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Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats
Human umbilical cord blood cells (HUCBC) are rich in stem and progenitor cells. In this study we tested whether intravenously infused HUCBC enter brain, survive, differentiate, and improve neurological functional recovery after stroke in rats. In addition, we tested whether ischemic brain tissue ext...
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Published in: | Stroke (1970) 2001-11, Vol.32 (11), p.2682-2688 |
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container_title | Stroke (1970) |
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creator | JIELI CHEN SANBERG, Paul R YI LI LEI WANG MEI LU WILLING, Allison E SANCHEZ-RAMOS, Juan CHOPP, Michael |
description | Human umbilical cord blood cells (HUCBC) are rich in stem and progenitor cells. In this study we tested whether intravenously infused HUCBC enter brain, survive, differentiate, and improve neurological functional recovery after stroke in rats. In addition, we tested whether ischemic brain tissue extract selectively induces chemotaxis of HUCBC in vitro.
Adult male Wistar rats were subjected to transient (2-hour) middle cerebral artery occlusion (MCAO). Experimental groups were as follows: group 1, MCAO alone (n=5); group 2, 3x10(6) HUCBC injected into tail vein at 24 hours after MCAO (n=6) (animals of groups 1 and 2 were killed at 14 days after MCAO); group 3, MCAO alone (n=5); group 4, MCAO injected with PBS at 1 day after stroke (n=8); and group 5, 3x10(6) HUCBC injected into tail vein at 7 days after MCAO (n=5). Rats of groups 3, 4, and 5 were killed at 35 days after MCAO. Behavioral tests (rotarod and Modified Neurological Severity Score [mNSS]) were performed. Immunohistochemical staining was used to identify cells derived from HUCBC. Chemotactic activity of ischemia brain tissue extracts toward HUCBC at different time points was evaluated in vitro.
Treatment at 24 hours after MCAO with HUCBC significantly improved functional recovery, as evidenced by the rotarod test and mNSS (P |
doi_str_mv | 10.1161/hs1101.098367 |
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Adult male Wistar rats were subjected to transient (2-hour) middle cerebral artery occlusion (MCAO). Experimental groups were as follows: group 1, MCAO alone (n=5); group 2, 3x10(6) HUCBC injected into tail vein at 24 hours after MCAO (n=6) (animals of groups 1 and 2 were killed at 14 days after MCAO); group 3, MCAO alone (n=5); group 4, MCAO injected with PBS at 1 day after stroke (n=8); and group 5, 3x10(6) HUCBC injected into tail vein at 7 days after MCAO (n=5). Rats of groups 3, 4, and 5 were killed at 35 days after MCAO. Behavioral tests (rotarod and Modified Neurological Severity Score [mNSS]) were performed. Immunohistochemical staining was used to identify cells derived from HUCBC. Chemotactic activity of ischemia brain tissue extracts toward HUCBC at different time points was evaluated in vitro.
Treatment at 24 hours after MCAO with HUCBC significantly improved functional recovery, as evidenced by the rotarod test and mNSS (P<0.05). Treatment at 7 days after MCAO with HUCBC significantly improved function only on the mNSS (P<0.05). Some HUCBC were reactive for the astrocyte marker glial fibrillary acidic protein and the neuronal markers NeuN and microtubule-associated protein 2. In vitro, significant HUCBC migration activity was present at 24 hours after MCAO (P<0.01) compared with normal brain tissue.
Intravenously administered HUCBC enter brain, survive, migrate, and improve functional recovery after stroke. HUCBC transplantation may provide a cell source to treat stroke.</description><identifier>ISSN: 0039-2499</identifier><identifier>EISSN: 1524-4628</identifier><identifier>DOI: 10.1161/hs1101.098367</identifier><identifier>PMID: 11692034</identifier><identifier>CODEN: SJCCA7</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Behavior, Animal ; Biological and medical sciences ; Brain - cytology ; Brain Ischemia - physiopathology ; Cell Differentiation ; Cell Extracts - pharmacology ; Cell Survival ; Chemotaxis - drug effects ; Cord Blood Stem Cell Transplantation - methods ; Fetal Blood - cytology ; Fetal Blood - physiology ; Humans ; Infarction, Middle Cerebral Artery - physiopathology ; Infarction, Middle Cerebral Artery - psychology ; Infarction, Middle Cerebral Artery - therapy ; Infusions, Intravenous ; Male ; Medical sciences ; Neurology ; Rats ; Rats, Wistar ; Stroke - physiopathology ; Stroke - psychology ; Stroke - therapy ; Vascular diseases and vascular malformations of the nervous system</subject><ispartof>Stroke (1970), 2001-11, Vol.32 (11), p.2682-2688</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Nov 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c488t-81beb419ee8c88c41d234dcfed8d0516757c3d4367ce7e88de77d23f707f4e4a3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14129511$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11692034$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>JIELI CHEN</creatorcontrib><creatorcontrib>SANBERG, Paul R</creatorcontrib><creatorcontrib>YI LI</creatorcontrib><creatorcontrib>LEI WANG</creatorcontrib><creatorcontrib>MEI LU</creatorcontrib><creatorcontrib>WILLING, Allison E</creatorcontrib><creatorcontrib>SANCHEZ-RAMOS, Juan</creatorcontrib><creatorcontrib>CHOPP, Michael</creatorcontrib><title>Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats</title><title>Stroke (1970)</title><addtitle>Stroke</addtitle><description>Human umbilical cord blood cells (HUCBC) are rich in stem and progenitor cells. In this study we tested whether intravenously infused HUCBC enter brain, survive, differentiate, and improve neurological functional recovery after stroke in rats. In addition, we tested whether ischemic brain tissue extract selectively induces chemotaxis of HUCBC in vitro.
