Midkine gene transfer protects against focal brain ischemia and augments neurogenesis

Eiichi Ishikawa, Hiroaki Ooboshi, Yasuhiro Kumai, Junnichi Takada, Kuniyuki Nakamura, Tetsuro Ago, Hiroshi Sugimori, Masahiro Kamouchi, Takanari Kitazono, Setsuro Ibayashi, Mitsuo Iida

研究成果: ジャーナルへの寄稿学術誌査読

24 被引用数 (Scopus)


Background and purpose: Midkine is a heparin-binding growth factor having various biological activities including chemotaxis of inflammatory cells, angiogenesis and migration of neuronal cells. These biological activities are expected to have a great impact on the pathology of brain infarction in subacute phase. Therefore, we investigated the effect of post-ischemic gene transfer of midkine in the phase. Methods: Brain ischemia was produced by the photothrombotic distal middle cerebral artery occlusion in spontaneously hypertensive rats. We measured cerebral blood flow by laser Doppler flowmetry. At 90 min after induction of brain ischemia, adenovirus vectors encoding mouse midkine (AdMK) or enhanced green fluorescence protein (AdGFP) were injected into the lateral ventricle. At 7 days after brain ischemia, the infarct volume, angiogenesis, inflammation and neuronal regeneration were evaluated. Results: There were no differences in cerebral blood flow changes between AdMK and AdGFP groups. However, infarct volume of AdMK group was significantly smaller than AdGFP group by 33%. The vascular density, the numbers of leukocytes in blood vessels, infiltrated macrophages and proliferated neuronal precursor cells were not significantly different between both groups. Contrastingly the numbers of migrating neuronal precursor cells toward the brain infarction were significantly increased in AdMK group than AdGFP group. Conclusions: Neuroprotective effect of midkine gene transfer persisted until the subacute phase of brain infarction. Midkine may contribute to neuronal regeneration. These results suggest the usefulness of midkine gene transfer for treatment of brain infarction.

ジャーナルJournal of the Neurological Sciences
出版ステータス出版済み - 10月 15 2009

!!!All Science Journal Classification (ASJC) codes

  • 神経学
  • 臨床神経学


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