R. Levy, S. Glozman, D. Milman, C. Seruty, Z. Hagay, E. Yavin, Y. Groner
Ischemic reperfusion brain injury in fetal transgenic mice with elevated levels of copper-zinc superoxide dismutase
Aim: To examine the effect of overexpression of human
intracellular copper-zinc superoxide dismutase (CuZnSOD1) gene on fetal mice brain exposed to in-utero
ischemic reperfusion injury.
Design: Transient in-utero ischemia (7 min) was induced
in pregnant transgenic mice overexpressing human
CuZnSOD1 and wild-type mice by occluding the blood
supply to the uterine artery on day 17 of pregnancy,
followed by 24 hours of reperfusion. The level of lipid
peroxidation in fetal mice brains was compared between
the transgenic and non-transgenic (control) fetal mice.
Motor and coordination skills of transgenic and control
adult mice (six to eight months old) which were exposed
to ischemic reperfusion injury in-utero were compared
by the rope grip test and visible platform task.
Results: We first measured CuZnSOD1 activity in the
brains of the transgenic fetal mice and confirmed that
the enzyme activity is 4.2-fold higher than control. We
also established that ischemia reperfusion on day 17 of
pregnancy led to increased level of TBARS (Thiobarbituric
acid reactive substance) in brains of wild-type fetal
mice when compared to sham operated mice (72.5 ± 3.4
vs. 49.4 ± 1.5 nmol/mg. p < 0.001). The increase was
markedly accentuated in the CuZnSOD1 transgenic
mice, and significantly higher compared to control mice
exposed to ischemia-reperfusion (85.6 ± 4.0 vs. 69.5 ± 2.3
nmol/mg, p < 0.001). Moreover, we found that the transgenic
mice that were subjected to in-utero ischemia
reperfusion exhibited a significantly higher rate of failures
in the rope grip test and poorer performance in the
visible platform task, when compared to non-transgenic
mice exposed to identical insult.
Conclusions: Oxygen free radicals play an important
role in the pathogenesis of perinatal hypoxia. Overexpression
of the enzyme CuZnSOD1 in transgenic mice
exposes their brains to increased damage during ischemic-reperfusion insult.
Journal of Perinatal Medicine, Walter de Gruyter
Print ISSN: 1619-3997
Volume: 30, 04/2002
Pages: 158 - 165
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