In vitro effects of β-cyclodextrin-complexed rufinamide on magnesium-free artificial cerebrospinal fluid-induced epileptiform neural activity

Temporal lobe epilepsy (TLE) is a disorder of the central nervous system characterized by abnormal neuronal synchronization. It is one of the most common forms of focal epilepsy and accounts for a substantial proportion of pharmacoresistant cases. A major limitation of many antiseizure medications (ASMs) is their poor bioavailability, which significantly reduces therapeutic efficacy. β-Cyclodextrin (BCD), by increasing the solubility of ASMs, may enhance drug bioavailability and thus represent a novel therapeutic strategy. The aim of this study was to quantify the effects of BCD and BCD-complexed rufinamide (RUF) on discharge frequency and to investigate the dose-dependent effects of RUF on hippocampal neural networks in an in vitro model of TLE. Local field potentials were recorded from the CA3 pyramidal cell layer of the rat hippocampus. Seizure-like events (SLEs) were induced by perfusing brain slices with magnesium-free artificial cerebrospinal fluid (0MgACSF). Following the recording of five stable SLEs, the perfusion solution was switched to 0MgACSF containing either BCD (control) or BCD-complexed RUF (50 and 100 µM). The timing of spike activity during the ictal phases was identified using a semi-automated method, after which frequency-based parameters were calculated. In our experiments, BCD alone significantly altered the decay slope compared with baseline conditions (0MgACSF), and the addition of RUF did not induce any further significant changes. BCD-complexed RUF retained its network-stabilizing effect and reduced hippocampal network load at both concentrations tested. Furthermore, a dose-dependent effect was observed: while 100 µM RUF significantly shortened the duration of intensive firing, no such effect was detected at the lower concentration. Our results demonstrate that BCD, when used as a carrier molecule, intrinsically modulates ictal dynamics. BCD-complexed RUF retains its anti-seizure properties and shortens the intensive discharge phase in a dose-dependent manner. These findings highlight the therapeutic potential of the BCD–RUF complex, which warrants further in vivo investigation.