Adenovirus-mediated gene transfer to ischemic brain: ischemic flow threshold for transgene expression.
Stroke
; 32(4): 1043-7, 2001 Apr.
Article
en En
| MEDLINE
| ID: mdl-11283409
ABSTRACT
BACKGROUND AND PURPOSE:
Gene therapy may be a promising approach for treatment of brain ischemia, although protein synthesis is generally inhibited in ischemic conditions. Our goal in this study was to examine effects of brain ischemia on transgene expression of adenovirus-mediated gene transfer to ischemic brain.METHODS:
Brain ischemia was produced by photochemical occlusion of the distal middle cerebral artery of spontaneously hypertensive rats (n=15). Ninety minutes after ischemia, adenoviral vectors encoding bacterial beta-galactosidase were injected into ipsilateral (nonischemic [I-n], peri-ischemic [I-p], and ischemic core [I-c] areas) and contralateral parietal (C) cortices. Cerebral blood flow before and during ischemia at each injected area was measured by laser-Doppler flowmetry. Expression of transgene was detected by histochemistry for semiquantitative scoring or by biochemical assay for quantitative analysis.RESULTS:
Blood flow to the cortex decreased to 72+/-10% (mean+/-SEM) at I-n, 41+/-6% at I-p, and 23+/-3% at I-c after 10 minutes of ischemia. Expression of the reporter gene was consistently detected at C and I-n at each survival period. The semiquantitative score for transgene expression decreased according to severity of ischemia (C, 2.3; I-n, 2.6; I-p, 1.1; I-c, 0.3; mean values). beta-Galactosidase activity detected by chemiluminescent assay revealed that the values (mean+/-SEM) in the ischemic area (I-p, 15.9+/-9.2 mU/mg protein; I-c, 1.3+/-0.5) were significantly smaller than that of the nonischemic area (C, 45.4+/-6.9). Analysis of cerebral blood flow at I-p revealed that cerebral blood flow threshold for transgene expression was approximately 40% of the resting value.CONCLUSIONS:
Adenovirus-mediated gene transfer into the ischemic brain provided effective expression of transgene at the nonischemic and peri-ischemic areas. Gene transfer to the ischemic brain may be a promising approach for treatment of ischemic penumbra.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
/
Isquemia Encefálica
/
Circulación Cerebrovascular
/
Adenoviridae
/
Transgenes
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Stroke
Año:
2001
Tipo del documento:
Article
País de afiliación:
Japón