Anti-monocyte chemoattractant protein-1 gene therapy protects against focal brain ischemia in hypertensive rats

Yasuhiro Kumai, Hiroaki Ooboshi, Junichi Takada, Masahiro Kamouchi, Takanari Kitazono, Kensuke Egashira, Setsuro Ibayashi, Mitsuo Iida

Research output: Contribution to journalArticle

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Abstract

Monocyte chemoattractant protein-1 (MCP-1) is expressed in the ischemic cortex after focal brain ischemia and appears to exacerbate ischemic damage. The authors examined the effect of gene transfer of dominant negative MCP-1, called 7ND, 90 minutes after induction of focal brain ischemia in hypertensive rats. Adenoviral vectors encoding mutant MCP-1 (Ad7ND; n = 11), or Escherichia coli β-galactosidase (AdlacZ; n = 17) as control were injected into the lateral ventricle of male spontaneously hypertensive rats. Both AdlacZ (n = 12) and Ad7ND (n = 6) administration provided transgene expression as early as 6 hours after injection and the expression further increased on day 1, followed by a sustained detection on day 5. Five days after ischemia, infarct volume (75 ± 13 mm3, n = 5, mean ±SD) significantly reduced to 72% of control (104 ± 22 mm3, n = 5, P < 0.05) by 7ND gene transfer. Numbers of leukocytes in the vessels (48.3 ± 32.9/cm 2) and macrophage/monocyte infiltration (475.2 ± 125.5/mm 2) of the infarct area in the Ad7ND group were significantly less than those measured in the AdlacZ group (143.8 ± 72.1/cm2 and 671.8 ± 125.5/mm2, P < 0.05, respectively). In summary, the postischemic gene transfer of dominant negative MCP-1 attenuated the infarct volume and infiltration of inflammatory cells, suggesting potential usefulness of the anti-MCP-1 gene therapy.

Original languageEnglish
Pages (from-to)1359-1368
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume24
Issue number12
DOIs
Publication statusPublished - Dec 2004

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Chemokine CCL2
Brain Ischemia
Genetic Therapy
Dominant Genes
Galactosidases
Lateral Ventricles
Inbred SHR Rats
Mutant Proteins
Transgenes
Leukocyte Count
Monocytes
Ischemia
Macrophages
Escherichia coli
Injections
Genes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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Anti-monocyte chemoattractant protein-1 gene therapy protects against focal brain ischemia in hypertensive rats. / Kumai, Yasuhiro; Ooboshi, Hiroaki; Takada, Junichi; Kamouchi, Masahiro; Kitazono, Takanari; Egashira, Kensuke; Ibayashi, Setsuro; Iida, Mitsuo.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 24, No. 12, 12.2004, p. 1359-1368.

Research output: Contribution to journalArticle

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