Acute effects of human protein S administration after traumatic brain injury in mice  

作　　者：Xiaowei Wang Jing Tong Xiaodi Han Xiaoming Qi Jun Zhang Erxi Wu Jason H.Huang 

机构地区：[1]Center for Translational Neuromedicine,University of Rochester,Rochester,NY,USA [2]Department of Neurosurgery,4th Affiliated Hospital of Hebei Medical University,Shijiazhuang,Hebei Province,China [3]Department of Neurosurgery,Tiantan Hospital,Beijing,China [4]Department of Neurosurgery,Baylor Scott&White Health,Temple,TX,USA [5]Department of Neurosurgery,PLA General Hospital,Beijing,China [6]College of Medicine,Texas A&M Health Science Center,Temple,TX,USA

出　　处：《Neural Regeneration Research》2020年第11期2073-2081,共9页中国神经再生研究（英文版）

基　　金：supported in part by a University of Rochester Institutional Grant(2011NSG-Huang,to JHH);National Institute of Health(NIH-R01-NS-067435,to JHH);the Hellen Vosberg McCrillus Plummer and Robert Edward Lee Plummer,Jr,Endowment fund from Baylor Scott&White Medical Center(to JHH)。

摘　　要：Despite years of effort,no effective acute phase treatment has been discovered for traumatic brain injury.One impediment to successful drug development is entangled secondary injury pathways.Here we show that protein S,a natural multifunctional protein that regulates coagulation,inflammation,and apoptosis,is able to reduce the extent of multiple secondary injuries in traumatic brain injury,and therefore improve prognosis.Mice subjected to controlled cortical impact were treated acutely(10–15 minutes post-injury)with a single dose of either protein S(1 mg/kg)or vehicle phosphate buffered saline via intravenous injection.At 24 hours post-injury,compared to the non-treated group,the protein S treated group showed substantial improvement of edema and fine motor coordination,as well as mitigation of progressive tissue loss.Immunohistochemistry and western blot targeting caspase-3,B-cell lymphoma 2(Bcl-2)along with terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay revealed that apoptosis was suppressed in treated animals.Immunohistochemistry targeting CD11 b showed limited leukocyte infiltration in the protein S-treated group.Moreover,protein S treatment increased the ipsilesional expression of aquaporin-4,which may be the underlying mechanism of its function in reducing edema.These results indicate that immediate intravenous protein S treatment after controlled cortical impact is beneficial to traumatic brain injury prognosis.Animal Use Protocols(AUPs)were approved by the University Committee on Animal Resources(UCAR)of University of Rochester Medical Center(approval No.UCAR-2008-102 R)on November 12,2013.

关 键 词：apoptosis AQUAPORIN-4 controlled CORTICAL impact EDEMA inflammation protein S TBI therapy TRAUMATIC brain injury 

分 类 号：R651.15[医药卫生—外科学]