Brain-derived neurotrophic factor-transfected and nontransfected 3T3 fibroblasts enhance migratory neuroblasts and functional restoration in mice with intracerebral hemorrhage

TY - JOUR

T1 - Brain-derived neurotrophic factor-transfected and nontransfected 3T3 fibroblasts enhance migratory neuroblasts and functional restoration in mice with intracerebral hemorrhage

AU - Chen, Shiu Jau

AU - Tsai, Jui Chang

AU - Lin, Chung Yi

AU - Chang, Cheng Kuei

AU - Tseng, Tai Hsiang

AU - Chien, Chung Liang

PY - 2012/12

Y1 - 2012/12

N2 - Neurogenesis via the activation of endogenous neural progenitor cells is a potential treatment strategy for brain injury, including intracerebral hemorrhage (ICH). We assessed the efficacy of combined cell and brain-derived neurotrophic factor (BDNF) treatment in a mouse model of ICH induced by intracerebral collagenase injection. Complementary DNAs of mouse BDNF were transfected into cell lines of 3T3 fibroblasts. The expression and bioactivity of BDNF were analyzed by immunocytochemistry, Western blot, ELISA, and functional assays. Hematoma area and brain tissue losswere assessed by magnetic resonance imaging. The BDNF-transfected or nontransfected 3T3 fibroblasts were implanted as a growth factor source in mice with ICH. Neurogenesis and functional recovery were evaluated 15 days after ICH. The BDNF-treated mice had the most doublecortin-positive cells near lesions and the least brain tissue loss in all groups. Both cell treatment groups had abundant newly proliferative glial fibrillary acidic protein-positive cells and better functional improvement than controls. These results indicate that fibroblast transplantation, together with recombinant BDNF treatment, after ICH is beneficial in mice. The early functional recovery may result from the growth factors that are provided or evoked by the implanted grafts. These results suggest a potential approach for combining gene and cell therapy for ICH treatment.

AB - Neurogenesis via the activation of endogenous neural progenitor cells is a potential treatment strategy for brain injury, including intracerebral hemorrhage (ICH). We assessed the efficacy of combined cell and brain-derived neurotrophic factor (BDNF) treatment in a mouse model of ICH induced by intracerebral collagenase injection. Complementary DNAs of mouse BDNF were transfected into cell lines of 3T3 fibroblasts. The expression and bioactivity of BDNF were analyzed by immunocytochemistry, Western blot, ELISA, and functional assays. Hematoma area and brain tissue losswere assessed by magnetic resonance imaging. The BDNF-transfected or nontransfected 3T3 fibroblasts were implanted as a growth factor source in mice with ICH. Neurogenesis and functional recovery were evaluated 15 days after ICH. The BDNF-treated mice had the most doublecortin-positive cells near lesions and the least brain tissue loss in all groups. Both cell treatment groups had abundant newly proliferative glial fibrillary acidic protein-positive cells and better functional improvement than controls. These results indicate that fibroblast transplantation, together with recombinant BDNF treatment, after ICH is beneficial in mice. The early functional recovery may result from the growth factors that are provided or evoked by the implanted grafts. These results suggest a potential approach for combining gene and cell therapy for ICH treatment.

KW - Brain-derived neurotrophic factor

KW - Fibroblast transplantation

KW - Intracerebral hemorrhage

KW - Neurogenesis

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U2 - 10.1097/NEN.0b013e3182779e96

DO - 10.1097/NEN.0b013e3182779e96

M3 - Article

VL - 71

SP - 1123

EP - 1136

JO - Journal of Neuropathology and Experimental Neurology

JF - Journal of Neuropathology and Experimental Neurology

SN - 0022-3069

IS - 12

ER -