Cell death and proliferation in NF-kappaB p50 knockout mouse after cerebral ischemia.
The transcription factor NF-kappaB is a key regulator of inflammation and cell survival. NF-kappaB activation increases following cerebral ischemia. We previously showed accelerated aging process in NF-kappaB p50 subunit knockout (p50 -/-) mice under physiological condition. The present investigation concerned the role of NF-kappaB p50 gene in ischemia-induced neuronal cell death. In an animal model of permanent middle cerebral artery occlusion (MCAO), infarct formation, apoptotic cell death and cell proliferation were examined in adult wild type (WT) and p50-/- mice. The ischemic infarct volume was significantly larger in p50-/- mice than that in WT mice. Consistently, the numbers of cells in the penumbra region positive to terminal deoxynucleotidyltransferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) and caspase-3 staining were significantly more in p50-/- mice than that in WT mice. To identify proliferation after cerebral ischemia, bromodeoxyurindine (BrdU) was intraperitoneal injected daily after MCAO. Ischemia increased BrdU positive cells in the penumbra, subventricular zone, corpus callosum, and cerebral cortex, while cell proliferation was hampered in p50-/- mice. These results suggest that NF-kappaB signaling is a neuroprotective mechanism and may play a role in cell proliferation in the stroke model of permanent MCAO.
Li
Jimei
J
Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Lu
Zhongyang
Z
Li
Wen-Lei
WL
Yu
Shan Ping
SP
Wei
Ling
L
D000818:Animals; D000963:Antimetabolites; D002545:Brain Ischemia / Q000235:genetics* / Q000473:pathology*; D001973:Bromodeoxyuridine; D002135:Calcium-Binding Proteins / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000502:physiology; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D052002:NF-kappa B p50 Subunit / Q000235:genetics* / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D020521:Stroke / Q000235:genetics / Q000473:pathology
C491049:Aif1 protein, mouse; D000963:Antimetabolites; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D052002:NF-kappa B p50 Subunit; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D053148:Caspase 3; D001973:Bromodeoxyuridine