Intracerebral transplantation of bone marrow with BDNF after MCAo in rat.
We tested the hypothesis that a composite graft of fresh bone marrow (BM) along with brain-derived neurotrophic factor (BDNF), transplanted into the ischemic boundary zone (IBZ) of rat brain, facilitates BM cells to survive and differentiate, and improves functional recovery after middle cerebral artery occlusion (MCAo). The fresh BM was harvested from adult rats injected with bromodeoxyuridine (BrdU) as a tracer. Rats (n=37) were subjected to 2h of MCAo, received grafts at 24h and were sacrificed at 7days after MCAo. Test groups consisted of: (1) control - MCAo alone (n=9); (2) injection of phosphate buffered saline (n=4); (3) transplantation of BM (n=8); (4) injection of BDNF (n=7); and (5) transplantation of BM with BDNF (n=9) into the IBZ. Immunohistochemistry was used to identify cells derived from the BM stem cells. Behavioral tests (rotarod motor test; adhesive-removal somatosensory test) were performed before and 7days after MCAo. The data indicate that intracerebral grafting of a combination of BM with BDNF enhances differentiation of BM cells and significantly improves motor recovery of rotarod (P<0.05) and adhesive-removal (P<0.05) tests. We anticipate that BM along with neurotrophic factors may provide a powerful autoplastic therapy for human neurological injury and degenerative disorders.
Chen
J
J
Henry Ford Health Sciences Center, Department of Neurology, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
Li
Y
Y
Chopp
M
M
D000818:Animals; D034961:Antigens, Nuclear; D001522:Behavior, Animal / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods*; D001921:Brain / Q000098:blood supply / Q000473:pathology* / Q000601:surgery; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage*; D001973:Bromodeoxyuridine; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006085:Graft Survival / Q000187:drug effects*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000628:therapy*; D007276:Injections, Intraventricular; D008297:Male; D009687:Nuclear Proteins / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects
D034961:Antigens, Nuclear; D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D009687:Nuclear Proteins; D001973:Bromodeoxyuridine