Lab Anim Res.  2019 Oct;35(3):124-131. 10.1186/s42826-019-0019-8.

Resveratrol modulates the Akt/GSK-3β signaling pathway in a middle cerebral artery occlusion animal model

• Park DJ
• Kang JB
• Shah FA
• Koh PO

• KMID: 2470008
• DOI: http://doi.org/10.1186/s42826-019-0019-8

Abstract

Cerebral ischemia is a major cause of neurodegenerative disease. It induces neuronal vulnerability and susceptibility, and leads to neuronal cell death. Resveratrol is a polyphenolic compound that acts as an anti-oxidant. It exerts a neuroprotective effect against focal cerebral ischemic injury. Akt signaling pathway is accepted as a representative cell survival pathway, including proliferation, growth, and glycogen synthesis. This study investigated whether resveratrol regulates Akt/glycogen synthase kinase-3β (GSK-3β) pathway in a middle cerebral artery occlusion (MCAO)-induced ischemic brain injury. Adult male rats were intraperitoneally injected with vehicle or resveratrol (30 mg/kg) and cerebral cortices were isolated 24 h after MCAO. Neurological behavior test, corner test, brain edema measurment, and 2,3,5-triphenyltetrazolium chloride staining were performed to elucidate the neuroprotective effects of resveratrol. Phospho-Akt and phospho-GSK-3β expression levels were measured using Western blot analysis. MCAO injury led to severe neurobehavioral deficit, infraction, and histopathological changes in cerebral cortex. However, resveratrol treatment alleviated these changes caused by MCAO injury. Moreover, MCAO injury induced decreases in phospho-Akt and phospho-GSK-3β protein levels, whereas resveratrol attenuated these decreases. Phosphorylations of Akt and GSK-3β act as a critical role for the suppression of apoptotic cell death. Thus, our finding suggests that resveratrol attenuates neuronal cell death in MCAO-induced cerebral ischemia and Akt/GSK-3β signaling pathway contributes to the neuroprotective effect of resveratrol.

Keyword

Akt; GSK-3β; MCAO; Resveratrol

MeSH Terms

Adult
Animals
Behavior Rating Scale
Blotting, Western
Brain Edema
Brain Injuries
Brain Ischemia
Cell Death
Cell Survival
Cerebral Cortex
Glycogen
Humans
Infarction, Middle Cerebral Artery*
Male
Middle Cerebral Artery*
Neurodegenerative Diseases
Neurons
Neuroprotective Agents
Phosphorylation
Rats
Glycogen
Neuroprotective Agents