Inhibiting endogenous tissue plasminogen activator enhanced neuronal apoptosis and axonal injury after traumatic brain injury

作     者：Jun-Jie Zhao Zun-Wei Liu Bo Wang Ting-Qin Huang Dan Guo Yong-Lin Zhao Jin-Ning Song Jun-Jie Zhao;Zun-Wei Liu;Bo Wang;Ting-Qin Huang;Dan Guo;Yong-Lin Zhao;Jin-Ning Song

作者机构：Department of Neurosurgerythe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi ProvinceChina Institute of Organ Transplantationthe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi ProvinceChina Department of Renal TransplantationNephropathy Hospitalthe First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi ProvinceChina Department of Neurosurgerythe Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi ProvinceChina Department of Science and TechnologyXi’an Medical UniversityXi’anShaanxi ProvinceChina Department of Oncologythe Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2020年第15卷第4期

页      面：667-675页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100104[医学-病理学与病理生理学] 100215[医学-康复医学与理疗学] 10[医学] 

主　　题：apoptosis astrocytes axonal injury inflammation microglia nerve regeneration neural regeneration neuronal injury neurons neuroserpin tissue plasminogen activator traumatic brain injury 

摘      要：Tissue plasminogen activator is usually used for the treatment of acute ischemic stroke,but the role of endogenous tissue plasminogen activator in traumatic brain injury has been rarely reported.A rat model of traumatic brain injury was established by weight-drop method.The tissue plasminogen activator inhibitor neuroserpin(5μL,0.25 mg/mL)was injected into the lateral ventricle.Neurological function was assessed by neurological severity score.Neuronal and axonal injuries were assessed by hematoxylin-eosin staining and Bielschowsky silver staining.Protein level of endogenous tissue plasminogen activator was analyzed by western blot assay.Apoptotic marker cleaved caspase-3,neuronal marker neurofilament light chain,astrocyte marker glial fibrillary acidic protein and microglial marker Iba-1 were analyzed by immunohistochemical staining.Apoptotic cell types were detected by immunofluorescence double labeling.Apoptotic cells in the damaged cortex were detected by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling staining.Degenerating neurons in the damaged cortex were detected by Fluoro-Jade B staining.Expression of tissue plasminogen activator was increased at 6 hours,and peaked at 3 days after traumatic brain injury.Neuronal apoptosis and axonal injury were detected after traumatic brain injury.Moreover,neuroserpin enhanced neuronal apoptosis,neuronal injury and axonal injury,and activated microglia and astrocytes.Neuroserpin further deteriorated neurobehavioral function in rats with traumatic brain injury.Our findings confirm that inhibition of endogenous tissue plasminogen activator aggravates neuronal apoptosis and axonal injury after traumatic brain injury,and activates microglia and astrocytes.This study was approved by the Biomedical Ethics Committee of Animal Experiments of Shaanxi Province of China in June 2015.