montelukast and Brain-Ischemia
montelukast has been researched along with Brain-Ischemia* in 4 studies
Other Studies
4 other study(ies) available for montelukast and Brain-Ischemia
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Montelukast sodium protects against focal cerebral ischemic injury by regulating inflammatory reaction via promoting microglia polarization.
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 | 2023 |
Cysteinyl leukotriene receptor type 1 antagonist montelukast protects against injury of blood-brain barrier.
The blood-brain barrier (BBB) is formed by tightly connected cerebrovascular endothelial cells. Injury of human brain endothelial cells can cause disruption of the BBB and severe injury to brain tissue. Signals mediated cysteinyl leukotrienes (cysLTs) and their receptors are involved in a variety of pathological conditions. In the current study, our results show that oxygen glucose-deprivation/reoxygenation (OGD/R) induced the expression of leukotriene receptor type 1 (cysLT1R) in brain endothelial cells. Blockage of cysLT1R by its specific antagonist montelukast suppressed OGD/R-induced altered permeability of the human brain endothelial cell (EC) monolayer. Mechanistically, montelukast treatment reversed OGD/R-induced reduction of the tight junction proteins occludin and zonula occludens-1 (ZO-1). Montelukast also ameliorated OGD/R-induced reduction of inhibitors of matrix metalloproteinases (TIMPs), such as TIMP-1 and TIMP-2. On the other hand, montelukast suppressed the expression and production of matrix metalloproteinases (MMPs) and cytokines including MMP-2, MMP-9, interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6). Using a murine middle cerebral artery occlusion brain injury model, we demonstrated that the administration of montelukast improved the surgery-induced brain injury and protected against disruption of brain endothelial junction proteins such as occludin and ZO-1. Collectively, our data suggest that montelukast might confer protective roles against injury in brain endothelial cells. Topics: Acetates; Animals; Blood-Brain Barrier; Brain; Brain Ischemia; Cell Line; Cyclopropanes; Endothelial Cells; Humans; Interleukin-1beta; Interleukin-6; Leukotriene Antagonists; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Quinolines; Receptors, Leukotriene; Sulfides; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Tumor Necrosis Factor-alpha | 2019 |
HAMI 3379, a CysLT2 receptor antagonist, attenuates ischemia-like neuronal injury by inhibiting microglial activation.
The cysteinyl leukotrienes (CysLTs) are inflammatory mediators closely associated with neuronal injury after brain ischemia through the activation of their receptors, CysLT1R and CysLT2R. Here we investigated the involvement of both receptors in oxygen-glucose deprivation/recovery (OGD/R)-induced ischemic neuronal injury and the effect of the novel CysLT2R antagonist HAMI 3379 [3-({[(1S,3S)-3- carboxycyclohexyl]amino}carbonyl)-4-(3-{4-[4-(cyclo-hexyloxy)butoxy]phenyl}propoxy)benzoic acid] in comparison with the CysLT1R antagonist montelukast. In primary neurons, neither the nonselective agonist leukotriene D4 (LTD4) nor the CysLT2R agonist N-methyl-leukotriene C4 (NMLTC4) induced neuronal injury, and HAMI 3379 did not affect OGD/R-induced neuronal injury. However, in addition to OGD/R, LTD4 and NMLTC4 induced cell injury and neuronal loss in mixed cultures of cortical cells, and neuronal loss and necrosis in neuron-microglial cocultures. Moreover, they induced phagocytosis and cytokine release (interleukin-1β and tumor necrosis factor-α) from primary microglia, and conditioned medium from the treated microglia induced neuronal necrosis. HAMI 3379 inhibited all of these responses, and its effects were the same as those of CysLT2R interference by CysLT2R short hairpin RNA, indicating CysLT2R dependence. In comparison, montelukast moderately inhibited OGD/R-induced primary neuronal injury and most OGD/R- and LTD4-induced (but not NMLTC4-induced) responses in mixed cultures, cocultures, and microglia. The effects of montelukast were both dependent and independent of CysLT1Rs because interference by CysLT1R small interfering RNA had limited effects on neuronal injury in neuron-microglial cocultures and on cytokine release from microglia. Our findings indicated that HAMI 3379 effectively blocked CysLT2R-mediated microglial activation, thereby indirectly attenuating ischemic neuronal injury. Therefore, CysLT2R antagonists may represent a new type of therapeutic agent in the treatment of ischemic stroke. Topics: Acetates; Animals; Animals, Newborn; Astrocytes; Brain Ischemia; Cell Hypoxia; Cells, Cultured; Cerebral Cortex; Coculture Techniques; Cyclohexanecarboxylic Acids; Cyclopropanes; Cytokines; Female; Glucose; Leukotriene Antagonists; Male; Microglia; Necrosis; Neurons; Oxygen; Phagocytosis; Phthalic Acids; Primary Cell Culture; Quinolines; Rats; Rats, Sprague-Dawley; Receptors, Leukotriene; Sulfides | 2013 |
Montelukast, a cysteinyl leukotriene receptor-1 antagonist, dose- and time-dependently protects against focal cerebral ischemia in mice.
Our previous studies showed that cysteinyl leukotriene receptor-1 (CysLT1) antagonist pranlukast has a neuroprotective effect on cerebral ischemia in rats and mice. However, whether the neuroprotective effect of pranlukast is its special action or a common action of CysLT1 receptor antagonists remains to be clarified. This study was performed to determine whether montelukast, another CysLT1 receptor antagonist, has the neuroprotective effect on focal cerebral ischemia in mice, and to observe its dose- and time-dependent properties. Permanent focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). Montelukast was injected intraperitoneally either as multiple doses (once a day for 3 days and 30 min before MCAO) or as a single dose (at 30 min before, 30 min after, or 1 h after MCAO), respectively, and pranlukast and edaravone were used as controls. The neurological deficits, infarct volumes, brain edema, neuron density, and Evans blue extravasation in the brain were determined 24 h after MCAO. Pretreatments with multiple doses or a single dose of montelukast (0.1 and 1.0 mg/kg) before MCAO significantly attenuated all the ischemic insults. Post-treatment with a single dose of montelukast (0.1 and 1.0 mg/kg) at 30 min after MCAO also significantly decreased brain edema and infarct volume, but not neurological deficits. However, post-treatment with a single dose of montelukast at 1 h after MCAO had no significant effect. Pranlukast showed the same effects as montelukast, but edaravone attenuated the ischemic insults only with multiple doses before MCAO. Thus, montelukast has a dose- and time-dependent neuroprotective effect on permanent focal cerebral ischemia in mice, with an effective dose range of 0.1-1.0 mg/kg and a therapeutic window of 30 min. These findings further support the therapeutic potential of CysLT1 receptor antagonists in the treatment of cerebral ischemia at earlier phases. Topics: Acetates; Animals; Antipyrine; Blood-Brain Barrier; Brain; Brain Edema; Brain Ischemia; Chromones; Cyclopropanes; Dose-Response Relationship, Drug; Edaravone; Free Radical Scavengers; Infarction, Middle Cerebral Artery; Leukotriene Antagonists; Mice; Nervous System; Neuroprotective Agents; Psychomotor Performance; Quinolines; Receptors, Leukotriene; Sulfides; Survival Analysis; Time Factors | 2005 |