Abstract
This study aimed to investigate the effects of morin on cerebral damage and blood–brain barrier (BBB) integrity in a middle cerebral artery occlusion (MCAO) and reperfusion model. Wistar rats were exposed to MCAO for 2 h, followed by reperfusion. Thirty mg/kg of morin was administered via intraperitoneal injection at the different time points: before ischemia, during ischemia, and at reperfusion. The rats were divided into five groups, including sham, vehicle, and three groups of morin. Twenty-four hours after reperfusion, the rats were tested for neurological deficits, and the brains were harvested to assess brain damage. In addition, brains were harvested 72 h to determine BBB disruption. We found that morin significantly reduced reactive oxygen species production and lipid peroxidation. It also decreased inflammation via reducing the expression of Toll-like receptor 4, nuclear factor kappa-beta. Morin ameliorated cerebral damage and reduced apoptosis through decreasing the cerebral infarct size, including apoptotic cell death. Moreover, morin decreased the BBB damage via reducing Evans blue extravasation, neutrophil infiltration, and increasing tight junction protein expression. Therefore, morin protected against cerebral and BBB damage by attenuating oxidative stress, inflammation, and apoptosis in MCAO and reperfusion models.
Highlights
This study aimed to investigate the effects of morin on cerebral damage and blood–brain barrier (BBB) integrity in a middle cerebral artery occlusion (MCAO) and reperfusion model
Cerebral I/R injury leads to the excessive production of ROS27, a phenomenon that can activate a cascade of pathophysiological processes, including oxidative stress, inflammation, and neuronal apoptosis[28,29,30]
Morin acts as a powerful anti-inflammatory agent by suppressing activation of NF-ĸB and the expression levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), IL-1β, and iNOS19
Summary
This study aimed to investigate the effects of morin on cerebral damage and blood–brain barrier (BBB) integrity in a middle cerebral artery occlusion (MCAO) and reperfusion model. We found that morin significantly reduced reactive oxygen species production and lipid peroxidation It decreased inflammation via reducing the expression of Toll-like receptor 4, nuclear factor kappa-beta. Morin protected against cerebral and BBB damage by attenuating oxidative stress, inflammation, and apoptosis in MCAO and reperfusion models. To restore blood flow in the brain with t-PA would encourage the excessive production of reactive oxygen species (ROS), which would lead to cerebral ischemia/reperfusion (I/R) injury[5,6,7]. Morin has been reported to improve transient global cerebral ischemia model and reduce oxidative stress, apoptosis, and inflammation in middle cerebral artery occlusion (MCAO) m odel[19]. We investigated the protective effects of morin during the acute phase of rats subjected to MCAO and reperfusion injury via attenuation of BBB and cerebral damage
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