CSF leukotriene C4 following subarachnoid hemorrhage

Abstract

Leukotrienes derive from arachidonic acid metabolism via the lipoxygenase pathway and modulate several cellular events. In the central nervous system, leukotrienes are mainly synthesized in the gray matter and in vascular tissues. Their production is enhanced in ischemic conditions and in experimental subarachnoid hemorrhage (SAH). Previous studies have indicated the ability of the leukotrienes C4 and D4 to constrict arterial vessels in vivo and in vitro and have suggested their involvement in the pathogenesis of cerebral arterial spasm. In the present study, the authors measured lumbar and cisternal cerebrospinal fluid (CSF) levels of leukotriene C4 in 48 patients who had suffered aneurysmal SAH. In 12 of the cases, symptomatic and radiological spasm was evident. The mean lumbar CSF level of immunoreactive-like activity of leukotriene C4 (i-LTC4) was significantly higher (p less than 0.005) than in control cases, while the cisternal CSF level was higher than the lumbar mean concentration (p less than 0.005). Patients presenting with vasospasm had significantly higher levels of i-LTC4 compared to patients without symptomatic vasospasm. This is the first report concerning monitoring of i-LTC4 levels in the CSF after SAH. The results of this study suggest that: 1) metabolism of arachidonic acid via the lipoxygenase pathway is enhanced after SAH; 2) the higher cisternal CSF levels of i-LTC4 may be part of the biological response in the perianeurysmal subarachnoid cisterns after the hemorrhage; and 3) the higher CSF levels of i-LTC4 in patients presenting with vasospasm suggest that a relationship exists between this compound and arterial spasm and/or reflect the development of cerebral ischemic damage.

Arachidonic acid metabolism and pathophysiologic aspects of subarachnoid hemorrhage in rats.

“…Radioactivity was measured using a liquid scintillation spectrometer (Model 3320, Packard Instruments) as previously described. 17 ' 28 Results are expressed as nanograms per milligram protein. Protein content was determined according to the method of Lowry et al 29 The assay sensitivity was 15 pg/mg protein.…”

Subarachnoid Hematoma Attenuates Vasodilation and Potentiates Vasoconstriction Induced by Vasoactive Agents in Newborn Pigs

“…In dog and monkey models of subarachnoid hematoma, reduced synthesis of dilator prostanoids has been observed (8,(14)(15)(16)(17), but no change was observed in the piglet model (18). Increased secretion of spasmogenic agents such as PGF,,, LTC,, and ET-1 have been reported after hemorrhage (8,(18)(19)(20). Studies in adult humans showed elevated levels of vasoconstrictor agents: thromboxanes, leukotrienes, PGF,,, ET-1, and oxyhemoglobin in the cerebrospinal fluid after subarachnoid hemorrhage (6)(7)(8)(21)(22)(23)(24)(25).…”

Effect of high-dose methylprednisolone and U74006F on eicosanoid synthesis after subarachnoid hemorrhage in rats.

“…- 28 In the same experimental model of SAH, a biphasic pattern of arterial spasm was shown 26 : an acute phase occurring 10-15 minutes after SAH, followed by a late phase up to 48 hours after SAH, which is more important from a metabolic point of view.…”

“…Radioactivity was measured using a liquid scintillation spectrometer (model 3320, Packard Instruments) as previously described. 28 Results are expressed in picograms per milligram of protein. The protein content of homogenate was assayed according to Lowry et al 29 with serum albumin as a standard.…”