Adult male Wistar rats were subjected to transient (2-hour) middle cerebral artery occlusion (MCAO). Experimental groups were as follows: group 1, MCAO alone (n=5); group 2, 3x10(6) HUCBC injected into tail vein at 24 hours after MCAO (n=6) (animals of groups 1 and 2 were killed at 14 days after MCAO); group 3, MCAO alone (n=5); group 4, MCAO injected with PBS at 1 day after stroke (n=8); and group 5, 3x10(6) HUCBC injected into tail vein at 7 days after MCAO (n=5). Rats of groups 3, 4, and 5 were killed at 35 days after MCAO. Behavioral tests (rotarod and Modified Neurological Severity Score [mNSS]) were performed. Immunohistochemical staining was used to identify cells derived from HUCBC. Chemotactic activity of ischemia brain tissue extracts toward HUCBC at different time points was evaluated in vitro.
Treatment at 24 hours after MCAO with HUCBC significantly improved functional recovery, as evidenced by the rotarod test and mNSS (P<0.05). Treatment at 7 days after MCAO with HUCBC significantly improved function only on the mNSS (P<0.05). Some HUCBC were reactive for the astrocyte marker glial fibrillary acidic protein and the neuronal markers NeuN and microtubule-associated protein 2. In vitro, significant HUCBC migration activity was present at 24 hours after MCAO (P<0.01) compared with normal brain tissue.
Intravenously administered HUCBC enter brain, survive, migrate, and improve functional recovery after stroke. HUCBC transplantation may provide a cell source to treat stroke.</description><subject>Animals</subject><subject>Behavior, Animal</subject><subject>Biological and medical sciences</subject><subject>Brain - cytology</subject><subject>Brain Ischemia - physiopathology</subject><subject>Cell Differentiation</subject><subject>Cell Extracts - pharmacology</subject><subject>Cell Survival</subject><subject>Chemotaxis - drug effects</subject><subject>Cord Blood Stem Cell Transplantation - methods</subject><subject>Fetal Blood - cytology</subject><subject>Fetal Blood - physiology</subject><subject>Humans</subject><subject>Infarction, Middle Cerebral Artery - physiopathology</subject><subject>Infarction, Middle Cerebral Artery - psychology</subject><subject>Infarction, Middle Cerebral Artery - therapy</subject><subject>Infusions, Intravenous</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neurology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Stroke - physiopathology</subject><subject>Stroke - psychology</subject><subject>Stroke - therapy</subject><subject>Vascular diseases and vascular malformations of the nervous system</subject><issn>0039-2499</issn><issn>1524-4628</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><recordid>eNpdkUFr3DAQRkVISbZJjrkWUUhvTjSybMnHEtJ2IdBLczayNGKV2NJWshfy76OwhkBOgtGbx8x8hFwDuwVo4W6XARjcsk7VrTwhG2i4qETL1SnZMFZ3FRddd06-5vzMGOO1as7IeensOKvFhvhtmJM-YIhLptpOPvhcCrOPgUZHd8ukA12mwY_e6JGamCwdxhgtTWgXg5kOuNMHH1P5tei88XMRuRkTLaL4gtQHWoT5knxxesx4tb4X5OnXw7_7P9Xj39_b-5-PlRFKzZWCAQcBHaIyShkBltfCGodWWdZAKxtpaivKsgYlKmVRyoI4yaQTKHR9QX4cvfsU_y-Y537y2eA46oBlyV5y3kgAUcDvn8DnuKRQZuuhk4q1TKoCVUfIpJhzQtfvk590eu2B9e8B9McA-mMAhf-2SpdhQvtBrxcvwM0K6Fwu6pIOxucPTgDvGoD6Dbu1jx0</recordid><startdate>20011101</startdate><enddate>20011101</enddate><creator>JIELI CHEN</creator><creator>SANBERG, Paul R</creator><creator>YI LI</creator><creator>LEI WANG</creator><creator>MEI LU</creator><creator>WILLING, Allison E</creator><creator>SANCHEZ-RAMOS, Juan</creator><creator>CHOPP, Michael</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>20011101</creationdate><title>Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats</title><author>JIELI CHEN ; SANBERG, Paul R ; YI LI ; LEI WANG ; MEI LU ; WILLING, Allison E ; SANCHEZ-RAMOS, Juan ; CHOPP, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-81beb419ee8c88c41d234dcfed8d0516757c3d4367ce7e88de77d23f707f4e4a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Behavior, Animal</topic><topic>Biological and medical sciences</topic><topic>Brain - cytology</topic><topic>Brain Ischemia - physiopathology</topic><topic>Cell Differentiation</topic><topic>Cell Extracts - pharmacology</topic><topic>Cell Survival</topic><topic>Chemotaxis - drug effects</topic><topic>Cord Blood Stem Cell Transplantation - methods</topic><topic>Fetal Blood - cytology</topic><topic>Fetal Blood - physiology</topic><topic>Humans</topic><topic>Infarction, Middle Cerebral Artery - physiopathology</topic><topic>Infarction, Middle Cerebral Artery - psychology</topic><topic>Infarction, Middle Cerebral Artery - therapy</topic><topic>Infusions, Intravenous</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neurology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Stroke - physiopathology</topic><topic>Stroke - psychology</topic><topic>Stroke - therapy</topic><topic>Vascular diseases and vascular malformations of the nervous system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JIELI CHEN</creatorcontrib><creatorcontrib>SANBERG, Paul R</creatorcontrib><creatorcontrib>YI LI</creatorcontrib><creatorcontrib>LEI WANG</creatorcontrib><creatorcontrib>MEI LU</creatorcontrib><creatorcontrib>WILLING, Allison E</creatorcontrib><creatorcontrib>SANCHEZ-RAMOS, Juan</creatorcontrib><creatorcontrib>CHOPP, Michael</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Stroke (1970)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>JIELI CHEN</au><au>SANBERG, Paul R</au><au>YI LI</au><au>LEI WANG</au><au>MEI LU</au><au>WILLING, Allison E</au><au>SANCHEZ-RAMOS, Juan</au><au>CHOPP, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats</atitle><jtitle>Stroke (1970)</jtitle><addtitle>Stroke</addtitle><date>2001-11-01</date><risdate>2001</risdate><volume>32</volume><issue>11</issue><spage>2682</spage><epage>2688</epage><pages>2682-2688</pages><issn>0039-2499</issn><eissn>1524-4628</eissn><coden>SJCCA7</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Human umbilical cord blood cells (HUCBC) are rich in stem and progenitor cells. In this study we tested whether intravenously infused HUCBC enter brain, survive, differentiate, and improve neurological functional recovery after stroke in rats. In addition, we tested whether ischemic brain tissue extract selectively induces chemotaxis of HUCBC in vitro.
Adult male Wistar rats were subjected to transient (2-hour) middle cerebral artery occlusion (MCAO). Experimental groups were as follows: group 1, MCAO alone (n=5); group 2, 3x10(6) HUCBC injected into tail vein at 24 hours after MCAO (n=6) (animals of groups 1 and 2 were killed at 14 days after MCAO); group 3, MCAO alone (n=5); group 4, MCAO injected with PBS at 1 day after stroke (n=8); and group 5, 3x10(6) HUCBC injected into tail vein at 7 days after MCAO (n=5). Rats of groups 3, 4, and 5 were killed at 35 days after MCAO. Behavioral tests (rotarod and Modified Neurological Severity Score [mNSS]) were performed. Immunohistochemical staining was used to identify cells derived from HUCBC. Chemotactic activity of ischemia brain tissue extracts toward HUCBC at different time points was evaluated in vitro.
Treatment at 24 hours after MCAO with HUCBC significantly improved functional recovery, as evidenced by the rotarod test and mNSS (P<0.05). Treatment at 7 days after MCAO with HUCBC significantly improved function only on the mNSS (P<0.05). Some HUCBC were reactive for the astrocyte marker glial fibrillary acidic protein and the neuronal markers NeuN and microtubule-associated protein 2. In vitro, significant HUCBC migration activity was present at 24 hours after MCAO (P<0.01) compared with normal brain tissue.
Intravenously administered HUCBC enter brain, survive, migrate, and improve functional recovery after stroke. HUCBC transplantation may provide a cell source to treat stroke.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>11692034</pmid><doi>10.1161/hs1101.098367</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Behavior, Animal Biological and medical sciences Brain - cytology Brain Ischemia - physiopathology Cell Differentiation Cell Extracts - pharmacology Cell Survival Chemotaxis - drug effects Cord Blood Stem Cell Transplantation - methods Fetal Blood - cytology Fetal Blood - physiology Humans Infarction, Middle Cerebral Artery - physiopathology Infarction, Middle Cerebral Artery - psychology Infarction, Middle Cerebral Artery - therapy Infusions, Intravenous Male Medical sciences Neurology Rats Rats, Wistar Stroke - physiopathology Stroke - psychology Stroke - therapy Vascular diseases and vascular malformations of the nervous system |
title | Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats |
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