Banati Richard B
Molecular Neuropsychiatry, Department of Neuropathology, Charing Cross Hospital, Imperial College School of Medicine, London W6 8RF, UK.
J Physiol Paris. 2002 Apr-Jun;96(3-4):289-99. doi: 10.1016/s0928-4257(02)00018-9.
Microglia are a subset of tissue-macrophages that are ubiquitously distributed throughout the entire CNS. In health, they remain largely dormant until activated by a pathological stimulus. The availability of more sensitive detection techniques has allowed the early measurement of the cell responses of microglia in areas with few signs of active pathology. Subtle neuronal injury can induce microglial activation in retrograde and anterograde projection areas remote from the primary lesion focus. There is also evidence that in cases of long-standing abnormal neuronal activity, such as in patients after limb amputation with chronic pain and phantom sensations, glial activation may occur transsynaptically in the thalamus. Such neuronally driven glial responses may be related to the emergence central sensitisation in chronic pain states or plasticity phenomena in the cerebral cortex. It is suggested, that such persistent low-level microglial activation is not adequately described by the traditional concept of phagocyte-mediated tissue damage that largely evolved from studies of acute brain lesion models or acute human brain pathology. Due to the presence of signal molecules that can act on neurons and microglia alike, the communication between neurons and microglia is likely to be bi-directional. Persistent subtle microglial activity may modulate basal synaptic transmission and thus neuronal functioning either directly or through the interaction with astrocytes. The activation of microglia leads to the emergence of microstructural as well as functional compartments in which neurokines, interleukins and other signalling molecules introduce a qualitatively different, more open mode of cell-cell communication that is normally absent from the healthy adult brain. This 'neo-compartmentalisation', however, occurs along predictable neuronal pathways within which these glial changes are themselves under the modulatory influence of neurons or other glial cells and are subject to the evolving state of the pathology. Depending on the disease state, yet relatively independent of the specific disease cause, fluctuations in the modulatory influence by non-neuronal cells may form the cellular basis for the variability of brain plasticity phenomena, i.e. the plasticity of plasticity.
小胶质细胞是组织巨噬细胞的一个亚群，广泛分布于整个中枢神经系统。在健康状态下，它们大多处于休眠状态，直到被病理刺激激活。更灵敏检测技术的出现使得在几乎没有明显病理活动迹象的区域早期测量小胶质细胞的细胞反应成为可能。轻微的神经元损伤可在远离原发性病变灶的逆行和顺行投射区域诱导小胶质细胞激活。也有证据表明，在长期异常神经元活动的情况下，如在患有慢性疼痛和幻肢感觉的截肢患者中，丘脑可能会发生跨突触的胶质细胞激活。这种由神经元驱动的胶质细胞反应可能与慢性疼痛状态下中枢敏化的出现或大脑皮质的可塑性现象有关。有人提出，传统的吞噬细胞介导的组织损伤概念主要源于对急性脑损伤模型或急性人类脑部病理学的研究，无法充分描述这种持续性的低水平小胶质细胞激活。由于存在可同时作用于神经元和小胶质细胞的信号分子，神经元与小胶质细胞之间的通讯可能是双向的。持续性的轻微小胶质细胞活动可能直接或通过与星形胶质细胞的相互作用来调节基础突触传递，进而影响神经元功能。小胶质细胞的激活导致微观结构和功能区室的出现，在这些区室中，神经因子、白细胞介素和其他信号分子引入了一种性质不同、更开放的细胞间通讯模式，而这种模式在健康的成人大脑中通常不存在。然而，这种“新的区室化”沿着可预测的神经元通路发生，在这些通路中，这些胶质细胞变化本身受到神经元或其他胶质细胞的调节影响，并受病理发展状态的支配。根据疾病状态，且相对独立于具体病因，非神经元细胞调节影响的波动可能构成脑可塑性现象变异性的细胞基础，即可塑性的可塑性。
