Neuroprotective effects of adenosine monophosphate-activated protein kinase inhibition and gene deletion in stroke.

Abstract:

BACKGROUND AND PURPOSE:5' adenosine monophosphate-dependent protein kinase (AMPK) acts as a metabolic sensor. AMPK is elevated under ischemic conditions, but the role of AMPK in ischemic brain remains controversial. In this study, we examined the effects of AMPK inhibition using both pharmacological and genetic approaches in an in vivo stroke model. METHODS:Focal stroke was induced by reversible middle cerebral artery occlusion in male wild-type mice as well as mice deficient in one of the isoforms of the catalytic subunit of AMPK, AMPK alpha-1 or alpha-2. RESULTS:AMPK inhibition was neuroprotective after focal stroke. Mice deficient in AMPK alpha-2 demonstrated significantly smaller infarct volumes compared with wild-type littermates, whereas deletion of AMPK alpha-1 had no effect. Phosphorylation of a major upstream regulator of AMPK, LKB1, was also induced in stroke brain. CONCLUSIONS:AMPK activation is detrimental in a model of focal stroke. The AMPK catalytic isoform alpha-2 contributes to the deleterious effects of AMPK activation. AMPK inhibition leads to neuroprotection even when these agents are administered poststroke.

journal_name

Stroke

journal_title

Stroke

authors

Li J,Zeng Z,Viollet B,Ronnett GV,McCullough LD

doi

10.1161/STROKEAHA.107.490904

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

2992-9

issue

11

eissn

0039-2499

issn

1524-4628

pii

STROKEAHA.107.490904

journal_volume

38

pub_type

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