Toll-Like Receptor 4-Mediated Neuroinflammation: Updates on Pathological Roles and Therapeutic Strategies in Chronic Cerebral Hypoperfusion.

Abstract

Neuroinflammation has been acknowledged as being one of the main pathologies that occur following chronic cerebral hypoperfusion (CCH). Since it significantly contributes to neuronal cell damage and thereby leads to cognitive impairment, the signals related to inflammation in hypoperfusion injury have been extensively investigated over the past few years. Toll-like receptor 4 (TLR4) is the key receptor responsible for immune and inflammatory reactions. It has been reported that TLR4 is involved in the pathology of several diseases and has emerged as a therapeutic target for developing a variety of anti-inflammatory compounds. This study explored the pathological roles of TLR4 that potentially cause the promotion of neuroinflammation in CCH damage. The evidence pertinent to the activation of TLR4 and its downstream inflammatory cascades following CCH are also summarized. This study also demonstrated the therapeutic potential of TLR4 inhibition, whether through drugs, substances, or other treatment strategies, in models of CCH-induced neurological dysfunction. The limitations of the accumulated evidence are addressed and discussed in this study. A deeper understanding of the roles of TLR4 in neuroinflammation following CCH damage may help inform the machinery behind pathological processes for advancing further neuroscientific research and developing therapeutic strategies for vascular dementia.