Immunosuppression promotes endogenous neural stem and progenitor cell migration and tissue regeneration after ischemic injury

被引:75
作者
Erlandsson, Anna [1 ]
Lin, Chia-Hsun Anthony [2 ]
Yu, Fenggang [2 ]
Morshead, Cindi M. [1 ]
机构
[1] Univ Toronto, Dept Surg, Div Anat, Donnelly Ctr, Toronto, ON M5S 3E1, Canada
[2] Uppsala Univ, Dept Neurosci, Uppsala, Sweden
关键词
Neural stem cells; Immunosuppression; Stroke; Neurogenesis; Migration; Neurosphere; NOD/SCID; Cyclosporine; Functional recovery; Regeneration; TRAUMATIC BRAIN-INJURY; ADULT MAMMALIAN FOREBRAIN; SUBVENTRICULAR ZONE; CYCLOSPORINE-A; GROWTH-FACTOR; INDUCED NEUROGENESIS; DIRECTED MIGRATION; MOUSE BRAIN; CNS INJURY; STROKE;
D O I
10.1016/j.expneurol.2010.05.018
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Recent work has demonstrated that self-repair in the adult brain can be augmented by the infusion of growth factors to activate endogenous neural precursor cells that contribute to new tissue formation and functional recovery in a model of stroke. Using both a genetic model and drug treatment, we demonstrate that immunosuppression mimics the effects of growth factor activation, including tissue regeneration, neural precursor cell migration and functional recovery following ischemic injury. In the absence of growth factor treatment, mice with a functional immune system develop a prominent cavity in the cortex underlying the ischemic injury. In untreated immunodeficient NOD/SCID mice, however, the cortical cavity forms but is then filled with regenerated cortical tissue containing glial cells and subependyma derived neural stem and progenitor cells that migrate from their niche lining the lateral ventricles. The daily administration of Cyclosporine A also results in endogenous neural precursor cell migration and regenerated cortical tissue at the site of the cortical injury. Different from growth factor-treated animals is the finding that the regenerated cortical tissue in immunosuppressed animals is devoid of new neurons. Interestingly, both the growth factor and immunosuppressed (NOD/SCID and Cyclosporine A) treated animals displayed functional behavioural recovery despite the lack of neurogenesis within the regenerated cortical tissue. This article is part of a Special Issue entitled "Interaction between repair, disease, & inflammation." (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:48 / 57
页数:10
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