Dihydromyricetin alleviates cerebral ischemia-reperfusion injury by attenuating apoptosis and astrogliosis in peri-infarct cortex

ABSTRACT

Objectives

In ischemic stroke, reperfusion after thrombolysis is associated with secondary brain damage. Dihydromyricetin (DHM), a flavonoid, has shown neuroprotective effects through anti-oxidant, anti-inflammatory and anti-apoptotic properties. This study investigates the potential of DHM, given postreperfusion in middle cerebral artery occlusion (MCAo) model of stroke in rats.

Methods

MCAo surgery was performed in male Wistar rats. Reperfusion was performed after 90 min of ischemia. DHM (50 and 100 mg/kg) was administered 10–15 min and 2 h postreperfusion followed by daily dosing for 2 more days. Neurobehavioral parameters and infarct size (TTC staining) were assessed after 72 h. The effective dose (100 mg/kg) was then used to study reduction in infarct size (measured by MRI) and effect on apoptosis (evaluated by protein expression of Bax, Bcl-2 and cleaved caspase-3 and TUNEL assay) in peri-infarct cortex. Furthermore, effects of DHM on neuronal damage and activation of astrocytes were studied by immunofluorescence.

Results

Poststroke DHM (100 mg/kg) administered for 3 days showed significant improvements in motor-coordination and infarct damage (TTC staining and MRI). MCAo-induced altered apoptotic proteins were normalized to a significant extent in peri-infarct cortex with DHM treatment. Data from TUNEL assay were complementary to the effects on apoptotic proteins. Additionally, DHM caused a significant reduction in the number of reactive astrocytes when compared with the MCAo group.

Discussion

This study demonstrated the efficacy of subacute DHM treatment in ischemia/reperfusion injury by modulating apoptosis and astrogliosis in the peri-infarct cortex. This suggests the potential of DHM in attenuating disease progression.

KEYWORDS:

• Ischemia
• MCAo
• dihydromyricetin
• ampelopsin
• apoptosis
• astrogliosis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

The author(s) reported that there is no funding associated with the work featured in this article.

Notes on contributors

Himika Wasan

Dr. Himika Wasan is currently a Research Associate in the Department of Pharmacology, AIIMS, New Delhi, India.

Devendra Singh

Dr. Devendra Singh is also a Research Associate in the Department of Pharmacology, AIIMS, New Delhi, India.

Balu Joshi

Dr. Balu Joshi was an MD student in the Department of Pharmcology, AIIMS, New Delhi, India.

Deepti Upadhyay

Dr. Deepti Upadhyay was a Research Associate in the Department of NMR, AIIMS, New Delhi, India and is currently a postdoctoral scholar at UCSF, San Francisco, California, USA.

Uma Sharma

Dr. Uma Sharma is an Additional Professor, Department of NMR, AIIMS, New Delhi, India.

Amit Kumar Dinda

Dr. Amit Kumar Dinda is an Emeritus Scientist, Department of Pathology, AIIMS, New Delhi, India.