Involvement of peroxynitrite and hydroxyradical generated from nitric oxide in hypoxia/reoxygenation injury in rat cerebrocortical slices
Section snippets
Hypoxia/reoxygenation-induced tissue injury in slices of the rat cerebral cortex
Male 10–14 week-old Sprague-Dawley rats (Japan Slc, Shizuoka, Japan) were used. They were housed in groups of five to six in a room controlled at 21–25°C, with 45–65% humidity and maintained in an alternating 12-h light/dark cycle (lights automatically on at 8:00 am). Food and water were freely given. Experiments were all carried out in accordance with the Guide for the Care and Use of Laboratory Animals, written by the Japanese Pharmacological Society. After immersing the whole brain in
Time course of changes in NO formation in rat cerebrocortical slices after exposure to hypoxia/glucose deprivation followed by reoxygenation
The accumulation of cGMP determined in the extracellular fluids after the addition of GTP, IBMX and crude extract of the rat cerebellum was markedly enhanced during hypoxia/glucose deprivation (Fig. 1). This increase in the cGMP production was totally abolished by an NOS inhibitor L-NAME or by an intracellular Ca2+ chelator BAPTA/AM. Therefore, the enhancement of cGMP during hypoxia/glucose deprivation may result from activation of Ca2+-dependent constitutive NOS. The enhancement of the NO
Discussion
We have recently reported that the exposure of rat cerebrocortical slices to hypoxia/glucose deprivation followed by reoxygenation causes an increase in LDH leakage into extracellular fluids (Tatsumi et al., 1998). This hypoxia/reoxygenation injury was completely blocked by the removal of extracellular Ca2+ or by chelating intracellular free Ca2+ with BAPTA/AM, thereby indicating an involvement of excessive Ca2+ entry in the tissue damage (Tatsumi et al., 1998). In the present study, changes in
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