The Nervous System

CHAPTER FIVE The Nervous System BERNARD S. ]ORTNER & DEAN H. PERCY K. Benirschke et al. (eds.), Pathology of Laboratory Animals © Springer-Verlag New York Inc. 1978 INTRODUCTION Disease of the nervous system in laboratory ani logic entities in animals or because of their po mals, in common with that of other regions of tential as animal models of human disease. the body, is an important factor in determining We have emphasized the pathologic anatomy husbandry practices. In addition, its potential ef of the disease under consideration but have not fect on the quality and reliability of experimen neglected other aspects of these conditions. In ad tal studies in such animals cannot be overempha dition, our discussion, by design, emphasizes the sized. We have approached the neuropathology neurologic features of these entities. In those con of laboratory animals with this in mind. ditions where our consideration of the nonneuro The discussion is restricted to the commoner logic aspects of the disease is somewhat abbrevi laboratory animals: mice, rats, hamsters, guinea ated, the reader is urged to consult other sections pigs, rabbits, chickens, dogs, cats, and nonhuman of this text or other appropriate references. We primates. Disease entities are considered in etio do not wish to foster a "head without a body" logic or pathologic-anatomic categories (infec approach to the study of neuropathology. It is tious diseases, neoplasms, malformations, etc.) , not our intention to produce a treatise on neuro although there are obvious overlaps. In general, anatomy in this chapter, but some knowledge of we have restricted our discussion to the so-called this important subject is necessary for an in naturally occurring or spontaneous diseases of telligent approach to neuropathology. Several laboratory animals. Clearly we could not include atlases and other references are listed under all neuropathology of the species of animals noted "General References" at the end of this chapter. above, and some selectivity was employed. We Although no claims for completeness of such a have attempted to discuss the conditions of im list is made, it may prove useful to individuals portance in laboratory animal and experimental studying disease of the nervous system in such medicine. A number of conditions are also in species. cluded because they represent classic neuropatho- VIRAL INFECTIONS in the dog (Kakuk et al., 1969), but there is little Canine Herpesvirus Encephalitis available evidence to indicate that CHV infec tion may be a factor in this disease. Canine INTRODUCTION. Canine herpesvirus (CHV) infec herpesvirus has been isolated from cases of tra tion, an acute hemorrhagic disease of newborn cheobronchitis in the dog, and attempts were puppies, was first reported as a distinct disease made to experimentally reproduce the disease entity in the United States in 1965 (Carmichael (Karpas et al., 1968). Other members of this et a/., 1965; Stewart et a/., 1965). The virus is group, such as feline rhinotracheitis virus and in apparently of widespread geographic distribution fectious bovine rhinotracheitis virus (IBR), may and, like many members of the herpesvirus group, produce a pronounced rhinotracheitis in the sus may exist as a latent infection in a suitable host. ceptible natural host. Furthermore, newborn pup CHV has been isolated from primary canine kid pies inoculated with CHV develop a necrotizing ney cell cultures that have undergone spontane rhinotracheitis (Kakuk and Conner, 1970), ample ous degeneration (Spertzel et al., 1965). proof of the ability of this virus to replicate in There have been a variety of disease ent~ties at the upper respiratory tract. Appel et al. (1969), tributed to infection with CHV. The virus has however, were not able to reproduce the typical been isolated from a case of malignant lymphoma tracheobronchitis syndrome in pups 5 weeks or 320 VIRAL INFECTIONS more of age inoculated with CHV, although the ever, lesions have been a result of a postnatal in virus could frequently be isolated from the oro fection with the virus. pharynx. Serologic and viral isolation studies in naturally occurring epizootics of canine respira ETIOLOGY. The causative agent, CHV, unlike most tory disease indicate that CHV is not an impor members of the herpesvirus group, appears to tant etiologic agent in such conditions. (Binn replicate only in canine cells. Experimental inocu et al., 1967, 1970). lation studies in gnotobiotic pups suggest that Classically CHV infection leads to a peracute secondary bacterial invaders play a relatively disease of pups during the first 2 weeks of life. minor role in the naturally occurring disease Newborn animals are exposed to the virus during (Kakuk and Conner, 1970). the perinatal