在围产期,发育中的神经系统特别容易受到病理生理线索和损伤的影响。星形胶质细胞是最早对神经组织的损伤作出反应的细胞之一,病原体的存在,局部组织稳态失衡,缺乏氧气和营养支持。在这样的背景下,尚不确定是否诱导星形胶质细胞激活,被认为是星形胶质增生,是发展新生儿神经发育的朋友或敌人。同样,星形胶质细胞反应性的状态被认为是区分内源性修复机制的启动补偿神经组织结构和功能的畸变或神经变性的触发的关键因素之一。激活细胞的反应由邻近的神经细胞调节,通过分泌过多的活性化合物(包括白细胞介素和趋化因子,神经营养因子,活性氧,一氧化氮合酶和补体成分),它们以旁分泌方式参与细胞串扰。由于发育中的神经系统对信号分子的影响极其敏感,即使细胞分泌组的组成或浓度的细微变化也会对发育中的新生儿大脑产生重大影响。因此,调节其他类型细胞的活性及其与过度反应性星形胶质细胞的相互作用可能是控制新生儿星形胶质细胞增生的有希望的策略。
A developing nervous system is particularly vulnerable to the influence of pathophysiological clues and injuries in the perinatal period. Astrocytes are among the first cells that react to insults against the nervous tissue, the presence of pathogens, misbalance of local tissue homeostasis, and a lack of oxygen and trophic support. Under this background, it remains uncertain if induced astrocyte activation, recognized as astrogliosis, is a friend or foe for progressing neonatal neurodevelopment. Likewise, the state of astrocyte reactivity is considered one of the key factors discriminating between either the initiation of endogenous reparative mechanisms compensating for aberrations in the structures and functions of nervous tissue or the triggering of neurodegeneration. The responses of activated cells are modulated by neighboring neural cells, which exhibit broad immunomodulatory and pro-regenerative properties by secreting a plethora of active compounds (including interleukins and chemokines, neurotrophins, reactive oxygen species, nitric oxide synthase and complement components), which are engaged in cell crosstalk in a paracrine manner. As the developing nervous system is extremely sensitive to the influence of signaling molecules, even subtle changes in the composition or concentration of the cellular secretome can have significant effects on the developing neonatal brain. Thus, modulating the activity of other types of cells and their interactions with overreactive astrocytes might be a promising strategy for controlling neonatal astrogliosis.