Selenium attenuates ischemia/reperfusion injury‑induced damage to the blood‑brain barrier in hyperglycemia through PI3K/AKT/mTOR pathway‑mediated autophagy inhibition

Abstract

Ischemic stroke is a leading cause of mortality and disability. diabetes mellitus, characterized by hyperglycemia, is a common concomitant disease of ischemic stroke, which is associated with autophagy dysfunction and blood-brain barrier (BBB) damage following cerebral ischemia/reperfusion (I/R) injury. At present, there is no effective treatment strategy for the disease. The purpose of the present study was to explore the molecular mechanisms underlying the protective effects of selenium on the BBB following I/R injury in hyperglycemic rats. Middle cerebral artery occlusion was performed in diabetic Sprague-dawley rats. Treatment with selenium and the autophagy inhibitor 3-methyladenine significantly reduced cerebral infarct volume, brain water content and Evans blue leakage, while increasing the expression of tight junction (TJ) proteins and decreasing that of autophagy-related proteins (P<0.05). In addition, selenium increased the phosphorylation levels of PI3K, AKT and mTOR (P<0.05). A mouse bEnd.3 brain microvascular endothelial cell line was co-cultured in vitro with an MA-h mouse astrocyte-hippocampal cell line to simulate the BBB. The cells were then subjected to hyperglycemia, followed by oxygen-glucose deprivation for 1 h and reoxygenation for 24 h. It was revealed that selenium increased TJ protein levels, reduced BBB permeability, decreased autophagy levels and enhanced the expression of phosphorylated (p)-AKT/AKT and p-mTOR/mTOR proteins (P<0.05). Treatment with wortmannin (an inhibitor of PI3K) significantly prevented the beneficial effects of selenium on the BBB, whereas insulin-like growth factor 1 (a PI3K activator) mimicked the effects of selenium. In conclusion, the present findings indicated that selenium can inhibit autophagy by regulating the PI3K/AKT/mTOR signaling pathway, significantly preventing BBB damage following cerebral I/R injury in hyperglycemic conditions.

A bibliometric analysis of research foci and trends in cerebral ischemia-reperfusion injury involving autophagy during 2008 to 2022

“…For instance, selenium can inhibit autophagy by modulating the PI3K/AKT/mTOR signaling pathway, effectively preventing BBB injury following CIRI, particularly under hyperglycemic conditions. [55] Curcumin, [56] Cornin, [57] and Cyclo-(Phe-Tyr) [58] also inhibit excessive autophagy through this pathway to offer neuroprotection and maintain BBB integrity. Additionally, (-)-Epigallocatechin-3-gallate (EGCG), a bioactive component found in green tea, can inhibit autophagy via the AKT/AMPK/mTOR phosphorylation pathway, thus preventing further reperfusion injury in the mouse brain.…”

Hyperglycemia disrupted the integrity of the blood‐brain barrier following diffuse axonal injury through the sEH/NF‐κB pathway

“…Prolonged hyperglycemia causes various microvascular changes and increases BBB permeability through the loss of tight junction integrity 28,29 . BBB disruption has been considered the initial step that induces neurological deficits and functional disabilities.…”

Tooth Loss-Associated Mechanisms That Negatively Affect Cognitive Function: A Systematic Review of Animal Experiments Based on Occlusal Support Loss and Cognitive Impairment

“…It plays a neuroprotective role by ingesting glutamate, releasing glutamine to reduce oxidative stress damage, repairing blood brain barrier (BBB) (Neuhaus et al, 2014), and so on. Activation of the glial cell network accompanied by release of a large number of cytokines and neurotoxic reactive oxygen species (ROS), which can lead to cognitive decline through PI3K/AKT/mTOR and many other pathways (Yang et al, 2021). The teeth and periodontal membrane are supplied by various branches of the trigeminal nerve.…”