The 2-(2-benzofuranyl)-2-imidazoline provides neuroprotection against focal cerebral ischemia-reperfusion injury in diabetic rats: Influence of microglia and possible mechanisms of action

• Published in: Brain research bulletin Vol. 174; pp. 230 - 239
• Main Authors: Xi, Hongjie, Tao, Tao, Zhang, Ruru, Xue, Xinxin, Zhu, Yana, Liu, Jiuyang, Xin, Xianyi, Zeng, Xianzhang
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-09-2021
• Subjects: 2-(2-Benzofuranyl)-2-imidazoline; Cerebral ischemia-reperfusion injury; Diabetes; Microglia; Neuroprotection; Stroke; MCAO; rCBF; Neuroprotection; TTC; Stroke; BBB; 2BFI; TBS; HG-OGD; ICA; 2-(2-Benzofuranyl)-2-imidazoline; IR; Microglia; DCFH-DA; ROS; Cerebral ischemia-reperfusion injury; Diabetes
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2021.06.016

•2BFI ameliorated the cerebral ischemia-reperfusion injury in diabetic rats.•2BFI decreased the neuron death in the in vitro model.•The mechanism was related with decreased inflammatory and reactive oxygen species.•2BFI inhibited the activation of microglia NOX2 depends on the existence of neurons.
Increased microglial NADPH oxidase (NOX2) production may make an important contribution to the increased incidence and severity of ischemic stroke associated with diabetes. Imidazoline receptors are closely associated with neuroprotection, but the neuroprotective effects of the selective I2-imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline (2BFI) in diabetes has not been established. The effect of 2BFI on microglial NOX2 production was investigated using a co-culture of neurons and microglia, and the effect on cerebral ischemia-reperfusion (IR) injury was determined in diabetic rats. Garcia neurological scores, brain infarct volumes, brain water content, TUNEL staining, blood-brain barrier, and immunofluorescent labeling for microglia were evaluated. Western blots were used to determine gp91phox and Tyr1472 expression. Anti-inflammatory cytokine (IL-10) and inflammatory cytokine secretion was determined using ELISA kits. The brain infarct volumes, TUNEL-positive neurons, expression of microglia, brain water content, blood-brain barrier structure damage, and gp91phox and Tyr1472 expression were increased, the Garcia neurological scores were significantly decreased in the IR group, and 2BFI relieved these alterations. The IL-10 concentration was increased in the IR group; 2BFI significantly improved this increase. The neuron apoptosis and necrosis rates, and production of reactive oxygen species (ROS) and inflammatory cytokines, including IL-6, IL-8, TNF-α, and 8-iso-PGF2α, were significantly increased by high glucose stimulation combined with oxygen-glucose deprivation treatment, which were inhibited by 2BFI. The 2BFI ameliorated cerebral ischemia-reperfusion injury in diabetes and decreased neuron death in an in vitro model. The mechanism underlying these findings may be related to the decreased production of inflammatory factors and reactive oxygen species from microglia.