A Neurovascular Niche for Neurogenesis after Stroke

Ohab, John; Fleming, Sheila M.; Blesch, Armin; Carmichael, S. Thomas

doi:10.1523/jneurosci.4323-06.2006

Cited by 792 publications

(831 citation statements)

References 59 publications

(118 reference statements)

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“…37 After experimental stroke in mice, CXCL12 promotes angiogenesis and migration of neuronal and endothelial progenitor cells (EPCs) in the ischemic territory. 23,38 Endothelial progenitor cells are thought to secrete growth factors and other neuroprotectants that in concert mediate beneficial actions in the ischemic hemsiphere. 38 In that context, it can be envisaged that the CXCL12 pathway is important in homing of EPCs to the ischemic territory, and hence blockade of the CXCR4 by AMD3100 would be detrimental.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of CXCL12 Signaling Attenuates the Postischemic Immune Response and Improves Functional Recovery after Stroke

Ruscher

Kuric

Liu

et al. 2013

J Cereb Blood Flow Metab

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After stroke, brain inflammation in the ischemic hemisphere hampers brain tissue reorganization and functional recovery. Housing rats in an enriched environment (EE) dramatically improves recovery of lost neurologic functions after experimental stroke. We show here that rats housed in EE after stroke induced by permanent occlusion of the middle cerebral artery (pMCAO), showed attenuated levels of proinflammatory cytokines in the ischemic core and the surrounding peri-infarct area, including a significant reduction in the stroke-induced chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor-1 (CXCL12). To mimic beneficial effects of EE, we studied the impact of inhibiting CXCL12 action on functional recovery after transient MCAO (tMCAO). Rats treated with the specific CXCL12 receptor antagonist 1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclo-tetradecan (AMD3100) showed improved recovery compared with saline-treated rats after tMCAO, without a concomitant reduction in infarct size. This was accompanied by a reduction of infiltrating immune cells in the ischemic hemisphere, particularly cluster of differentiation 3-positive (CD3 þ ) and CD3 þ /CD4 þ T cells. Spleen atrophy and delayed death of splenocytes, induced by tMCAO, was prevented by AMD3100 treatment. We conclude that immoderate excessive activation of the CXCL12 pathway after stroke contributes to depression of neurologic function after stroke and that CXCR4 antagonism is beneficial for the recovery after stroke.

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Section: Discussionmentioning

confidence: 99%

“…22 Moreover, CXCL12 is involved in migration and mobilization of stem cells in the brain after stroke. 23 After experimental stroke, CXCL12 expression is elevated for several days 24 and closely associated with the infiltration of CXCR4 expressing cells. 25 The action of CXCL12 is not unambiguous.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of CXCL12 Signaling Attenuates the Postischemic Immune Response and Improves Functional Recovery after Stroke

Ruscher

Kuric

Liu

et al. 2013

J Cereb Blood Flow Metab

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“…Blockage of stromal derived factor 1a (SDF-1a) and angiopoietin 1 in remodeling cerebral vessels attenuates neuroblast migration toward the cortical ischemic boundary (Ohab et al, 2006). These data suggest that angiogenesis affects neurogenesis and neuroblast migration in the adult ischemic brain.…”

Section: Introductionmentioning

confidence: 94%

Coupling of Angiogenesis and Neurogenesis in Cultured Endothelial Cells and Neural Progenitor Cells after Stroke

Hua

Zhang

Wang

et al. 2007

J Cereb Blood Flow Metab

228

176

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Angiogenesis and neurogenesis are coupled processes. Using a coculture system, we tested the hypothesis that cerebral endothelial cells activated by ischemia enhance neural progenitor cell proliferation and differentiation, while neural progenitor cells isolated from the ischemic subventricular zone promote angiogenesis. Coculture of neural progenitor cells isolated from the subventricular zone of the adult normal rat with cerebral endothelial cells isolated from the stroke boundary substantially increased neural progenitor cell proliferation and neuronal differentiation and reduced astrocytic differentiation. Conditioned medium harvested from the stroke neural progenitor cells promoted capillary tube formation of normal cerebral endothelial cells. Blockage of vascular endothelial growth factor receptor 2 suppressed the effect of the endothelial cells activated by stroke on neurogenesis as well as the effect of the supernatant obtained from stroke neural progenitor cells on angiogenesis. These data suggest that angiogenesis couples to neurogenesis after stroke and vascular endothelial growth factor likely mediates this coupling.

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“…Immature neurons in the largest germinal matrix, the subventricular zone (SVZ), respond to the stroke, migrate to the area of damage, and may participate in Fig. 1 Stroke progresses in time from initial to secondary injury and to tissue repair as a continuum in which the initial pathological events trigger later regenerative events neural repair [30,45]. Blocking free radical generation, such as with an antioxidant, reduces poststroke neurogenesis [21].…”

Section: Radial Stroke: Triggers For Neural Repairmentioning

confidence: 99%

“…Blocking free radical generation, such as with an antioxidant, reduces poststroke neurogenesis [21]. It appears that free radical generation in peri-infarct tissue is one of the signals to multipotent neural stem cells and their progeny in the SVZ, together with other cytokines and growth factors activated in peri-infarct cortex [27,30,45].…”

Section: Radial Stroke: Triggers For Neural Repairmentioning

confidence: 99%

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

Carmichael

2016

Neurotherapeutics

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Stroke not only causes initial cell death, but also a limited process of repair and recovery. As an overall biological process, stroke has been most often considered from the perspective of early phases of ischemia, how these inter-relate and lead to expansion of the infarct. However, just as the biology of later stages of stroke becomes better understood, the clinical realities of stroke indicate that it is now more a chronic disease than an acute killer. As an overall biological process, it is now more important to understand how early cell death leads to the later, limited recovery so as develop an integrative view of acute to chronic stroke. This progression from death to repair involves sequential stages of primary cell death, secondary injury events, reactive tissue progenitor responses, and formation of new neuronal circuits. This progression is radial: from the tissue that suffers the infarct secondary injury signals, including free radicals and inflammatory cytokines, radiate out from the stroke core to trigger later regenerative events. Injury and repair processes occur not just in the local stroke site, but are also triggered in the connected networks of neurons that had existed in the stroke center: damage signals are relayed throughout a brain network. From these relayed, distributed damage signals, reactive astrocytosis, inflammatory processes, and the formation of new connections occur in distant brain areas. In short, emerging data in stroke cell death studies and the development of the field of stroke neural repair now indicate a continuum in time and in space of progressive events that can be considered as the 3 Rs of stroke biology: radial, relayed, and regenerative.

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A Neurovascular Niche for Neurogenesis after Stroke

Cited by 792 publications

References 59 publications

Inhibition of CXCL12 Signaling Attenuates the Postischemic Immune Response and Improves Functional Recovery after Stroke

Inhibition of CXCL12 Signaling Attenuates the Postischemic Immune Response and Improves Functional Recovery after Stroke

Coupling of Angiogenesis and Neurogenesis in Cultured Endothelial Cells and Neural Progenitor Cells after Stroke

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

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