Intracerebral xenografts of mouse bone marrow cells in adult rats facilitate restoration of cerebral blood flow and blood-brain barrier.
We examined in the present study alterations in cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability following intrastriatal transplantation of mouse bone marrow stromal cells (BMSCs) or saline infusion in adult Sprague-Dawley rats. Laser Doppler revealed that transplanted animals exhibited near normal cerebral blood flow (CBF, 150 perfusion units) at a much earlier period post-transplantation (day 4) compared to animals that received saline infusion (day 12) (p's<0.05). Similarly, Evans Blue assay demonstrated that transplanted animals exhibited near complete BBB reconstitution at day 5 post-transplantation, whereas animals that received saline infusion continued to display a compromised BBB up to 11 days post-transplantation. Transplanted animals displayed a cell dose-dependent CBF and BBB restoration. Enzyme-linked immunosorbent assay (ELISA) of transplanted BMSCs revealed elevated levels of transforming growth factor-beta superfamily of neurotrophic factors. Moreover, despite the absence of immunosuppression in this cross-species transplantation, at least in the acute phase (12 days post-transplantation), surviving xenografts were detected during periods of restored CBF and BBB permeability. These observations suggest that restoration of CBF and BBB permeability accompanies the reported functional outcomes associated with intracerebral transplantation of BMSCs.
Borlongan
Cesario V
CV
Department of Neurology, Medical College of Georgia, Augusta, GA 30912-3200, USA.
Lind
Jeffrey G
JG
Dillon-Carter
Ora
O
Yu
Guolong
G
Hadman
Martin
M
Cheng
Charles
C
Carroll
James
J
Hess
David C
DC
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D001930:Brain Injuries / Q000601:surgery; D002199:Capillary Permeability / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005070:Evans Blue; D049452:Green Fluorescent Proteins; D017078:Laser-Doppler Flowmetry / Q000379:methods; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology; D013238:Stereotaxic Techniques; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000379:methods
D008164:Luminescent Proteins; D009414:Nerve Growth Factors; D049452:Green Fluorescent Proteins; D005070:Evans Blue