Toxic
oxidants (
oxygen free radicals) have been implicated in the formation of
brain edema from
ischemia-reperfusion injury or
tumor growth. We investigated the ability of an
iron chelator, a
calcium channel blocker, and a
xanthine oxidase inhibitor to reduce formation of
brain edema following a cold lesion in cats. The agents were given independently of each other in an attempt to inhibit the Haber-Weiss reaction, prevent Ca++ modulated uncoupling of oxidative phosphorylation, and inhibit the generation of toxic
oxidants via
xanthine oxidase, respectively.
Pentastarch-
deferoxamine conjugate at a dose of 50 mg/kg was given 15 minutes before and 60 minutes after the cold lesion.
Nimodipine was given at a dose of 1 mg/kg 1 hour before and 2 hours after the cold lesion.
Allopurinol was given at a dose of 50 mg/kg 24 hours before, at the time of the lesion and, 24 and 48 hours after the lesion. Gravimetric measurements of multiple brain areas were performed at 24 hours post-lesion in the
pentastarch-
deferoxamine and
nimodipine groups and at 72 hours post-lesion in the
allopurinol group. None of these agents led to significant reduction in
brain edema formation as measured with a gravimetric column of
kerosene and
bromobenzene.
Pentastarch-
deferoxamine conjugate was utilized to avoid the confounding effects of arterial
hypotension which is seen with intravenous
deferoxamine. There was even a suggestion of increased
edema in the periventricular white matter in animals treated with
nimodipine. Taken together, independent inhibition of the Haber-Weiss reaction, of
calcium channels, or of
xanthine oxidase does not reduce formation of
brain edema in the cold lesion model.