Zhang Haifeng, Zhang Xian, Chai Yan, Wang Yuhua, Zhang Jianning, Chen Xin
Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
Tianjin Neurological Institute, Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China.
Front Immunol. 2025 May 8;16:1584577. doi: 10.3389/fimmu.2025.1584577. eCollection 2025.
Astrocytes play a pivotal role in the inflammatory response triggered by traumatic brain injury (TBI). They are not only involved in the initial inflammatory response following injury but also significantly contribute to Astrocyte activation and inflammasome release are key processes in the pathophysiology of TBI, significantly affecting the progression of secondary injury and long-term outcomes. This comprehensive review explores the complex triggering mechanisms of astrocyte activation following TBI, the intricate pathways controlling the release of inflammasomes from activated astrocytes, and the subsequent neuroinflammatory cascade and its multifaceted roles after injury. The exploration of these processes not only deepens our understanding of the neuroinflammatory cascade but also highlights the potential of astrocytes as critical therapeutic targets for TBI interventions. We then evaluate cutting-edge research aimed at targeted therapeutic approaches to modulate pro-inflammatory astrocytes and discuss emerging pharmacological interventions and their efficacy in preclinical models. Given that there has yet to be a relevant review elucidating the specific intracellular mechanisms targeting astrocyte release of inflammatory substances, this review aims to provide a nuanced understanding of astrocyte-mediated neuroinflammation in TBI and elucidate promising avenues for therapeutic interventions that could fundamentally change TBI management and improve patient outcomes. The development of secondary brain injury and long-term neurological sequelae. By releasing a variety of cytokines and chemokines, astrocytes regulate neuroinflammation, thereby influencing the survival and function of surrounding cells. In recent years, researchers have concentrated their efforts on elucidating the signaling crosstalk between astrocytes and other cells under various conditions, while exploring potential therapeutic interventions targeting these cells. This paper highlights the specific mechanisms by which astrocytes produce inflammatory mediators during the acute phase post-TBI, including their roles in inflammatory signaling, blood-brain barrier integrity, and neuronal protection. Additionally, we discuss current preclinical and clinical intervention strategies targeting astrocytes and their potential to mitigate neurological damage and enhance recovery following TBI. Finally, we explore the feasibility of pharmacologically assessing astrocyte activity post-TBI as a biomarker for predicting acute-phase neuroinflammatory changes.
星形胶质细胞在创伤性脑损伤（TBI）引发的炎症反应中起关键作用。它们不仅参与损伤后的初始炎症反应，还对继发性脑损伤的发展和长期预后产生重大影响。星形胶质细胞活化和炎性小体释放是TBI病理生理学中的关键过程，显著影响继发性损伤的进展和长期预后。这篇综述探讨了TBI后星形胶质细胞活化的复杂触发机制、控制活化星形胶质细胞释放炎性小体的复杂途径，以及随后的神经炎症级联反应及其在损伤后的多方面作用。对这些过程的探索不仅加深了我们对神经炎症级联反应的理解，还突出了星形胶质细胞作为TBI干预关键治疗靶点的潜力。然后，我们评估了旨在调节促炎性星形胶质细胞的靶向治疗方法的前沿研究，并讨论了新兴的药理学干预措施及其在临床前模型中的疗效。鉴于尚未有相关综述阐明针对星形胶质细胞释放炎性物质的具体细胞内机制，本综述旨在对TBI中星形胶质细胞介导的神经炎症进行细致入微的理解，并阐明有望从根本上改变TBI治疗和改善患者预后的治疗干预途径。继发性脑损伤和长期神经后遗症的发展。通过释放多种细胞因子和趋化因子，星形胶质细胞调节神经炎症，从而影响周围细胞的存活和功能。近年来，研究人员致力于阐明各种条件下星形胶质细胞与其他细胞之间的信号串扰，同时探索针对这些细胞的潜在治疗干预措施。本文重点介绍了TBI急性期星形胶质细胞产生炎症介质的具体机制，包括它们在炎症信号传导、血脑屏障完整性和神经元保护中的作用。此外，我们讨论了目前针对星形胶质细胞的临床前和临床干预策略及其减轻TBI后神经损伤和促进恢复的潜力。最后，我们探讨了通过药理学评估TBI后星形胶质细胞活性作为预测急性期神经炎症变化生物标志物的可行性。
