期刊
MOLECULAR NEUROBIOLOGY
卷 59, 期 4, 页码 2009-2026出版社
SPRINGER
DOI: 10.1007/s12035-021-02700-7
关键词
NMDA receptors (NMDAR); Glial dynamics; PVL; Ischemic Injury; Glutamate transporters; Neurodegeneration; Stem cell therapy
资金
- National Natural Science Foundation of China [81700729]
In this review, the authors discuss multiple aspects of the pathophysiology of white matter injury, including glial dynamics and pharmacotherapies, as well as the recent insights into the application of MSCs in treating white matter injury.
Periventricular leukomalacia (PVL) and cerebral palsy are two neurological disease conditions developed from the premyelinated white matter ischemic injury (WMI). The significant pathophysiology of these diseases is accompanied by the cognitive deficits due to the loss of function of glial cells and axons. White matter makes up 50% of the brain volume consisting of myelinated and non-myelinated axons, glia, blood vessels, optic nerves, and corpus callosum. Studies over the years have delineated the susceptibility of white matter towards ischemic injury especially during pregnancy (prenatal, perinatal) or immediately after child birth (postnatal). Impairment in membrane depolarization of neurons and glial cells by ischemia-invoked excitotoxicity is mediated through the overactivation of NMDA receptors or non-NMDA receptors by excessive glutamate influx, calcium, or ROS overload and has been some of the well-studied molecular mechanisms conducive to the injury of white matter. Expression of glutamate receptors (GluR) and transporters (GLT1, EACC1, and GST) has significant influence in glial and axonal-mediated injury of premyelinated white matter during PVL and cerebral palsy. Predominantly, the central premyelinated axons express extensive levels of functional NMDA GluR receptors to confer ischemic injury to premyelinated white matter which in turn invoke defects in neural plasticity. Several underlying molecular mechanisms are yet to be unraveled to delineate the complete pathophysiology of these prenatal neurological diseases for developing the novel therapeutic modalities to mitigate pathophysiology and premature mortality of newborn babies. In this review, we have substantially discussed the above multiple pathophysiological aspects of white matter injury along with glial dynamics, and the pharmacotherapies including recent insights into the application of MSCs as therapeutic modality in treating white matter injury.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据