Beta2 Adrenergic Receptor-mediated Abnormal Myelopoiesis Drives Neuroinflammation in Aged Patients with Traumatic Brain Injury

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2024 Jul 19

PMID 39028822

Authors

Rui Jiang

Zhichao Lu

Chenxing Wang

Jun Xiao

Qianqian Liu

Xide Xu

Jinlong Shi

Jianhong Shen

Xingjia Zhu

Peipei Gong

Qian-Xing Zhuang

Kaibin Shi

Wei Shi

Affiliations

Soon will be listed here.

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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