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

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)78-84
Number of pages7
JournalJournal of the Neurological Sciences
Volume285
Issue number1-2
DOIs
Publication statusPublished - Oct 15 2009

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Neurogenesis
Brain Ischemia
Brain Infarction
Cerebrovascular Circulation
Fluorescence
Genes
Blood Vessels
Regeneration
Proteins
Laser-Doppler Flowmetry
Lateral Ventricles
Middle Cerebral Artery Infarction
Neuroprotective Agents
Inbred SHR Rats
Chemotaxis
Leukocyte Count
Adenoviridae
Cell Movement
Heparin
midkine

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Midkine gene transfer protects against focal brain ischemia and augments neurogenesis. / Ishikawa, Eiichi; Ooboshi, Hiroaki; Kumai, Yasuhiro; Takada, Junnichi; Nakamura, Kuniyuki; Ago, Tetsuro; Sugimori, Hiroshi; Kamouchi, Masahiro; Kitazono, Takanari; Ibayashi, Setsuro; Iida, Mitsuo.

In: Journal of the Neurological Sciences, Vol. 285, No. 1-2, 15.10.2009, p. 78-84.

Research output: Contribution to journalArticle

Ishikawa, Eiichi ; Ooboshi, Hiroaki ; Kumai, Yasuhiro ; Takada, Junnichi ; Nakamura, Kuniyuki ; Ago, Tetsuro ; Sugimori, Hiroshi ; Kamouchi, Masahiro ; Kitazono, Takanari ; Ibayashi, Setsuro ; Iida, Mitsuo. / Midkine gene transfer protects against focal brain ischemia and augments neurogenesis. In: Journal of the Neurological Sciences. 2009 ; Vol. 285, No. 1-2. pp. 78-84.
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abstract = "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.",
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AU - Ago, Tetsuro

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