Department of Cellular Neurophysiology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague. Czech Republic.
Curr Pharm Des. 2017;23(33):5056-5074. doi: 10.2174/1381612823666170710161858.
Brain ischemic injury represents one of the greatest medical challenges for the aging population in developed countries, yet despite strong efforts, possibilities to treat ischemic injury still remain poor. Stroke, the most common type of brain ischemic injury in humans, is caused by brain artery occlusion, and represents a focal form of ischemia, which leads to neuronal loss in the ischemic core, and glial scar formation in the penumbral region around the core. Such glial scar mainly comprises reactive astrocytes, reactive NG2 glia and activated microglia. Reactive astrocytes display distinct features when compared to healthy astroglia, including changes in their morphology, metabolism, gene expression profiles, production of extracellular matrix proteins or proliferation rate. Similarly to astrocytes in the healthy nervous tissue, reactive astrocytes surrounding the glial scar strongly influence the activity of surviving neurons around the ischemic lesion. Bringing insight into pathophysiological functions of reactive astrocytes within the glial scar might thus open new possibilities for stroke treatment. Here, we summarize the properties of reactive astrocytes, with emphasis on the expression and function of ion channels, transporters and neurotransmitter receptors; all of which possess the ability to change the functional state of astrocytes, such as the membrane equilibrium potentials for different ions. This may have major effects on the functioning of surviving neurons, consequently leading to changes in neuronal excitability and progression of secondary pathologies, such as epilepsy. Moreover, we provide possible clues for therapy, based on functional modulation of astrocytic ion transporting mechanisms.
脑缺血性损伤是发达国家老年人口面临的最大医学挑战之一，但尽管付出了巨大努力，治疗缺血性损伤的可能性仍然很小。中风是人类最常见的脑缺血性损伤类型，由脑动脉阻塞引起，是一种局灶性缺血，导致缺血核心区神经元丧失和核心区周围半影区胶质瘢痕形成。这种神经胶质瘢痕主要由反应性星形胶质细胞、反应性 NG2 神经胶质细胞和激活的小胶质细胞组成。与健康星形胶质细胞相比，反应性星形胶质细胞表现出明显的特征，包括形态、代谢、基因表达谱、细胞外基质蛋白的产生或增殖率的改变。与健康神经组织中的星形胶质细胞一样，围绕胶质瘢痕的反应性星形胶质细胞强烈影响缺血性损伤周围存活神经元的活性。因此，深入了解胶质瘢痕中反应性星形胶质细胞的病理生理功能可能为中风治疗开辟新的可能性。在这里，我们总结了反应性星形胶质细胞的特性，重点介绍了离子通道、转运体和神经递质受体的表达和功能；所有这些都有能力改变星形胶质细胞的功能状态，例如不同离子的膜平衡电位。这可能对存活神经元的功能产生重大影响，进而导致神经元兴奋性的变化和继发性病理的进展，如癫痫。此外，我们还基于星形胶质细胞离子转运机制的功能调节，为治疗提供了可能的线索。
