Furious and paralytic rabies of canine origin: Neuroimaging with virological and cytokine studies

Abstract

Furious and paralytic rabies differ in clinical manifestations and survival periods. The authors studied magnetic resonance imaging (MRI) and cytokine and virus distribution in rabies-infected dogs of both clinical types. MRI examination of the brain and upper spinal cord was performed in two furious and two paralytic dogs during the early clinical stage. Rabies viral nucleoprotein RNA and 18 cytokine mRNAs at 12 different brain regions were studied. Rabies viral RNA was examined in four furious and four paralytic dogs during the early stage, and in one each during the late stage. Cytokine mRNAs were examined in two furious and two paralytic dogs during the early stage and in one each during the late stage. Larger quantities of rabies viral RNA were found in the brains of furious than in paralytic dogs. Interleukin-1beta and interferon-gamma mRNAs were found exclusively in the brains of paralytic dogs during the early stage. Abnormal hypersignal T2 changes were found at hippocampus, hypothalamus, brainstem, and spinal cord of paralytic dogs. More widespread changes of less intensity were seen in furious dog brains. During the late stage of infection, brains from furious and paralytic rabid dogs were similarly infected and there were less detectable cytokine mRNAs. These results suggest that the early stage of furious dog rabies is characterized by a moderate inflammation (as indicated by MRI lesions and brain cytokine detection) and a severe virus neuroinvasiveness. Paralytic rabies is characterized by delayed viral neuroinvasion and a more intense inflammation than furious rabies. Dogs may be a good model for study of the host inflammatory responses that may modulate rabies virus neuroinvasiveness.

Rabies Virus Is Recognized by the NLRP3 Inflammasome and Activates Interleukin-1β Release in Murine Dendritic Cells

“…ELISA of brain lysates collected at 15 days postinfection showed significantly more IL-1␤ in RABV-infected mice than in mock-immunized mice, confirming previously published results (47-49). Marquette et al found that resident microglial cells and infiltrating macrophages were positive for IL-1␤ (47); Laothamatas et al showed that IL-1␤ appeared during the early stages of infection with RABV (48). In view of these results, our data strongly suggest that in cells found at the site of RABV infection in the brain, the increased IL-1␤ production is the result of NLRP3 inflammasome activation.…”

Parasites: evolution’s neurobiologists

“…Berenreiterová et al (Berenreiterová et al, 2011) hypothesise that if parasites infest wide regions of the brain, the odds are good that at least one parasite will hit neural areas crucial for the targeted host behaviours. Like T. gondii, the rabies virus is widely disseminated in the host's brain (Laothamatas et al, 2008). Nevertheless, the occurrence of the pathogen is not entirely random.…”

“…For example, the rabies virus is thought to induce increased aggressive behaviour in its host by directly invading a variety of brain areas and by changing the levels of a number of cytokines (Laothamatas et al, 2008). Neurobiologists can increase aggression in many mammals by raising the amount of a single cytokine (IL-1) in a single brain area [i.e.…”

Acute flaccid paralysis following spinal anaesthesia , A diagnostic dilemma

“…2 Incubation period for rabies is the most variable of all acute CNS infections. 3 This patient probably presented during the prodromal phase as in paralytic rabies. The local manifestations are the earliest symptoms which perhaps were neglected by the patient.…”