Pathological findings of adenine arabinoside (ARA-A) and cytarabine (ARA-C) in the treatment of herpes simplex encephalitis in rabbit model.

The injection of herpes simplex virus type 1 (HSV-1) into the vitreous body of the eye in the 18 day old albino rabbits consistently induced herpes encephalitis with 90% survival. In the untreated rabbits the lesions follow a defined anatomical pathway producing a progressive disease not dissimilar to the natural human disease in that HSV travels slowly by cell-to-cell infection of neuroglia. The effects of adenine arabinoside (ara-A) and cytarabine (ara-C) on HSV encephalitis in rabbit model were studied by starting the treatment on 4th day post-inoculation of HSV. Deaths due to toxic side effects were caused by ara-A and ara-C in 30% and 50% of animals respectively, compared with 10% in untreated animals. Neurological signs, such as head jerking, ataxia and frequent epileptiform fits, occurred in ara-A, and ara-C and untreated rabbits. Comparative histological studies of optic nerves and brains showed that ara-A and ara-C had no beneficial effect, but surprisingly enhanced the disease.