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

doi:10.1016/j.nbd.2010.11.011

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 journal › Article › peer-review

14 Scopus citations

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 language	English (US)
Pages (from-to)	624-629
Number of pages	6
Journal	Neurobiology of Disease
Volume	41
Issue number	3
DOIs	https://doi.org/10.1016/j.nbd.2010.11.011
State	Published - Mar 2011
Externally published	Yes

Keywords

Calcium
Calpain
Cerebral ischemia
Neuronal death
Pregabalin
Presynaptic calcium channels

ASJC Scopus subject areas

Neurology

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10.1016/j.nbd.2010.11.011

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title = "Pregabalin suppresses calcium-mediated proteolysis and improves stroke outcome",

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.",

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author = "Yoon, {Jeong Seon} and Lee, {Jong Hwan} and Son, {Tae Gen} and Mughal, {Mohamed R.} and Greig, {Nigel H.} and Mattson, {Mark P.}",

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AU - Yoon, Jeong Seon

AU - Lee, Jong Hwan

AU - Son, Tae Gen

AU - Mughal, Mohamed R.

AU - Greig, Nigel H.

AU - Mattson, Mark P.

PY - 2011/3

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AB - 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.

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KW - Presynaptic calcium channels

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Pregabalin suppresses calcium-mediated proteolysis and improves stroke outcome

Abstract

Keywords

ASJC Scopus subject areas

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