Nuclear Factor-κB Contributes to Infarction after Permanent Focal Ischemia

Antti Nurmi, Perttu J. Lindsberg, Milla Koistinaho, Wen Zhang, Eric Juettler, Marja Liisa Karjalainen-Lindsberg, Falk Weih, Norbert Frank, Markus Schwaninger, Jari Koistinaho*

*Corresponding author for this work
227 Citations (Scopus)


Background and Purpose-Activation of transcription factor nuclear factor-κB (NF-κB) 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-κB after permanent MCAO (pMCAO) was investigated. Methods-Mice transgenic for a NF-κB-driven β-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-κB and wild-type controls were exposed to pMCAO with or without treatment with pyrrolidinedithiocarbamate (PDTC), an NF-κB inhibitor. Brain sections of human stroke patients were immunostained for the activated NF-κB. Results-pMCAO increased NF-κB transcriptional activity to 260% (36.9±4.5 compared with 14.4±2.6; n= 10; P<0.01) in the brain; this NF-κB 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=112) smaller infarcts compared with wild-type controls (32.9±3.8 mm 3; 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, κB was activated in neurons in the penumbral areas. Conclusions-NF-Kβ is induced in neurons. during human stroke, and activation of NF-κB in the brain may contribute to infarction in pMCAO.

Original languageEnglish
Issue number4
Pages (from-to)987-991
Number of pages5
Publication statusPublished - 01.04.2004

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


Dive into the research topics of 'Nuclear Factor-κB Contributes to Infarction after Permanent Focal Ischemia'. Together they form a unique fingerprint.

Cite this