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ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.
Pan, Jonathan Z; Wang, Zhanqiang; Sun, Wei; Pan, Peipei; Li, Wei; Sun, Yongtao; Chen, Shoulin; Lin, Amity; Tan, Wulin; He, Liangliang; Greene, Jacob; Yao, Virginia; An, Lijun; Liang, Rich; Li, Qifeng; Yu, Jessica; Zhang, Lingyi; Kyritsis, Nikolaos; Fernandez, Xuan Duong; Moncivais, Sara; Mendoza, Esmeralda; Fung, Pamela; Wang, Gongming; Niu, Xinhuan; Du, Qihang; Xiao, Zhaoyang; Chang, Yuwen; Lv, Peiyuan; Huie, J Russell; Torres-Espin, Abel; Ferguson, Adam R; Hemmerle, Debra D; Talbott, Jason F; Weinstein, Philip R; Pascual, Lisa U; Singh, Vineeta; DiGiorgio, Anthony M; Saigal, Rajiv; Whetstone, William D; Manley, Geoffrey T; Dhall, Sanjay S; Bresnahan, Jacqueline C; Maze, Mervyn; Jiang, Xiangning; Singhal, Neel S; Beattie, Michael S; Su, Hua; Guan, Zhonghui.
Afiliación
  • Pan JZ; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Wang Z; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Sun W; Center for Cerebrovascular Research, University of California San Francisco, San Francisco, California, USA.
  • Pan P; Department of Neurology, Cangzhou People's Hospital, Cangzhou, China.
  • Li W; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Sun Y; Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, China.
  • Chen S; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Lin A; Center for Cerebrovascular Research, University of California San Francisco, San Francisco, California, USA.
  • Tan W; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • He L; Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, China.
  • Greene J; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Yao V; Department of Anesthesiology, Qianfoshan Hospital, Shandong University, Jinan, China.
  • An L; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Liang R; Department of Anesthesiology, The Second Affiliated Hospital, Nanchang University, Nanchang, China.
  • Li Q; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Yu J; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Zhang L; Department of Anesthesiology, Guangzhou Medical University, Guangzhou, China.
  • Kyritsis N; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Fernandez XD; Department of Pain Management, Xuanwu Hospital, Capital Medical University, Beijing, China.
  • Moncivais S; Medical School, University of California San Francisco, San Francisco, California, USA.
  • Mendoza E; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Fung P; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Wang G; Department of Anesthesiology, No. 1 People's Hospital, Huaian, China.
  • Niu X; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Du Q; Center for Cerebrovascular Research, University of California San Francisco, San Francisco, California, USA.
  • Xiao Z; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Chang Y; Center for Cerebrovascular Research, University of California San Francisco, San Francisco, California, USA.
  • Lv P; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
  • Huie JR; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Torres-Espin A; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Ferguson AR; Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
  • Hemmerle DD; Brain and Spinal Injury Center, University of California San Francisco, San Francisco, California, USA.
  • Talbott JF; Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
  • Weinstein PR; Brain and Spinal Injury Center, University of California San Francisco, San Francisco, California, USA.
  • Pascual LU; Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
  • Singh V; Brain and Spinal Injury Center, University of California San Francisco, San Francisco, California, USA.
  • DiGiorgio AM; Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
  • Saigal R; Brain and Spinal Injury Center, University of California San Francisco, San Francisco, California, USA.
  • Whetstone WD; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Manley GT; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Dhall SS; Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, China.
  • Bresnahan JC; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Maze M; Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, China.
  • Jiang X; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Singhal NS; Department of Anesthesiology, Shandong Provincial Hospital, Shandong University, Jinan, China.
  • Beattie MS; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
  • Su H; Department of Anesthesiology, The Second Affiliated Hospital, Dalian Medical University, Dalian, China.
  • Guan Z; Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California, USA.
Clin Transl Med ; 14(4): e1650, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38649772
ABSTRACT

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. 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.

CONCLUSIONS:

ATF3 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.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Traumatismos de la Médula Espinal / Biomarcadores / Factor de Transcripción Activador 3 / Accidente Cerebrovascular Isquémico / Neuronas Límite: Animals / Female / Humans / Male Idioma: En Revista: Clin Transl Med Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Traumatismos de la Médula Espinal / Biomarcadores / Factor de Transcripción Activador 3 / Accidente Cerebrovascular Isquémico / Neuronas Límite: Animals / Female / Humans / Male Idioma: En Revista: Clin Transl Med Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos