Inhibition of leukotriene B4 synthesis protects against early brain injury possibly via reducing the neutrophil-generated inflammatory response and oxidative stress after subarachnoid hemorrhage in rats

Behav Brain Res. 2018 Feb 26:339:19-27. doi: 10.1016/j.bbr.2017.11.011. Epub 2017 Nov 11.

Abstract

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.

Keywords: Early brain injury; Inflammation; Leukotriene B4; Neutrophil recruitment; Oxidative stress; Subarachnoid hemorrhage.

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Brain Edema / drug therapy
  • Brain Edema / metabolism
  • Brain Injuries / drug therapy
  • Brain Injuries / metabolism
  • Disease Models, Animal
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Leukotriene B4 / metabolism*
  • Male
  • Neutrophils / drug effects
  • Neutrophils / metabolism*
  • Oxidative Stress / drug effects*
  • Rats, Sprague-Dawley
  • Subarachnoid Hemorrhage / drug therapy
  • Subarachnoid Hemorrhage / metabolism*
  • beta-Alanine / analogs & derivatives
  • beta-Alanine / pharmacology

Substances

  • SC 57461
  • beta-Alanine
  • Leukotriene B4