Alpha-Lipoic acid alleviates cerebral ischemic injury-induced cognitive impairment and Alzheimer’s Disease-like pathologies through modulation of GSK-3β in a rat model of transient middle cerebral artery occlusion
Wu Ming-Hsiu, PhD, MD 1, 2 , Chang Chia- Yu , PhD, MD ,
1 柳營奇美醫院神經內科, 台南, 台灣
2 敏惠醫護管理專科學校長期照顧與健康促進管理科, 台南, 台灣
1 Division of Neurology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan;
2 Department of Long-Term Care and Health Promotion, Min-Hwei Junior College of Health Care Management, Tainan, Taiwan
Wu Ming-Hsiu , PhD, MD
柳營奇美醫院神經內科, 台南, 台灣; 敏惠醫護管理專科學校長期照顧與健康促進管理科, 台南, 台灣
Division of Neurology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan; Department of Long-Term Care and Health Promotion, Min-Hwei Junior College of Health Care Management, Tainan, Taiwan
Dementia is composed of mainly two subtypes: Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID). Alpha-lipoic acid (ALA) has properties of anti-oxidation and anti-inflammation, and is protective against cerebral ischemia-reperfusion (I/R) injury. We aimed to investigate the protective role of ALA in cerebral I/R injury-related cognitive impairment in a rat model of transient middle cerebral artery occlusion (tMCAO), which mimics VCID in humans.
MATERIAL and METHOD:
The rats after I/R injury were treated with either intraperitoneal injection of ALA, 25 mg/kg, or vehicle. Infarction volume, brain edema, modified neurologic severity scores (mNSS) and Y Maze Test for cognitive impairment were assessed. In addition, activation of glycogen synthase kinase-3β (GSK-3β) and microglia, and expressions of amyloid-β precursor protein (APP), β-site APP cleaving enzyme 1 (BACE1), amyloid-β (Aβ), tau and synaptophysin were measured 7 days after tMCAO.
We found that the administration of ALA after cerebral I/R injury reduced cerebral infarction, brain edema, and improved neurologic deficits and cognitive impairment. In parallel, ALA reduced the expressions of APP, BACE1, Aβ and phosphorylated tau in the hippocampus, down-regulated the activation of GSK-3β and microglia, and improved integrity of neuronal synapses.
ALA alleviated the severity of cerebral I/R injury and AD-like pathologies, preserved neuronal integrity, and improved cognitive impairment by down-regulating the activation of GSK-3β and microglia.