Animal models nervous system disease

There are multitudes of namrally occurring diseases of the central nervous system, including degenerative, traumatic, neoplastic, and metabolic disorders. Naturally occurring diseases for which there are potential models include models for include Parkinson s disease (PD), Huntington s disease (HD), Alzheimer s disease (AD), cerebral ischemia, miscellaneous neoplastic conditions, and lysosomal storage diseases. Examples of selected animal models of human disease will be briefly suimnarized. 

Pentylenetetrazol (188) is a drug with profound stimulatory activity on the central nervous system. As such, the agent was at one time used in shock therapy for treatment of mental disease. Although it has since been supplanted by safer methods, the agents still occupy an important role in various experimental animal models in pharmacology. Addition of hydrazine to the imino ether (186) obtained from caprolactam affords 187. Treat-... 

The human leukodystrophies are inherited disorders of central nervous system white matter. These disorders are characterized by a diffuse deficiency of myelin caused by a variety of genetic lesions and often manifest before 10 years of age (Table 38-1). Some are caused by mutations in the PLP gene and resemble the PLP animal mutants described in Chapter 4 [ 1,23]. As with the animal models, depending on the nature of the mutation, they vary from a severe form in connatal Pelizaeus-Merzbacher disease (PMD) through an intermediate phenotype in classical PMD to a mild phenotype in spastic paraplegia. It is noteworthy that some mutations of the PLP gene also cause a peripheral neuropathy [24], very probably related to the expression of low levels of PLP in peripheral nerve (see Ch. 4). 

Walters, C.E., Pryce, G., Hankey, D.J., Sebti, S.M., Hamilton, A.D., Baker, D., Greenwood, J., and Adamson, P. (2002). Inhibition of Rho GTPases with protein pre-nyltransferase inhibitors prevents leukocyte recruitment to the central nervous system and attenuates clinical signs of disease in an animal model of multiple sclerosis. J Immunol 168 4087-4094. 

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