Review of corynetoxins poisoning of livestock, a neurological disorder produced by a nematode-bacterium complex.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
J W Finnie
Publications and source records attributed to J W Finnie.
Avian riboflavin deficiency: an acquired tomaculous neuropathy.
The finding of tomacula, focal areas of sausage-shaped hypermyelination in peripheral nerves, is reported for the first time in avian riboflavin deficiency. Day-old, meat-type chickens were fed a riboflavin-deficient diet (1.8 mg/kg) and were killed on postnatal days 6, 11, 16, and 21, while control chickens were fed a conventional diet containing 5.0 mg/kg riboflavin. Tomacula were found in sciatic and brachial nerves from day 11 onward, became more frequent and prominent with increasing time, and preceded the onset of segmental demyelination.
Animal Feed↗
Early paranodal myelin swellings (tomacula) in an avian riboflavin deficiency model of demyelinating neuropathy.
INTRODUCTION: Disruption of the complex architectural and molecular organization of the paranodal region of myelinated peripheral nerve fiber may initiate the evolving time dependent process of segmental demyelination. In support of this notion was the finding of focal paranodal myelin swellings (tomacula) due to redundant folding of myelin sheaths, early in the time course of an avian riboflavin deficiency model of demyelinating neuropathy. METHODS: Newborn broiler meat chickens were maintained either on a routine diet containing 5.0 mg/kg riboflavin (control group) or a riboflavin-deficient diet containing 1.8 mg/kg riboflavin. Riboflavin concentrations in the liver were measured at postnatal day 11. Peripheral nerves were morphologically examined at days 6, 11, 16 and 21 using light and electron microscopy and teased nerve fiber techniques. RESULTS: Riboflavin-deficient chickens showed signs of a neuropathy from days 8 and pathological examination of peripheral nerves revealed a demyelinating neuropathy with paranodal tomacula formation starting on day 11. Paranodal tomacula consisted of redundant myelin infoldings or outfoldings, increased in size and frequency after day 11. After day 16, the paranodal swellings showed prominent degenerative changes accompanied by an increased frequency of myelinated fibers showing demyelination. CONCLUSION: Tomacula due to redundant myelin folds are generally considered a remyelination phenomenon, yet in this avian riboflavin deficiency model of demyelination, the paranodal tomacula occurred early in the course of demyelination.
Animals↗
Effect of tunicamycin on peripheral nerves in the guinea pig.
Explore the source record for details and available documents.
Animals↗
Brain damage in pigs produced by impact with a non-penetrating captive bolt pistol.
OBJECTIVE: To assess the effect of impact with a nonpenetrating captive bolt pistol in pigs by studying the resulting traumatic brain injury (TBI) and to compare the pathological changes with those found previously in the brains of sheep using a similar experimental paradigm. PROCEDURE: The unrestrained heads of six, anaesthetised, 7- to 8-week-old, Large White pigs were impacted in the temporal region with a nonpenetrating captive bolt pistol. Four hours postimpact, brains were perfusion-fixed with 4% paraformaldehyde. Coronal sections from six levels along the brain were cut and stained with haematoxylin and eosin and immunohistochemically for amyloid precursor protein, a sensitive marker of axonal injury (AI) in the brain after trauma. RESULTS: TBI in pigs was characterised only by very mild AI, whereas AI in sheep after captive bolt impact to the same head region was much more severe and widely distributed and often associated with vascular damage such as contusions, subarachnoid and intraparenchymal haemorrhage. CONCLUSIONS: TBI in pigs was much less severe than in sheep after non-penetrating mechanical impact of similar magnitude, confirming the importance of interspecies differences in determining an appropriate physical method of euthanasia.
Animal Welfare↗
Pathogenesis of brain damage produced in sheep by Clostridium perfringens type D epsilon toxin: a review.
