Adenovirus-mediated gene transfer to ischemic brain ischemic flow threshold for transgene expression

Hiroaki Ooboshi, Setsuro Ibayashi, Junichi Takada, Hiroshi Yao, Takanari Kitazono, Masatoshi Fujishima

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


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 β-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). β-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.

Original languageEnglish
Pages (from-to)1043-1047
Number of pages5
Issue number4
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing


Dive into the research topics of 'Adenovirus-mediated gene transfer to ischemic brain ischemic flow threshold for transgene expression'. Together they form a unique fingerprint.

Cite this