MEASLES VIRUS-INDUCED HIPPOCAMPAL NEURODEGENERATION IN THE MOUSE - A NOVEL, SUBACUTE MODEL FOR TESTING NEUROPROTECTIVE AGENTS

The hamster neurotropic (HNT) strain of measles virus causes non-inflammatory encephalopathy in Balb/c mice, associated with neurodegeneration in hippocampal CA1 and CA3 regions. This loss of pyramidal cells can be prevented by twice daily systemic treatment with 1 mg/kg dizocilpine (5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5, 10-imine maleate; MK-801) for 7 days. By varying the MK-801 treatment protocol, we now found that drug administration during the last 4 days prior to sacrifice (i.e. days 4-7 post inoculation, p.i.) is essential for neuroprotection. In contrast, MK-801 treatment during the first days (days 0-4 p.i.) did not prevent the neuronal necrosis. These data suggest that the concentration of an excitotoxic factor in the mouse brain increases after virus inoculation, reaching toxic levels by days 4-5 p.i. This novel 'subacute' mouse model of neurodegeneration therefore constitutes an attractive tool for mechanistic and interventional studies in excitotoxicity research.