Document Detail


Intravenous multipotent adult progenitor cell therapy for traumatic brain injury: preserving the blood brain barrier via an interaction with splenocytes.
MedLine Citation:
PMID:  20637752     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent investigation has shown an interaction between transplanted progenitor cells and resident splenocytes leading to the modulation of the immunologic response in neurological injury. We hypothesize that the intravenous injection of multipotent adult progenitor cells (MAPC) confers neurovascular protection after traumatic brain injury through an interaction with resident splenocytes, subsequently leading to preservation of the blood brain barrier. Four groups of rats underwent controlled cortical impact injury (3 groups) or sham injury (1 group). MAPC were injected via the tail vein at two doses (2*10(6) MAPC/kg or 10*10(6) MAPC/kg) 2 and 24h after injury. Blood brain barrier permeability was assessed by measuring Evans blue dye extravasation (n=6/group). Additionally, splenic mass was measured (n=12/group) followed by splenocyte characterization (n=9/group) including: cell cycle analysis (n=6/group), apoptosis index (n=6/group), cell proliferation (n=6/group), and inflammatory cytokine measurements (n=6/group). Vascular architecture was determined by immunohistochemistry (n=3/group). Traumatic brain injury results in a decrease in splenic mass and increased blood brain barrier permeability. Intravenous infusion of MAPC preserved splenic mass and returned blood brain barrier permeability towards control sham injured levels. Splenocyte characterization indicated an increase in the number and proliferative rate of CD4+ T cells as well as an increase in IL-4 and IL-10 production in stimulated splenocytes isolated from the MAPC treatment groups. Immunohistochemistry demonstrated stabilization of the vascular architecture in the peri-lesion area. Traumatic brain injury causes a reduction in splenic mass that correlates with an increase in circulating immune cells leading to increased blood brain barrier permeability. The intravenous injection of MAPC preserves splenic mass and the integrity of the blood brain barrier. Furthermore, the co-localization of transplanted MAPC and resident CD4+ splenocytes is associated with a global increase in IL-4 and IL-10 production and stabilization of the cerebral microvasculature tight junction proteins.
Authors:
Peter A Walker; Shinil K Shah; Fernando Jimenez; Michael H Gerber; Hasen Xue; Rochelle Cutrone; Jason A Hamilton; Robert W Mays; Robert Deans; Shibani Pati; Pramod K Dash; Charles S Cox
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-07-15
Journal Detail:
Title:  Experimental neurology     Volume:  225     ISSN:  1090-2430     ISO Abbreviation:  Exp. Neurol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-13     Completed Date:  2010-10-01     Revised Date:  2012-02-16    
Medline Journal Info:
Nlm Unique ID:  0370712     Medline TA:  Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  341-52     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Surgery, University of Texas Medical School at Houston, Houston, TX, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult Stem Cells / transplantation*
Analysis of Variance
Animals
Blood-Brain Barrier / metabolism*,  pathology
Brain Injuries / metabolism,  pathology,  therapy*
CD4-Positive T-Lymphocytes / cytology
Cell Count
Cell Proliferation
Cells, Cultured
Immunohistochemistry
Inflammation / metabolism,  pathology
Infusions, Intravenous
Interleukin-10 / metabolism
Interleukin-4 / metabolism
Male
Organ Size
Permeability
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Spleen / cytology*,  metabolism,  pathology
Stem Cell Transplantation / methods*
Grant Support
ID/Acronym/Agency:
M01 RR 02558/RR/NCRR NIH HHS; T32 GM 08 79201/GM/NIGMS NIH HHS; T32 GM008792-09/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
130068-27-8/Interleukin-10; 207137-56-2/Interleukin-4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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