2. Academic Validation
  3. Knockout of neutrophil cytosolic factor 1 ameliorates neuroinflammation and motor deficit after traumatic brain injury

Knockout of neutrophil cytosolic factor 1 ameliorates neuroinflammation and motor deficit after traumatic brain injury

  • Exp Neurol. 2024 Dec:382:114983. doi: 10.1016/j.expneurol.2024.114983.
Tian-Xu Gao 1,  Yu Liang 2,  Jian Li 2,  Dan Zhao 2,  Bai-Jun Dong 3,  Chen Xu 4,  Wei-Dong Zhao 5,  Xia Li 6,  Chuan-Sheng Zhao 7
Affiliations

Affiliations

  • 1 Department of Neurology, First Affiliated Hospital, China Medical University, Shenyang 110001, China; Department of Developmental Cell Biology, School of Life Sciences, China Medical University, Shenyang 110122, China.
  • 2 Department of Developmental Cell Biology, School of Life Sciences, China Medical University, Shenyang 110122, China.
  • 3 School of Basic Medical Sciences, China Medical University, Shenyang 110122, China.
  • 4 Department of Laboratory, Xilinguole Central Hospital, Xilinhot 026000, China. Electronic address: 413533156@qq.com.
  • 5 Department of Developmental Cell Biology, School of Life Sciences, China Medical University, Shenyang 110122, China. Electronic address: wdzhao@cmu.edu.cn.
  • 6 Department of Gynecology and Obstetrics, Hohhot Maternal and Child Health Care Hospital, Hohhot 110000, China. Electronic address: 1259434220@qq.com.
  • 7 Department of Neurology, First Affiliated Hospital, China Medical University, Shenyang 110001, China. Electronic address: cszhao@cmu.edu.cn.
PMID: 39357591 DOI: 10.1016/j.expneurol.2024.114983
Abstract

Traumatic brain injury (TBI) is a predominant cause of long-term disability in adults, yet the molecular mechanisms underpinning the neuropathological processes associated with it remain inadequately understood. Neutrophil cytosolic factor 1 (NCF1, also known as p47phox) is one of the cytosolic components of NADPH Oxidase NOX2. In this study, we observed a reduction in the volume of TBI-induced brain lesions in NCF1-knockout mice compared to controls. Correspondingly, the neuronal loss induced by TBI was mitigated in the NCF1-knockout mice. Behavioral analysis also demonstrated that the motor coordination deficit following TBI was mitigated by the depletion of NCF1. Mechanistically, our findings revealed that NCF1 deficiency attenuated TBI-induced inflammatory responses by inhibiting the release of proinflammatory factors and reducing neutrophil infiltration into the brain parenchyma. Additionally, our results indicated that NCF1 deficiency significantly decreased the levels of Reactive Oxygen Species in neutrophils. Taken together, our findings indicate that NCF1 plays a crucial role in the regulation of brain injury and secondary inflammation post-TBI.

Keywords

NCF1; Neuroinflammation; Reactive oxygen species; Traumatic brain injury.

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