Dihydromyricetin Alleviates Ischemic Brain Injury by Antagonizing Pyroptosis in Rats

Area of Science:

• Neuroscience
• Pharmacology
• Cell Biology

Background:

• Ischemic stroke is a major global health concern with limited effective treatments.
• Pyroptosis, a pro-inflammatory form of programmed cell death, is implicated in ischemic stroke.
• Dihydromyricetin (DHM) exhibits anti-inflammatory, antioxidant, and antiapoptotic properties.

Purpose of the Study:

• To investigate the therapeutic effect of Dihydromyricetin (DHM) on ischemic stroke.
• To determine if DHM can mitigate pyroptosis following ischemic stroke.

Main Methods:

• Middle Cerebral Artery Occlusion (MCAO) rat model established for ischemic stroke induction.
• mRNA sequencing of the ischemic penumbra to identify molecular pathways.
• Morphological and molecular analyses to assess pyroptosis markers and neuronal damage.
• Dihydromyricetin (DHM) administered intraperitoneally for 7 days post-MCAO.

Main Results:

• Transcriptomics revealed activation of the NLRP3-mediated pyroptosis pathway after MCAO.
• DHM treatment significantly reduced infarct volume (TTC staining) and improved neurological deficit scores (Longa score).
• DHM mitigated MCAO-induced neuronal damage and suppressed pyroptosis-related molecular markers.

Conclusions:

• Dihydromyricetin (DHM) demonstrates significant neuroprotective effects in an ischemic stroke model.
• DHM's therapeutic action is, at least partly, mediated by the inhibition of NLRP3-dependent pyroptosis.
• DHM represents a potential therapeutic agent for treating ischemic stroke.