Pregabalin suppresses calcium-mediated proteolysis and improves stroke outcome

Pregabalin, a Ca2+ channel α2δ-subunit antagonist with analgesic and antiepileptic activity, reduced neuronal loss and improved functional outcome in a mouse model of focal ischemic stroke. Pregabalin administration (5–10 mg/kg, i.p.) 30–90 min after transient middle cerebral artery occlusion/reperfusion reduced infarct volume, neuronal death in the ischemic penumbra and neurological deficits at 24 h post-stroke. Pregabalin significantly decreased the amount of Ca2+/calpain-mediated α-spectrin proteolysis in the cerebral cortex measured at 6 h post-stroke. Together with the extensive clinical experience with pregabalin for other neurological indications, our findings suggest the potential for a therapeutic benefit of pregabalin in stroke patients.

Research Highlights
► Pregabalin, an antagonist of α2δ Ca2+ channels, improves outcome in a mouse model of stroke.
► Pregabalin is effective in reducing neuronal damage when administered after a stroke.
► A reduction in calpain-mediated proteolysis contributes to the neuroprotective action of pregabalin.
► Widely used to treat chronic pain, our findings suggest that pregabalin may benefit stroke patients.