Treatment of traumatic brain injury in mice with marrow stromal cells

Abstract This study was designed to investigate the potential beneficial effects of bone marrow stromal cell (MSC) treatment of traumatic brain injury (TBI) in mice. Twelve female C57BL/6J mice (weight, 21–26 g) were injured with controlled cortical impact and divided into 2 groups ( n = 6 each). Th...

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Veröffentlicht in:Brain research 2008-05, Vol.1208, p.234-239
Hauptverfasser: Qu, Changsheng, Mahmood, Asim, Lu, Dunyue, Goussev, Anton, Xiong, Ye, Chopp, Michael
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container_start_page 234
container_title Brain research
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creator Qu, Changsheng
Mahmood, Asim
Lu, Dunyue
Goussev, Anton
Xiong, Ye
Chopp, Michael
description Abstract This study was designed to investigate the potential beneficial effects of bone marrow stromal cell (MSC) treatment of traumatic brain injury (TBI) in mice. Twelve female C57BL/6J mice (weight, 21–26 g) were injured with controlled cortical impact and divided into 2 groups ( n = 6 each). The experimental group was injected with MSCs (0.3 × 106 ) intravenously one day after TBI, whereas the control group was injected with saline. MSCs were harvested from male mice, and male to female transplantation was performed to identify male donor cells within female recipient animals. This was achieved by localizing Y chromosomes within the female mice. Neurological function was assessed using the Morris water maze and foot fault tests. All mice were sacrificed 35 days after TBI. Brain sections were stained using in situ hybridization and immunohistochemistry to identify MSCs as well as to analyze vascular density following MSC treatment. Both modalities of testing demonstrated significant improvement in neurological function in the MSC-treated group compared to the saline-treated control group ( p < 0.05). Histologically, Y chromosome labeled MSCs were easily identified in the injured brain, localized primarily around the lesion boundary zone. There was also a significant increase in vascular density in the lesion boundary zone and hippocampus of MSC-treated mice compared to control mice. This is the first study to show beneficial effects of MSC treatment after TBI in mice.
doi_str_mv 10.1016/j.brainres.2008.02.042
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Twelve female C57BL/6J mice (weight, 21–26 g) were injured with controlled cortical impact and divided into 2 groups ( n = 6 each). The experimental group was injected with MSCs (0.3 × 106 ) intravenously one day after TBI, whereas the control group was injected with saline. MSCs were harvested from male mice, and male to female transplantation was performed to identify male donor cells within female recipient animals. This was achieved by localizing Y chromosomes within the female mice. Neurological function was assessed using the Morris water maze and foot fault tests. All mice were sacrificed 35 days after TBI. Brain sections were stained using in situ hybridization and immunohistochemistry to identify MSCs as well as to analyze vascular density following MSC treatment. Both modalities of testing demonstrated significant improvement in neurological function in the MSC-treated group compared to the saline-treated control group ( p &lt; 0.05). Histologically, Y chromosome labeled MSCs were easily identified in the injured brain, localized primarily around the lesion boundary zone. There was also a significant increase in vascular density in the lesion boundary zone and hippocampus of MSC-treated mice compared to control mice. This is the first study to show beneficial effects of MSC treatment after TBI in mice.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2008.02.042</identifier><identifier>PMID: 18384759</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>London: Elsevier B.V</publisher><subject>Adult and adolescent clinical studies ; Analysis of Variance ; Animals ; Antigens - metabolism ; Behavior, Animal - physiology ; Biological and medical sciences ; Bone Marrow Cells - physiology ; Bone Marrow Transplantation - methods ; Brain Injuries - therapy ; Disease Models, Animal ; Female ; Hindlimb - physiopathology ; Injuries of the nervous system and the skull. Diseases due to physical agents ; Marrow stromal cell (MSC) ; Maze Learning - physiology ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Neurology ; Organic mental disorders. Neuropsychology ; Psychology. Psychoanalysis. Psychiatry ; Psychomotor Performance ; Psychopathology. Psychiatry ; Rats ; Recovery of Function ; Stromal Cells - physiology ; Time Factors ; Traumas. Diseases due to physical agents ; Traumatic brain injury (TBI) ; von Willebrand Factor - immunology ; Y Chromosome - metabolism</subject><ispartof>Brain research, 2008-05, Vol.1208, p.234-239</ispartof><rights>2008</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c585t-90546c872731042f2dc099a018302f93751d310f15eb1778fe605053c034501d3</citedby><cites>FETCH-LOGICAL-c585t-90546c872731042f2dc099a018302f93751d310f15eb1778fe605053c034501d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006899308003594$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=20383762$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18384759$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qu, Changsheng</creatorcontrib><creatorcontrib>Mahmood, Asim</creatorcontrib><creatorcontrib>Lu, Dunyue</creatorcontrib><creatorcontrib>Goussev, Anton</creatorcontrib><creatorcontrib>Xiong, Ye</creatorcontrib><creatorcontrib>Chopp, Michael</creatorcontrib><title>Treatment of traumatic brain injury in mice with marrow stromal cells</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>Abstract This study was designed to investigate the potential beneficial effects of bone marrow stromal cell (MSC) treatment of traumatic brain injury (TBI) in mice. Twelve female C57BL/6J mice (weight, 21–26 g) were injured with controlled cortical impact and divided into 2 groups ( n = 6 each). The experimental group was injected with MSCs (0.3 × 106 ) intravenously one day after TBI, whereas the control group was injected with saline. MSCs were harvested from male mice, and male to female transplantation was performed to identify male donor cells within female recipient animals. This was achieved by localizing Y chromosomes within the female mice. Neurological function was assessed using the Morris water maze and foot fault tests. All mice were sacrificed 35 days after TBI. Brain sections were stained using in situ hybridization and immunohistochemistry to identify MSCs as well as to analyze vascular density following MSC treatment. Both modalities of testing demonstrated significant improvement in neurological function in the MSC-treated group compared to the saline-treated control group ( p &lt; 0.05). Histologically, Y chromosome labeled MSCs were easily identified in the injured brain, localized primarily around the lesion boundary zone. There was also a significant increase in vascular density in the lesion boundary zone and hippocampus of MSC-treated mice compared to control mice. This is the first study to show beneficial effects of MSC treatment after TBI in mice.</description><subject>Adult and adolescent clinical studies</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Antigens - metabolism</subject><subject>Behavior, Animal - physiology</subject><subject>Biological and medical sciences</subject><subject>Bone Marrow Cells - physiology</subject><subject>Bone Marrow Transplantation - methods</subject><subject>Brain Injuries - therapy</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Hindlimb - physiopathology</subject><subject>Injuries of the nervous system and the skull. Diseases due to physical agents</subject><subject>Marrow stromal cell (MSC)</subject><subject>Maze Learning - physiology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neurology</subject><subject>Organic mental disorders. Neuropsychology</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychomotor Performance</subject><subject>Psychopathology. Psychiatry</subject><subject>Rats</subject><subject>Recovery of Function</subject><subject>Stromal Cells - physiology</subject><subject>Time Factors</subject><subject>Traumas. Diseases due to physical agents</subject><subject>Traumatic brain injury (TBI)</subject><subject>von Willebrand Factor - immunology</subject><subject>Y Chromosome - metabolism</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk9v1DAQxS0EotvCV6hygVvC2I6T-FKBqlKQKnGgnC2vM6EOSVzspNV--07Ypfy59GRZ85vnN37D2CmHggOv3vXFNlo_RUyFAGgKEAWU4hnb8KYWeSVKeM42AFDljdbyiB2n1NNVSg0v2RFvZFPWSm_YxXVEO484zVnosjnaZbSzd9kv9cxP_RJ3dGSjd5jd-_kmG22M4T5LcwyjHTKHw5BesRedHRK-Ppwn7NvHi-vzT_nVl8vP5x-ucqcaNecaVFk5MlhLTm470TrQ2gLZAdFpWSveUqXjCre8rpsOK1CgpANZKqDaCTvb694u2xFbR7ajHcxt9ORqZ4L15t_K5G_M93BnZA0155wE3h4EYvi5YJrN6NM6gp0wLMlUmktd8fJJUJCeFrCC1R50MaQUsXt0w8GsUZne_I7KrFEZEIaGp8bTv2f503bIhoA3B8AmZ4cu2sn59MgJkI2sq1Xo_Z5D-vk7j9Ek53Fy2PqIbjZt8E97OftPwg1-8vTqD9xh6sMSJ8rVcJOowXxdF2vdK2hopZQu5QMj2smJ</recordid><startdate>20080507</startdate><enddate>20080507</enddate><creator>Qu, Changsheng</creator><creator>Mahmood, Asim</creator><creator>Lu, Dunyue</creator><creator>Goussev, Anton</creator><creator>Xiong, Ye</creator><creator>Chopp, Michael</creator><general>Elsevier B.V</general><general>Elsevier</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>7TK</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20080507</creationdate><title>Treatment of traumatic brain injury in mice with marrow stromal cells</title><author>Qu, Changsheng ; Mahmood, Asim ; Lu, Dunyue ; Goussev, Anton ; Xiong, Ye ; Chopp, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c585t-90546c872731042f2dc099a018302f93751d310f15eb1778fe605053c034501d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult and adolescent clinical studies</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Antigens - metabolism</topic><topic>Behavior, Animal - physiology</topic><topic>Biological and medical sciences</topic><topic>Bone Marrow Cells - physiology</topic><topic>Bone Marrow Transplantation - methods</topic><topic>Brain Injuries - therapy</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Hindlimb - physiopathology</topic><topic>Injuries of the nervous system and the skull. Diseases due to physical agents</topic><topic>Marrow stromal cell (MSC)</topic><topic>Maze Learning - physiology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neurology</topic><topic>Organic mental disorders. Neuropsychology</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychomotor Performance</topic><topic>Psychopathology. Psychiatry</topic><topic>Rats</topic><topic>Recovery of Function</topic><topic>Stromal Cells - physiology</topic><topic>Time Factors</topic><topic>Traumas. Diseases due to physical agents</topic><topic>Traumatic brain injury (TBI)</topic><topic>von Willebrand Factor - immunology</topic><topic>Y Chromosome - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qu, Changsheng</creatorcontrib><creatorcontrib>Mahmood, Asim</creatorcontrib><creatorcontrib>Lu, Dunyue</creatorcontrib><creatorcontrib>Goussev, Anton</creatorcontrib><creatorcontrib>Xiong, Ye</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>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qu, Changsheng</au><au>Mahmood, Asim</au><au>Lu, Dunyue</au><au>Goussev, Anton</au><au>Xiong, Ye</au><au>Chopp, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Treatment of traumatic brain injury in mice with marrow stromal cells</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2008-05-07</date><risdate>2008</risdate><volume>1208</volume><spage>234</spage><epage>239</epage><pages>234-239</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>Abstract This study was designed to investigate the potential beneficial effects of bone marrow stromal cell (MSC) treatment of traumatic brain injury (TBI) in mice. Twelve female C57BL/6J mice (weight, 21–26 g) were injured with controlled cortical impact and divided into 2 groups ( n = 6 each). The experimental group was injected with MSCs (0.3 × 106 ) intravenously one day after TBI, whereas the control group was injected with saline. MSCs were harvested from male mice, and male to female transplantation was performed to identify male donor cells within female recipient animals. This was achieved by localizing Y chromosomes within the female mice. Neurological function was assessed using the Morris water maze and foot fault tests. All mice were sacrificed 35 days after TBI. Brain sections were stained using in situ hybridization and immunohistochemistry to identify MSCs as well as to analyze vascular density following MSC treatment. Both modalities of testing demonstrated significant improvement in neurological function in the MSC-treated group compared to the saline-treated control group ( p &lt; 0.05). Histologically, Y chromosome labeled MSCs were easily identified in the injured brain, localized primarily around the lesion boundary zone. There was also a significant increase in vascular density in the lesion boundary zone and hippocampus of MSC-treated mice compared to control mice. This is the first study to show beneficial effects of MSC treatment after TBI in mice.</abstract><cop>London</cop><cop>Amsterdam</cop><cop>New York, NY</cop><pub>Elsevier B.V</pub><pmid>18384759</pmid><doi>10.1016/j.brainres.2008.02.042</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; Elsevier ScienceDirect Journals
subjects Adult and adolescent clinical studies
Analysis of Variance
Animals
Antigens - metabolism
Behavior, Animal - physiology
Biological and medical sciences
Bone Marrow Cells - physiology
Bone Marrow Transplantation - methods
Brain Injuries - therapy
Disease Models, Animal
Female
Hindlimb - physiopathology
Injuries of the nervous system and the skull. Diseases due to physical agents
Marrow stromal cell (MSC)
Maze Learning - physiology
Medical sciences
Mice
Mice, Inbred C57BL
Neurology
Organic mental disorders. Neuropsychology
Psychology. Psychoanalysis. Psychiatry
Psychomotor Performance
Psychopathology. Psychiatry
Rats
Recovery of Function
Stromal Cells - physiology
Time Factors
Traumas. Diseases due to physical agents
Traumatic brain injury (TBI)
von Willebrand Factor - immunology
Y Chromosome - metabolism
title Treatment of traumatic brain injury in mice with marrow stromal cells
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