In the present study, we have assessed the efficacy of
eliprodil, a
neuroprotective agent which blocks both the modulatory
polyamine site of the
NMDA receptor and neuronal voltage-sensitive
calcium channels, alone or in combination with the
thrombolytic agent, rt-PA, in a rat
embolic stroke model using a neurological score and the volume of the
infarct as endpoints. Embolization was induced by intracarotid injection of an arterial
blood clot.
Eliprodil, administered at the dose of 1 mg/kg, iv. 10 min and 2 h 30 after embolization, reduced the neurological deficit by 54% (P < 0.01) and the total volume of the brain lesion by 49%. Thrombolysis with rt-PA (2.5 mg/kg, as a 30 min iv infusion beginning 1 h after embolization) decreased the neurological deficit by 48% (P < 0.05) and the size of the total
infarct by 55% (P < 0.05). Combined
therapy greatly improved the degree of neuroprotection as assessed by neurological and histological outcomes (70% (P < 0.001) and 89% (P < 0.01) neuroprotection, respectively). These results demonstrate that the administration of a
neuroprotective drug (
eliprodil) or a
thrombolytic agent (rt-PA) similarly reduce the volume of brain damage and the neurological deficit in a rat
embolic stroke model. Combined cytoprotective
therapy and thrombolysis markedly improved the degree of neuroprotection and may, thus, represent a valuable approach for the treatment of
stroke in humans.