Edward Sikora

The production of focal herpes encephalitis in mice by stereotaxic inoculation of virus: Anatomical and behavioral effects

A low virulence strain of herpes simplex type 1 was microinjected into the hippocampus of BALB/c mice. Intense replication of virus at the inoculum site was followed by spread of viral antigen to the afferent connections of the hippocampus. Surviving animals showed focal damage of limbic structures and specific behavioral abnormalities generally consistent with hippocampal damage. This procedure thus produces an animal model which more closely resembles human herpes encephalitis than those previously reported.

Disappearance of Scrapie Virus from Tissues of the Mouse

Examination of newborn mice, inoculated intraperitoneally with high doses of scrapie virus, revealed that the virus could not be reisolated from their tissues after about 1 week following inoculation, until almost 1 year later. The inoculum was rapidly removed and was not detectable, although the animals became latently infected. Homogenization of whole inoculated newborn animals showed that only about 3% of virus could be recovered by the 2nd day postinoculation (p.i.). During the first 6 days p.i. the half-life of titratable scrapie was about 15 h. A further study of the rate of disappearance of clarified scrapie virus from blood after intravenous inoculation showed an even more rapid disappearance, with a half-life of 5.16 min. Prior treatment of the recipient mice with either carbon black or silica to block the reticuloendothelial system (RES) did not affect the rate of disappearance. It was concluded that the mouse possesses a very efficient means of scrapie virus removal from the blood which is not dependent upon an active RES. However, after 1 h the rate of disappearance changed dramatically; the residual virus level was very stable, with no significant drop during the next 21 h. This finding was compatible with the possibility that two forms of scrapie virus, with different removal rates, coexisted in the inoculum. Silica treatment caused a shortened scrapie incubation period.

Age at infection as a determinant of the behavioral effects of herpes encephalitis in mice

The influence of age at infection on the nature of the behavioral effects of herpes simplex type 1 encephalitis in mice was examined. Weanling and adult mice were initially immunized with a footpad (FP) inoculation of virus, followed 2 weeks later by an intracerebral (IC) inoculation. Subsequent open-field testing 2 weeks later revealed that weanling mice were hypoactive and showed a reduced proportion of center-field entries. In contrast, adult mice were hyperactive. No significant effects on Y-maze alternation or activity were observed. These results indicate that the qualitative nature of the effects of herpes encephalitis on behavior depends upon characteristics of the host.

Locomotor effects of catecholaminergic drugs on herpes-infected mice.

Changes in spontaneous, amphetamine (AMP) and apomorphine (APO) induced locomotor activity were used to assess the effects of central nervous system (CNS) infection with herpes type 1 virus. A dual herpesvirus inoculation procedure was used in which the animals received an immunizing footpad inoculation followed at 2 weeks by an identical intracerebral challenge. Four weeks later the animals were tested with intraperitoneal injections of saline or d-l-amphatmine (0.5 and 2.0 mg/kg). When footpad herpes-virus was given via one or two injections, it had no effect on spontaneous or AMP induced activity. When food-pad-intracerebral herpes mice were tested 28-33 days post intracerebral inoculation, they demonstrated depressed AMP-induced but not spontaneous activity. AMP at a dosage of 5.0 mg/kg overcame the herpesvirus blockage of 0.5 and 2.0 mg/kg AMP induced activity. Intraperitoneal injection of APO in day 3 post-IC animals produced less suppression of activity in the virus group than in the controls. These results suggest that non-fatal CNS herpes infection produces hypoactivity, in contrast to thehyperactivity during acute fatal CNS herpes encephalitis (Lycke & Roos, 1975), and that the effect may be due to alterations in postsynaptic receptor sensitivity.

Central herpes virus infection: Altered toxicity to d-amphetamine sulfate

Abstract We have examined the effects of peritoneal injections of d-amphetamine sulfate (d-amp) on mortality in mice inoculated peripherally and then intracerebrally (IC) infected with herpes simplex virus type 1 (HSV). On day 5 post-IC infection, the mice were significantly less sensitive to the lethal effects of d-amp than were control mice. No differences in mortality were noted after exposure to d-amp 14 days after IC infection. Animals that had received HSV-IC only were significantly more sensitive to the lethal effects of d-amp than control animals. We conclude that: (a) the effect is temporary in nature; (b) the protective mechanism can be overcome by particularly high levels of d-amp; (c) the protective effect may involve alterations in endogenous levels of central catecholamines. The peripherally and then centrally infected mouse not only provides a means of examining long-term interactions between infectious agents and drugs, but may also provide a model for examining virus-induced neurological disorders of brain catecholamines.

Long-Term Effects of Virus Infection on Behavior and Aging in Mice

Summary Large groups of newborn mice were each inoculated with one of 30 different Coxsackie viruses. Weight changes and mortality were followed for a period of 3 years by which time all mice had died. Results showed that different viruses caused marked differences in weight change and mortality rate; these two variables seem to be directly related to each other. There was no correlation between early mortality following virus inoculation and subsequent chronic mortality. Groups of male mice surviving initial virus inoculation showed an absence of aggression compared with controls, with a shift in response to that of female mice. It was concluded that neonatal virus infection can affect behavior and/or weight change patterns; factors which appear to exert significant effects on the aging process.

Regional tyrosine hydroxylase and choline acetyltransferase concentrations in the brains of lymphocytic choriomeningitis-infected mice

The neurotransmitter biosynthesis enzymes tyrosine hydroxylase and choline acetyltransferase were investigated in selected brain areas of Nya : NYLAR mice infected with lymphocytic choriomeningitis (LCM) virus. Statistically significant alterations in the concentrations of both enzymes occurred in the olfactory, caudate, and neocortical regions at 5 days postinfection. No such alterations occurred in mice given cytoxan (150 mg/kg) 3 days postinfection and examined 5 days postinfection. At 10 days postinfection, however, the cytoxan-treated animals had significantly altered enzyme concentrations in the olfactory region, though not in the caudate or neocortex. This alteration appeared to be transitory, since it was not found in cytoxan-treated animals 60 days postinfection. A possible explanation is that virus production or interference in a brain region cycles over a period of hours or days. Still undetermined is whether these neurochemical changes are a primary effect of the virus or a secondary effect due to the immune response. It is noteworthy that cytoxan caused a marked increase in the enzyme activities studied in most of the brain areas.