Levkromakalimin Sıçanlarda Akut Migren Benzeri Fenotip İndükleyici Etkisi ve Kortikal Yayılan Depolarizasyon ile İlişkisi

Abstract

Migraine attacks can be triggered by various substances. Levcromakalim elicits aura in individuals with migraine with aura. In this study, we explored the migraine-like phenotype inducing properties of levcromakalim (LVC) on rats. We examined if a single injection of LVC could cause a migraine-like.phenotype and affect cortical spreading.depolarization (CSD) in rats, a model of migraine aura. Rats were given 1 mg/kg LVC, and were compared to control and 10 mg/kg nitroglycerin groups. We measured periorbital and hind paw mechanical allodynia using Von Frey filaments. Anxiety-related behaviors and light sensitivity were assessed using the elevated plus maze, dark-light box and open field arena. We also examined the effects of LVC on CSD parameters, somatosensory.evoked.potentials, dural.electroencephalography, and blood-brain barrier integrity. Both LVC and NTG reduced periorbital mechanical thresholds, induced anxiety-like behaviors, and caused photophobia within 30 and 120 minutes, respectively. The migraine-like.phenotype induced by LVC recovered in 2 hours, while the NTG group took 4 hours.to fully recover. LVC did not provoke any CSD or CSD-like.change such as DC shift, EEG alterations, or cortical c-fos expression. LVC did not induce CSD de novo and.had minimal effects on CSD parameters, except.for an increase in propagation.failure. However, NTG significantly increased.both CSD.susceptibility and propagation failure. SSEP.latencies were prolonged after.CSD in LVC group. Acute LVC or NTG injection did not increase blood-brain barrier permeability. In conclusion, a single administration of LVC induced a migraine-like.phenotype with fast onset.and recovery, which is not mediated by CSD waves in the cerebral cortex. LVC-triggered.rapid-onset migraine-like symptoms may be.related to functional changes.in the trigeminal.system and the potassium channel.opening properties of LVC. Understanding.these neurobiological mechanisms could offer a new target for migraine treatment.