Chemical Events Behind Leukoaraiosis: Medicinal Chemistry Offers New Insight into a Specific Microcirculation Disturbance in the Brain (a Chemical Approach to a Frequent Cerebral Phenotype)

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Abstract:

Leukoaraiosis (LA), one of the most frequent causes of cognitive disturbances, is presumed to involve vascular demyelinization and cerebral small-vessel diseases. Although it has been suggested that the development of LA is associated with cerebral circulatory disturbances, the pathomechanism of this circulatory problem is not completely understood. Extensive debate is continuing as regards the detailed features of the circulatory disturbances in LA. An endothelial dysfunction may lead to breakdown of the blood-brain barrier, thereby resulting in chronic toxic edema in the perivascular areas. This can then cause the slow development of LA. Endothelial dysfunctions may also give rise to molecular events involving a shift in the O2 and CO2 trafficking system in the red blood cells, which will result in special complex microcirculation disturbances in the white matter of the brain; these molecular phenomena may therefore account for chronic slight hypoxia leading to the development of LA. This article discusses these hypothetical alternative molecular events behind LA. The review also illustrates how medicinal chemistry can offer new insight into a common, but still mysterious cerebral phenotype.

Keywords: Endothelial dysfunction; blood-brain barrier; demyelinization; leukoaraiosis; medicinal chemistry; microcirculation; red blood cells

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986707780362907

Affiliations: H-5600 Bekescsaba, Pipacs koz 9, Hungary.

Publication date: April 1, 2007

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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