The influence of MK-801 on the hippocampal free arachidonic acid level and Na+,K+-ATPase activity in global cerebral ischemia-exposed rats

Chronic daily administration of ethyl docosahexaenoate protects against gerbil brain ischemic damage through reduction of arachidonic acid liberation and accumulation

“…Previous studies have reported a significant decrease in brain Na,K-ATPase activity after ischemia [6,10,42]. There are several reasons for the ischemia-induced fall in Na,KATPase activity, such as the decline of ATP content and increased production of enzymatic inhibitors [43].…”

“…An aliquot of lipid extract was separated by one-dimensional thin-layer chromatography (TLC) on silica gel-60 (E. Merck, Germany). Petroleum ether/ether/ acetic acid (97:3:1, vol/vol/vol) and petroleum ether/ether/ acetic acid (80:20:1, vol/vol/vol) were used as developing solvents for free fatty acids [6]. Bands were visualized with 1% 2V7V-dichlorofluorescein in methanol solution under a UV lamp and were identified by comparison with fatty acid standards.…”

“…It is well known that arachidonic acid (AA; 20:4nÀ6), comprising the major portion of free fatty acids, is liberated from membrane phospholipids by phospholipase after ischemia [1][2][3]. There is an agreement that free AA is either reesterified to phosphatidylinositol and phosphatidylcholine, as well as polyphosphoinositides, for the renewal of membrane lipids after ischemia-reperfusion [3,4], or is oxidized by lipooxygenases and cyclooxygenases, producing prostaglandins (PGs), leukotrienes and other bioactive eicosanoids [5,6]. Free AA accumulation during ischemia correlated with time for ATP depletion [7] because ATP is required for the activation of free AA to its acyl-CoA and for the reincorporation of liberated AA into phospholipids [8].…”

“…Free AA accumulation during ischemia correlated with time for ATP depletion [7] because ATP is required for the activation of free AA to its acyl-CoA and for the reincorporation of liberated AA into phospholipids [8]. The accumulation of free AA and its metabolites induces pathological events such as membrane destruction [6,9], which may affect the activities and functions of different ion channels, transporters and other membrane-associated enzymes, particularly the most vulnerable -Na,K-ATPase, since its activity is very sensitive to even small changes in the plasma membrane lipid microenvironment [9,10]. Na,K-ATPase normally maintains intracellular and extracellular Na + and K + concentrations.…”

Chronic administration of ethyl docosahexaenoate reduces gerbil brain eicosanoid productions following ischemia and reperfusion

“…The liberated free AA after ischemia is generally thought to be either reincorporated into the membrane phospholipids [2,3] or the precursor of thromboxanes (TXs), prostaglandins (PGs), leukotrienes (LTs) and other bioactive eicosanoids [4,5], several of which have been implicated in the brain damage following ischemia and reperfusion [6][7][8]. Arachidonate metabolism is stimulated by ischemia, but the molecular oxygen is required in both cyclooxygenase and lipoxygenase pathways [9].…”