Neural dysfunction

Neurotoxicity can be defined as any adverse effect on the structure or function of the nervous system related to exposure to a chemical substance (US-EPA 1998, OECD 2004c). According to the TGD (EC 2003), neurotoxicity can be defined as the induction by a chemical of adverse effects in the central or peripheral nervous system, or in sense organs and a substance is neurotoxic if it induces a reproducible lesion in the nervous system or a reproducible pattern of neural dysfunction. ... 

Exposure to neurotoxicants or neurotoxic chemical substances causes severe adverse health effects to the nervous system, which is very sensitive to organometallic compounds and sulfide compounds. These compounds disrupt the normal functioning of the central nervous system, peripheral nerves or sensory organs, and the conduction of nerve impulses. Thus, chemical substances are considered neurotoxicants when they induce a consistent pattern of neural dysfunction. The chemical substances include but are not limited to carbon disulfide, manganese, methyl mercury, organic phosphorous insecticides, tetraethyl lead, thallium, and trialkyl tin compounds. 

Boles Ponto LL, Hichwa RD. Regional neural dysfunctions in 46. chronic schizophrenia smdied with positron emission tomography. Am. J. Psychiatry 2000 157 542-548. 

In a survey by the Indian Council of Medical Research, a total of 186 samples of 20 brands of infant formula milk were collected from retail diops in and around Pune, Bombay, Mysore, Lucknow, and Ludhiana, and analyzed for HCH isomers and DDT-complex. Residues of total HCH and DDT-complex were detected in 175 (94.1%), and 130 (69.9%) of samples, respectively. The study also indicated high levels of metal contamination (As, Cd, Pb, Cu, and Zn) in infant formula milk [22] (see Table 8.6). These collectively cause neural dysfunction. 

Diabetes and hyperglycaemia induce an increase in the synthesis of diacylglycerol resulting in the activation of Protein Kinase C (PKC). The activation of vascular PKC is considered to lead to impairment in vasodilatation and an increase in vasoconstriction, which can occur in the endoneur-ial microvessels and cause a decrease in neural blood flow, resulting in neural dysfunction in diabetes. PKC inhibition has shown beneficial effects in animal studies and preliminary studies in diabetic patients. However, disappointing results in recent phase 2 studies have led to the discontinuation of the development of this compound for the diabetic neuropathy indication. 

Garrow AP, Boulton AIM. Vibration perception threshold- a valuable assessment of neural dysfunction in people with diabetes. Diabet Metab Res Rev 2006 22 411 41. 

Hautkappe, M., M.F. Roizen, A. Toledano, et al. 1998. Review of the effectiveness of capsaicin for painful cutaneous disorders and neural dysfunction. Clin.. Pain 14 (2) 97. 

Boyer, I.J., D.A. Cory-Slechta, and V. Di Stefano. 1985. Lead induction of crop dysfunction in pigeons through a direct action on neural or smooth muscle components of crop tissue. Jour. Pharmacol. Exp. Ther. 234 607-615. 

Figure 17.4. Epigenetics in the nervous system. Regulation occurs in response to synaptic inputs and/or other psychosocial-environmental stimuli. The external stimuli result in changes in the transcriptional profile of the neuron and eventually affects neural function(s). Many disorders of human cognition might involve dysfunction of epigenetic tagging. (See color insert.)...

Reversibility of Noncarcinogenic Systemic Effects. Most case reports of humans intoxicated with carbon tetrachloride indicate that, if death can be averted, clinical signs of renal and hepatic dysfunction diminish within 1-2 weeks, and recovery often appears to be complete. This is primarily because both liver and kidney have excellent regenerative capacity and can repair injured cells or replace dead cells (Dragiani et al. 1986 Norwood et al. 1950). However, high doses or repeated exposure can lead to fibrosis or cirrhosis that may not be reversible. The depressant effects of carbon tetrachloride on the central nervous system do appear to be reversible, although any neural cell death that occurs (Cohen 1957) is presumably permanent. 

Obsessive-compulsive disorder is a disorder of the frontal-subcortical system. A characteristic of this group of disorders is a complex interaction between the exogenous and endogenous stimuli and the neural systems that link stimuli to cognitive and behavioral responses. Although cortical dysfunction cannot be excluded as a basis for OCD symptoms, there is evidence that basal... 

Davidson, R.J., Putnam, K.M., and Larson, C.L. (2000) Dysfunction in the neural circuitry of emotion regulation—a possible prelude to violence. Science 289(5479) 591-594. 

The fact that some DA neurons encode expectancy of reward is especially provocative, as it implies that dysfunctions within these circuits may give rise to erroneous computations of reward expectancy, which may in turn relate to the aberrant drug cravings observed so commonly in drug addiction. Satisfying such aberrant neural expectancies, then, may be a necessary component of any successful pharmacotherapy for addiction. 

Ourednik, J., Ourednik, V., Lynch, W.P., Schachner, M., Snyder, E.Y. (2002). Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons. Nat Biotechnol, 20, 1103-10. 

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