period either at birth or as an intra uterine infection (Carmichael et al., 1965; Stewart CLINICAL FEATURES. Affected animals frequently et al., 1965). The selective susceptibility of new exhibit serous nasal discharges, diarrhea, dyspnea, born puppies to CHV may be due to poorly de crying, abdominal tenderness, and incoordination. veloped defense mechanisms. It has been shown Usually puppies die within 1 to 4 days after the that peritoneal macrophages from adult mice are onset of detectable clinical signs attributable to more effective in controlling the spread of Herpes the disease. simplex virus than similar cells from newborn mice (Hirsch et al., 1970; Johnson, 1964). Viral LESIONS. Extensive pulmonary edema with cir replication occurs in cells from both age groups, cumscribed hemorrhagic areas, multiple pale foci but virions are released in much smaller numbers of hepatic necrosis, marked splenomegaly, and from the infected macrophages of adult animals disseminated renal cortical hemorrhages are char (Hirsch, et al., 1970). In addition, newborn pup acteristic gross findings in fatal cases of CHV in pies have relatively low and poorly regulated fection. Foci of acute necrosis in liver and kid body temperatures (Crighton, 1968). Some mem ney are frequently accompanied by a minimal bers of the herpesvirus group, such as feline inflammatory response. Eosinophilic intranuclear rhinotracheitis and bovine rhinotracheitis virus, inclusions may be present in such tissues as nasal normally infect cooler areas of the body, such as mucosa, lung, liver, kidney, and the central the upper respiratory tract and, in cases of IBR, nervous system, but they are seldom numerous. the external genitalia. Similarly, the maximal vi There is a non suppurative meningoencephalo rus growth of CHV in tissue culture is at 35 to myelitis with focal neuritis, ganglionitis, and oc 36°C (Carmichael and Barnes, 1969). The opti casionally acute retinitis (Percy et al., 1968, mal temperature range for multiplication of this 1970). The gray matter is usually more severely virus is therefore below the normal body tem involved than the white matter, especially that of peratures of dogs but approximates the body tem the caudate nuclei and the diencephalon, mesen peratures of newborn pups raised at ambient cephalon, and metencephalon. Characteristic le temperatures of 70 to 80°F. Survival of neonatal sions consist of focal aggregations of mononuclear animals inoculated with CHV may be prolonged cells with obliteration of the normal architecture and the rate of viral growth reduced when ani in these areas (Figure 5.1). Lesions are usually mals are kept in an environment that elevates focal, but regions of diffuse necrosis and gliosis body temperatures to 101.5°P or higher (Car measuring up to several hundred microns may michael et al., 1969). occur. Vascular changes consist of hypertrophy Developmental defects have been observed in a and hyperplasia with minimal perivascular cellu few inoculated puppies that were housed at high lar infiltration. Areas of segmental necrosis some environmental temperatures and that survived times occur in the cerebellar cortices, frequently the disease. Segmental renal cortical dysplasia with concurrent nonsuppurative leptomeningitis was the predominant histologic feature seen in (Figure 5.2). Unlike many herpetic encephali these animals. In a naturally occurring case, le tides, inclusion bodies in the canine disease are sions included segmental cerebellar dysplasia and relatively sparse and are not the classic type A segmental renal cortical dysplasia (Percy et al., inclusions associated with H. simplex encephalitis 1971). Developmental defects in infants attributed (Figure 5.3). Lesions may be present in nerve to intrauterine infection with cytomegalovirus in trunks and ganglia (Figures 5.4 and 5.5), includ clude microencephaly, microgyria, and hepato ing those of the autonomic nervous system, and splenomegaly (Sever and London, 1969). In the trigeminal ganglia are frequently affected. There case of developmental defects due to CHV, how- is focal degeneration of ganglion cells, prolifera- 321 THE NERVOUS SYSTEM FIGURE 5.1 Lesion in the frontal cerebral cortex of a pup with CRV encephalitis; it consists of aggregates of FIGURE 5.3 Area of segmental destruction involving mononuclear cells around a degenerating neuron. H&E the internal granular layer of the cerebellum in a pup with stain. CRV encephalitis. Note the necrotic Purkin;e cells (top) and the intranuclear "inclusions" present in cells of the internal granular layer. H&E stain. (Photograph courtesy cion of capsular cells, and mononuclear cell in of Pathologia Veterinaria.) filtration (Figure 5.5). The pathogenesis of

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