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Stroke. 2004 Apr;35(4):987-91. Epub 2004 Feb 26.

Nuclear factor-kappaB contributes to infarction after permanent focal ischemia.

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  • 1A.I. Virtanen Institute, Department of Neurobiology, University of Kuopio, Kuopio, Finland.

Abstract

BACKGROUND AND PURPOSE:

Activation of transcription factor nuclear factor-kappaB (NF-kappaB) may induce expression of either proinflammatory/apoptotic genes or antiapoptotic genes. Because a considerable number of middle cerebral artery occlusions (MCAOs) in humans are not associated with reperfusion during the first 24 hours, the role of NF-kappaB after permanent MCAO (pMCAO) was investigated.

METHODS:

Mice transgenic for a NF-kappaB-driven beta-globin reporter were exposed to pMCAO, and the expression of the reporter gene was quantified with real-time polymerase chain reaction. Mice lacking the p50 subunit of NF-kappaB and wild-type controls were exposed to pMCAO with or without treatment with pyrrolidinedithiocarbamate (PDTC), an NF-kappaB inhibitor. Brain sections of human stroke patients were immunostained for the activated NF-kappaB.

RESULTS:

pMCAO increased NF-kappaB transcriptional activity to 260% (36.9+/-4.5 compared with 14.4+/-2.6; n=10; P<0.01) in the brain; this NF-kappaB activation was completely blocked by PDTC (17.2+/-2.6; n=9; P<0.05). In p50-/- mice, pMCAO resulted in 41% (18+/-3.2 mm3; n=12) smaller infarcts compared with wild-type controls (32.9+/-3.8 mm3; n=9; P<0.05), which was comparable to the protection achieved with PDTC in wild-type mice (19.6+/-4.2 mm3; n=8). Pro-DTC, a PDTC analogue that does not cross the blood-brain barrier, had no effect, even though Pro-DTC and PDTC were equally protective in vitro. During the first 2 days of human stroke, NF-kappaB was activated in neurons in the penumbral areas.

CONCLUSIONS:

NF-kappaB is induced in neurons during human stroke, and activation of NF-kappaB in the brain may contribute to infarction in pMCAO.

PMID:
14988572
[PubMed - indexed for MEDLINE]
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