title: Suppression of stroke-induced progenitor proliferation in adult subventricular zone by tumor necrosis factor receptor 1.
abstract: Stroke induced by middle cerebral artery occlusion leads to transiently increased progenitor proliferation in the subventricular zone (SVZ) and long-lasting striatal neurogenesis in adult rodents. Tumor necrosis factor-alpha (TNF-alpha) is upregulated in stroke-damaged brain. Whether TNF-alpha and its receptors influence SVZ progenitor proliferation after stroke is unclear. Here we show that the increased proliferation 1 week after stroke occurred concomitantly with elevated microglia numbers and TNF-alpha and TNF receptor-1 (TNF-R1) gene expression in the SVZ of wild-type mice. TNF receptor-1 was expressed on sorted SVZ progenitor cells from nestin-green fluorescent protein reporter mice. In animals lacking TNF-R1, stroke-induced SVZ cell proliferation and neuroblast formation were enhanced. In contrast, deletion of TNF-R1 did not alter basal or status epilepticus-stimulated cell proliferation in SVZ. Addition of TNF-alpha reduced the size and numbers of SVZ neurospheres through a TNF-R1-dependent mechanism without affecting cell survival. Our results provide the first evidence that TNF-R1 is a negative regulator of stroke-induced SVZ progenitor proliferation. Blockade of TNF-R1 signaling might be a novel strategy to promote the proliferative response in SVZ after stroke.
authors.affiliation: Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, Lund, Sweden.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Iosif
authors.forename: Henrik
authors.initials: H
authors.lastname: Ahlenius
authors.forename: Christine T
authors.initials: CT
authors.lastname: Ekdahl
authors.forename: Vladimer
authors.initials: V
authors.lastname: Darsalia
authors.forename: Pär
authors.initials: P
authors.lastname: Thored
authors.forename: Stefan
authors.initials: S
authors.lastname: Jovinge
authors.forename: Zaal
authors.initials: Z
authors.lastname: Kokaia
authors.forename: Olle
authors.initials: O
authors.lastname: Lindvall
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D020244:Infarction, Middle Cerebral Artery; D020547:Lateral Ventricles; D051379:Mice; D018345:Mice, Knockout; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology*; D020521:Stroke / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha