leukotriene-b4 and Subarachnoid-Hemorrhage

Leukotriene B4 (LTB4) is a highly potent neutrophil chemoattractant and neutrophils induces inflammatory response and oxidative stress when they recruit to and infiltrate in the injuried/inflamed site, such as the brain parenchyma after aneurysmal subarachnoid hemorrhage (SAH). This study is to investigate the potential effects of inhibition of LTB4 synthesis on neutrophil recruitment, inflammatory response and oxidative stress, as well as early brain injury (EBI) in rats after SAH. A pre-chiasmatic cistern SAH model of rats was used in this experiment. SC 57461A was used to inhibit LTB4 synthesis via intracerebroventricular injection. The brain tissues of temporal lobe after SAH were analyzed. Neuronal injury, brain edema and neurological function were evaluated to investigate the development of EBI. We found that inhibition of LTB4 synthesis after SAH could reduce the level of myeloperoxidase, alleviate the inflammatory response and oxidative stress, and reduce neuronal death in the brain parenchyma, and ameliorate brain edema and neurological behavior impairment at 24h after SAH. These results suggest that inhibition of LTB4 synthesis might alleviate EBI after SAH possibly via reducing the neutrophil-generated inflammatory response and oxidative stress.

Topics: Animals; beta-Alanine; Blood-Brain Barrier; Brain Edema; Brain Injuries; Disease Models, Animal; Inflammation; Leukotriene B4; Male; Neutrophils; Oxidative Stress; Rats, Sprague-Dawley; Subarachnoid Hemorrhage

Smoking is one of the most important risk factors for subarachnoid hemorrhage (SAH). The purpose of this study was to investigate the influence of experimental SAH and arachidonic acid metabolites on nicotine-induced contraction in the rat basilar artery.. Rats were killed at 1 hour and 1 week after SAH, and the basilar artery was isolated and cut into a spiral strip. The effects of various eicosanoid receptor antagonists on nicotine-induced contraction in the rat basilar artery were investigated.. Antagonists of thromboxane A2 (TXA2) and cysteinyl leukotriene (CysLT) receptors did not affect nicotine-induced contraction. In contrast, the antagonists of leukotriene B4 (LTB4) receptors (BLT1 and BLT2) attenuated the nicotine-induced contraction in the rat basilar artery. We also observed that SAH did not influence the effect of TXA2, LTB4, and CysLTs receptor antagonists on the nicotine-induced contraction. These results suggest that TXA2 and CysLTs are not involved in nicotine-induced contraction, while LTB4 potentates this contraction in rat basilar artery.. BLT2 receptor seemed to be more involved in the nicotine-induced contraction than the BLT1 receptor. SAH did not affect the involvement of eicosanoids in the nicotine-induced contraction of the rat basilar artery. The present study shows the involvement of some of the arachidonic acid metabolites into signaling pathways of nicotine-induced contraction. It will serve to improve therapeutic interventions of SAH and suggests a promising approach to protect the cerebral vasculature of cigarette smokers.

Topics: Animals; Basilar Artery; Female; In Vitro Techniques; Leukotriene Antagonists; Leukotriene B4; Muscle Contraction; Muscle, Smooth, Vascular; Nicotine; Nicotinic Agonists; Rats; Rats, Sprague-Dawley; Receptors, Eicosanoid; Receptors, Thromboxane A2, Prostaglandin H2; Subarachnoid Hemorrhage

Severe cerebral vasospasm as confirmed by angiography was induced in dogs by injection of autologous blood into the cisterna magna, and the resultant leukotriene formation in the isolated basilar artery was examined. When stimulated with calcium ionophore (A 23187), the arteries of the treated animals produced a significant amount of leukotrienes B4 (85 +/- 12 pmol/mg protein, n = 3) and C4 (72 +/- 14 pmol/mg), in addition to 5(S)-hydroxy-6,8,11,14-eicosatetraenoic acid. Structural elucidations of these metabolites were performed by radioimmunoassays or gas chromatography-mass spectrometry, following purification with HPLC. The artery of the untreated dog produced none of these compounds from either exogenous or endogenous arachidonic acid, under stimulation with the calcium ionophore. However, the homogenates from both animals converted exogenous leukotriene A4 to leukotrienes B4 and C4. These observations suggest that the normal basilar artery contains no detectable amount of 5-lipoxygenase, and that a prominent activation of this enzyme occurred (2.1 nmol 5-HETE/5 min/mg of protein) after subarachnoidal hemorrhage. The observation that fatty acid hydroperoxides stimulated the 5-lipoxygenase activity indicates a possible role of lipid peroxides in the development of vasospasm.

Topics: Animals; Arachidonate 5-Lipoxygenase; Arachidonate Lipoxygenases; Arachidonic Acid; Arachidonic Acids; Basilar Artery; Chromatography, High Pressure Liquid; Dogs; Enzyme Activation; Gas Chromatography-Mass Spectrometry; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Leukotrienes; Lipid Peroxides; Radioimmunoassay; SRS-A; Subarachnoid Hemorrhage