Increased release of
glutamate is thought to contribute to
ischemia-induced neuronal damage. Since
general anesthetics such as
thiopental and
ketamine are thought to provide some degree of cerebral protection, this study was intended to 1) compare the effectiveness of
ketamine and
thiopental on
ischemia-induced tissue damage; and, if so, 2) determine whether attenuation of the increased
amino acid release is the sole mechanism for the protective effects demonstrated. Striatal slices prepared from Wistar Albino rats were incubated in an ischemic medium for 1 hour followed by 5 hours in a reoxygenation (REO) medium.
Ketamine and
thiopental were added medium during
ischemia and/or REO periods, and the medium was collected at the end of each incubation period for measurement of
amino acid release and
lactate dehydrogenase (LDH) leakage.
Ischemia significantly increased
amino acid release without altering LDH leakage.
Ischemia-induced increments in
glutamate and
aspartic acid releases returned to control levels during REO, but LDH leakage increased (P > 0.001) during this period. Although
ketamine (100 microM) and
thiopental (100 microM) failed to decrease
ischemia-induced
excitatory amino acid release, they protected the slices against REO-induced LDH leakage.
Ketamine, but not
thiopental, was effective even if added after
ischemia (P < 0.05). These results indicate that
ketamine and
thiopental protect the slices against REO-induced LDH leakage. However, mechanisms other than attenuation of the enhanced
glutamate release might be responsible for their protective effects.