bromochloroacetic-acid and Demyelinating-Diseases

In an experimental autoimmune animal model, retinal ganglion cell (RGC) loss was induced through immunization with glaucoma-related antigens. The target of this study was to investigate the pathomechanism behind this decline and the serum antibody reactivity against ocular and neuronal tissues after immunization with glaucoma- and non-glaucoma-associated antigens.. Rats immunized with optic nerve antigen homogenate (ONA) or keratin (KER) were compared to control rats (CO). Intraocular pressure (IOP) was measured, and the fundi were examined regularly. Four weeks afterward, cells were counted in retinal flat mounts. Retina, optic nerve, and brain sections from healthy animals and optic nerve sections from immunized animals were incubated with serum collected at different time points. The occurrence of autoreactive antibodies was examined. Signs of antibody deposits, microglia activation, and demyelination were sought in optic nerves of immunized animals. Brain sections were examined for abnormalities.. No IOP or fundus changes were observed. Animals immunized with ONA showed a significant cell loss compared with the CO group. Elevated autoreactive antibodies against retina, optic nerve, and brain were observed. Animals immunized with KER, despite their immunologic response against KER, demonstrated neither RGC loss, nor increased development of autoreactive antibodies. Optic nerve from animals immunized with ONA demonstrated antibody accumulation, glia activation, and demyelination. No such observations were made in the KER or CO groups. Brain sections were without pathologic findings.. Systemic autoimmunity against ocular and neuronal epitopes, mediated by accordant autoreactive antibodies, is involved in the inflammatory processes that cause RGC degeneration in this experimental animal model.

Topics: Animals; Autoantibodies; Brain; Demyelinating Diseases; Disease Models, Animal; Epitopes; Glaucoma; Immunization; Immunoglobulin G; Intraocular Pressure; Keratins; Male; Microglia; Nerve Degeneration; Nerve Tissue Proteins; Optic Nerve; Rats; Rats, Inbred Lew; Retinal Ganglion Cells

Species and sex differences in susceptibility to vincristine sulphate (VCR)-induced olfactory epithelial lesions were investigated among the BALB/c mice, Crj: CD(SD) IGS rats and common marmoset monkeys following a single intravenous administration on day 1. As dosage levels, the 0.17-fold LD10, 0.6-fold LD10 and LD10 were used for mice and rats, and a maximum tolerated dose (MTD) was chosen only for monkeys. The order of strength of VCR action on peripheral neuropathic signs, body weight gain, and hematological parameters was mice > rats > monkeys, without clear sex differences. Histopathologically, on day 2, single cell death in the olfactory epithelium and vomeronasal organ was observed only in male mice at LD10, and in female mice at 0.6-fold LD10 or more. On day 5, the olfactory epithelium in these mice showed regenerative proliferation suggesting a sign of recovery. On day 10, axonopathy and demyelination in the sciatic and trigeminal nerves were noted in mice of both sexes at 0.6-fold LD10 or more. In rats and monkeys of either sex, however, no morphological changes were observed at any dose level. In conclusion, mice, particularly females, were shown to be more susceptible to VCR-induced apoptosis in the olfactory epithelium than rats and monkeys.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Callithrix; Demyelinating Diseases; Dose-Response Relationship, Drug; Female; Immunohistochemistry; In Situ Nick-End Labeling; Injections, Intravenous; Keratins; Lethal Dose 50; Male; Maximum Tolerated Dose; Mice; Microscopy, Electron, Transmission; Olfactory Mucosa; Rats; Sciatic Neuropathy; Sex Factors; Species Specificity; Trigeminal Nerve Diseases; Vincristine