Improvement of fiber connectivity and functional recovery after stroke by montelukast, an available and safe anti-asthmatic drug

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Paolo GelosaLuigi Sironi

Abstract

Stroke is one of the main causes of death, neurological dysfunctions or disability in elderly. Neuroprotective drugs have been proposed to improve long-term recovery after stroke, but failed to reach clinical effectiveness. Hence, recent studies suggested that restorative therapies should combine neuroprotection and remyelination. Montelukast, an anti-asthmatic drug, was shown to exert neuroprotection in animal models of CNS injuries, but its ability to affect oligodendrocytes, restoring fiber connectivity, remains to be determined. In this study, we evaluated whether montelukast induces long-term repair by promoting fiber connectivity up to 8 weeks after middle cerebral artery occlusion (MCAo), using different experimental approaches such as in vivo diffusion magnetic resonance imaging (MRI), electrophysiological techniques, ex vivo diffusion tensor imaging (DTI)-based fiber tracking and immunohistochemistry. We found that, in parallel with a reduced evolution of ischemic lesion and atrophy, montelukast increased the DTI-derived axial diffusivity and number of myelin fibers, the density of myelin binding protein (MBP) and the number of GSTpi+ mature oligodendrocytes. Together with the rescue of MCAo-induced impairments of loca...Continue Reading

Citations

Apr 5, 2020·International Journal of Molecular Sciences·Elisabetta BonfantiMarta Fumagalli
Oct 6, 2020·Frontiers in Pharmacology·Jean BarréCédric Annweiler
Feb 20, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Julia MarschallingerLudwig Aigner
Jan 5, 2021·Frontiers in Molecular Biosciences·Ludwig AignerMichael Studnicka
Dec 15, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Stefano RaffaeleMarta Fumagalli
May 1, 2021·Brain Sciences·Fabian SchwimmbeckYvonne Höller
May 19, 2021·European Journal of Pharmacology·Hayder M Al-KuraishyGaber El-Saber Batiha
Apr 6, 2021·Pharmacological Reports : PR·Heena KhanAmarjot Kaur

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