Cerebral edema induced by arachidonic acid: role of leukocytes and 5-lipoxygenase products.
Arachidonic acid is released from cellular phospholipid membranes after brain injury associated with vasogenic edema. Intracerebral injection of arachidonic acid results in rapid breakdown of the blood-brain barrier, followed by an increase in brain water and sodium content. This effect is diminished by a 5-lipoxygenase inhibitor, but is unaffected by indomethacin, an inhibitor of cyclooxygenase. Leukocytes are rich in 5-lipoxygenase and mediate posttraumatic extracellular edema in other tissues. We sought to determine whether leukocytes are necessary for arachidonic acid-induced vasogenic edema and whether they are the primary source of 5-lipoxygenase activity. Intracerebral injection of arachidonic acid (10 micrograms) was performed in 21 rats divided into three groups. One hour after injection, the area of Evans blue stain extravasation on the corona slice through the needle tract was quantitated by polar planimetry and taken as a measure of blood-brain barrier permeability. Control animals (n = 7) had a 3.44 +/- 0.19 mm2 area of Evans blue cortical stain. Rats (n = 7) pretreated with a lipoxygenase inhibitor (BW755C) had a significant decrease (P less than 0.05) in the area of Evans blue extravasation was not significantly different from that seen in the control animals. Intracerebral injection of saline or eicosapentaenoic acid showed only minimal staining along the needle tract (0.14 +/- 0.08 mm2). We have confirmed the role of the 5-lipoxygenase products in arachidonic acid-induced vasogenic edema. The primary source of cerebral 5-lipoxygenase activity does not appear to be in leukocytes and is most likely within the brain parenchyma.
Papadopoulos
S M
SM
Section of Neurosurgery, University of Michigan, Ann Arbor.
Black
K L
KL
Hoff
J T
JT
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology*; D001091:Arachidonate Lipoxygenases / Q000502:physiology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000502:physiology*; D001812:Blood-Brain Barrier; D001929:Brain Edema / Q000503:physiopathology*; D002199:Capillary Permeability; D006400:Hematocrit; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D001091:Arachidonate Lipoxygenases; D001094:Arachidonate 5-Lipoxygenase