Rabies virus infection of primary neuronal cultures and adult mice: failure to demonstrate evidence of excitotoxicity.
Cultures derived from the cerebral cortices and hippocampi of 17-day-old mouse fetuses infected with the CVS strain of rabies virus showed loss of trypan blue exclusion, morphological apoptotic features, and activated caspase 3 expression, indicating apoptosis. The NMDA (N-methyl-D-aspartate acid) antagonists ketamine (125 microM) and MK-801 (60 microM) were found to have no significant neuroprotective effect on CVS-infected neurons, while the caspase inhibitor Ac-Asp-Glu-Val aspartic acid aldehyde (25 microM) exerted a marked neuroprotective effect. Glutamate-stimulated increases in levels of intracellular calcium were reduced in CVS-infected hippocampal neurons. Ketamine (120 mg/kg of body weight/day intraperitoneally) given to CVS-infected adult mice produced no beneficial effects. We have found no supportive evidence that excitotoxicity plays an important role in rabies virus infection.
Weli
Simon C
SC
Kingston General Hospital, 76 Stuart Street, Connell 725, Kingston, ON, Canada K7L 2V7.
Scott
Courtney A
CA
Ward
Christopher A
CA
Jackson
Alan C
AC
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009474:Neurons / Q000821:virology*; D009842:Oligopeptides / Q000494:pharmacology; D011818:Rabies; D011820:Rabies virus / Q000254:growth & development*
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D009842:Oligopeptides; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; D016202:N-Methylaspartate; D007649:Ketamine; C505409:Casp3 protein, mouse; D053148:Caspase 3