RRC ID 191
Author Takada J, Ooboshi H, Ago T, Kitazono T, Yao H, Kadomatsu K, Muramatsu T, Ibayashi S, Iida M.
Title Postischemic gene transfer of midkine, a neurotrophic factor, protects against focal brain ischemia.
Journal Gene Ther.
Abstract Gene therapy may be a promising approach for treatment of brain ischemia. In this study, we examined the effect of postischemic gene transfer of midkine, a heparin-binding neurotrophic factor, using a focal brain ischemia model with the photothrombotic occlusion method. At 90 min after induction of brain ischemia in spontaneously hypertensive rats, a replication-deficient recombinant adenovirus encoding mouse midkine (AdMK, n=7) or a control vector encoding beta-galactosidase (Adbetagal, n=7) was injected into the lateral ventricle ipsilateral to ischemia. At 2 days after ischemia, we determined infarct volume by 2,3,5-triphenyltetrazolium chloride staining. There were no significant differences in cerebral blood flow 1 h after ischemia between AdMK and Adbetagal groups. Infarct volume of AdMK group was 51+/-27 mm3, which was significantly smaller than that of Adbetagal group (86+/-27 mm3, P<0.05). TUNEL-positive and cleaved caspase-3-positive cells in the periischemic area of AdMK-treated rats were significantly fewer than those in Adbetagal-treated rats, suggesting that the reduction of infarct volume by midkine was partly mediated by its antiapoptotic action. Thus, gene transfer of midkine to the ischemic brain may be effective in the treatment of brain ischemia.
Volume 12(6)
Pages 487-93
Published 2005-3
DOI 10.1038/sj.gt.3302434
PII 3302434
PMID 15703767
MeSH Adenoviridae / genetics* Animals Apoptosis Brain / metabolism Brain / pathology Brain Ischemia / metabolism Brain Ischemia / pathology Brain Ischemia / therapy* Cytokines / analysis Cytokines / genetics* Cytokines / metabolism Genetic Therapy / methods* Genetic Vectors / administration & dosage* Genetic Vectors / genetics Immunohistochemistry / methods Male Midkine Models, Animal Rats Rats, Inbred SHR beta-Galactosidase / genetics
IF 3.749
Times Cited 29
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL BIOTECHNOLOGY & APPLIED MICROBIOLOGY GENETICS & HEREDITY BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Rats