Department of Pharmacy, University of Pisa, Pisa, Italy.
CNS Neurol Disord Drug Targets. 2022;21(2):118-129. doi: 10.2174/1871527320666210208130412.
Neuroinflammation is characterized by dysregulated inflammatory responses localized within the brain and spinal cord. Neuroinflammation plays a pivotal role in the onset of several neurodegenerative disorders and is considered a typical feature of these disorders. Microglia perform primary immune surveillance and macrophage-like activities within the central nervous system. Activated microglia are predominant players in the central nervous system response to damage related to stroke, trauma, and infection. Moreover, microglial activation per se leads to a proinflammatory response and oxidative stress. During the release of cytokines and chemokines, cyclooxygenases and phospholipase A2 are stimulated. Elevated levels of these compounds play a significant role in immune cell recruitment into the brain. Cyclic phospholipase A2 plays a fundamental role in the production of prostaglandins by releasing arachidonic acid. In turn, arachidonic acid is biotransformed through different routes into several mediators that are endowed with pivotal roles in the regulation of inflammatory processes. Some experimental models of neuroinflammation exhibit an increase in cyclic phospholipase A2, leukotrienes, and prostaglandins such as prostaglandin E2, prostaglandin D2, or prostacyclin. However, findings on the role of the prostacyclin receptors have revealed that their signalling suppresses Th2-mediated inflammatory responses. In addition, other in vitro evidence suggests that prostaglandin E2 may inhibit the production of some inflammatory cytokines, attenuating inflammatory events such as mast cell degranulation or inflammatory leukotriene production. Based on these conflicting experimental data, the role of arachidonic acid derivatives in neuroinflammation remains a challenging issue.
神经炎症的特征是大脑和脊髓内失调的炎症反应。神经炎症在几种神经退行性疾病的发病中起关键作用，被认为是这些疾病的典型特征。小胶质细胞在中枢神经系统中执行主要的免疫监视和巨噬细胞样活动。激活的小胶质细胞是中枢神经系统对中风、创伤和感染相关损伤反应的主要参与者。此外，小胶质细胞的激活本身会导致促炎反应和氧化应激。在细胞因子和趋化因子的释放过程中，环氧化酶和磷脂酶 A2 被刺激。这些化合物水平的升高在免疫细胞招募到大脑中起着重要作用。环型磷脂酶 A2 通过释放花生四烯酸在前列腺素的产生中起着基础性作用。反过来，花生四烯酸通过不同途径被生物转化为几种介质，这些介质在炎症过程的调节中起着关键作用。一些神经炎症的实验模型显示环型磷脂酶 A2、白三烯和前列腺素（如前列腺素 E2、前列腺素 D2 或前列环素）的水平增加。然而，关于前列环素受体作用的研究结果表明，它们的信号传导抑制了 Th2 介导的炎症反应。此外，其他体外证据表明，前列腺素 E2 可能抑制某些炎症细胞因子的产生，减轻炎症事件，如肥大细胞脱颗粒或炎症性白三烯的产生。基于这些相互矛盾的实验数据，花生四烯酸衍生物在神经炎症中的作用仍然是一个具有挑战性的问题。
