Arachidonic acid cerebral

A series of 4-arylpyrimidines that arc amine substituted at pyrimidine C-2 was prepared. FK360 was most effective from this group on both arachidonate-induced cerebral oedema in rats and as an in vitro inhibitor of lipid peroxidation. The authors link effects of FK360 to the arachidonic acid cascade (Kuno et al., 1992). This is an unusual structure. 

Free arachidonic acid, along with diacylglycerols and free docosahexaenoic acid, is a product of membrane lipid breakdown at the onset of cerebral ischemia, seizures and other forms of brain trauma 585... 

Under physiologic conditions, the balance of membrane lipid metabolism, particularly that of arachidonoyl and docosahexaenoyl chains, favors a very small and tightly controlled cellular pool of free arachidonic acid (AA, 20 4n-3) and docosahexaenoic acid (DHA, 22 6n-3), but levels increase very rapidly upon cell activation, cerebral ischemia, seizures and other types of brain trauma [1, 2], Other free fatty acids (FFAs) in addition to AA, released during cell activation and the initial stages of focal and global cerebral ischemia, are stearic acid (18 0), palmitic acid (16 0) and oleic acid (18 1). 

Free arachidonic acid, along with diacylglycerols and free docosahexaenoic acid, is a product of membrane lipid breakdown at the onset of cerebral ischemia, seizures and other forms of brain trauma. Because polyunsaturated fatty acids are the predominant FFA pool components that accumulate under these conditions, this further supports the notion that fatty acids released from the C2 position of membrane phospholipids are major contributors to the FFA pool, implicating PLA2 activation as the critical step in FFA release [1,2] (Fig. 33-6). 

Ellis, E.F., Wright, K.F., Wei, E.P. and Kontos, H.A. (1981) Cyclooxygenase products of arachidonic acid metabolism in cat cerebral cortex after experimental concussive brain injury, J. Neurochem. 37, 892-896. 

It has been shown that arachidonic acid metabolism could contribute to the pathogenesis of cerebral edema. Treatment with indomethacin, a COX inhibitor, nordihydroguaiaretic acid, a LOX inhibitor, or their combination significantly reduced vasogenic edema induced by freezing lesions (Yen and Lee, 1987). 

Kooli, A., Keimorvant-Duchemin, E., Sermlaub, F., Bossolasco, M., Hou, X., Honore, J.C., Deimery, P.A., Sapieha, P., Varma, D.R., Lachapelle, P., Zhu, T., Tremblay, S., Hardy, P., Jain, K., Balazy, M., Chemtob, S. (2008). Trani -arachidonic acids induce a heme-oxygenase-dependent vasorelaxation of cerebral micro vasculature. Free Rad. Biol. Med. 44 815-25. 

It was observed that rats with a transient MCA occlusion have a larger brain infarction when recombinant human IL-1 P is injected into the lateral ventricle immediately after reperfusion [7,41]. Similar results have been obtained in rats with a permanent MCA occlusion [7,42]. The intraventricular injection of recombinant human IL-1 p also enhances the formation of brain edema and increases both the number of neutrophils in ischemic areas and neutrophil-endothelial cell adhesion. The most widely recognized functions of IL-1 appear to be the induction of endothelial cell adhesion molecule expression and the promotion of neutrophil tissue infiltration [7,41]. These observations suggest that IL-1 may play a deleterious role in cerebral ischemia. Studies showing a reduction in infarct size after the administration of IL-1 antagonists or inhibitors provide further evidence of the importance of IL-1 in cerebral ischemia [41,43-49]. The possible harmful mechanisms induced or activated by IL-1 include fever, increased heart rate and arterial blood pressure, enhancement of N-methyl-D-aspartate-mediated injury, proliferation of microglia, release of arachidonic acid, and stimulation of NO synthesis [7,50]. 

Yu ACH, Chan PH, Fishman RA (1986) Effects of arachidonic acid on glutamate and gamma-aminobutyric acid uptake in primary cultures of rat cerebral cortical astrocytes and newtons. J Neurochem 47 1181-1189. 

Aside from essential amino acids, the n-3 and n-6 fatty acids constitute the largest chemical component of the cerebral cortex and retina that can be obtained only from the diet. The body cannot synthesize either the n-3 or the n-6 structure. Once the basic n-3 structure is consumed in the form of linolenic acid (18 3), the body can synthesize the longer-chained and highly polyunsaturated fatty acid docosahexaenoic acid (22 6), which is the n-3 fatty acid so predominant in the nervous system. Similarly, in the n-6 series, linoleic acid (18 2) is converted to arachidonic acid (20 4), the predominant n-6 fatty acid... 

Using the serial data for the cerebral cortex, plasma, and erythrocytes, we constructed accumulation and decay curves for several key fatty acids in these tissues, which provided gross estimates of their turnover times after fish-oil feeding to n-3 fatty acid-deficient monkeys (Table 2). For cerebral cortex, a steady state was reached after 12 wk of fish-oil feeding for DHA, but 22 5n-6 took longer to decline to the low levels found in the cortex of control animals. The half-lives of DHA in cerebral phospholipids ranged from 17 to 21 d 21 d for phosphatidylethanolamine, 21 d for phosphatidylserine, 18 d for phosphatidylinositol, and 17 d for phosphatidylcholine. The corresponding values for 22 5n-6 in these same phospholipids were 32,49,14, and 28 d, respectively. The half-lives of linoleic acid, EPA, and DHA in plasma phospholipids were estimated to be 8,18, and 29 d, respectively. In the phospholipids of erythrocytes, linoleic acid, arachidonic acids, EPA, and DHA had half-lives of 28, 32, 14, and 21 d, respectively. 

Inhibition of brain P-450 arachidonic acid epoxygenase decreases baseline cerebral blood flow. Am. J. Physiol. 271, H1541-H1546. 

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