PMID- 15625410
OWN - NLM
STAT- MEDLINE
DCOM- 20050114
LR  - 20121115
IS  - 0271-678X (Print)
IS  - 0271-678X (Linking)
VI  - 24
IP  - 12
DP  - 2004 Dec
TI  - Anti-monocyte chemoattractant protein-1 gene therapy protects against focal brain 
      ischemia in hypertensive rats.
PG  - 1359-68
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 
      beta-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 mm, 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/cm2) and macrophage/monocyte infiltration (475.2 +/- 125.5/mm2) 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.
FAU - Kumai, Yasuhiro
AU  - Kumai Y
AD  - Department of Medicine and Clinical Science, Graduate School of Medical Sciences, 
      Kyushu University, Fukuoka, Japan.
FAU - Ooboshi, Hiroaki
AU  - Ooboshi H
FAU - Takada, Junichi
AU  - Takada J
FAU - Kamouchi, Masahiro
AU  - Kamouchi M
FAU - Kitazono, Takanari
AU  - Kitazono T
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Ibayashi, Setsuro
AU  - Ibayashi S
FAU - Iida, Mitsuo
AU  - Iida M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cereb Blood Flow Metab
JT  - Journal of cerebral blood flow and metabolism : official journal of the 
      International Society of Cerebral Blood Flow and Metabolism
JID - 8112566
RN  - 0 (Chemokine CCL2)
RN  - EC 3.2.1.23 (beta-Galactosidase)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Brain Ischemia/genetics/metabolism/*pathology/*therapy
MH  - Cerebrovascular Circulation
MH  - Chemokine CCL2/*antagonists & inhibitors/genetics/metabolism
MH  - Gene Expression
MH  - *Genetic Therapy
MH  - Hypertension/physiopathology
MH  - Immunohistochemistry
MH  - Leukocytes/immunology
MH  - Macrophages/immunology
MH  - Male
MH  - Rats
MH  - Transgenes/genetics
MH  - beta-Galactosidase/genetics/metabolism
EDAT- 2004/12/31 09:00
MHDA- 2005/01/15 09:00
CRDT- 2004/12/31 09:00
PHST- 2004/12/31 09:00 [pubmed]
PHST- 2005/01/15 09:00 [medline]
PHST- 2004/12/31 09:00 [entrez]
AID - 00004647-200412000-00005 [pii]
AID - 10.1097/01.WCB.0000143534.76388.3C [doi]
PST - ppublish
SO  - J Cereb Blood Flow Metab. 2004 Dec;24(12):1359-68. doi: 
      10.1097/01.WCB.0000143534.76388.3C.