NDLI: Human neural stem cell grafts modify microglial response and enhance axonal sprouting in neonatal hypoxic-ischemic brain injury.

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Human neural stem cell grafts modify microglial response and enhance axonal sprouting in neonatal hypoxic-ischemic brain injury.

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Human neural stem cell grafts modify microglial response and enhance axonal sprouting in neonatal hypoxic-ischemic brain injury.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Maag, Anne-Lise Arac, Ahmet Sun, Guohua Wu, Joseph C. Li, Zongjin Davis, Alexis S. Daadi, Marcel M. Bhatnagar, Rishi Steinberg, Gary K. Jiang, Kewen
Description	Country affiliation: United States Author Affiliation: Daadi MM ( Department of Neurosurgery, Stanford Stroke Center, Stanford University School of Medicine, Stanford, Calif 94305-5487, USA. mdaadi@stanford.edu)
Abstract	BACKGROUND AND PURPOSE: Hypoxic-ischemic (HI) brain injury in newborn infants represents a major cause of cerebral palsy, development delay, and epilepsy. Stem cell-based therapy has the potential to rescue and replace the ischemic tissue caused by HI and to restore function. However, the mechanisms by which stem cell transplants induce functional recovery are yet to be elucidated. In the present study, we sought to investigate the efficacy of human neural stem cells derived from human embryonic stem cells in a rat model of neonatal HI and the mechanisms enhancing brain repair. METHODS: The human neural stem cells were genetically engineered for in vivo molecular imaging and for postmortem histological tracking. Twenty-four hours after the induction of HI, animals were grafted with human neural stem cells into the forebrain. Motor behavioral tests were performed the fourth week after transplantation. We used immunocytochemistry and neuroanatomical tracing to analyze neural differentiation, axonal sprouting, and microglia response. Treatment-induced changes in gene expression were investigated by microarray and quantitative polymerase chain reaction. RESULTS: Bioluminescence imaging permitted real time longitudinal tracking of grafted human neural stem cells. HI transplanted animals significantly improved in their use of the contralateral impeded forelimb and in the Rotorod test. The grafts showed good survival, dispersion, and differentiation. We observed an increase of uniformly distributed microglia cells in the grafted side. Anterograde neuroanatomical tracing demonstrated significant contralesional sprouting. Microarray analysis revealed upregulation of genes involved in neurogenesis, gliogenesis, and neurotrophic support. CONCLUSIONS: These results suggest that human neural stem cell transplants enhance endogenous brain repair through multiple modalities in response to HI.
ISSN	00392499
e-ISSN	15244628
Journal	Stroke
Issue Number	3
Volume Number	41
Language	English
Publisher	Lippincott Williams & Wilkins (on behalf of the American Heart Association)
Publisher Date	2010-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Axons Physiology Embryonic Stem Cells Transplantation Hypoxia-ischemia, Brain Surgery Microglia Neurons Stem Cell Transplantation Animals Animals, Newborn Pathology Neuronal Plasticity Rats, Sprague-dawley Transplants Comparative Study Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Cardiology
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Neuroscience Advanced and Specialized Nursing Neurology (clinical)

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