Effect of Experimental Subarachnoid Hemorrhage on CSF Eicosanoids in the Rat

Abstract

A simple and inexpensive experimental model of subarachnoid hemorrhage (SAH) was developed in the rat. Based on accumulating data indicating the important role of arachidonic acid metabolites in the etiology of delayed cerebral vasospasm, we investigated changes induced by SAH on cerebrospinal fluid (CSF) levels of prostaglandin E₂ (PGE₂), F_2α (PGF_2α), and thromboxane B₂ (TXB₂). SAH was produced by the cisternal injection of blood via percutaneous suboccipital puncture. SAH rats (n = 200) were injected with 300 μl of fresh autologous arterial blood; Control rats (n = 100) received the same volume of mock CSF. In 60 additional animals, no injections were made. To follow the changes induced by SAH on both the spectrum and time course of CSF eicosanoids, cisternal CSF samples were collected under basal conditions, 6, 12, and 36 after cisternal injection. PGE₂, PGF_2α, and TXB₂ were assayed in aliquots of CSF obtained by pooling samples from each experimental group. Eicosanoids were assayed using radioimmunoassay techniques. Arterial spasm was verified in parallel groups of SAH and control rats by comparison of the angiographic diameters of the basilar arteries (BA) and middle cerebral arteries (MCA) to that of the stapedial artery. CSF levels of all three eicosanoids were significantly higher in the SAH groups compared to both noninjected and mock-CSF injected control rats. These increases in concentrations of eicosanoids were accompanied by a decrease in the mean vascular diameter (77.5–82.0% of control) on day 2 following cisternal injection. We conclude that marked elevations of spasmogenic eicosanoids in the CSF are associated with experimental SAH. The simplicity of the model, combined with the ready availability and low cost of rats, highlights its potential usefulness for investigating cerebral vasospasm following SAH.