In vivo gene transfer to cerebral white matter lesions with a recombinant adenovirus vector.
Ischemic white matter lesions have been reported in rats after bilateral common carotid ligation (BCAL). Previously, comparing normotensive rats (WKY) with spontaneously hypertensive rats (SHR), we too found that sustained moderate ischemia with spontaneous hypertension accelerated the formation of ischemic white matter lesions. In this study, we explored the feasibility of gene therapy for lesioned white matter by means of an adenovirus vector expressing a reporter gene, LacZ. Using sham-operated and hypoperfused SHR as well as sham-operated and hypoperfused WKY, we demonstrated that (i) adenovirus vectors could deliver a foreign gene into oligodendrocytes and astrocytes in the cerebral white matter; (ii) the transduction efficiency was most effective in SHR after BCAL; and (iii) the level of alpha(V)-integrin was significantly correlated with adenoviral transduction efficiency.
Masumura
M
M
c/o National Cardiovascular Center, BF Research Institute, 7-1, 5-Chome, Fujishiro-dai, Suita, Osaka 565-0873, Japan. Makoto_Masumura@suntory.co.jp
Hata
R
R
Uetsuki
T
T
Nishimura
I
I
Nagai
Y
Y
Sawada
T
T
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000502:physiology / Q000821:virology; D002540:Cerebral Cortex / Q000502:physiology* / Q000821:virology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007150:Immunohistochemistry; D008297:Male; D009836:Oligodendroglia / Q000502:physiology / Q000821:virology; D009842:Oligopeptides / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D019030:Receptors, Vitronectin / Q000378:metabolism*; D014161:Transduction, Genetic / Q000379:methods
D009842:Oligopeptides; D019030:Receptors, Vitronectin; C047981:arginyl-glycyl-aspartic acid