Microvascular endothelial damage by the epsilon toxin of Clostridium perfringens type D appears to be the fundamental cause of cerebral parenchymal injury and lesions occur in a seemingly dose- and time-dependent manner. Large doses of circulating toxin produce a severe, generalised, vasogenic cerebral oedema and an acute or peracute clinical course to death. With lower doses of toxin, or in partially immune sheep, focal necrosis, often bilaterally symmetrical, occurs in certain selectively vulnerable brain regions, which appear to become fewer as the toxin dose is reduced. These cases follow a more protracted clinical course, but death is the usual outcome. The precise pathogenesis of the focal brain damage found in subacutely intoxicated sheep is unresolved, but several possible mechanisms are discussed.
Animals↗
Traumatic brain injury.
Animal models have played a critical role in elucidating the complex pathogenesis of traumatic brain injury, the major cause of death and disability in young adults in Western countries. This review discusses how different types of animal models are useful for the study of neuropathologic processes in traumatic, blunt, nonmissile head injury.
Animals↗
Clostridium perfringens prototoxin-induced alteration of endothelial barrier antigen (EBA) immunoreactivity at the blood-brain barrier (BBB).
It has been reported that the severe cerebral edema produced in experimental animals by Clostridium perfringens (Cl p) type D epsilon toxin can be prevented by prior treatment with its precursor prototoxin due to competitive binding to endothelial cells (ECs) at the blood-brain barrier (BBB). In this study we investigate the effects of the prototoxin on the BBB, without added toxin. The integrity of the BBB was assessed by its ability to prevent leakage of endogenous albumin. ECs at the BBB were studied by immunocytochemistry for any alteration in the endothelial barrier antigen (EBA), a molecular marker for the intact BBB. Immunocytochemistry showed rapid but mild opening of the BBB to endogenous albumin. Light and electron immunocytochemistry showed qualitative and quantitative reduction in EBA immunoreactivity, with a spectrum of changes at time intervals from 1 h to 14 days post-prototoxin injection. Some vessels with ultrastructural changes and widening of the perivascular space retained EBA immunoreactivity. Many vessels showed partial or complete loss of EBA staining with minimal widening of the perivascular space and edema. Recovery of EBA expression was still incomplete at 14 days postinjection. This is the first report to show endothelial cell damage, mild reversible cerebral edema, and alteration in BBB markers following administration of Cl p prototoxin. This model of mild brain edema may be useful for BBB studies.
Animals↗
Effect of tunicamycin on hepatocytes in vitro.
Cultured rat hepatocytes exposed to tunicamycin, a substance biologically indistinguishable from the corynetoxin responsible for a toxic hepatocerebral disorder in Australian ruminant livestock, had degenerative changes characterized by marked cytoplasmic lipid accumulation and dilatation of cisternae of rough endoplasmic reticulum or necrosis. The findings, which resemble those found previously in vivo after tunicamycin administration, suggest that, after gaining ready access to liver parenchyma via leaky hepatic sinusoids, tunicamycin directly damages the hepatocytes.
Animals↗
Effect of global system for mobile communication (gsm)-like radiofrequency fields on vascular permeability in mouse brain.
The effect of global system for mobile communication (GSM) radiofrequency fields on vascular permeability in the brain was studied using a purpose-designed exposure system at 898.4 MHz. Mice (n= 30) were given a single far field, whole body exposure for 60 minutes at a specific absorption rate of 4 W/kg. Control mice were also sham-exposed (n = 10) or permitted free movement in a cage (n = 10) to exclude any stress-related effects. Vascular permeability changes were detected using albumin immunohistochemistry and the efficacy of this vascular tracer was confirmed with a positive control group exposed to a clostridial toxin known to increase vascular permeability in the brain. No significant difference in albumin extravasation was detected between any of the groups at the light microscope level using the albumin marker.
Albumins↗
Toxin-induced vasogenic cerebral oedema in a rat model.
