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

Department of Neuroscience, Uppsala University, Uppsala, Sweden.
Experimental Neurology (Impact Factor: 4.62). 07/2011; 230(1):48-57. DOI: 10.1016/j.expneurol.2010.05.018
Source: PubMed

ABSTRACT 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."

  • [Show abstract] [Hide abstract]
    ABSTRACT: Inflammation entails a complex set of defense mechanisms acting in concert to restore the homeostatic balance in organisms after damage or pathogen invasion. This immune response consists of the activity of various immune cells in a highly complex manner. Inflammation is a double-edged sword as it is reported to have both detrimental and beneficial consequences. In this review, we discuss the effects of inflammation on stem cell activity, focusing primarily on neural stem/progenitor cells in mammals and zebrafish. We also give a brief overview of the effects of inflammation on other stem cell compartments, exemplifying the positive and negative role of inflammation on stemness. The majority of the chronic diseases involve an unremitting phase of inflammation due to improper resolution of the initial pro-inflammatory response that impinges on the stem cell behavior. Thus, understanding the mechanisms of crosstalk between the inflammatory milieu and tissue-resident stem cells is an important basis for clinical efforts. Not only is it important to understand the effect of inflammation on stem cell activity for further defining the etiology of the diseases, but also better mechanistic understanding is essential to design regenerative therapies that aim at micromanipulating the inflammatory milieu to offset the negative effects and maximize the beneficial outcomes. © 2015 The Authors.
    EMBO Reports 03/2015; 16(4). DOI:10.15252/embr.201439702 · 7.86 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Stroke is the second leading cause of death and the preeminent cause of neurological disability. Attempts to limit brain injury after ischemic stroke with clot-dissolving drugs have met with great success but their use remains limited due to a narrow therapeutic time window and concern over serious side effects. Unfortunately, the neuroprotective strategy failed in clinical trials. A more promising approach is to promote recovery of function in people affected by stroke. Following stroke, there is a heightened critical period of plasticity that appears to be receptive to exogenous interventions (e.g., delivery of growth factors) designed to enhance neuroplasticity processes important for recovery. An emerging concept is that combinational therapies appear much more effective than single interventions in improving stroke recovery. One of the most promising interventions, with clinical feasibility, is enriched rehabilitation, a combination of environmental enrichment and task-specific therapy.
    Progress in brain research 04/2015; 218:413-34. DOI:10.1016/bs.pbr.2014.12.002 · 5.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease, a progressive neurodegenerative illness, is the most common form of dementia. So far, there is neither an effective prevention nor a cure for Alzheimer's disease. In recent decades, stem cell therapy has been one of the most promising treatments for Alzheimer's disease patients. This article aims to summarize the current progress in the stem cell treatments for Alzheimer's disease from an experiment to a clinical research.
    Neural Regeneration Research 01/2012; 7(1):66-71. DOI:10.3969/j.issn.1673-5374.2012.01.011 · 0.23 Impact Factor