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 language | English |
|---|---|
| Pages (from-to) | 1359-1368 |
| Number of pages | 10 |
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| Volume | 24 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 2004 |
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All Science Journal Classification (ASJC) codes
- Neurology
- Clinical Neurology
- Cardiology and Cardiovascular Medicine
Cite this
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 journal › Article
}
TY - JOUR
T1 - Anti-monocyte chemoattractant protein-1 gene therapy protects against focal brain ischemia in hypertensive rats
AU - Kumai, Yasuhiro
AU - Ooboshi, Hiroaki
AU - Takada, Junichi
AU - Kamouchi, Masahiro
AU - Kitazono, Takanari
AU - Egashira, Kensuke
AU - Ibayashi, Setsuro
AU - Iida, Mitsuo
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=10944231103&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10944231103&partnerID=8YFLogxK
U2 - 10.1097/01.WCB.0000143534.76388.3C
DO - 10.1097/01.WCB.0000143534.76388.3C
M3 - Article
C2 - 15625410
AN - SCOPUS:10944231103
VL - 24
SP - 1359
EP - 1368
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 12
ER -