2. Academic Validation
  3. Reticuline modulates astrocyte and microglial responses to enhance prognosis after traumatic brain injury

Reticuline modulates astrocyte and microglial responses to enhance prognosis after traumatic brain injury

  • Neurotherapeutics. 2025 Aug 5:e00709. doi: 10.1016/j.neurot.2025.e00709.
Shuhui Xu 1,  Jue Zhu 1,  Jiajia Wen 1,  Chenxing Wang 1,  Xuanfeng Chen 1,  Weiquan Liao 1,  Zhichao Lu 2,  Ziheng Wang 3,  Peipei Gong 4
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, 226001, China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China.
  • 2 Department of Neurosurgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, 226001, China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China. Electronic address: 2013310106@stmail.ntu.edu.cn.
  • 3 MOE Frontier Science Centre for Precision Oncology, University of Macau, Macao Special Administrative Region of China. Electronic address: zihengwang@um.edu.mo.
  • 4 Department of Neurosurgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, 226001, China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China. Electronic address: ntgpp@ntu.edu.cn.
PMID: 40769849 DOI: 10.1016/j.neurot.2025.e00709
Abstract

Traumatic brain injury (TBI) poses a serious threat to public health due to its high disability and mortality rates. Therefore, it is crucial to explore effective therapeutic strategies. Studies have shown that reticuline may exert a cardioprotective effect by blocking the JAK-STAT signaling pathway, but its effect in TBI has not been explored. Therefore, this study aimed to evaluate the potential clinical value of reticuline after TBI and its impact on the inflammatory quiescent state. This study assessed the therapeutic effect of reticuline administered intraperitoneally using the controlled cortical impact (CCI) model in adult rats. In addition, to clarify the mechanism of action of reticuline, we used Colivelin, a STAT3 agonist, to restore the function of related signal pathways and explore its intervention effect. The study showed that reticuline inhibited neuroinflammation and promoted neurological function recovery after TBI by regulating the JAK-STAT signaling pathway, reducing the toxic response of astrocytes and microglia while retaining its neuroprotective effect. In summary, this study reveals that reticuline may promote neural repair after TBI through a JAK-STAT-dependent anti-inflammatory effect. Our findings further expand its potential application value in brain injury treatment and provide new ideas for intervention strategies for TBI.

Keywords

Astrocyte; Microglia; Neuroinflammation; Neurological function; Reticuline; Traumatic brain injury.

Figures
Products