GLB regulates microglial M1/M2 polarization after cerebral ischemic injury via the TLR4 signaling pathway.

Abstract

Inflammatory injury after ischemic stroke (IS) severely limits the treatment of stroke. Microglial polarization involved in the regulation of neuroinflammatory responses and brain injury related to IS. Glibenclamide (GLB) has been proven to inhibit microglial activation and alleviate neuroinflammation. However, the effect of GLB on microglial polarization and its mechanism remain unclear in IS. Here, we study the neuroprotective effect of GLB and its possible mechanism. In this study, the area of infarction, blood-brain barrier (BBB) permeability, and zea longa score of the mice were detected. Neurobehavioral functions were evaluated using the Rota-Rod and Open Field Test (OFT). Western blotting was performed to assess the protein levels of Sur1, Trpm4, TLR4, NF-κB, IL-1β, and TGF-β, while immunofluorescence (IF) was used to detect Iba-1, iNOS, and Arg-1. Our results demonstrated that GLB-mediated inhibition of the Sur1-Trpm4 channel reduced infarct size, preserved BBB integrity, and improved neurological function. GLB upregulated TGF-β and Arg-1 expression while downregulating TLR4, NF-κB, IL-1β, Iba-1, and iNOS in IS mice. It exerted neuroprotective effects and alleviated neuroinflammation. In summary, GLB may mitigate IS by modulating microglial M1/M2 polarization and suppressing TLR4/NF-κB pathway activation.