2. Academic Validation
  3. Beta2 adrenergic receptor-mediated abnormal myelopoiesis drives neuroinflammation in aged patients with traumatic brain injury

Beta2 adrenergic receptor-mediated abnormal myelopoiesis drives neuroinflammation in aged patients with traumatic brain injury

  • Sci Adv. 2024 Jul 19;10(29):eadp5239. doi: 10.1126/sciadv.adp5239.
Rui Jiang 1 2,  Zhichao Lu 1 2,  Chenxing Wang 1 2,  Jun Xiao 1 3,  Qianqian Liu 1 4,  Xide Xu 1 4,  Jinlong Shi 1 4,  Jianhong Shen 1 4,  Xingjia Zhu 1 4,  Peipei Gong 1 4,  Qian-Xing Zhuang 5,  Kaibin Shi 2 6,  Wei Shi 1 4
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu 226001, China.
  • 2 Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
  • 3 Key Laboratory of RNA Science and Engineering, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • 4 Neuro-Microscopy and Minimally Invasive Translational Medicine Innovation Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China.
  • 5 Department of Physiology, School of Medicine, Nantong University, Nantong, Jiangsu 226001, China.
  • 6 Chinese Institutes for Medical Research, Beijing 100069, China.
PMID: 39028822 DOI: 10.1126/sciadv.adp5239
Abstract

Aged patients often suffer poorer neurological recovery than younger patients after traumatic brain injury (TBI), but the mechanisms underlying this difference remain unclear. Here, we demonstrate abnormal myelopoiesis characterized by increased neutrophil and classical monocyte output but impaired nonclassical patrolling monocyte population in aged patients with TBI as well as in an aged murine TBI model. Retrograde and anterograde nerve tracing indicated that increased adrenergic input through the central amygdaloid nucleus-bone marrow axis drives abnormal myelopoiesis after TBI in a β2-adrenergic receptor-dependent manner, which is notably enhanced in aged mice after injury. Selective blockade of β2-adrenergic receptors rebalances abnormal myelopoiesis and improves the outcomes of aged mice after TBI. We therefore demonstrate that increased β2-adrenergic input-driven abnormal myelopoiesis exacerbates post-TBI neuroinflammation in the aged, representing a mechanism underlying the poorer recovery of aged patients and that blockade of β2-adrenergic receptor is a potential approach to promote neurological recovery after TBI.

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