Gj. Lees et W. Leong, RESEARCH REPORT BETWEEN EXCITOTOXINS AND THE NA+ K+-ATPASE INHIBITOR OUABAIN IN CAUSING NEURONAL LESIONS IN THE RAT HIPPOCAMPUS/, Brain research, 714(1-2), 1996, pp. 145-155
A possible indirect role of glutamate in causing the neuronal death fo
und after intracerebral administration of a low dose of ouabain (0.1 n
mol) has been evaluated. This dose of ouabain produces a more extensiv
e neuronal lesion than those caused by glutamate receptor agonists (ka
inate at an equimolar dose, or NMDA (N-methyl-D-aspartate) at a 50-fol
d higher dose). The selective glutamate receptor antagonists, dizocilp
ine (MK-801) and NBQX ihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline
), in doses which blocked the direct toxicity of glutamate receptor ag
onists acting on either the NMDA and non-NMDA classes of glutamate rec
eptor, failed to provide more than a minor protection against ouabain-
induced neuronal death in the rat dorsal hippocampus. In contrast, the
non-selective glutamate receptor antagonist, kynurenate (100 nmol) re
duced the damage by around 70%. The difference in neuroprotection foun
d between the glutamate receptor antagonists suggests that kynurenate
may protect by a non-glutamatergic mechanism. Co-administration of oua
bain and glutamate receptor agonists (kainate, NMDA or glutamate) resu
lted in additive rather than synergistic damage to hippocampal neurons
. The results suggest that in vivo, ouabain and excitotoxins probably
cause neuronal death by independent mechanisms.