A Neurovascular Niche for Neurogenesis after Stroke

Journal of Neuroscience - Tập 26 Số 50 - Trang 13007-13016 - 2006
John Ohab1, Sheila M. Fleming, Armin Blesch, S. Thomas Carmichael
1Department of Neurology, University of California, Los Angeles, Los Angeles, California 90095-1735, USA.

Tóm tắt

Stroke causes cell death but also birth and migration of new neurons within sites of ischemic damage. The cellular environment that induces neuronal regeneration and migration after stroke has not been defined. We have used a model of long-distance migration of newly born neurons from the subventricular zone to cortex after stroke to define the cellular cues that induce neuronal regeneration after CNS injury. Mitotic, genetic, and viral labeling and chemokine/growth factor gain- and loss-of-function studies show that stroke induces neurogenesis from a GFAP-expressing progenitor cell in the subventricular zone and migration of newly born neurons into a unique neurovascular niche in peri-infarct cortex. Within this neurovascular niche, newly born, immature neurons closely associate with the remodeling vasculature. Neurogenesis and angiogenesis are causally linked through vascular production of stromal-derived factor 1 (SDF1) and angiopoietin 1 (Ang1). Furthermore, SDF1 and Ang1 promote post-stroke neuroblast migration and behavioral recovery. These experiments define a novel brain environment for neuronal regeneration after stroke and identify molecular mechanisms that are shared between angiogenesis and neurogenesis during functional recovery from brain injury.

Từ khóa


Tài liệu tham khảo

10.1097/00004647-199909000-00012

10.1523/JNEUROSCI.3572-04.2004

10.1002/dvdy.20643

10.1016/S0896-6273(04)00111-4

10.1016/j.cell.2004.07.004

10.1038/nm747

10.1038/nm973

10.1002/cne.10874

10.1602/neurorx.2.3.396

10.1006/nbdi.2001.0425

10.1006/exnr.2001.7827

10.1111/j.1460-9568.2004.03813.x

10.1523/JNEUROSCI.3256-05.2005

De Clercq, 2000, Inhibition of HIV infection by bicyclams, highly potent and specific CXCR4 antagonists, Mol Pharmacol, 57, 833

10.1016/j.yexcr.2004.04.013

10.1097/01.sap.0000123022.98361.c5

Folkman, 2001, Angiogenesis research: guidelines for translation to clinical application, Thromb Haemost, 86, 23, 10.1055/s-0037-1616197

10.1016/S0092-8674(04)00255-7

10.1038/nn1340

10.1016/S0166-4328(99)00130-8

10.1038/nature04481

Gritti, 2002, Multipotent neural stem cells reside into the rostral extension and olfactory bulb of adult rodents, J Neurosci, 22, 437, 10.1523/JNEUROSCI.22-02-00437.2002

10.1016/S0002-9440(10)65006-7

10.1182/blood-2002-06-1634

10.1016/j.expneurol.2003.11.005

10.1111/j.1582-4934.2004.tb00474.x

10.1073/pnas.0408258102

10.1073/pnas.081011098

10.1016/S1044-7431(03)00159-3

10.1073/pnas.0603512103

10.1038/35067005

10.1073/pnas.0404474101

Kirschenbaum, 1999, Adult subventricular zone neuronal precursors continue to proliferate and migrate in the absence of the olfactory bulb, J Neurosci, 19, 2171, 10.1523/JNEUROSCI.19-06-02171.1999

10.1038/sj.jcbfm.9600214

10.1111/j.1460-9568.2005.04072.x

10.1006/mcne.1999.0762

Li, 2003, Endothelial apoptosis initiates acute blood-brain barrier disruption after ionizing radiation, Cancer Res, 63, 5950

10.1016/S0896-6273(02)00722-5

10.1016/j.expneurol.2004.07.011

10.1002/ana.10393

Paxinos G Franklin KBJ (2001) Mouse brain in stereotaxic coordinates (Academic, San Diego).

10.1038/sj.jcbfm.9600172

10.1124/jpet.105.086553

10.1126/science.1095505

Stumm, 2002, A dual role for the SDF-1/CXCR4 chemokine receptor system in adult brain: isoform-selective regulation of SDF-1 expression modulates CXCR4-dependent neuronal plasticity and cerebral leukocyte recruitment after focal ischemia, J Neurosci, 22, 5865, 10.1523/JNEUROSCI.22-14-05865.2002

10.1172/JCI200420622

10.1172/JCI200317170

10.1634/stemcells.2005-0281

10.1523/JNEUROSCI.4480-05.2006

10.1161/01.STR.0000173408.94728.79

10.1016/j.bbrc.2004.01.059

10.1161/01.STR.0000132196.49028.a4

10.1038/nm0297-158

10.1097/00004647-200008000-00001

10.1074/jbc.273.29.18514

10.1126/science.1099344

10.1523/JNEUROSCI.0149-06.2006

Yu SW Friedman B Cheng Q Lyden PD (2006) Stroke-evoked angiogenesis results in a transient population of microvessels. J Cereb Blood Flow Metab, in press.

10.1523/JNEUROSCI.1109-04.2004

10.1161/hh0302.104460

Thông tin
Thông tin xuất bản

Journal of Neuroscience

Tập 26 Số 50

13007-13016

Thông tin tác giả