Vasogenic cerebral oedema (VCO) was induced in Hooded Wistar rats by intraperitoneal injection of Clostridium perfringens type D epsilon prototoxin. Animals were killed, 1 h to 14 d postinjection, by perfusion fixation under general anaesthesia. VCO was detected by the presence of endogenous albumin in the brain, visualised by immunocytochemistry. As early as 1 h postinjection, albumin was detected in the walls of cerebral microvessels. Maximal diffuse leakage within the neural parenchyma was seen at 24 and 48 h and immunoreactivity was still present at 4 d. At 7 d only few foci were seen, and at 14 d albumin distribution was similar to that in controls. Ultrastructural assessment of the microvessels showed swelling of many astrocytic processes and abnormalities of the endothelial cells varying from swelling with loss of cytoplasmic organelles to cells showing increased electron density. Immunostaining for the endothelial barrier antigen (EBA) showed strongly immunoreactive vessels throughout normal brains. Experimental animals showed partial reduction in EBA expression, most evident at 24 and 48 h, with gradual recovery to normal by 14 d. The exact role that EBA plays in the intact BBB remains obscure.
Animals↗
Upregulation of neuronal amyloid precursor protein (APP) and APP mRNA following magnesium sulphate (MgSO4) therapy in traumatic brain injury.
The aim of this study was to assess and quantitate topographically the effects of posttraumatic intravenous magnesium sulphate (MgSO4) on neuronal perikaryal APP antigen and messenger RNA (mRNA) expression in sheep brains 2 h after a controlled focal head impact. The percentage brain area with APP immunoreactive neuronal perikarya was 71, 56, 27.5 and 5.5%, respectively, in MgSO4-treated head-injured animals, head-injured animals without any treatment, MgSO4 treated nonimpacted animals, and nontreated nonimpacted control sheep. Although there was no statistically significant difference in APP immunoreactive neuronal perikarya in the MgSO4-treated HI group (mean 71%) compared to the HI group without any treatment (mean 56%), northern analysis showed that there was a 2.3-+/-0.2-fold increase in APP mRNA in the thalamus of treated impacted animals compared to untreated impacted animals (p < 0.005). However, MgSO4 treated nonimpacted control animals also showed a 1.6-+/-0.1-fold increase in APP mRNA compared to untreated nonimpacted controls (p < 0.005). MgSO4 therapy results in upregulation of neuronal APP mRNA and APP expression that is quantitatively greater following a focal head impact.
Amyloid beta-Protein Precursor↗
Evaluation of brain damage resulting from penetrating and non-penetrating captive bolt stunning using lambs.
OBJECTIVE: To compare the brain damage in sheep resulting from penetrating and non-penetrating captive bolt stunning. DESIGN: The unrestrained heads of anaesthetised lambs were impacted in the temporal region with penetrating and non-penetrating captive bolt pistols (humane stunners) using a constant charge. Two hours after head impact, brains were perfusion-fixed with 4% paraformaldehyde. Coronal sections were stained with haematoxylin and eosin and immunohistochemically for amyloid precursor protein, a sensitive marker of axonal and neuronal reaction in brains after trauma. Pathological changes in these brains were then quantified by morphometric analysis. RESULTS: The skull was fractured in 50% of lambs after a non-penetrating head impact and in all animals after a penetrating head wound. Impact contusions were present in 80% of lambs receiving a non-penetrating head injury and in all of those with a penetrating wound. Total contusion area was similar in both groups. Amyloid precursor protein-positive axons and neurons, and haemorrhage, were widely distributed in the brain after both head impact types, but there was no statistically significant difference between the two groups. Multifocal necrosis of the cerebellar granular layer was found in all lambs with non-penetrating head injury, but in none with a penetrating injury. CONCLUSIONS: The structural brain damage, a mixture of focal and diffuse injury, produced by penetrating and non-penetrating captive bolt pistols was overall similar and of sufficient severity to suggest that both types of weapon are acceptable for euthanasia.
Animal Welfare↗
Axonal and neuronal amyloid precursor protein immunoreactivity in the brains of guinea pigs given tunicamycin.
Amyloid precursor protein (APP) immunocytochemistry was used to study axonal and neuronal changes in guinea pig brains exposed to tunicamycin. Substantial axonal injury was found in ischemic-hypoxic foci and more generally, but this injury was not readily appreciable in conventionally stained sections. Neuronal perikaryal APP expression was also widely distributed, possibly as an acute phase response to this neurotoxin.
Amyloid beta-Protein Precursor↗
Upregulation of amyloid precursor protein messenger RNA in response to traumatic brain injury: an ovine head impact model.
