Functional Recovery After Ischemic Stroke Is Associated With Reduced GABAergic Inhibition in the Cerebral Cortex: A GABA PET Study

Abstract

Background: γ-Aminobutyric acid (GABA) plasticity plays an important role in stroke motor recovery in a mouse model. However, little is known about changes over time in neuronal excitability mediated by GABA receptors in human stroke patients.

Objectives: To establish the mechanism of neuroplasticity during the recovery phase following ischemic stroke by assessing the changes in cerebral GABA activity using [(18)F]flumazenil ([(18)F]FMZ) positron emission tomography (PET).

Methods: A total of 10 patients with unilateral ischemic stroke were studied at 1 month (T0) and 3 months (T1) postonset using [(18)F]FMZ PET. Changes in regional GABAergic activity were assessed longitudinally, and values were also compared with those in 15 age-matched controls. Upper-extremity motor function was evaluated using the Fugl-Meyer score (FMS).

Results: During the follow-up period, statistical parametric mapping analysis demonstrated a decrease in GABAA receptor availability throughout the cerebral cortex and cerebellum, especially the contralateral hemisphere. GABAA availability in the bilateral primary motor cortex, contralateral supplemental motor cortex, and globus pallidus at T0 was positively correlated with the FMS score at T1 CONCLUSIONS: This is the first prospective, controlled longitudinal study showing that the change in GABA receptor availability over time is significantly related to motor recovery after stroke in humans. This work supports the rationale for a novel strategy to promote motor recovery after stroke.

Keywords: [18F]flumazenil PET; neuroplasticity; stroke rehabilitation; γ-aminobutyric acid.