Targeting GABA_C Receptors Improves Post-Stroke Motor Recovery

Area of Science:

• Neuroscience
• Pharmacology
• Stroke Research

Background:

• Ischemic stroke is a major cause of global disability with limited therapeutic options.
• GABA_C receptors are investigated as potential targets for enhancing stroke recovery.

Purpose of the Study:

• To explore the role of GABA_C receptors (ρ1 and ρ2 subunits) in post-stroke recovery.
• To evaluate the efficacy of GABA_C receptor antagonists in improving motor function after ischemic stroke.

Main Methods:

• Assessed ρ1 and ρ2 mRNA expression in peri-infarct tissue post-stroke.
• Utilized electrophysiology to characterize GABA_C receptor antagonists ((R)-4-ACPBPA and (S)-4-ACPBPA).
• Administered antagonists to stroke-induced mice and evaluated infarct size, GAT3 expression, astrogliosis, and motor function recovery.

Main Results:

• ρ1 and ρ2 mRNA expression increased post-stroke, particularly ρ2.
• (R)- and (S)-4-ACPBPA demonstrated potent antagonism at ρ2 receptors.
• Treatment with GABA_C receptor antagonists significantly improved motor function in grid-walking and cylinder tasks.
• (R)-4-ACPBPA also increased GAT3 expression and reduced reactive astrogliosis.

Conclusions:

• Inhibition of GABA_C receptors significantly enhances motor function recovery following ischemic stroke.
• Targeting the ρ-subunit of GABA_C receptors presents a novel therapeutic strategy for delayed stroke treatment.