Composition of the cerebral white matter sterol ester fraction in severe experimental hypoxia

Abstract

Severe hypoxia was induced in adult Wistar rats by means of exposure to an atmosphere containing 2.0 kPa of oxygen for a period of 3 minutes. The animals were sacrificed at 4 different periods following the hypoxia incident: 4 and 24 hours, 14 days and 2 months, respectively, and sterol esters (ES) were isolated from the myelin fraction of the cerebral white matter. After hydrolysis, the isolated sterols were fed into a GC-MS system (gas chromatography-mass spectrometry). The following sterols were identified in the hydrolysates: cholesterol, cholesta-3,5-dien, cholesta-4-en-3-on, 22-propyl-3 beta-hydroxy-5,24-cholestadien. The induced severe hypoxia lead to a twofold increase of the SE content in the myelin fraction of experimental rats (24 hrs, 14 days and 2 months samples). Cholesterol was the dominating sterol species in this fraction, however other minor sterols were found as well. The dynamic equilibrium between free and esterified sterols in the brain is controlled by the activity of respective sterol ester hydrolases. Esterification of free sterols renders them inaccessible for other metabolic changes, such as demethylation, reduction, isomerisation of double bonds, hydroxylation, and thus may lead to compositional changes of the myelin sterol spectrum under conditions of severe hypoxia.