Eicosanoids in human ventricular cerebrospinal fluid following severe brain injury.
Recent evidence has shown that a variety of prostaglandins and leukotrienes can be produced in brain tissue after injury in animals. It has also been speculated that increases in brain prostaglandins occur in humans following injury. Ventricular cerebrospinal fluid (CSF) samples have been obtained from children with static lesions (controls) as well as children with acute brain injury and eicosanoids measured by immunologic techniques. Metabolites of prostacyclin (6-keto-PGF1 a) and thromboxane A2 (thromboxane B2) were the major eicosanoids found in CSF, and levels of these compounds were increased 3-10 times in acutely injured patients. Prostaglandin E2 was also found in lower amounts, although in one case its level was very high. Prostaglandin D2 was also present, but in low amounts. No leukotrienes were found in CSF samples that were purified by HPLC prior to immunoassay. Elevated levels of hydroxyeicosatetraenoic acids (HETEs) were observed in those samples stored frozen, but these metabolites were most probably due to autooxidation of arachidonic acid in CSF. Arachidonic acid concentration in CSF was typically found to be in the range of 10-200 ng/ml, but was found to be 5-10 fold higher in one severely injured patient. Thus, elevated free arachidonic acid and various oxygenated metabolites were observed in CSF following brain injury.
Westcott
J Y
JY
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Murphy
R C
RC
Stenmark
K
K
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015121:6-Ketoprostaglandin F1 alpha / Q000134:cerebrospinal fluid; D000293:Adolescent; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone; D004537:Eicosanoic Acids / Q000134:cerebrospinal fluid*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000134:cerebrospinal fluid; D007223:Infant; D007231:Infant, Newborn; D007975:Leukotriene B4 / Q000134:cerebrospinal fluid; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000134:cerebrospinal fluid; D011458:Prostaglandins E / Q000134:cerebrospinal fluid; D013189:SRS-A / Q000134:cerebrospinal fluid; D013929:Thromboxane B2 / Q000134:cerebrospinal fluid
D001095:Arachidonic Acids; D004537:Eicosanoic Acids; D006893:Hydroxyeicosatetraenoic Acids; D011457:Prostaglandins D; D011458:Prostaglandins E; D013189:SRS-A; D007975:Leukotriene B4; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015232:Dinoprostone; D015230:Prostaglandin D2