Deng Yi Yu, Lu Jia, Ling Eng-Ang, Kaur Charanjit
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Front Biosci (Schol Ed). 2011 Jun 1;3(3):884-900. doi: 10.2741/194.
The developing brain is susceptible to hypoxic damage because of its high oxygen and energy requirements. Hypoxia-induced inflammatory response has been recognized as one of the main culprits in the development of hypoxic brain injury. In this regard, a hallmark feature is microglial activation which results in overproduction of inflammatory cytokines, free radicals and nitric oxide. Concomitantly, activated microglia exhibit enhanced expression of ion channels such as Kv1.2, Kv1.1 and Nav which further promote the release of inflammatory cytokines, chemokines and reactive oxygen species. Through the above-mentioned inflammatory mediators, activated microglia induce neuronal loss, axonal damage and oligodendroglial death along with myelination disturbances. Our recent studies have extended that tumor necrosis factor-alpha, interleukin-1beta, monocyte chemoattractant protein-1 and macrophage colony stimulating factor produced by activated microglia are linked to the pathogenesis of periventricular white matter damage in the hypoxic brain. It is envisaged that a better understanding of the interactions between microglia and neurons, axons and oligodendrocytes is key to the development of effective preventive and therapeutic strategies for mitigation of hypoxic brain injury.
发育中的大脑因其对氧气和能量的高需求而易受缺氧损伤。缺氧诱导的炎症反应已被认为是缺氧性脑损伤发展的主要元凶之一。在这方面，一个标志性特征是小胶质细胞活化，这会导致炎性细胞因子、自由基和一氧化氮的过度产生。与此同时，活化的小胶质细胞表现出离子通道如Kv1.2、Kv1.1和Nav的表达增强，这进一步促进了炎性细胞因子、趋化因子和活性氧的释放。通过上述炎性介质，活化的小胶质细胞诱导神经元丢失、轴突损伤和少突胶质细胞死亡以及髓鞘形成障碍。我们最近的研究扩展发现，活化的小胶质细胞产生的肿瘤坏死因子-α、白细胞介素-1β、单核细胞趋化蛋白-1和巨噬细胞集落刺激因子与缺氧性脑损伤中脑室周围白质损伤的发病机制有关。可以设想，更好地理解小胶质细胞与神经元、轴突和少突胶质细胞之间的相互作用是制定有效预防和治疗策略以减轻缺氧性脑损伤的关键。
