小胶质细胞和星形胶质细胞在神经炎症反应中发挥重要作用，有助于邻近组织的破坏以及中风后炎症的消退。这些反应性神经胶质细胞在转录组和功能水平上都具有高度异质性。根据刺激，小胶质细胞和星形胶质细胞会产生由不同的小胶质细胞和星形胶质细胞亚状态组成的复杂且特定的反应。这些子状态最终推动不利刺激的启动和恢复。在一种状态下，炎症和损伤诱导的小胶质细胞释放肿瘤坏死因子 (TNF)、白细胞介素 1α (IL1α) 和补体成分 1q (C1q)，一起称为“TIC”。这种细胞因子混合物驱动星形胶质细胞进入神经毒性反应性星形胶质细胞 (nRA) 亚状态。这种 nRA 亚状态与许多生理性星形胶质细胞功能的丧失（例如突触形成和成熟、吞噬作用等）以及杀死邻近细胞的神经毒性长链脂肪酸的功能获得性释放有关。在这里，我们报告说，转基因去除 TIC 导致神经胶质增生减少、梗塞扩张以及中风后急性期和迟发期功能缺陷恶化。我们的结果表明，TIC 细胞因子和可能的 nRA 发挥着重要作用，可能维持神经炎症并抑制缺血性中风后功能性运动恢复。这是第一份报告表明这种模式与中风相关，并且针对 nRA 的疗法可能是治疗患者的新方法。由于 nRA 从啮齿动物到人类在进化上是保守的，并且存在于多种神经退行性疾病和损伤中，因此进一步鉴定 nRA 的机制作用将有助于更好地了解神经炎症反应和新疗法的开发。

Microglia and astrocytes play an important role in the neuroinflammatory response and contribute to both the destruction of neighboring tissue as well as the resolution of inflammation following stroke. These reactive glial cells are highly heterogeneous at both the transcriptomic and functional level. Depending upon the stimulus, microglia and astrocytes mount a complex, and specific response composed of distinct microglial and astrocyte substates. These substates ultimately drive the landscape of the initiation and recovery from the adverse stimulus. In one state, inflammation- and damage-induced microglia release tumor necrosis factor (TNF), interleukin 1α (IL1α), and complement component 1q (C1q), together 'TIC'. This cocktail of cytokines drives astrocytes into a neurotoxic reactive astrocyte (nRA) substate. This nRA substate is associated with loss of many physiological astrocyte functions (e.g., synapse formation and maturation, phagocytosis, among others), as well as a gain-of-function release of neurotoxic long-chain fatty acids which kill neighboring cells. Here we report that transgenic removal of TIC led to reduction of gliosis, infarct expansion, and worsened functional deficits in the acute and delayed stages following stroke. Our results suggest that TIC cytokines, and likely nRAs play an important role that may maintain neuroinflammation and inhibit functional motor recovery after ischemic stroke. This is the first report that this paradigm is relevant in stroke and that therapies against nRAs may be a novel means to treat patients. Since nRAs are evolutionarily conserved from rodents to humans and present in multiple neurodegenerative diseases and injuries, further identification of mechanistic role of nRAs will lead to a better understanding of the neuroinflammatory response and the development of new therapies.