EARLY EVENTS IN RABIES VIRUS-INFECTION OF THE CENTRAL-NERVOUS-SYSTEM IN SKUNKS (MEPHITIS-MEPHITIS)

Twenty-four striped skunks were inoculated intramuscularly (long digit al extensor muscle of right pelvic limb) with street rabies virus. Gro ups of two clinically nor mal skunks were killed at various times afte r inoculation; skunks that developed rabies were killed in early stage s of the clinical signs. Four clinically normal skunks (numbered 1-4) had slight infection in lumbar spinal ganglia, spinal cord and brain. These four skunks were used for detailed immunohistochemical (rabies a ntigen) studies that included examination of sections from every segme nt of the spinal cord, most of the spinal ganglia from the 2nd cervica l to the 2nd coccygeal (sections at 25-mu m intervals of lumbar, sacra l and coccygeal ganglia) and brain (sections at 50-mu m intervals). In skunks 1-4, there was increasing distribution of antigen-containing n eurons that was not correlated with the time elapsed since inoculation . In three skunks (nos. 1, 2 and 3), antigen-containing neurons were p redominantly in caudal regions of the spinal cord, caudal right lumbar and sacral spinal ganglia and certain nuclei/regions of the brain (me dial reticular formation, right interpositus and lateral vestibular nu clei, left red nucleus, left motor cortex, and left reticular nucleus of the thalamus). Skunk 4 had more extensive infection than skunks 1-3 , but the previous pattern was still evident. The results are consiste nt with viral entrance into the lumbar spinal cord, initial replicatio n mainly at the L2 and L3 levels, local spread in the cord by proprios pinal neurons and early transit to the brain via long ascending and de scending fiber tracts (bypassing the grey matter of the rostral spinal cord). These mechanisms could provide for early and rapid disseminati on in the brain before a significant immune response develops and coul d induce behavioral changes before the animal is incapacitated by exte nsive spinal cord infection. Based on the distribution of antigen-cont aining neurons, the tracts considered most likely to serve as viral tr ansitways from spinal cord to brain include: rubrospinal, corticospina l, spinothalamic, spino-olivary, vestibulospinal and/or spinovestibula r, reticulospinal and/or spinoreticular, cerebellospinal and/or spinoc erebellar, and dorsal column pathways.