montelukast and Infarction--Middle-Cerebral-Artery

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

Topics: Acetates; Animals; Anti-Asthmatic Agents; Brain; Cyclopropanes; Infarction, Middle Cerebral Artery; Macrophages; Male; Mice; Microglia; Neuroprotective Agents; Quinolines; Stroke; Sulfides

Previously we demonstrated the neuroprotective effect of montelukast, a cysteinyl leukotriene receptor-1 (CysLT(1) ) antagonist, on acute brain injury after focal cerebral ischaemia in mice. In this study, we have determined its effect on chronic brain injury after focal cerebral ischaemia in mice and rats.. After transient focal cerebral ischaemia was induced by middle cerebral artery occlusion, montelukast was intraperitoneally injected in mice or orally administered to rats for five days. Behavioural dysfunction, brain infarct volume, brain atrophy and neuron loss were determined to evaluate brain lesions.. Montelukast (0.1 mg/kg) attenuated behavioural dysfunction, brain infarct volume, brain atrophy and neuron loss in mice, which was similar to pranlukast, another CysLT(1) receptor antagonist. Oral montelukast (0.5 mg/kg) was effective in rats and was more effective than edaravone, a free radical scavenger.. Montelukast protected mice and rats against chronic brain injury after focal cerebral ischaemia, supporting the therapeutic potential of CysLT(1) receptor antagonists.

Topics: Acetates; Administration, Oral; Animals; Antipyrine; Atrophy; Behavior, Animal; Brain Injury, Chronic; Chromones; Cyclopropanes; Disease Models, Animal; Drug Evaluation, Preclinical; Edaravone; Free Radical Scavengers; Infarction, Middle Cerebral Artery; Injections, Intraperitoneal; Leukotriene Antagonists; Male; Mice; Mice, Inbred ICR; Nerve Degeneration; Quinolines; Rats; Rats, Sprague-Dawley; Sulfides

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