Animal models of myoclonus: an overview.

Attempts to characterize the mechanism(s) associated with myoclonus have led to the development of several naturally occurring and pharmacologically based animal models of myoclonus. Congenital disorders in animals that result in myoclonic seizures have been found in subpopulations of baboons that exhibit photoresponsive myoclonus and in herds of Hereford cattle that possess a fatal, autosomal-inherited imbalance in spinal glycine neurotransmission. Pharmacologically based models of myoclonus use a variety of approaches to product myoclonic seizures in test animals.

Animal model of posthypoxic myoclonus: II. Neurochemical, pathologic, and pharmacologic characterization.

The sudden, brief, shock-like, involuntary movements caused by active muscular contractions or inhibitions characterize myoclonus. It is manifested in a wide variety of pathologic conditions affecting the brain, spinal cord, or peripheral nerves, and is thought to be related to neuronal hyperexcitability. The pathology, physiology, and pharmacology of myoclonus are not well understood as a result of the rarity of the disorder in people and the lack of a suitable animal model. Posthypoxic myoclonus is a major myoclonus syndrome which occurs as a result of severe cerebral ischemia/hypoxia. There has been tremendous interest in the development of a suitable animal model that reflects the etiology and clinical pathology of posthypoxic myoclonus. Recently, we have developed a new animal model of posthypoxic myoclonus in which rats were subjected to a mechanically induced cardiac arrest procedure. Herein, we describe the neurochemical, pharmacologic, and pathologic characteristics of this animal model of posthypoxic myoclonus.

Subchronic administration of N-[2-(3,4-dichlorophenyl) ethyl]-N-methyl-2-(dimethylamino) ethylamine (BD1047) alters sigma 1 receptor binding.

BD1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine) is known to bind with high affinity and selectivity to sigma sites in vitro. In prior in vivo studies, it has been shown to attenuate the dystonic postures and orofacial dyskinesias that are produced by sigma receptor ligands, including the neuroleptic haloperidol. Since abnormal movements, such as dystonic postures and orofacial dyskinesias, are side effects that are associated with many sigma-active neuroleptics, compounds such as BD1047 may have therapeutic potential for preventing and treating these unwanted movements. A possible limitation to the therapeutic potential of BD1047, however, is that at least in cell culture and albeit weak, it can be cytotoxic. Therefore, the present study analyzed the possible neurotoxic effects of in vivo subchronic intracerebroventricular infusion of BD1047 (10 nmol/h) or artificial cerebrospinal fluid (CSF) into rat brains using osmotic minipumps for 7 or 14 days. Following a 24 h wash-out period, the animals were killed, the brains removed, and P2 membranes prepared. Membranes from rats treated for 7 or 14 days with BD1047 showed a marked decrease in [3H](+)-pentazocine binding as compared to membranes from CSF-treated animals, suggesting a loss of sigma 1 receptor binding. Histological examination of brain sections processed for Nissl stains and glial fibrillary acidic protein (GFAP) immunohistochemistry excluded the possibility of a cytotoxically induced down-regulation, suggesting possible receptor internalization or desensitization mediated via sigma 1 sites. Under the conditions used in our study, BD1047 does not appear to be neurotoxic, and the data, when taken together with other studies, suggest that BD1047 acts as a partial agonist at sigma sites.

Vitreous contains a cartilage-related protein.

The vitreous is a clear, gel-like mass in the posterior cavity of the eye. Its major components are type II collagen, hyaluronic acid, and water. A small amount of proteoglycan is also present. All of these molecules are found in cartilage as well. We have now identified a non-collagenous protein in bovine and human vitreous samples which has hitherto been found only in hyaline cartilage and fibrocartilage. This protein has a molecular weight of 550,000 and subunits of 130,000 MW and appears to be a shared cartilage and eye antigen. Its role, if any, in ocular disease associated with rheumatic disorders remains to be determined.