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 journalArticle

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

Fingerprint

Proteolysis
Stroke
Calcium
Spectrin
Calpain
Middle Cerebral Artery Infarction
Cerebral Cortex
Anticonvulsants
Reperfusion
Analgesics
Pregabalin
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Neurology

Cite this

Yoon, J. S., Lee, J. H., Son, T. G., Mughal, M. R., Greig, N. H., & Mattson, M. P. (2011). Pregabalin suppresses calcium-mediated proteolysis and improves stroke outcome. Neurobiology of Disease, 41(3), 624-629. https://doi.org/10.1016/j.nbd.2010.11.011

Pregabalin suppresses calcium-mediated proteolysis and improves stroke outcome. / Yoon, Jeong Seon; Lee, Jong Hwan; Son, Tae Gen; Mughal, Mohamed R.; Greig, Nigel H.; Mattson, Mark P.

In: Neurobiology of Disease, Vol. 41, No. 3, 03.2011, p. 624-629.

Research output: Contribution to journalArticle

Yoon, JS, Lee, JH, Son, TG, Mughal, MR, Greig, NH & Mattson, MP 2011, 'Pregabalin suppresses calcium-mediated proteolysis and improves stroke outcome', Neurobiology of Disease, vol. 41, no. 3, pp. 624-629. https://doi.org/10.1016/j.nbd.2010.11.011
Yoon, Jeong Seon ; Lee, Jong Hwan ; Son, Tae Gen ; Mughal, Mohamed R. ; Greig, Nigel H. ; Mattson, Mark P. / Pregabalin suppresses calcium-mediated proteolysis and improves stroke outcome. In: Neurobiology of Disease. 2011 ; Vol. 41, No. 3. pp. 624-629.
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