Abstract
In this study the clinical signs and pathology of five plant poisonings and a mycotoxicosis affecting the nervous system of domestic ruminants in southern Africa are described. For comparative purposes, an inherited storage disease (bèta-mannosidosis) and a drug-induced neurotoxicosis (closantel overdose) are also presented. The aims of this thesis were:
(1)
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to document the pathology of those conditions where detailed descriptions were lacking,
(2) to study the light and transmission electron microscopical lesions from a differential diagnostic perspective, and,
(3) to consider the possible causative mechanisms of the nervous lesions.
A novel lysosomal storage disease in goats induced by the plant Ipomoea carnea is reported. Analysis of plant material confirmed the presence of swainsonine and two glycosidase inhibitors, namely, calystegine B2 and calystegine C1. The storage disease is analogous to the lysosomal storage disease in ruminants induced by ingestion of locoweeds (Astragalus and Oxytropis spp.) and poison peas (Swainsona spp) and closely mimics inherited a-mannosidosis in animals. ?-Mannosidosis is documented in Hereford calves, a breed not previously known to be afflicted by this inherited disorder. The condition was biochemically confirmed by an absence of lymphocyte ?-mannosidase activity in one of the affected calves.
‘Maldronksiekte’ in cattle, caused by ingestion of the plant Solanum kwebense, is characterised by degeneration, necrosis and loss of cerebellar Purkinje cells and, to a lesser extent, neurons in cerebellar nuclei. Affected Purkinje neurons were either swollen, pale and finely vacuolated or shrunken and more eosinophilic than normal. In the present study, some Purkinje cells and neurons in cerebellar nuclei stained strongly with Canavalia ensiformis (ConA) agglutinin and weakly with Triticum vulgaris (WGA) and succinyl-WGA (S-WGA) agglutinins. The neuronal lesions were not caused by apoptosis as tested by a commercial deoxyuridine triphosphate nick-end labeling (TUNEL) method. Based on the selective involvement and nature of lesions in cerebellar Purkinje cells, ‘maldronksiekte’ is classified as an acquired cerebellar cortical degeneration and not a lysosomal storage disease.
Four toxic myelinopathies are described; three are induced by plants (Helichrysum argyrosphaerum, Ornithogalum prasinum and O. saundersiae and Crotalaria sparthioides) and one is caused by overdosage of the anthelmintic compound closantel. The four conditions are characterized by indistinguishable spongy changes (status spongiosis) in the central nervous system caused by splitting of myelin lamellae at the intraperiod line consistent with myelin oedema. The brain lesions in toxicity with Crotalaria sparthioides in cattle are typical for hepatic encephalopathy secondary to cirrhosis. The pyrrolizidine alkaloid senkirkine was isolated from toxic plant material. Primary toxic retinal degeneration was present in poisoning by Helichrysum argyrosphaerum and in closantel poisoning.
Finally, the pathology of acute and chronic Aspergillus clavatus intoxication in cattle is studied. In acute cases there is chromatolysis and cytoplasmic vacuolation particularly of motor neurons in the ventral horns throughout the spinal cord. Electron microscopy revealed disintegration of Nissl bodies, abundant free ribosomes and increased numbers of mitochondria and dense bodies comparable to the axonal reaction. In chronic cases fed sorghum beer residues, extensive, bilaterally symmetrical Wallerian degeneration in ascending and descending tracts throughout the length of the spinal cord were seen. This neuromycotoxicosis is classified as a neuronopathy/axonopathy.
A histological feature of all the conditions that are described in this thesis is the presence of vacuolation of varying severity in neurons and/or neuropil in the central nervous system of affected animals. Apart from the storage diseases, the pathogenesis of the nervous lesions is largely unknown.
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