PATHOGENETIC ROLE OF GLYMPHATIC INSUFFICIENCY IN CHRONIC CEREBRAL ISCHEMIA
Keywords:
chronic cerebral ischemia, glymphatic insufficiency, cognitive impairmentAbstract
Chronic cerebral ischemia is accompanied by impaired function of the glymphatic system, leading to reduced clearance of metabolites and accumulation of toxic proteins (β-amyloid, tau protein). These changes aggravate neurodegeneration, contribute to the development of cognitive impairment, and promote vascular-degenerative dementia. The key mechanisms of glymphatic insufficiency include decreased arterial pulsatility, loss of aquaporin-4 polarity, and impaired cerebrospinal fluid dynamics. Promising therapeutic strategies involve restoration of vascular function, modulation of aquaporin-4, and normalization of sleep.
References
Iliff J.J., Wang M., Liao Y. et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med. 2012;4(147):147ra111.
Mestre H., Mori Y., Nedergaard M. The brain's glymphatic system: Current controversies. Trends Neurosci. 2020;43(7):458–466.
Tarasoff-Conway J.M., Carare R.O., Osorio R.S. et al. Clearance systems in the brain—implications for Alzheimer disease. Nat Rev Neurol. 2015;11(8):457–470.
Bacyinski A., Xu M., Wang W., Hu J. The paravascular pathway for brain waste clearance: Current understanding, significance and controversy. Front Neuroanat. 2017;11:101.
Zhang Y., Zhang X., Yang J. Glymphatic system impairment in vascular cognitive impairment and dementia. Front Neurol. 2022;13:894229.
