Effects of constraint-induced movement therapy on neurogenesis and functional recovery after early hypoxic-ischemic injury in mice (original) (raw)
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Neuroscience Research, 2009
BrdU 5-bromo-2-deoxyuridine CIMT Constraint-induced movement therapy CIMT-EE Constraint-induced movement therapy with an enriched-environment ICH Intracerebral hemorrhage AIM Constraint-induced movement therapy (CIMT) has emerged as a promising therapeutic strategy for improving affected upper limb function in children with hemiplegic cerebral palsy (CP). However, little is known about the changes in the brain that are induced by CIMT. This study was designed to investigate these changes and behavioural performance after CIMT intervention in mice with neonatal hypoxic-ischemic brain injury.
Stroke, 2006
Background and Purpose-Cells proliferate continuously in the adult mammalian brain, and in rodents, cell genesis is affected by housing conditions and brain injury. Increase in neurogenesis after brain ischemia has been postulated to be linked to functional recovery after stroke. Housing rodents in an enriched environment improves motor function after stroke injury. We have investigated whether changes in cell genesis can explain the beneficial effects of an enriched environment. Methods-Intact mice and mice subjected to transient occlusion of the middle cerebral artery were exposed to an enriched environment for 1 month. Bromodeoxyuridine was injected daily to label proliferating cells during the first postischemic week. Newborn cells were analyzed immunohistochemically after 4 weeks. Results-The enriched environment increased neurogenesis in the dentate gyrus in both intact and stroke-injured animals. An increased number of newborn cells was found in the subventricular zone of stroke-injured mice, but not in injured mice exposed to an enriched environment. Also, the number of newborn astrocytes (BrdUϩ/S-100ϩ cells), neuroblasts (dcxϩ cells), and reactive astrocytes (vimentin mRNA) in the striatum ipsilateral to the ischemic injury was markedly attenuated and new adult neurons (BrdUϩ/NeuNϩ) were not found. The enriched environment did not affect infarct size or mortality.
Effectiveness of Neurogenesis in treating Children with Cerebral Palsy
Iranian Journal of Child Neurology, 2012
Tissue-specific stem cells divide to generate different cell types for the purpose of tissue repair in the adult. The aim of this study was to detect the significance of neurogenesis in the central nervous system in patients with cerebral palsy (CP). . The outcomes measured in the review were classified to origins, proliferation, and migration of new neurons, and neurogenesis in CP.
Experimental Neurology, 2008
Neurogenesis increases in the adult rodent forebrain subventricular zone (SVZ) after experimental stroke. Newborn neurons migrate to the injured striatum, but few survive long-term and little evidence exists to suggest that they integrate or contribute to functional recovery. One potential strategy to improve stroke recovery is to stimulate neurogenesis and integration of adult-born neurons by using treatments that enhance neurogenesis. We examined the influence of retinoic acid (RA), which stimulates neonatal SVZ and adult hippocampal neurogenesis, and environmental enrichment (EE), which enhances survival of adult-born hippocampal neurons. We hypothesized that the combination of RA and EE would promote survival of adult-generated SVZ-derived neurons and improve functional recovery after stroke. Adult rats underwent middle cerebral artery occlusion, received BrdU on days 5-11 after stroke and were treated with RA/EE, RA alone, EE/vehicle or vehicle alone and were killed 61 days after stroke. Rats underwent repeated MRI and behavioral testing. We found that RA/EE treatment preserved striatal and hemisphere tissue and increased SVZ neurogenesis as demonstrated by Ki67 and doublecortin (DCx) immunolabeling. All treatments influenced the location of BrdU-and DCx-positive cells in the post-stroke striatum. RA/EE increased the number of BrdU/NeuN-positive cells in the injured striatum but did not lead to improvements in behavioral function. These results demonstrate that combined pharmacotherapy and behavioral manipulation enhances post-stroke striatal neurogenesis and decreases infarct volume without promoting detectable functional recovery. Further study of the integration of adult-born neurons in the ischemic striatum is necessary to determine their restorative potential.
Brain plasticity and regeneration
AJNR. American journal of neuroradiology
Brain plasticity includes the enormous changes of normal prenatal and postnatal development, responses to normal experience such as the springtime reemergence of bird song, and responses to injury. This broad view of plasticity brings together the large and growing fields of developmental neuroscience, learning and memory, and responses to injury. Such a synthetic view is essential now that these fields are being elucidated at cellular and molecular levels. The major stages of normal brain development are very similar to those of plasticity induced by experience. Particular cellular or subcellular de,.. tails are similar, depending on the specific case. Importantly, these common steps are the very ones we most need to understand if the outcome of brain and spinal cord injury is to be improved. Knowledge of brain plasticity will be the basis for innovative treatmenf of such injuries. Relevant mechanisms reviewed here include chemical stimulation of receptors, regulation of gene expression in surviving cells, gene introduction by viral or cellular vectors, cell-cell interactions such as guidance of axons, and replacing neurons lost by injury. Increasing knowledge of plasticity and its application to therapy offers promising approaches for improving the outcome of cerebral and spinal injury, making optimism unavoidable.
Developmental Neuroscience
Stem cell transplantation is a promising intervention for neonatal hypoxic-ischemic encephalopathy (HIE); however, universal feasibility and safety have not been thoroughly evaluated. AMD3100 and insulin-like growth factor 1 (IGF1) mobilize progenitor cells into peripheral circulation. The objective of this study was to assess the short-term efficacy of inducing endogenous stem cell mobilization after injury in a model of neonatal HIE. Postnatal day 9 CD1 pups received sham surgery or unilateral carotid artery ligation and 30 min of hypoxia followed by saline, AMD3100, IGF1, or both agents. Intraperitoneal injections of 5-ethynyl-2′-deoxyuridine (EdU) and 5-bromo-2′-deoxyuridine were used to label replicating progenitor cells. At P14, animals underwent rotarod testing, and the brains were sectioned for area measurements and immunofluorescence staining. Comparisons were made using one-way analysis of variance. Spearman's rho was calculated to assess correlation between rotarod results and markers of brain injury. Pups treated with both agents had improved rotarod performance (p = 0.02) and increased EdU+ progenitor cells in the subgranular zone (SGZ) compared to injured controls (p = 0.10). An increase in active cells within the SGZ was correlated with improved rotarod performance (r = 0.84, p = 0.04). There were no differences in overall injury score or in brain area or number of activated cells in the subventricular zone between the treatment groups. Combined treatment with AMD3100 and IGF1 shows promise for decreasing brain injury and improving motor function in pups after HIE which correlated with changes in the number of active progenitor cells in the SGZ.
Specific Features of SVZ Neurogenesis After Cortical Ischemia: a Longitudinal Study
Scientific reports, 2017
Stroke is a devastating disease with an increasing prevalence. Part of the current development in stroke therapy is focused in the chronic phase, where neurorepair mechanisms such as neurogenesis, are involved. In the adult brain, one of the regions where neurogenesis takes place is the subventricular zone (SVZ) of the lateral ventricles. Given the possibility to develop pharmacological therapies to stimulate this process, we have performed a longitudinal analysis of neurogenesis in a model of cortical ischemia in mice. Our results show an initial decrease of SVZ proliferation at 24 h, followed by a recovery leading to an increase at 14d and a second decrease 28d after stroke. Coinciding with the 24 h proliferation decrease, an increase in the eutopic neuroblast migration towards the olfactory bulb was observed. The analysis of the neuroblast ectopic migration from the SVZ toward the lesion showed an increase in this process from day 14 after the insult. Finally, our data revealed a...