Bone marrow grafts restore cerebral blood flow and blood brain barrier in stroke rats.
We monitored alterations in cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability following middle cerebral artery occlusion (MCAo) and intrastriatal transplantation of mouse bone marrow stromal cells (BMSCs) or saline infusion in adult Sprague-Dawley rats. Laser Doppler and Evans Blue assay revealed that BMSC grafts dose-dependently restored CBF and BBB to near normal levels at a much earlier period (Days 4-5 post-MCAo) in transplanted stroke animals compared to stroke animals that received saline infusion (Days 11-14 post-MCAo). Xenografted BMSCs survived in the absence of immunosuppression, and elevated levels of transforming growth factor-beta superfamily of neurotrophic factors were detected in transplanted stroke animals. These data suggest that early restoration of CBF and BBB following transplantation of BMSCs could mediate the reported functional outcomes in stroke animals.
Borlongan
Cesario V
CV
Department of Neurology, Medical College of Georgia, 1120 15th Street, BI-3080, Augusta, GA 30912-3200, USA. cborlongan@mail.mcg.edu
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*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003342:Corpus Striatum / Q000098:blood supply / Q000503:physiopathology / Q000601:surgery; D004195:Disease Models, Animal; D006085:Graft Survival / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology / Q000628:therapy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D020521:Stroke / Q000503:physiopathology / Q000628:therapy*; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome; D015854:Up-Regulation / Q000502:physiology
D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta