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.
Andersson
T
T
Clinical Research Center, Karolinska Institutet, Huddinge Hospital, Sweden.
Schwarcz
R
R
Löve
A
A
Kristensson
K
K
D000818:Animals; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D008457:Measles / Q000473:pathology*; D008459:Measles virus; D051379:Mice; D008807:Mice, Inbred BALB C; D009410:Nerve Degeneration / Q000187:drug effects*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate