keywords: TBI; animal studies; axonal regeneration; hypothermia; neuroplasticity