CD38 exacerbates focal cytokine production, postischemic inflammation and brain injury after focal cerebral ischemia.

<h4>Background</h4>Converging evidence suggests that inflammatory processes significantly influence brain injury and clinical impairment in ischemic stroke. Although early studies suggested a key role of lymphocytes, recent data has emphasized the orchestrating function of innate immunit...

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Autores principales:	Chi-un Choe, Kerstin Lardong, Mathias Gelderblom, Peter Ludewig, Frank Leypoldt, Friedrich Koch-Nolte, Christian Gerloff, Tim Magnus
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b875f31e7224b18ad106daa0e57ecf0
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spelling	oai:doaj.org-article:3b875f31e7224b18ad106daa0e57ecf02021-11-18T06:53:59ZCD38 exacerbates focal cytokine production, postischemic inflammation and brain injury after focal cerebral ischemia.1932-620310.1371/journal.pone.0019046https://doaj.org/article/3b875f31e7224b18ad106daa0e57ecf02011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21625615/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Converging evidence suggests that inflammatory processes significantly influence brain injury and clinical impairment in ischemic stroke. Although early studies suggested a key role of lymphocytes, recent data has emphasized the orchestrating function of innate immunity, i.e., macrophages and microglia. The bifunctional receptor and ectoenzyme CD38 synthesizes calcium-mobilizing second messengers (e.g., cyclic ADP-ribose), which have been shown to be necessary for activation and migration of myeloid immune cells. Therefore, we investigated the dynamics of CD38 in stroke and the impact of CD38-deficiency on cytokine production, inflammation and cerebral damage in a mouse model of cerebral ischemia-reperfusion.<h4>Methodology/principal findings</h4>We show that the local expression of the chemokine MCP-1 was attenuated in CD38-deficient mice compared with wildtype mice after focal cerebral ischemia and reperfusion. In contrast, no significant induction of MCP-1 expression was observed in peripheral blood after 6 hours. Flow cytometry analysis revealed less infiltrating macrophages and lymphocytes in the ischemic hemisphere of CD38-deficient mice, whereas the amount of resident microglia was unaltered. An up-regulation of CD38 expression was observed in macrophages and CD8(+) cells after focal cerebral ischemia in wildtype mice, whereas CD38 expression was unchanged in microglia. Finally, we demonstrate that CD38-deficiency decreases the cerebral ischemic injury and the persistent neurological deficit after three days of reperfusion in this murine temporary middle cerebral artery occlusion (tMCAO) model.<h4>Conclusion/significance</h4>CD38 is differentially regulated following stroke and its deficiency attenuates the postischemic chemokine production, the immune cell infiltration and the cerebral injury after temporary ischemia and reperfusion. Therefore CD38 might prove a therapeutic target in ischemic stroke.Chi-un ChoeKerstin LardongMathias GelderblomPeter LudewigFrank LeypoldtFriedrich Koch-NolteChristian GerloffTim MagnusPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e19046 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chi-un Choe Kerstin Lardong Mathias Gelderblom Peter Ludewig Frank Leypoldt Friedrich Koch-Nolte Christian Gerloff Tim Magnus CD38 exacerbates focal cytokine production, postischemic inflammation and brain injury after focal cerebral ischemia.
description	<h4>Background</h4>Converging evidence suggests that inflammatory processes significantly influence brain injury and clinical impairment in ischemic stroke. Although early studies suggested a key role of lymphocytes, recent data has emphasized the orchestrating function of innate immunity, i.e., macrophages and microglia. The bifunctional receptor and ectoenzyme CD38 synthesizes calcium-mobilizing second messengers (e.g., cyclic ADP-ribose), which have been shown to be necessary for activation and migration of myeloid immune cells. Therefore, we investigated the dynamics of CD38 in stroke and the impact of CD38-deficiency on cytokine production, inflammation and cerebral damage in a mouse model of cerebral ischemia-reperfusion.<h4>Methodology/principal findings</h4>We show that the local expression of the chemokine MCP-1 was attenuated in CD38-deficient mice compared with wildtype mice after focal cerebral ischemia and reperfusion. In contrast, no significant induction of MCP-1 expression was observed in peripheral blood after 6 hours. Flow cytometry analysis revealed less infiltrating macrophages and lymphocytes in the ischemic hemisphere of CD38-deficient mice, whereas the amount of resident microglia was unaltered. An up-regulation of CD38 expression was observed in macrophages and CD8(+) cells after focal cerebral ischemia in wildtype mice, whereas CD38 expression was unchanged in microglia. Finally, we demonstrate that CD38-deficiency decreases the cerebral ischemic injury and the persistent neurological deficit after three days of reperfusion in this murine temporary middle cerebral artery occlusion (tMCAO) model.<h4>Conclusion/significance</h4>CD38 is differentially regulated following stroke and its deficiency attenuates the postischemic chemokine production, the immune cell infiltration and the cerebral injury after temporary ischemia and reperfusion. Therefore CD38 might prove a therapeutic target in ischemic stroke.
format	article
author	Chi-un Choe Kerstin Lardong Mathias Gelderblom Peter Ludewig Frank Leypoldt Friedrich Koch-Nolte Christian Gerloff Tim Magnus
author_facet	Chi-un Choe Kerstin Lardong Mathias Gelderblom Peter Ludewig Frank Leypoldt Friedrich Koch-Nolte Christian Gerloff Tim Magnus
author_sort	Chi-un Choe
title	CD38 exacerbates focal cytokine production, postischemic inflammation and brain injury after focal cerebral ischemia.
title_short	CD38 exacerbates focal cytokine production, postischemic inflammation and brain injury after focal cerebral ischemia.
title_full	CD38 exacerbates focal cytokine production, postischemic inflammation and brain injury after focal cerebral ischemia.
title_fullStr	CD38 exacerbates focal cytokine production, postischemic inflammation and brain injury after focal cerebral ischemia.
title_full_unstemmed	CD38 exacerbates focal cytokine production, postischemic inflammation and brain injury after focal cerebral ischemia.
title_sort	cd38 exacerbates focal cytokine production, postischemic inflammation and brain injury after focal cerebral ischemia.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/3b875f31e7224b18ad106daa0e57ecf0
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CD38 exacerbates focal cytokine production, postischemic inflammation and brain injury after focal cerebral ischemia.

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