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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
Main Authors: JIELI CHEN, SANBERG, Paul R, YI LI, LEI WANG, MEI LU, WILLING, Allison E, SANCHEZ-RAMOS, Juan, CHOPP, Michael
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container_end_page 2688
container_issue 11
container_start_page 2682
container_title Stroke (1970)
container_volume 32
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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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&lt;0.05). Treatment at 7 days after MCAO with HUCBC significantly improved function only on the mNSS (P&lt;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&lt;0.01) compared with normal brain tissue. Intravenously administered HUCBC enter brain, survive, migrate, and improve functional recovery after stroke. 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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&lt;0.05). Treatment at 7 days after MCAO with HUCBC significantly improved function only on the mNSS (P&lt;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&lt;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 &amp; 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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identifier ISSN: 0039-2499
ispartof Stroke (1970), 2001-11, Vol.32 (11), p.2682-2688
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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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