TY - JOUR
T1 - Adenovirus-mediated gene transfer to ischemic brain is augmented in aged rats
AU - Takada, Junichi
AU - Ooboshi, Hiroaki
AU - Yao, Hiroshi
AU - Kitazono, Takanari
AU - Ibayashi, Setsuro
AU - Iida, Mitsuo
N1 - Funding Information:
This work was supported in part by the research grant in aid from the Ministry of Health and Welfare Comprehensive Research on Aging and Health (H11-008), Japan. We would like to thank the University of Iowa Gene Transfer Vector Core, especially Beverly L. Davidson and Richard D. Anderson, for viral vector preparations.
PY - 2003/4/1
Y1 - 2003/4/1
N2 - Gene therapy may be a promising approach for the treatment of brain ischemia. Because older populations are susceptible to ischemic stroke, we examined the effects of aging on adenovirus-mediated gene transfer to the ischemic brain of rats. Brain ischemia was produced by photochemical occlusion of the distal middle cerebral artery of aged and adult spontaneously hypertensive rats. Ninety minutes after ischemia, an adenoviral vector encoding β-galactosidase was injected into the contralateral (C) and ipsilateral [peri-ischemic (I-p) and ischemic core (I-c)] parietal cortices. Cerebral blood flow (CBF) was measured by laser Doppler flowmetry. Transgene expression was scored semiquantitatively as an expression score by histochemistry and also quantitatively analyzed by chemiluminescence assay. Changes in CBF after ischemia in aged rats were not significantly different from those in adult rats, although the infarct rim in the older rats tended to be closer to the midline than in the younger rats. β-galactosidase was detected in both neurons and non-neuronal cells at C and I-p, and was primarily present in non-neuronal cells at I-c. The expression scores 1 and 4 days after ischemia in the aged rats were similar to those in the adult rats. However, the score for the I-c at 7 days after injection was significantly greater in the older rats than in the younger adult rats. β-galactosidase activity at I-c 7 days after ischemia in the aged rats (8.0±1.7mU/mg protein) was significantly greater than that in the adult rats (1.3±0.4, p<0.01). Adenovirus-mediated gene transfer to the ischemic brain may thus be more effective in aged rats than in adult rats.
AB - Gene therapy may be a promising approach for the treatment of brain ischemia. Because older populations are susceptible to ischemic stroke, we examined the effects of aging on adenovirus-mediated gene transfer to the ischemic brain of rats. Brain ischemia was produced by photochemical occlusion of the distal middle cerebral artery of aged and adult spontaneously hypertensive rats. Ninety minutes after ischemia, an adenoviral vector encoding β-galactosidase was injected into the contralateral (C) and ipsilateral [peri-ischemic (I-p) and ischemic core (I-c)] parietal cortices. Cerebral blood flow (CBF) was measured by laser Doppler flowmetry. Transgene expression was scored semiquantitatively as an expression score by histochemistry and also quantitatively analyzed by chemiluminescence assay. Changes in CBF after ischemia in aged rats were not significantly different from those in adult rats, although the infarct rim in the older rats tended to be closer to the midline than in the younger rats. β-galactosidase was detected in both neurons and non-neuronal cells at C and I-p, and was primarily present in non-neuronal cells at I-c. The expression scores 1 and 4 days after ischemia in the aged rats were similar to those in the adult rats. However, the score for the I-c at 7 days after injection was significantly greater in the older rats than in the younger adult rats. β-galactosidase activity at I-c 7 days after ischemia in the aged rats (8.0±1.7mU/mg protein) was significantly greater than that in the adult rats (1.3±0.4, p<0.01). Adenovirus-mediated gene transfer to the ischemic brain may thus be more effective in aged rats than in adult rats.
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U2 - 10.1016/S0531-5565(02)00241-3
DO - 10.1016/S0531-5565(02)00241-3
M3 - Article
C2 - 12670629
AN - SCOPUS:0037380876
SN - 0531-5565
VL - 38
SP - 423
EP - 429
JO - Experimental Gerontology
JF - Experimental Gerontology
IS - 4
ER -