6th International Symposium on Pharmacology of Cerebral Ischemia,
22. - 24.7.1996, Marburg.
Staurosporine attenuates the protective effect of class I
metabotropic glutamate receptor agonists against
hypoxic/hypoglycemic injury in hippocampal slices
Jaeger, T., Schroeder, U.H., Opitz, T., Sabelhaus, C.F.,
Breder, J. and Reymann, K.
To investigate the influence of metabotropic glutamate receptors (mGluRs)
on neuronal injury caused by cerebral hypoxia/ischemia, we employed an
in vitro model of hypoxia/hypoglycemia. Hippocampal slices were transiently
exposed to an oxygen and glucose free environment which causes a pronounced
drop of both ATP and creatine phosphate, an anoxic depolarization, and an
incomplete recovery of synaptically evoked population spike in the CA1 region
after one hour (48.5 ± 3.6% of baseline values). This recovery was used as a
measure of neuronal viability.
In this model, we applied different agonists specific for class I mGluRs.
The agonists trans azetidine2,4 dicarboxylic acid (trans ADA) and
3,5 dihydroxy-phenylglycine (DHPG) appeared to be highly protective, but
only when applied before the hypoxia/hypoglycemia. The protein kinase
inhibitor staurosporine attenuated the protective effect of the class I
mGluR agonists.
In conclusion we suggest that the activation of the phospholipase C pathway
prior to hypoxia/hypoglycemia exhibits a pronounced protective effect which
depends on protein phosphorylation.
This study was supported by BMBF grant 0319998B.
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