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

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