Neuropathological Mechanisms

The electrophysiological and neuropathological changes are similar to the axonal neuropathy and prominent loss of unmyelinated fibers seen in DSP (Simpson and Tagliati 1995). Although the specific pathological mechanisms of ATN are not fully known, there is abundant indirect evidence of mitochondrial dysfunction as a principal mechanism. Prominent mitochondrial disruption and cristae abnormalities... 

Chang, L.W. 1986. Neuropathology of trimethyltin a proposed pathogenetic mechanism. Fundam. Appl. Toxicol. 6 217-232. 

Chang LW Neuropathology of trimethyltin A proposed pathogenic mechanism. Fundam Appl Toxicol 6 217-232, 1986... 

Lees G. J. (1991). Inhibition of sodium-potassium-ATPase a potentially ubiquitous mechanism contributing to central nervous system neuropathology. Brain Res Brain Res Rev. 16 283-300. 

Volterra A., Trotti D., Floridi S., and Racagni G. (1994). Reactive oxygen species inhibit high-affinity glutamate uptake molecular mechanism and neuropathological implications. Ann. N.Y. Acad. Sci. 738 153-162 153-162. 

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. 

---