title: Brain-derived neurotrophic factor from bone marrow-derived cells promotes post-injury repair of peripheral nerve.
abstract: Brain-derived neurotrophic factor (BDNF) stimulates peripheral nerve regeneration. However, the origin of BNDF and its precise effect on nerve repair have not been clarified. In this study, we examined the role of BDNF from bone marrow-derived cells (BMDCs) in post-injury nerve repair. Control and heterozygote BDNF knockout mice (BDNF+/-) received a left sciatic nerve crush using a cerebral blood clip. Especially, for the evaluation of BDNF from BMDCs, studies with bone marrow transplantation (BMT) were performed before the injury. We evaluated nerve function using a rotarod test, sciatic function index (SFI), and motor nerve conduction velocity (MNCV) simultaneously with histological nerve analyses by immunohistochemistry before and after the nerve injury until 8 weeks. BDNF production was examined by immunohistochemistry and mRNA analyses. After the nerve crush, the controls showed severe nerve dysfunction evaluated at 1 week. However, nerve function was gradually restored and reached normal levels by 8 weeks. By immunohistochemistry, BDNF expression was very faint before injury, but was dramatically increased after injury at 1 week in the distal segment from the crush site. BDNF expression was mainly co-localized with CD45 in BMDCs, which was further confirmed by the appearance of GFP-positive cells in the BMT study. Variant analysis of BDNF mRNA also confirmed this finding. BDNF+/- mice showed a loss of function with delayed histological recovery and BDNF+/+→BDNF+/- BMT mice showed complete recovery both functionally and histologically. These results suggested that the attenuated recovery of the BDNF+/- mice was rescued by the transplantation of BMCs and that BDNF from BMDCs has an essential role in nerve repair.
authors.affiliation: Department of Orthopaedic Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takemura
authors.forename: Shinji
authors.initials: S
authors.lastname: Imai
authors.forename: Hideto
authors.initials: H
authors.lastname: Kojima
authors.forename: Miwako
authors.initials: M
authors.lastname: Katagi
authors.forename: Isamu
authors.initials: I
authors.lastname: Yamakawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kasahara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Urabe
authors.forename: Tomoya
authors.initials: T
authors.lastname: Terashima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yasuda
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chan
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Matsusue
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010525:Peripheral Nerves / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D020196:Trauma, Nervous System / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor