NEUROPROTECTIVE EFFECTS OF TIAGABINE IN A RABBIT MODEL OF SPINAL CORD ISCHEMIA/ REPERFUSION INJURY

Objective: Spinal cord ischemia/reperfusion (I/R) injury is a serious clinical problem. The reperfusion phase leads to excessive glutamate release which produces toxic conditions that result in neuronal damage. Tiagabine functions as a gamma-aminobutyric acid (GABA) transporter 1 (GAT-1) inhibitor because it specifically blocks the process of GABA reuptake. It is known to exhibit neuroprotective effects in various central nervous system injury models by enhancing GABAergic transmission. Previous studies demonstrated the neuroprotective effects of Tiagabine, but no previous study has examined of Tiagabine on spinal cord ischemia/reperfusion (I/R) injury. In this study, we aimed to investigate whether how Tiagabine has a neuroprotective effect in an experimental rabbit spinal cord I/R injury model. Material and Methods: A total of 50 rabbits were randomised into five groups of ten animals as follows: group 1 (control), group 2 (I/R), and treatment groups as shown; group 3 (I/R with 10 mg/kg dose Tiagabine), group 4 (I/R with 20 mg/kg dose Tiagabine) and group 5 (I/R with 40 mg/kg dose Tiagabine). In the control group only a laparotomy was performed. In all other groups, the spinal cord ischemia model was created by the occlusion of the aorta just caudal to the renal artery with an atraumatic vascular clamp for 45 minutes. After the occlusion period, the clamp was removed and reperfusion was initiated. Rabbits were followed in individual cages for 48 hours of reperfusion. We performed Tiagabine administration through intraperitoneal injection 30 minutes before the start of ischemia. We conducted histopathological evaluation along with TUNEL staining to identify apoptotic cells and biochemical assessments of oxidative stress indicators. Levels of malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were analysed, as were the oxidative stress parameters. The study included measurements of inflammatory cytokines which included TNF-α and IL-1β and IL-6 and caspase-3 activity. Neurological evaluation was assessed at 48 hours reperfusion using the Tarlov scoring system.Results: The groups which received Tiagabine showed better neurological recovery than the I/R group. The paraplegia rate was determined to be 80% in the I/R group, while this rate decreased to 10% in the group administered 40 mg/kg Tiagabine (p