Human glial cell production of lipoxygenase-generated eicosanoids: a potential role in the pathophysiology of vascular changes following traumatic brain injury.
Acute cerebrovascular changes which occur following traumatic brain injury represent a highly complex, multifactorial pathophysiologic process which is poorly understood. It is now recognized that, under normal conditions, the brain is a source of a variety of arachidonic acid metabolites which are synthesized by both cyclooxygenase and lipoxygenase. The specific cellular source of these highly vasoactive substances remains controversial. Recent work has demonstrated that lipoxygenase products were detected by immunosensitive assay in whole brain samples from a gerbil concussive injury model, yet the production of leukotrienes could not be accounted for by cerebral vessels and their contents alone. It has been theorized that the probable source for these metabolites is the cortical neuron. We sought to elucidate whether cultured human glial cells, obtained from specimens removed at the time of surgery, are a significant source of lipoxygenase products as measured by high performance liquid chromatography (HPLC). We observed that these cells consistently produced 5, 12, and 15-HETE class eicosanoids despite failure to produce significant cyclooxygenase products. These preliminary findings are of considerable interest because these lipoxygenase products are known to be highly vasoactive as well as potent mediators of increased vascular permeability. Since it is known that mechanical perturbation of cell membranes stimulates the release of arachidonic acid from membrane phospholipids, it is conceivable that the production of these eicosanoids following traumatic brain injury could account for local cerebrovascular changes including both vasospasm and interstitial edema formation.
Hariri
R J
RJ
Aitken Neurosurgery Laboratory, Division of Neurosurgery, Cornell University Medical Center, New York, NY 10021.
Ghajar
J B
JB
Pomerantz
K B
KB
Hajjar
D P
DP
Giannuzzi
R F
RF
Tomich
E
E
Andrews
D W
DW
Patterson
R H
RH
D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D008084:Lipoxygenase / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*
D006893:Hydroxyeicosatetraenoic Acids; D000001:Calcimycin; D008084:Lipoxygenase