http://journals.lww.com/jneuropath/Abstract/publishahead/Brain_Derived_Neurotrophic_Factor_Transfected_and.99525.aspx
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.
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