Pregabalin suppresses calcium-mediated proteolysis and improves stroke outcome

Jeong Seon Yoon, Jong Hwan Lee, Tae Gen Son, Mohamed R. Mughal, Nigel H. Greig, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

Abstract

Pregabalin, a Ca 2+ channel α 2δ-subunit antagonist with analgesic and antiepileptic activity, reduced neuronal loss and improved functional outcome in a mouse model of focal ischemic stroke. Pregabalin administration (5-10mg/kg, i.p.) 30-90min after transient middle cerebral artery occlusion/reperfusion reduced infarct volume, neuronal death in the ischemic penumbra and neurological deficits at 24h post-stroke. Pregabalin significantly decreased the amount of Ca 2+/calpain-mediated α-spectrin proteolysis in the cerebral cortex measured at 6h 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.

Original languageEnglish (US)
Pages (from-to)624-629
Number of pages6
JournalNeurobiology of Disease
Volume41
Issue number3
DOIs
StatePublished - Mar 2011
Externally publishedYes

Keywords

  • Calcium
  • Calpain
  • Cerebral ischemia
  • Neuronal death
  • Pregabalin
  • Presynaptic calcium channels

ASJC Scopus subject areas

  • Neurology

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