Wolfson CARD, Kings College London, UK.
Exp Neurol. 2012 Apr;234(2):271-82. doi: 10.1016/j.expneurol.2011.08.018. Epub 2011 Aug 26.
Microglia are the resident macrophages in the central nervous system (CNS). Any insult to the CNS homeostasis will induce a rapid change in microglia morphology, gene expression profile and functional behaviour. These responses of microglia have been collectively known as 'microgliosis'. Interestingly, damage to the nervous system outside the CNS, such as axotomy of a peripheral nerve, can lead to microgliosis in the spinal cord. There is a variation in the degree of microgliosis depending on the model of nerve injury employed for instance this response is more marked following traumatic nerve injury than in models of chemotherapy induced neuropathy. Following peripheral nerve injury nociceptive inputs from sensory neurons appear to be critical in triggering the development of spinal microgliosis. A number of signalling pathways including growth factors such as Neuregulin-1, matrix metalloproteases such as MMP-9 and multiple chemokines enable direct communication between injured primary afferents and microglia. In addition, we describe a group of mediators which although not demonstrably shown to be released from neurons are known to modulate microglial phenotype. There is a great functional diversity of the microglial response to peripheral nerve injury which includes: Cellular migration, proliferation, cytokine release, phagocytosis, antigen presentation and recruitment of T cells. It should also be noted that in certain contexts microglia may have a role in the resolution of neuro-inflammation. Although there is still no direct evidence demonstrating that spinal microglia have a role in neuropathic pain in humans, these patients present a pro-inflammatory cytokine profile and it is a reasonable hypothesis that these cells may contribute to this inflammatory response. Modulating microglial functions offers a novel therapeutic opportunity following nerve injury which ideally would involve reducing the pro-inflammatory nature of these cells whilst retaining their potential beneficial functions.
小胶质细胞是中枢神经系统 (CNS) 中的常驻巨噬细胞。任何对 CNS 内环境稳定的损伤都会导致小胶质细胞形态、基因表达谱和功能行为的快速变化。这些小胶质细胞的反应被统称为“小胶质细胞增生”。有趣的是，CNS 以外的神经系统损伤，如周围神经轴突切断，会导致脊髓中的小胶质细胞增生。根据所采用的神经损伤模型，小胶质细胞增生的程度有所不同，例如，创伤性神经损伤后的反应比化疗诱导的神经病模型更为明显。周围神经损伤后，感觉神经元的伤害性传入似乎是触发脊髓小胶质细胞增生发展的关键。包括神经调节素 1 等生长因子、MMP-9 等基质金属蛋白酶和多种趋化因子在内的许多信号通路，使受损的初级传入神经和小胶质细胞之间能够直接进行通讯。此外，我们还描述了一组介质，尽管它们显然不是从神经元中释放出来的，但已知可以调节小胶质细胞表型。外周神经损伤后小胶质细胞的反应具有很大的功能多样性，包括：细胞迁移、增殖、细胞因子释放、吞噬作用、抗原呈递和 T 细胞募集。还应该注意的是，在某些情况下，小胶质细胞可能在神经炎症的消退中发挥作用。尽管仍然没有直接证据表明脊髓小胶质细胞在人类神经性疼痛中起作用，但这些患者表现出促炎细胞因子谱，一个合理的假设是这些细胞可能有助于这种炎症反应。调节小胶质细胞功能为神经损伤后提供了一个新的治疗机会，理想情况下，这将涉及减少这些细胞的促炎性质，同时保留其潜在的有益功能。
