ATF3 is a neuron‐specific biomarker for spinal cord injury and ischaemic stroke

作者：Jonathan Z. Pan, Zhanqiang Wang, Wei Sun, Peipei Pan, Wei Li, Yongtao Sun, Shoulin Chen, Amity Lin, Wulin Tan, Liangliang He, Jacob J. Greene, Virginia Yao, Lijun An, Rich Liang, Qifeng Li, Jessica Yu, Lingyi Zhang, Nikos Kyritsis, Xuan Duong Fernandez, Sara L. Moncivais, Esmeralda Mendoza, Pamela Fung, Gongming Wang, Xinhuan Niu, Qihang Du, Zhaoyang Xiao, Yuwen Chang, Peiyuan Lv, J. Russell Huie, Abel Torres‐Espín, Adam R. Ferguson, Debra D. Hemmerle, Jason F. Talbott, Philip R. Weinstein, Lisa U. Pascual, Vineeta Singh, Anthony M. DiGiorgio, Rajiv Saigal, William D. Whetstone, Geoffrey T. Manley, Sanjay S. Dhall, Jacqueline C. Bresnahan, Mervyn Maze, Xiangning Jiang, Neel S. Singhal, Michael S. Beattie, Hua Su, Zhonghui Guan · 发表于：Clinical and Translational Medicine · 年份：2024 · DOI：10.1002/ctm2.1650 · 被引用次数：20 · 研究领域：Spinal Cord Injury Research、Neuroinflammation and Neurodegeneration Mechanisms、Nerve injury and regeneration

BACKGROUND: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions. METHODS: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. RESULTS: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively....