Ralph W. Storts

The Effects of Restraint Stress on the Neuropathogenesis of Theiler's Virus Infection: I. Acute Disease

Restraint stress was found to have a profound effect on the acute phase of Theilers virus infection. Increased mortality rates were observed in restrained CBA mice infected with the BeAn strain of Theilers virus. In addition, restrained mice developed higher CNS viral titers than infected/nonrestrained mice. Thymic atrophy was observed in both infected and uninfected restrained mice. Decreased microgliosis, perivascular cuffing, and astrocytosis were observed in restrained mice compared to nonrestrained infected mice at 7 days postinfection. Restraint-stressed mice also developed decreased numbers of lymphocytes and increased numbers of neutrophils in the blood. The mechanism proposed for these alterations involves stress-induced corticosterone, which causes immunosuppression, decreased trafficking of inflammatory cells in the CNS, and, consequently, increased viral replication.

Chronic restraint stress during early Theiler's virus infection exacerbates the subsequent demyelinating disease in SJL mice.

Chronic restraint stress, administered during early infection with Theilers virus, was found to exacerbate the acute central nervous system (CNS) viral infection and the subsequent demyelinating phase of disease (an animal model of Multiple Sclerosis (MS)) in SJL male and female mice. During early infection, stressed mice displayed decreased body weights and spontaneous activity; while increased behavioral signs of illness and plasma corticosterone (CORT) levels. During the subsequent chronic demyelinating phase of disease, previously stressed mice had greater behavioral signs of the chronic phase, worsened rotarod performance, and increased inflammatory lesions of the spinal cord. In addition, mice developed autoantibodies to myelin basic protein (MBP), proteolipid protein peptide (PLP139-151), and myelin oligodendrocyte glycoprotein peptide (MOG33-55).

Social stress alters the severity of acute Theiler's virus infection

Our laboratory has previously shown that restraint stress resulted in decreased Theilers virus-induced CNS inflammation, while exacerbating illness behaviors during the acute phase of disease. In contrast, social disruption stress (SDR) applied prior to infection led to the development of glucocorticoid (GC) resistance, and these animals developed more severe disease course, with increased inflammation. However, when SDR was applied concurrent with infection, GC resistance fails to develop, disease course is less severe and inflammation was moderate. These results suggest that the effects of SDR on Theilers virus infection are dependent upon the timing of SDR application in relation to infection.

Natural and Experimental Bovine Immunodeficiency Virus Infection in Cattle

Since 1989, the LSU dairy herd, with its high seroprevalence of BIV, was recognized to have a high incidence of common diseases that reduced the economic viability of the dairy. The herd had a high percentage of cows with encephalitis associated with depression and stupor, alteration of the immune system associated with secondary bacterial infections, and chronic inflammatory lesions of the feet and legs. The occurrence of disease problems was associated with the stresses of parturition and early lactation and/or with unusual environmental stress cofactors.

Neuroimmune Interactions in a Model of Multiple Sclerosis

Psychological stress has been implicated in both the onset and exacerbation of multiple sclerosis (MS). Our research has focused on the role of stress at the onset of MS, using the mouse model Theilers murine encephalomyelitis virus‐induced demyelination. Theilers virus is a natural pathogen of mice that causes a persistent infection of the central nervous system (CNS) and inflammatory immune‐mediated demyelination that is very similar to MS. Our research has shown that restraint stress sufficiently increases corticosterone secretion to cause immunosuppression. Stressed mice develop decreased innate and adaptive immune responses, including decreased chemokine and cytokine responses, to virus, which leads to increased viral replication within the CNS. Higher levels of virus then cause increased later demyelinating disease. These findings may have important implications in our understanding of the interactions between stress and the development of autoimmune diseases induced by infectious agents.

Toxicity of Nerium oleander in the Monkey (Cebus apella)

The toxic effects of Nerium oleander were evaluated in capuchin monkeys (Cebus apella) by examination of clinical signs, hematologic and serum chemical values, and gross and microscopic lesions. Dried and ground oleander leaves were given at intervals of 48 h in doses of 30, 7.5, and 3 mg/kg body weight. The cumulative lethal dose ranged from 30 to 60 mg/kg body weight in monkeys that were given doses of 30 and 7.5 mg/kg body weight. Monkeys that received doses of 3 mg/kg body weight (total cumulative dose: 60 mg/kg) survived. Clinical signs were vomiting, salivation, polyuria, bradycardia, vaginal hemorrhage, abortion, anorexia, constipation, loss of body weight, narcosis, restlessness, weakness, and shallow and rapid respirations. Changes in blood values were leukocytosis; neutrophilia; increased potassium, glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase, blood urea nitrogen and α-globulins; reticulo-cytopenia; and decreased calcium, glucose, total serum protein, albumin, γ-globulin levels and albumin-globulin ratios. Hemorrhages, degeneration, or necrosis, or all of these, were observed in the heart, gastrointestinal tract, skeletal muscles, ovaries, adrenal glands, liver, kidneys, and pancreas. The organ weights of the pancreas were significantly reduced. Adrenal weights were significantly increased in monkeys that received the highest dose level.

Colonic Ganglioneuromatosis in a Horse

Ganglioneuromas are complex tumors that arise in peripheral ganglia and are composed of well-differentiated neurons, nerve processes, Schwann cells, and enteric glial cells. The term ganglioneuromatosis (GN) denotes a regional or segmental proliferation of ganglioneuromatous tissue. This report describes an 8-year-old mixed breed horse with GN in a 25-cm segment of small colon. Grossly, the lesion consisted of numerous sessile to pedunculated nodules extending from the serosal surface. Histologic examination revealed the nodules to consist of fascicles of spindle-shaped cells consistent with Schwann cells, clusters of neurons, supporting enteric glial cells, and thick bands of perineurial collagen. Most of the nodules coincided with the location of the myenteric plexus and extended through the outer layer of the tunica muscularis to the serosal surface. Neuronal processes were demonstrated within the lesion with electron microscopy. With immunohistochemistry neurons were positive for neuron specific enolase (NSE) and S-100 and the Schwann cells and enteric glial cells were positive for S-100 and glial fibrillary acidic protein (GFAP). The pathogenesis of GN is poorly understood. GN, although rare, should be included in the differential diagnosis of gastrointestinal tumors in the horse.

Hereditary striatonigral and cerebello-olivary degeneration of the Kerry blue terrier. I. Gross and light microscopic central nervous system lesions.

The character and progression of gross and light microscopic central nervous system lesions associated with a hereditary neurodegenerative disease with juvenile onset are described in ten affected Kerry blue terriers. The central nervous system lesions were progressive and, although there was some variability, followed a relatively well-defined temporal course. Degeneration of Purkinje cells in the cerebellar cortex was evident at the onset of clinical signs (approximately 4.5 months of age). After two weeks to one month of clinical illness, retrograde transsynaptic neuronal degeneration occurred in the olivary nucleus. Degeneration of both large and small neurons in the caudate nucleus began approximately two to three months after the onset of clinical signs, and by seven to eight months of clinical illness, the caudate nucleus was reduced to numerous microcystic cavities and almost was devoid of neurons except for a narrow subependymal zone and the tail of the nucleus. Neuronal depletion in the pars reticularis of the substantia nigra, which was evident after five to seven months of clinical illness, was attributed to an anterograde transsynaptic mechanism of neuronal degeneration. The disease in the Kerry blue terrier is compared with similar neurodegenerative diseases in man. The pathogenesis may involve altered neurotransmitter systems in the cerebellar cortex and caudate nucleus.

Surgical removal of an intramedullary spinal cord foreign body granuloma in a dog

A 2-year-old, spayed female, mixed-breed dog was presented for evaluation of a progressive asymmetric tetraparesis and cranial nerve deficits with a 3-week duration. Computed tomography showed a contrast-enhancing lesion along the left side of the junction of the medulla and the cervical spinal cord. An exploratory surgery determined the presence of an intramedullary lesion of the first cervical spinal cord segment. The mass was removed through a dorsal midline myelotomy. Microscopic examination identified a foreign body granuloma that contained a dense, anisotropic outer wall, supporting the conclusion that the foreign body was of plant origin. The dog recovered to a more improved ambulatory status than prior to surgery.

Immunohistochemical Evaluation of Mx Protein Expression in Canine Encephalitides

Mx proteins are a group of interferon-induced GTPases whose expression has been demonstrated in a number of human viral infections and in some idiopathic inflammatory diseases. In this study, the expression of Mx protein was evaluated in known viral, nonviral, and idiopathic encephalitides in the dog via immunohistochemistry using an antibody against human MxA. All 12 cases of confirmed viral encephalitis, including 7 cases of canine distemper, 4 cases of canine herpesvirus, and 1 case of rabies, were Mx positive. In canine distemper cases, staining was particularly strong and a variety of cell types were positive, including astrocytes, macrophages/microglia, and neurons. Immunoreactivity for Mx protein was evident in a few cases of nonviral infectious encephalitis, including neosporosis (1/1), Chagas disease (2/3), aspergillosis (1/2), and encephalitozoonosis (1/1). Consistent staining was observed in most cases of idiopathic encephalitis, including granulomatous meningoencephalomyelitis (7/7), necrotizing meningoencephalitis of pug dogs (6/7), and necrotizing encephalitis of the Yorkshire Terrier (3/3) and Maltese (1/1) breeds. Mx staining was negative in 5 normal dog brains; 3 cases of cryptococcosis; and single cases of blastomycosis, protothecosis, and bacterial meningitis.