Neuropathology animals

Two types of OPIDN have been described in animals (Abou-Donia and Lapadula 1990). Type I is produced by compounds with a pentavalent phosphorus (like TOCP), and Type II is produced by compounds with a trivalent phosphorus. Characteristics used to differentiate between the types of OPIDN include species selectivity, age sensitivity, length of latent period, and morphology of neuropathologic lesions. Thus, at doses that did not produce death due to acetylcholinesterase inhibition, TOCP (a Type I compound) produced lesions in the spinal cord of rats without producing ataxia. In contrast, triphenyl phosphite (a Type II compound) produced delayed (1 week) ataxia in the rat and a distribution of spinal cord lesions distinct from those produced by TOCP (Abou-Donia and Lapadula 1990). 

Neuropathologic studies in animals with experimental thiamine deficiency consistently show early damage to glial cells rather than neurons. Studies in human patients with Wernicke s encephalopathy likewise show changes in astroglia, together with microglial proliferation, which is... 

A recent study showed significant increases of expression of eNOS in the brains of rats treated with pyrithia-mine [20]. Increased eNOS expression was apparent prior to the onset of neurological symptoms and was restricted to vulnerable medial thalamus and inferior colliculus. Expression of inducible (iNOS) and neuronal (nNOS) isoforms were minimally altered in brain in thiamine deficiency and it has also been shown that targeted disruption of the eNOS (but not the iNOS or nNOS) gene results in reduced extent of neuropathological damage in thalamus of thiamine deficient animals [21] (Fig. 34-5). 

D Mello, G.D. 1987. Neuropathological and behavioural sequelae of acute cyanide toxicosis in animal species. Pages 156-183 in B. Ballantyne and T.C. Marrs (eds.). Clinical and Experimental Toxicology of Cyanides. Wright, Bristol. 

HD In Drosophila models of Huntington s disease, the HDAC inhibitors SAHA and sodium butyrate arrest the progressive neuronal degeneration and lethality (Steffan et al, 2001). SAHA and sodium butyrate have also been demonstrated to extend survival, ameliorate motor deficits and delay characteristic neuropathology in the mouse Huntington s disease model, R6/2 (Ferrante et al, 2003 Hockly et al, 2003). In NaBu-treated animals, animals displayed enhanced acetylation status of histones and pro-survival transcription factors like Spl and reduction in several neuropatho-logical hallmarks like striatal neuronal atrophy (Ferrante et al, 2003). Consistent with the idea that HDAC inhibition relieves transcriptional repression and that protection is downstream of mutant htt, neither SAHA nor sodium butyrate decreased mutant htt expression or aggregates (Ferrante et al, 2003 Hockly et al, 2003). 

Autism Neuropathology, Alterations of the GA-BAergic System, and Animal Models... 

BBB disruption is associated with significant side-effects including seizures in experimental animals and neuropathologic changes. The mechanism of the neurotoxicity of BBB disruption is not clear, but may be related to the influx of albumin into brain interstitium from the circulation. Albumin is neurotoxic for astrocytes and normally exists at concentrations in brain interstitial fluid that are approximately 1,000-fold lower than the concentrations of albumin in the circulation. This approach is not therefore recommended as an effective strategy for drag delivery to the CNS. 

---