The impairment of mitochondrial electron transport can result in higher levels of oxidative stress and release of reactive oxygen species.Glutamine is known to be excitotoxic when present in large amounts, that can cause damage to numerous cellular structures. Excessive glutamine is not found in HD, but the interactions of the altered huntingtin protein with numerous proteins in neurons lead to an increased vulnerability to glutamine. The increased vulnerability is thought to result in excitotoxic effects from normal glutamine levels. Macroscopic changes
Initially, damage to the brain is regionally specific with the dorsal striatum in the subcortical basal ganglia being primarily affected, followed later by cortical involvement in all areas. Other areas of the basal ganglia affected include the substantia nigra; cortical involvement includes cortical layers 3, 5, and 6; also evident is involvement of the hippocampus, Purkinje cells in the cerebellum, lateral tuberal nuclei of the hypothalamus and parts of the thalamus. These areas are affected according to their structure and the types of neurons they contain, reducing in size as they lose cells. Striatal medium spiny neurons are the most vulnerable, particularly ones with projections towards the external globus pallidus, with interneurons and spiny cells projecting to the internal globus pallidus being less affected. HD also causes an abnormal increase in astrocytes and activation of the brains immune cells, microglia.The basal ganglia play a key role in movement and behavior control. Their functions are not fully understood, but theories propose that they are part of the cognitive executive system and the motor circuit.
Nicardipine (Cardene) is a medication used to treat high blood pressure and angina. It belongs to the dihydropyridine class of calcium channel blockers. It is also used for Raynauds phenomenon. It is available in by mouth and intravenous formulations. It has been used in percutaneous coronary intervention. Nicardipine has been used as an alternative to sodium nitroprusside, especially because sodium nitroprusside is light sensitive and a fresh solution must be prepared. Its mechanism of action and clinical effects closely resemble those of nifedipine and the other dihydropyridines (amlodipine, felodipine), except that nicardipine is more selective for cerebral and coronary blood vessels. Nicardipine also has a longer half-life than nifedipine. Nicardipine was approved by the FDA in December 1988. The patent for both Cardene and Cardene SR expired in October 1995.It was patented in 1973 and approved for medical use in 1981. See also
Calcium channel blocker toxicity


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