REPARIXIN AS A POTENTIAL ANTI-EPILEPTOGENIC AGENT: MODULATION OF CXCL1-CXCR1/2 AXIS AND SEIZURE ACTIVITY IN KINDLING MODEL OF TEMPORAL LOBE EPILEPSY

• DOI: 10.20944/preprints202502.0583.v1
• Publication Date: 2025-02-12T01:23:41Z
• Authors: Nihan Carcak; Nursima Mutlu; Elif Tuğçe Erdev; Taygun Turan; Özge Sarıyıldız; Canan Ulusoy; Elif Sanli; Erdem Tuzun; Cem Ismail Kucukali; Laura Brandolini; Andrea Aramini; Marcello Allegretti; Filiz Onat; Lidia De Filippis
• Keywords: Kindling model; CXCL1

Chemokine (CXC motif) ligand 8 (CXCL8) is a pro-inflammatory chemokine binding to CXCR1/2 receptors, elevated in the serum of patients with Temporal Lobe Epilepsy (TLE). Its murine ortholog CXCL1, implicated seizure generation and neuronal loss. This study evaluates anti-epileptogenic anti-seizure effect reparixin, an allosteric antagonist amygdaloid kindling rat model TLE. Reparixin was administered via osmotic pumps (8mg/kg/h) during period over 14 days seizures induced twice daily by electrical stimulation. To asses effects, fully kindled animals reparixin given before stimulations at 24 48 hours post-implantation. Brain tissue analyzed for CXCL1-CXCR1/2 axis activation. delayed secondary generalization kindling.. While it did not completely prevent kindling, reduced severity after-discharge duration post-treatment. AKT pathway proteins showed no significant changes, phospho-ERK:ERK ratio cortex hippocampus. CXCL1 expression also significantly decreased cortex. exhibits partial effects modulating reducing ERKsignalling, underscoring its potential as neuroinflammation-targeting epilepsy treatment. Already clinical trials respiratory diseases, could be repurposed therapy.