4.7 Article

Intracerebral transplantation of bone marrow with BDNF after MCAo in rat

Journal

NEUROPHARMACOLOGY
Volume 39, Issue 5, Pages 711-716

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0028-3908(00)00006-X

Keywords

middle cerebral artery occlusion; bone marrow; transplantation; brain-derived neurotropic factor; behavioral tests

Funding

  1. NINDS NIH HHS [P01 NS23393, R01 NS35504] Funding Source: Medline
  2. NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P01NS023393, R01NS035504] Funding Source: NIH RePORTER

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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 2 h of MCAo, received grafts at 24 h and were sacrificed at 7 days 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 7 days 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. (C) 2000 Elsevier Science Ltd. All rights reserved.

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