机构：[1]Department of Anesthesia andPerioperative Care, University ofCalifornia San Francisco, San Francisco,California, USA[2]Center for Cerebrovascular Research,University of California San Francisco,San Francisco, California, USA[3]Department of Neurology, CangzhouPeople’s Hospital, Cangzhou, China[4]Department of Anesthesiology,Shandong Provincial Hospital, ShandongUniversity, Jinan, China[5]Department of Anesthesiology,Qianfoshan Hospital, ShandongUniversity, Jinan, China[6]Department of Anesthesiology, TheSecond Affiliated Hospital, NanchangUniversity, Nanchang, China[7]Department of Anesthesiology,Guangzhou Medical University,Guangzhou, China[8]Department of Pain Management,Xuanwu Hospital, Capital MedicalUniversity, Beijing, China外科系统疼痛科首都医科大学宣武医院[9]Medical School, University of CaliforniaSan Francisco, San Francisco, California,USA[10]Department of Anesthesiology, No. 1People’s Hospital, Huaian, China[11]Department of Neurosurgery, TianjinMedical University General Hospital,Tianjin, China[12]Department of Neurological Surgery,University of California San Francisco,San Francisco, California, USA[13]Brain and Spinal Injury Center,University of California San Francisco,San Francisco, California, USA[14]Department of Anesthesiology, TheSecond Affiliated Hospital, DalianMedical University, Dalian, China[15]Department of Neurology, HebeiMedical University, Shijiazhuang, China[16]Department of Radiology, University ofCalifornia San Francisco, San Francisco,California, USA[17]Department of Orthopedic Surgery,Orthopaedic Trauma Institute, Universityof California San Francisco, SanFrancisco, California, USA[18]Department of Neurology, University ofCalifornia San Francisco, San Francisco,California, USA[19]Department of Emergency Medicine,University of California San Francisco,San Francisco, California, USA[20]Department of Neurosurgery, HarborUCLA Medical Center, Torrance,California, USA
BackgroundAlthough 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.MethodsIn 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.ResultsActivating 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 naive mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function.ConclusionsATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties.Highlights ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke. center dot Activating transcription factor 3 (ATF3) is induced in spinal cord and cortex neurons 1 day after spinal cord injury (SCI) and ischaemic stroke, respectively.center dot Serum ATF3 is elevated in patients 1 day after SCI or ischaemic stroke, and this elevation correlates linearly with the severity of SCI and ischaemic stroke.center dot ATF3 is neuroprotective in SCI and ischaemic stroke. image
基金：
UCSF Anesthesia Department Research Fund; UCSF Chancellor Faculty Resource Fund; NINDS [R01NS100801]; Department of Defense [SC190233, SC150198, A139952]
第一作者机构：[1]Department of Anesthesia andPerioperative Care, University ofCalifornia San Francisco, San Francisco,California, USA
共同第一作者：
通讯作者：
通讯机构：[1]Department of Anesthesia andPerioperative Care, University ofCalifornia San Francisco, San Francisco,California, USA[2]Center for Cerebrovascular Research,University of California San Francisco,San Francisco, California, USA[*1]Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California San Francisco, Box 1363, 1001 Potrero Ave, San Francisco, CA 94110, USA[*2]UCSF Pain Management Center, Department of Anesthesia and Perioperative Care, University of California San Francisco, 2255 Post Street, Box 1654, San Francisco, CA 94143, USA
推荐引用方式(GB/T 7714)：
Jonathan Z. Pan,Zhanqiang Wang,Wei Sun,et al.ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke[J].CLINICAL AND TRANSLATIONAL MEDICINE.2024,14(4):doi:10.1002/ctm2.1650.
APA：
Jonathan Z. Pan,Zhanqiang Wang,Wei Sun,Peipei Pan,Wei Li...&Zhonghui Guan.(2024).ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.CLINICAL AND TRANSLATIONAL MEDICINE,14,(4)
MLA：
Jonathan Z. Pan,et al."ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke".CLINICAL AND TRANSLATIONAL MEDICINE 14..4(2024)
