Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement.

<h4>Background and purpose</h4>Microglia are resident immunocompetent and phagocytic cells of central nervous system (CNS), which produce various cytokines and growth factors in response to injury and thereby regulate disease pathology. The purpose of this study is to investigate the eff...

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Autores principales:	Dashdemberel Narantuya, Atsushi Nagai, Abdullah Md Sheikh, Junichi Masuda, Shotai Kobayashi, Shuhei Yamaguchi, Seung U Kim
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ffa54785354e4f9384ac05d2ff9cb8bb
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spelling	oai:doaj.org-article:ffa54785354e4f9384ac05d2ff9cb8bb2021-12-02T20:19:49ZHuman microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement.1932-620310.1371/journal.pone.0011746https://doaj.org/article/ffa54785354e4f9384ac05d2ff9cb8bb2010-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20668522/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background and purpose</h4>Microglia are resident immunocompetent and phagocytic cells of central nervous system (CNS), which produce various cytokines and growth factors in response to injury and thereby regulate disease pathology. The purpose of this study is to investigate the effects of microglial transplantation on focal cerebral ischemia model in rat.<h4>Methods</h4>Transient middle cerebral artery occlusion (MCAO) in rats was induced by the intraluminal filament technique. HMO6 cells, human microglial cell line, were transplanted intravenously at 48 hours after MCAO. Functional tests were performed and the infarct volume was measured at 7 and 14 days after MCAO. Migration and cell survival of transplanted microglial cells and host glial reaction in the brain were studied by immunohistochemistry. Gene expression of neurotrophic factors, cytokines and chemokines in transplanted cells and host rat glial cells was determined by laser capture microdissection (LCM) and quantitative real time-PCR.<h4>Results</h4>HMO6 human microglial cells transplantation group demonstrated significant functional recovery compared with control group. At 7 and 14 days after MCAO, infarct volume was significantly reduced in the HMO group. In the HMO6 group, number of apoptotic cells was time-dependently reduced in the infarct core and penumbra. In addition, number of host rat microglia/macrophages and reactive astrocytes was significantly decreased at 7 and 14 days after MCAO in the penumbra. Gene expression of various neurotrophic factors (GDNF, BDNF, VEGF and BMP7) and anti-inflammatory cytokines (IL4 and IL5) was up-regulated in transplanted HMO6 cells of brain tissue compared with those in culture. The expression of GDNF and VEGF in astrocytes in penumbra was significantly up-regulated in the HMO6 group.<h4>Conclusions</h4>Our results indicate that transplantation of HMO6 human microglial cells reduces ischemic deficits and apoptotic events in stroke animals. The results were mediated by modulation of gliosis and neuroinflammation, and neuroprotection provided by neurotrophic factors of endogenous and transplanted cells-origin.Dashdemberel NarantuyaAtsushi NagaiAbdullah Md SheikhJunichi MasudaShotai KobayashiShuhei YamaguchiSeung U KimPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 7, p e11746 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dashdemberel Narantuya Atsushi Nagai Abdullah Md Sheikh Junichi Masuda Shotai Kobayashi Shuhei Yamaguchi Seung U Kim Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement.
description	<h4>Background and purpose</h4>Microglia are resident immunocompetent and phagocytic cells of central nervous system (CNS), which produce various cytokines and growth factors in response to injury and thereby regulate disease pathology. The purpose of this study is to investigate the effects of microglial transplantation on focal cerebral ischemia model in rat.<h4>Methods</h4>Transient middle cerebral artery occlusion (MCAO) in rats was induced by the intraluminal filament technique. HMO6 cells, human microglial cell line, were transplanted intravenously at 48 hours after MCAO. Functional tests were performed and the infarct volume was measured at 7 and 14 days after MCAO. Migration and cell survival of transplanted microglial cells and host glial reaction in the brain were studied by immunohistochemistry. Gene expression of neurotrophic factors, cytokines and chemokines in transplanted cells and host rat glial cells was determined by laser capture microdissection (LCM) and quantitative real time-PCR.<h4>Results</h4>HMO6 human microglial cells transplantation group demonstrated significant functional recovery compared with control group. At 7 and 14 days after MCAO, infarct volume was significantly reduced in the HMO group. In the HMO6 group, number of apoptotic cells was time-dependently reduced in the infarct core and penumbra. In addition, number of host rat microglia/macrophages and reactive astrocytes was significantly decreased at 7 and 14 days after MCAO in the penumbra. Gene expression of various neurotrophic factors (GDNF, BDNF, VEGF and BMP7) and anti-inflammatory cytokines (IL4 and IL5) was up-regulated in transplanted HMO6 cells of brain tissue compared with those in culture. The expression of GDNF and VEGF in astrocytes in penumbra was significantly up-regulated in the HMO6 group.<h4>Conclusions</h4>Our results indicate that transplantation of HMO6 human microglial cells reduces ischemic deficits and apoptotic events in stroke animals. The results were mediated by modulation of gliosis and neuroinflammation, and neuroprotection provided by neurotrophic factors of endogenous and transplanted cells-origin.
format	article
author	Dashdemberel Narantuya Atsushi Nagai Abdullah Md Sheikh Junichi Masuda Shotai Kobayashi Shuhei Yamaguchi Seung U Kim
author_facet	Dashdemberel Narantuya Atsushi Nagai Abdullah Md Sheikh Junichi Masuda Shotai Kobayashi Shuhei Yamaguchi Seung U Kim
author_sort	Dashdemberel Narantuya
title	Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement.
title_short	Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement.
title_full	Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement.
title_fullStr	Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement.
title_full_unstemmed	Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement.
title_sort	human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/ffa54785354e4f9384ac05d2ff9cb8bb
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Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement.

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