Glibenclamide Attenuates Neuroinflammation and Promotes Neurological Recovery After Intracerebral Hemorrhage in Aged Rats

Abstract

Intracerebral hemorrhage (ICH) is a common disease in the elderly population. Inflammation following ICH plays a detrimental role in secondary brain injury, which is associated with a poor prognosis of patients with ICH, and no efficient pharmacological preventions are available. Here, we investigated the effects of glibenclamide (GLC) on neuroinflammation in an autoblood-induced aged rat (18 months old) model of ICH. Rats were randomized into the sham, vehicle, and GLC groups. First, we investigated the expression level of sulfonylurea receptor 1 (Sur1) surrounding the hematoma after ICH. Then, neurological scores were calculated, and water maze tests, brain water content analysis, western blotting, and immunofluorescence assays were implemented to detect the neuroprotective effect of GLC. The expression of the Sur1-Trpm4 channel was significantly increased in the perihematomal tissue following ICH in aged rats. The GLC administration effectively reduced brain edema and improved neurofunction deficits following ICH. In addition, GLC increased the expression of brain-derived neurotrophic factors and decreased the expression of proinflammatory factors [tumor necrosis factor (TNF)-α,interleukin (IL)-1, and IL-6]. Moreover, GLC markedly reduced Ikappa-B (IκB) kinase (IKK) expression in microglia and nuclear factor (NF)-κB-P65 levels in perihematomal tissue. GLC ameliorated ICH-induced neuroinflammation and improved neurological outcomes in aged rats. In part, GLC may exert these effects by regulating the NF-κB signaling pathway through the Sur1-Trpm4 channel.

Development and validation of a nomogram to predict the 30-day mortality risk of patients with intracerebral hemorrhage

“…CAA is believed to be directly related to aging ( Dallaire-Théroux et al, 2022 ). It has also been suggested that the hematoma volume ( Kuramatsu et al, 2011 ; Forti et al, 2016 ; Inoue et al, 2018 ) and neuroinflammation ( Jiang et al, 2021 ; Watson et al, 2022 ) are more critical in elderly patients with ICH. The GCS score is the most widely used indicator for assessing the degree of coma in patients, and lower GCS scores are associated with a higher risk of death ( Saika et al, 2015 ; Widyadharma et al, 2021 ).…”

Glibenclamide promoted functional recovery following sciatic nerve injury in male Wistar rats

“…As a result, a large rise in BDNF might have a role in NF-kB pathway activation. The expression of BDNF is reduced by neuroinflammation, which has a deleterious impact on various processes of neurogenesis [48]. NGF, being the first neurotrophin identified, plays a role in the formation and preservation of the peripheral nervous system's phenotypic [49].…”

Pharmacological Modulation and (Patho)Physiological Roles of TRPM4 Channel—Part 2: TRPM4 in Health and Disease

“…Glibenclamide administration exerted a beneficial effect on subarachnoid [248,249], but not in intracerebral, hemorrhages [250,251]. In the case of an intracerebral hemorrhage model with aged rats, glibenclamide treatment improved neurological outcomes and ameliorated neuroinflammation [252]. Glibenclamide treatment exerted beneficial actions in a model of hemorrhagic encephalopathy of prematurity [253], just as it did in inflammation-associated conditions of the CNS [248,249,254] and other organs (respiratory, digestive, urological, and cardiac) [255].…”