Suppression of stroke-induced progenitor proliferation in adult subventricular zone by tumor necrosis factor receptor 1.

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Suppression of stroke-induced progenitor proliferation in adult subventricular zone by tumor necrosis factor receptor 1. / Iosif, Robert; Ahlenius, Henrik; Ekdahl, Christine T; Darsalia, Vladimer; Thored, Pär; Jovinge, Stefan; Kokaia, Zaal; Lindvall, Olle.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 28, 2008, p. 1574-1587.

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T1 - Suppression of stroke-induced progenitor proliferation in adult subventricular zone by tumor necrosis factor receptor 1.

AU - Iosif, Robert

AU - Ahlenius, Henrik

AU - Ekdahl, Christine T

AU - Darsalia, Vladimer

AU - Thored, Pär

AU - Jovinge, Stefan

AU - Kokaia, Zaal

AU - Lindvall, Olle

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neurology, Lund (013027000), Hematopoietic Stem Cell Laboratory (013022012), Faculty of Medicine (000022000)

PY - 2008

Y1 - 2008

N2 - 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.Journal of Cerebral Blood Flow & Metabolism advance online publication, 21 May 2008; doi:10.1038/jcbfm.2008.47.

AB - 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.Journal of Cerebral Blood Flow & Metabolism advance online publication, 21 May 2008; doi:10.1038/jcbfm.2008.47.

U2 - 10.1038/jcbfm.2008.47

DO - 10.1038/jcbfm.2008.47

M3 - Article

VL - 28

SP - 1574

EP - 1587

JO - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

JF - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

SN - 1559-7016

ER -