There is evidence that the amyloid precursor protein (APP) plays an important role in neuronal growth and synaptic plasticity and that its increased expression following traumatic brain injury represents an acute phase response to trauma. We hypothesized that the previously described increased APP expression in response to injury (Van den Heuvel et al., Acta Neurochir. Suppl. 71, 209-211) is due to increased mRNA expression and addressed this by examining the expression of APP mRNA and APP within neuronal cell bodies over time in an ovine head impact model. Twenty-five anesthetized and ventilated 2-year-old Merino ewes sustained a left temporal head impact using a humane stunner and 9 normal sheep were used as nonimpact controls. Following postimpact survival periods of 15, 30, 45, 60, and 120 min, brains were perfusion fixed in 4% paraformaldehyde and examined according to standard neuropathological protocol. APP mRNA and antigen expression were examined in 5-microm sections by nonisotopic in situ hybridization and APP immunocytochemistry. The percentage of brain area with APP immunoreactivity within neuronal cell bodies in the impacted animals increased with time from a mean of 7.5% at 15 min to 54.5% at 2 h. Control brains showed only very small numbers of weakly APP-positive neuronal cell bodies ranging from 2 to 14% (mean 7%). Increased expression of APP mRNA was first evident in impacted hemispheres at 30 min after impact and progressively increased over time to involve neurons in all sampled regions of the brain, suggesting increased transcription of APP. In contrast, APP mRNA was undetectable in tissue from nonimpacted sheep. These data show that APP mRNA and antigen expression are sensitive early indicators of neuronal injury with widespread upregulation occurring as early as 30 min after head impact.
Amyloid beta-Protein Precursor↗
Neuronal damage produced in rat brains by Clostridium perfringens type D epsilon toxin.
This paper reports neuronal changes in rat brains subacutely intoxicated with Copyright Clostridium perfringens type D epsilon toxin. Neuronal damage was characterized by either (1) progressive cytoplasmic vacuolation leading to necrosis, or (2) shrunken hyperchromatic cells with nuclear pyknosis. The neuronal injury was also often bilaterally symmetrical, particularly in the brainstem. These findings suggest that, after gaining access to brain tissue by producing an increase in vascular permeability, epsilon toxin later exerts a directly cytotoxic effect on neurons.
Animals↗
Adenovirus pneumonia in guinea pigs.
Explore the source record for details and available documents.
Adenoviridae Infections↗
Alpha-mannosidosis in the guinea pig: a new animal model for lysosomal storage disorders.
Alpha-mannosidosis is a lysosomal storage disorder resulting from deficient activity of lysosomal alpha-mannosidase. It has been described previously in humans, cattle, and cats, and is characterized in all of these species principally by neuronal storage leading to progressive mental deterioration. Two guinea pigs with stunted growth, progressive mental dullness, behavioral abnormalities, and abnormal posture and gait, showed a deficiency of acidic alpha-mannosidase activity in leukocytes, plasma, fibroblasts, and whole liver extracts. Fractionation of liver demonstrated a deficiency of lysosomal (acidic) alpha-mannosidase activity. Thin layer chromatography of urine and tissue extracts confirmed the diagnosis by demonstrating a pattern of excreted and stored oligosaccharides almost identical to that of urine from a human alpha-mannosidosis patient. Widespread neuronal vacuolation was observed throughout the CNS, including the cerebral cortex, hippocampus, thalamus, cerebellum, midbrain, pons, medulla, and the dorsal and ventral horns of the spinal cord. Lysosomal vacuolation also occurred in many other visceral tissues and was particularly severe in pancreas, thyroid, epididymis, and peripheral ganglion. Axonal spheroids were observed in some brain regions, but gliosis and demyelination were not observed. Ultrastructurally, most vacuoles in both the CNS and visceral tissues were lucent or contained fine fibrillar or flocculent material. Rare large neurons in the cerebral cortex contained fine membranous structures. Skeletal abnormalities were very mild. Alpha-mannosidosis in the guinea pig closely resembles the human disease and will provide a convenient model for investigation of new therapeutic strategies for neuronal storage diseases, such as enzyme replacement and gene replacement therapies.
Animals↗