Neuropathological lesions

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). 

On the one hand, the biochemical study of the neuro-pathological lesions led to the identification of their main molecular components. On the other hand, the study of rare, familial forms of Alzheimer s disease, frontotemporal dementia and Parkinson s disease led to the identification of gene defects that cause inherited variants of the different diseases. Remarkably, in these cases, the defective genes have been found to encode or increase the expression of the main components of the neuropathological lesions. It has therefore been established that the basis of the familial forms of these diseases is a toxic property conferred by mutations in the proteins that make up the filamentous lesions. A corollary of this insight is that a similar toxic property may also underlie the much more common, sporadic forms of the diseases. 

Coombs DW, Fratkin JD, Meier FA, Nierenberg DW, Saunders RL. Neuropathologic lesions and CSF morphine concentrations during chronic continuous intraspinal morphine infusion. A clinical and post-mortem study. Pain 1985 22(4) 337-51. 

FIGURE 21.2 Characteristic neurodegenerative disease neuropathological lesions involve deposition of abnormal proteins. From Ross Poirier, 2004. Copyright 2004 with permission from Nature Publishing Group.)... 

By combining these methods for PrPSc typing with neuropathological lesion profiles [49] and, importantly, patterns of brain PrPSc deposits [50-53], prion strains can be fairly well characterized. However, current protocols are quite cumbersome and time-consuming. Therefore, other approaches for discriminating between prion strains, using conformation-sensitive probes [54] or cell culture systems [55], have been advocated. 

Abou-Donia ex al. (1996b) Hen PB, DEET, chlorpyrifos Combined exposure. enhanced inhibition of bruin AChE, BuChE, and NTE, neurutogie dysfunction, and neuropathologic lesions... 

Given that termination of seizure activity protects against development of neuropathological lesions (especially neuronal necrosis) in brain tissues of experimental animals (Martin et al., 1985 Shih et al., 2003 Marrs and Sellstrom, 2007), focus on anticonvulsant therapy is critical. Reduced potential for permanent brain damage in... 

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