montelukast and Brain-Injuries

Neuroinflammation plays an important role in brain injury and repair. Regulation of post-stroke inflammation may be a reasonable strategy to treat ischemic stroke. The present study demonstrates that montelukast sodium protected brain tissue by regulating the post-stroke inflammatory reaction.. Adult male mice underwent distal occlusion of the middle cerebral artery (d-MCAO) surgery, followed by intraperitoneal injection of montelukast sodium or equivalent saline, from day 0-7 after the operation. On the 7th day, Rotarod and adhesive-removal test were performed. M AP2 staining, and Iba1, CD206, and CD16/32 co staining were performed. BV2 microglial cell lines were co-cultured with different concentrations of montelukast sodium with or without lipopolysaccharide (LPS). Real-time polymerase chain reaction (rt-PCR) and enzyme linked immunosorbent assay (ELISA) were used to detect the mRNA expression of M1 and M2 phenotypic microglia markers and the release of cytokines representing from different phenotypes of microglia cells.. Montelukast sodium prolonged the time that d-MCAO mice remained on the rotating bar, shortened the time to remove the sticker on the opposite claw, and reduced the infarct volume, promoting the transformation of microglial cells/macrophages around the infarct to the M2 phenotype. Montelukast sodium increased the mRNA expression of Arg-1, CD206, TGF-β, and IL-10 in BV2 microglial cell lines stimulated by LPS, while decreased the expression of iNOS, TNF-α, and CD16/32.. Montelukast sodium can protect against focal cerebral ischemic injury by regulating inflammatory reaction via promoting microglia polarization.

Topics: Animals; Brain Injuries; Brain Ischemia; Infarction; Infarction, Middle Cerebral Artery; Inflammation; Lipopolysaccharides; Male; Mice; Microglia; RNA, Messenger; Stroke

Traumatic brain injury is highly associated with the over-production of reactive oxygen species. The aim of this study was to investigate the putative neuroprotective effect of montelukast, a cysteinyl-leukotriene receptor antagonist, in a rat model of traumatic brain injury (TBI).. Sprague Dawley rats were subjected to TBI with a weight-drop device using 300 g-1 m weight-height impact. The groups were: control (saline), montelukast (10 mg kg(-1) per day, ip), trauma and trauma + montelukast. Two days post-trauma, neurological examination scores were measured and animals were decapitated and the brain tissues were taken for the histologic and biochemical [malondialdehyde (MDA)-an index for lipid peroxidation, reduced glutathione (GSH), myeloperoxidase (MPO)-an index for neutrophil infiltration and Na+/K+-ATPase activity] evaluations. Brain oedema and blood-brain barrier (BBB) permeability were also evaluated.. The neurological examination scores mildly increased in trauma groups at 48 hours. Although the scores were decreased in the montelukast treated group, they were still significantly higher than the control. The trauma caused a significant increase in brain water content and Evans blue (EB) extravasation. Montelukast treatment reduced BBB permeability. It also decreased lipid peroxidation and MPO activity.. The present study suggests that montelukast may have beneficial effects against TBI-induced oxidative stress of the brain.

Topics: Acetates; Animals; Blood-Brain Barrier; Brain Edema; Brain Injuries; Cyclopropanes; Immunologic Factors; Leukotriene Antagonists; Neuroprotective Agents; Oxidative Stress; Permeability; Quinolines; Rats; Rats, Sprague-Dawley; Sulfides