Edema and increased endoneurial fluid pressure developed in peripheral nerves of rats that received a diet containing 40% galactose during a study of the role of sugar alcohols in producing neuropathy. Fluid pressure was elevated starting in the third month and progressed to a fivefold increase over control values by the fifth month. Microscopic examination confirmed the presence of edema as predicted by the sorbitol theory, which is often invoked to explain the pathogenesis of diabetic neuropathy.

Animals↗

PubMedDate not supplied

Schwann cell changes and demyelination in chronic galactose neuropathy.

Dystrophic changes of Schwann cells and demyelination occurred in rats with chronic nerve edema induced by feeding a galactose-rich diet for two years. The mechanism for edema is the sorbitol pathway which generates osmotically active polyols from galactose or glucose. The blood-nerve barrier impedes diffusion of macromolecules from peripheral nerves, and endoneurial fluid pressure (EFP) becomes elevated. After 24-26 months of feeding with 40% galactose diet, myelinated nerve fibers showed segmental demyelination with bubbly disintegration of myelin sheaths, axonal degeneration, and remyelination. These pathologic changes were significantly more common than similar abnormalities in age-matched controls. Massive glycogen accumulation in Schwann cells, a unique morphologic finding, appeared only in experimental rats. Since edema and increased EFP are the earliest pathologic changes and are present for months before demonstrable nerve fiber injury, we suggest that they are responsible for the changes of myelinated fibers in chronic galactose neuropathy.

Animals↗

PubMedDate not supplied

Endoneurial injection of antisera to myelin antigens.

When antisera to purified myelin antigens were injected into rat sciatic nerves, some produced significant demyelination, whereas others merely induced an inflammatory infiltrate. Extensive demyelination was produced by antisera to galactocerebroside and the peripheral nerve glycoprotein P0. Demyelination resulting from injections of antisera to ganglioside GM1, P2, myelin basic protein, sulfatide, and glucocerebroside did not exceed that produced by normal rabbit serum. Addition of guinea pig complement had no effect. It is of interest that the greatest demyelination followed injection of antisera to two molecules, galactocerebroside and P0, the main antigenic determinants of which present at the Schwann cell surface.

Animals↗

PubMedDate not supplied

Crystalloid inclusions in brain macrophages and hemopoietic tissue in GFAP-IL3 mice resemble inclusions identified in multiple sclerosis.

Crystalloid inclusions or "pole bodies" observed in brain macrophages in human demyelinating disease represent a morphological enigma. Similar inclusions were detected in brain macrophages from the GFAP-IL3 mouse, a transgenic murine model for macrophage mediated demyelination. Mice also showed inclusions in hematopoietic tissue. They appear to be related to phagocytosis and secretion, respectively, as evidenced by the fact that in phagocytosing cells they often merged with lysozomes and that affected cells showed empty channels open to the interstitium. Based on ultrastructural and immunolocalization studies using chaperonin-10, lysozyme, and cathepsin the authors suggest that these inclusions are consistent with phagocytosis-related secretory products. This study may provide insight into the nature and significance of similar macrophage inclusions recently identified in multiple sclerosis.

Animals↗

PubMedDate not supplied

Cycloleucine encephalopathy.

Cycloleucine, a non-metabolizable amino acid analogue produces status spongiosus in cerebral white matter of rats and mice as well as a distinctive lesion of astrocytes. Its mechanisms of action include competition with natural amino acids from transport across the blood-brain barrier leading to inhibition of entry of circulating amino acids into brain, interference with ribosomal RNA maturation, and blockage of transmethylation reactions, including the conversion of homocystine to methionine. Cycloleucine also affects the kidney, producing aminoaciduria. Electron microscopy of cerebral white matter reveals spongiform changes of myelin sheaths caused by separation of myelin lamellae along intraperiod lines and accumulation of whorls of filaments in astrocytes. The myelinopathy is dose related and its toxicity is cumulative due to its long half-life in animals. The findings are discussed with reference to other spongiform myelinopathies, including status spongiosus observed in homocystinuria and other aminoacidurias.

Acute Disease↗

PubMedDate not supplied

Nemaline rods in canine myopathies: 4 case reports and literature review.

The diagnosis of nemaline rod myopathy (NM) is based on the presence of numerous pathognomonic rods within a fresh frozen muscle biopsy specimen. Three forms of congenital NM have been described in humans, and rods have been found to occur in various other conditions. A similar myopathy was described in 1986 in a family of cats. In this report, we describe a case of congenital NM in a 10-month-old Border Collie, an adult-onset NM in an 11-year-old Schipperke, and 2 acquired myopathies with nemaline rods in adult dogs associated with hypothyroidism and Cushing's syndrome. Common clinical features included exercise intolerance, abnormal electromyography, and the presence of nemaline rods in fresh, frozen, and glutaraldehyde-fixed biopsies from proximal appendicular limb muscles. Staining of cryostat sections of muscle biopsy specimens by the modified Gomori trichrome technique disclosed numerous rod bodies that were localized to type 1 fibers by the histochemical adenosine triphosphatase reaction. Accumulation of rods also was demonstrated by electron microscopy in 2 of the cases with localized enlargement and streaming of Z lines. Documentation of NM in a young Border Collie and the adult-onset form in the Schipperke alerts clinicians to the existence of this disorder in these breeds.

Animals↗

PubMedDate not supplied

Ventricular fibrillation in the cat: a model for global cerebral ischemia.

A minimally invasive and standardized means of resuscitating cats from defined periods of ventricular fibrillation (VF) has been developed using methods little different from human cardiopulmonary resuscitation techniques. After a 12 min arrest, the rate of successful resuscitation is greater than 90%, witha resuscitation time of 2.5 +/- 0.7 (SD) min, and a 7 day survival of 70%. All deaths could be related to a specific electroencephalographic event observed acutely post-resuscitation, and were not due to obvious non-neurologic complications. The post-arrest variation in a variety of parameters (blood pressure, blood gases, etc.) was minimal, and the degree of neurologic damage was severe enough to permit evaluation. Such a model is clinically relevant, and may be useful in studying the pathophysiology of global ischemia, and assessing different types of post-arrest therapy.

Animals↗

PubMedDate not supplied

Adenovirus infection of the duodenum in an AIDS patient: an ultrastructural study.

Intractable diarrhea in a 40-year-old woman with terminal acquired immunodeficiency syndrome resulted from adenovirus infection of the duodenal mucosa. Electron microscopic examination of a duodenal biopsy specimen performed because of clinical suspicion of cryptosporidiosis or microsporidiosis showed pathognomonic viral particles in the nuclei of mucosal epithelium. Extensive sloughing of damaged mucosal cells may have contributed to the diarrhea, for which no other cause was found during either pathologic or microbiologic analysis.

AIDS-Related Opportunistic Infections↗