University of Padua, Padua, Italy.
Int Rev Neurobiol. 2017;137:29-45. doi: 10.1016/bs.irn.2017.08.004. Epub 2017 Oct 16.
A number of nervous system disorders are characterized by a state of inflammation (neuroinflammation) in which members of the innate immune system, most notably mast cells and microglia-acting as single entities and in unison-produce inflammatory molecules that play major roles. A neuroinflammatory environment can weaken not only blood-nerve and blood-brain barrier (BBB) integrity but also that of the blood-spinal cord barrier. Mast cells, with their distribution in peripheral nerves and the central nervous system, are positioned to influence blood-nerve barrier characteristics. Being close also to the perivasculature and on the brain side of the BBB, the mast cell is well positioned to disrupt BBB function. Interestingly, tissue damage and/or stress activates homeostatic mechanisms/molecules expressed by mast cells and microglia, and includes N-acylethanolamines. Among the latter, N-palmitoylethanolamine has distinguished itself as a key component in supporting homeostasis of the organism against external stressors capable of provoking inflammation. This review will discuss the pathobiology of neuroinflammation with emphasis on mast cells and microglia, their roles in BBB health, and novel therapeutic opportunities, including nanoscale delivery for targeting these immune cells with a view to maintain the BBB.
许多神经系统疾病的特征是炎症状态（神经炎症），其中先天免疫系统的成员，尤其是肥大细胞和小胶质细胞——作为单一实体并协调一致地产生炎症分子，这些分子发挥着主要作用。神经炎症环境不仅会削弱血-神经和血脑屏障（BBB）的完整性，还会削弱血-脊髓屏障的完整性。肥大细胞在周围神经和中枢神经系统中的分布，使其能够影响血-神经屏障的特征。由于靠近血管周围和 BBB 的脑侧，肥大细胞很容易破坏 BBB 的功能。有趣的是，组织损伤和/或应激激活了肥大细胞和小胶质细胞表达的稳态机制/分子，包括 N-酰基乙醇胺。在后者中，N-棕榈酰乙醇胺已成为支持机体对抗能够引发炎症的外部应激源的内稳态的关键组成部分。这篇综述将讨论神经炎症的病理生物学，重点讨论肥大细胞和小胶质细胞，它们在 BBB 健康中的作用，以及新的治疗机会，包括纳米级递送来靶向这些免疫细胞，以维持 BBB。
