Investigating neuropathological changes and underlying neurobiological mechanisms in the early stages of primary blast-induced traumatic brain injury: Insights from a rat model

作者全名："Zhu, Xiyan; Chu, Xiang; Wang, Hao; Liao, Zhikang; Xiang, Hongyi; Zhao, Wenbing; Yang, Li; Wu, Pengfei; Liu, Xing; Chen, Diyou; Xie, Jingru; Dai, Wei; Li, Lei; Wang, Jianmin; Zhao, Hui"

作者地址："[Zhu, Xiyan; Liao, Zhikang; Xiang, Hongyi; Zhao, Wenbing; Yang, Li; Wu, Pengfei; Liu, Xing; Chen, Diyou; Xie, Jingru; Dai, Wei; Zhao, Hui] Army Med Univ, Daping Hosp, Dept Mil Traff Injury Prevent & Control, Chongqing, Peoples R China; [Chu, Xiang] Chongqing Med Univ, Childrens Hosp, Cognit Dev & Learning & Memory Disorders Translat, Chongqing, Peoples R China; [Chu, Xiang] Army Med Univ, Daping Hosp, Emergency Dept, Chongqing, Peoples R China; [Wang, Hao] Army Med Univ, Daping Hosp, Neurosurg Dept, Chongqing, Peoples R China; [Li, Lei] Army Med Univ, Daping Hosp, Trauma Med Ctr, Chongqing, Peoples R China; [Wang, Jianmin] Army Med Univ, Daping Hosp, Dept Weap Bioeffect Assessment, Chongqing, Peoples R China; [Wang, Jianmin; Zhao, Hui] Daping Hosp, 10 Changjiang Branch Rd,Yuzhong Dist, Chongqing 400042, Peoples R China"

通信作者："Wang, JM; Zhao, H (通讯作者)，Daping Hosp, 10 Changjiang Branch Rd,Yuzhong Dist, Chongqing 400042, Peoples R China."

来源：EXPERIMENTAL NEUROLOGY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001196677100001

JCR分区：Q1

影响因子：4.6

年份：2024

卷号：375

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Blast waves; Traumatic brain injury; Neuropathology; Quantitative proteomics; Signaling pathways; G protein subunits

摘要："The utilization of explosives and chemicals has resulted in a rise in blast-induced traumatic brain injury (bTBI) in recent times. However, there is a dearth of diagnostic biomarkers and therapeutic targets for bTBI due to a limited understanding of biological mechanisms, particularly in the early stages. The objective of this study was to examine the early neuropathological characteristics and underlying biological mechanisms of primary bTBI. A total of 83 Sprague Dawley rats were employed, with their heads subjected to a blast shockwave of peak overpressure ranging from 172 to 421 kPa in the GI, GII, and GIII groups within a closed shock tube, while the body was shielded. Neuromotor dysfunctions, morphological changes, and neuropathological alterations were detected through modified neurologic severity scores, brain water content analysis, MRI scans, histological, TUNEL, and caspase-3 immunohistochemical staining. In addition, label-free quantitative (LFQ)-proteomics was utilized to investigate the biological mechanisms associated with the observed neuropathology. Notably, no evident damage was discernible in the GII and GI groups, whereas mild brain injury was observed in the GIII group. Neuropathological features of bTBI were characterized by morphologic changes, including neuronal injury and apoptosis, cerebral edema, and cerebrovascular injury in the shockwave's path. Subsequently, 3153 proteins were identified and quantified in the GIII group, with subsequent enriched neurological responses consistent with pathological findings. Further analysis revealed that signaling pathways such as relaxin signaling, hippo signaling, gap junction, chemokine signaling, and sphingolipid signaling, as well as hub proteins including Prkacb, Adcy5, and various G-protein subunits (Gnai2, Gnai3, Gnao1, Gnb1, Gnb2, Gnb4, and Gnb5), were closely associated with the observed neuropathology. The expression of hub proteins was confirmed via Western blotting. Accordingly, this study proposes signaling pathways and key proteins that exhibit sensitivity to brain injury and are correlated with the early pathologies of bTBI. Furthermore, it highlights the significance of Gprotein subunits in bTBI pathophysiology, thereby establishing a theoretical foundation for early diagnosis and treatment strategies for primary bTBI."

基金机构：National Natural Science Foundation of China [81901220]; Natural Science Foundation of Chongqing [csct2020jcyj-bshX0062]

基金资助正文：<B>Funding</B> This work was funding by the National Natural Science Foundation of China (Grant number 81901220) and Natural Science Foundation of Chongqing (Grant number csct2020jcyj-bshX0062) .