Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1123-1136 |
| Number of pages | 14 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Volume | 71 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 2012 |
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Keywords
- Brain-derived neurotrophic factor
- Fibroblast transplantation
- Intracerebral hemorrhage
- Neurogenesis
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Clinical Neurology
- Neurology
- Cellular and Molecular Neuroscience
Cite this
Brain-derived neurotrophic factor-transfected and nontransfected 3T3 fibroblasts enhance migratory neuroblasts and functional restoration in mice with intracerebral hemorrhage. / Chen, Shiu Jau; Tsai, Jui Chang; Lin, Chung Yi; Chang, Cheng Kuei; Tseng, Tai Hsiang; Chien, Chung Liang.
In: Journal of Neuropathology and Experimental Neurology, Vol. 71, No. 12, 12.2012, p. 1123-1136.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=84870802914&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870802914&partnerID=8YFLogxK
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 -