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-1β and interferon-γ 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.
This work has been supported in part by grants from the National Science and Technology Development Agency, Thailand, and Advanced Diagnostic Imaging and Image-Guided Minimal Invasive Therapy Center (AIMC), Ramathibodi Hospital.
Authors' contributions: JL performed the MRI examination, designed the cradle for dogs for MRI examination and MR protocol for the dog study, and analyzed and interpreted data and was involved in drafting the manuscript. SW developed the protocol for rabies virus and cytokine RNA quantification and analyzed the RNA data and was involved in drafting the manuscript. BL examined the rabid dogs, collected specimens for laboratory confirmation, and developed the cradle for dogs for MR examination. He also cared for dogs during the quarantine period and during the neuroimaging examination. SAm, VT, and SS also took care of the dogs during the quarantine period and during the neuroimaging examination of the animals. PP did the laboratory work in diagnosing rabies and in quantification of rabies virus and cytokine RNA. SAs and LW participated in the designing of the MR protocol and MR examination and analyzing the data. YA and NI were involved in developing cytokine quantification protocol and analysis of the data and in drafting manuscript. ML suggested design, analyzed and interpreted the data, and critically reviewed the manuscript. HW analyzed the data and reviewed the manuscript. TH designed the whole study, confirmed diagnosis, and participated in analyzing and interpreting the data and writing the manuscript. All authors read and approved the final manuscript.