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

Abstract

We studied the ex vivo production of prostaglandin D 2 , prostaglandin E^, 6-ketoprostaglandin F la , and leukotriene C 4 in the brain tissue of rats subjected to experimental subarachnoid hemorrhage. The ex vivo method allows the study of arachidonic acid metabolites released from brain slices at different times after subarachnoid hemorrhage induction and reflects the residual capacity for arachidonic acid metabolism after the pathologic event The rats were sacrificed 30 minutes, 1 and 6 hours, and 2 days after subarachnoid hemorrhage was induced by the injection of 0 JO ml autologous arterial blood into the cisterna magna. Concentration of prostaglandin D 2 and 6-ketoprostaglandin F, a was increased significantly relative to control 2 days after induction. The concentration of prostaglandin E 2 was increased significantly 6 hours after induction, while ex vivo production of leukotriene C 4 was increased significantly at 1 and 6 hours and 2 days. The correlation between these results and the occurrence of vasospasm after subarachnoid hemorrhage is discussed. The results obtained from the ex vivo incubation of brain tissue slices after experimental subarachnoid hemorrhage suggest that after the hemorrhage there is a significant modification of brain eicosanoid metabolism, which could be of great importance in interpreting the pathogenesis of subarachnoid hemorrhage-related neuronal impairment (Stroke 1990;21:328-332)

Early Events After Aneurysmal Subarachnoid Hemorrhage

“…In experimental animals, oxidative stress is present within the fi rst 24 h [ 59 ] and, in patients, within the fi rst 72 h after SAH [ 60 ]. In patients, an increase in lipid peroxidation products during the early phase of SAH is associated with the pathogenesis of delayed vasospasm and with poor outcome [ 61 , 62 ].…”

Significance of Brain Tissue Oxygenation and the Arachidonic Acid Cascade in Stroke

“…Preclinical models of stroke have revealed substantive evidence of elevated oxidants as early as 20 minutes following the onset of stroke (89,113), and uncontrolled oxidative metabolism of AA as early as 1 hour following hemorrhagic and ischemic stroke (45,148 Threedimensional reconstruction of coronal slices permits visualization of the brain from dorsal and oblique positions. HBO during MCAO significantly decreased stroke-induced lesion volume in iHBO animals, while in rHBO animals is increased lesion volume.…”

The Novel 5-Lipoxygenase Inhibitor ABT-761 Attenuates Cerebral Vasospasm in a Rabbit Model of Subarachnoid Hemorrhage

“…These substances are produced in the brain by cerebral arteries and by neurons (8,10,17,19,23,30,44,59).…”

“…These include a direct vasoconstrictor effect on cerebral arteries as a result of the following: activation of phospholipase C, which induces intracellular calcium mobilization; the direct action of cysteinyl leukotrienes, HPETE acid, and HETE acid; the stimulation of free radical production by the reduction of 5-HPETE acid to 5-HETE acid; the antagonism of the vasodilatory effects of prostacyclin by the activity of leukocytes attracted by leukotriene B 4 ; and the promotion of an inflammatory reaction in the arterial wall and in the subarachnoid space. The inflammatory response resulting from the leukocyte infiltration of the arterial wall further promotes the release of lipoxygenase products and modifies the normal structure of the vessel, possibly sustaining a self-maintaining reaction that leads to chronic vasospasm (10).…”