Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Neuroprotective Effects of Lasmiditan and Sumatriptan in an Experimental Model of Post-Stroke Seizure in Mice: Higher Effects With Concurrent Opioid Receptors or Katp Channels Inhibitors Publisher Pubmed



Shayan M1, 2 ; Eslami F1, 2 ; Amanlou A1, 2 ; Solaimanian S1, 2 ; Rahimi N1, 2 ; Rashidian A1, 2 ; Ejtemaeimehr S1, 2 ; Ghasemi M3 ; Dehpour AR1, 2
Authors
Show Affiliations
Authors Affiliations
  1. 1. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Neurology, University of Massachusetts Chan Medical School, Worcester, 01655, MA, United States

Source: Toxicology and Applied Pharmacology Published:2022


Abstract

Background: Early post-stroke seizure frequently occurs in stroke survivors within the first few days and is associated with poor functional outcomes. Therefore, efficient treatments of such complications with less adverse effects are pivotal. In this study, we investigated the possible beneficial effects of lasmiditan and sumatriptan against post-stroke seizures in mice and explored underlying mechanisms in their effects. Methods: Stroke was induced by double ligation of the right common carotid artery in mice. Immediately after the ligation, lasmiditan (0.1 mg/kg, intraperitoneally [i.p.]) or sumatriptan (0.03 mg/kg, i.p.) were administered. Twenty-four hours after the stroke induction, seizure susceptibility was evaluated using the pentylenetetrazole (PTZ)-induced clonic seizure model. In separate experiments, naltrexone (a non-specific opioid receptor antagonist) and glibenclamide (a KATP channel blocker) were administered 15 min before lasmiditan or sumatriptan injection. To evaluate the underlying signaling pathways, ELISA analysis of inflammatory cytokines (TNF-α and IL-1β) and western blot analysis of anti- and pro-apoptotic markers (Bcl-2 and Bax) were performed on mice isolated brain tissues. Results: Lasmiditan (0.1 mg/kg, i.p.) and sumatriptan (0.03 mg/kg, i.p.) remarkably decreased seizure susceptibility in stroke animals by reducing inflammatory cytokines and neuronal apoptosis. Concurrent administration of naltrexone (10 mg/kg, i.p.) or glibenclamide (0.3 mg/kg, i.p.) with lasmiditan or sumatriptan resulted in a higher neuroprotection against clonic seizures and efficiently reduced the inflammatory and apoptotic markers. Conclusion: Lasmiditan and sumatriptan significantly increased post-stroke seizure thresholds in mice by suppressing inflammatory cytokines and neuronal apoptosis. Lasmiditan and sumatriptan seem to exert higher effects on seizure threshold with concurrent administration of the opioid receptors or KATP channels modulators. © 2022
Experts (# of related papers)
Other Related Docs
14. Anticonvulsant Effect of Melatonin Through Atp-Sensitive Channels in Mice, Fundamental and Clinical Pharmacology (2020)
32. Mode and Site of Action of Therapies Targeting Cgrp Signaling, Journal of Headache and Pain (2023)
43. Incidence, Early Case Fatality and Determinants of Stroke in Iran: Golestan Cohort Study, Journal of Stroke and Cerebrovascular Diseases (2022)