N-Acetylcysteine protects hippocampal neurons against kainate-induced Temporal lobe epilepsy

Background and Aim : Temporal lobe epilepsy (TLE) is recognized as the most frequent form of acquired epilepsy in adults. Partial evidence indicates that one of the main complaints of patients with TLE; is hippocampal sclerosis. Hippocampal sclerosis is characterized by the loss of neurons, specifically in the CA1/CA3 and the hilus areas of the hippocampus. Apparently, prolonged seizures lead to progressive hippocampal neuronal death. N-Acetylcysteine (NAC) is a thiol-containing compound that has been used in clinical practice since the mid-1950s.It has the molecular formula HSCH 2 CH (NHCOCH 3) CO 2 H, and is currently being further investigated across a range of illnesses as an antidote for specific toxins, as a protective agent against oxidative stress and ischemic injury, and as a treatment for certain mental and physical illnesses. It has also reported that NAC treatment has reversed neuronal degeneration in Alzheimer’s disease model rats. In this study, we wanted to estimate NAC effect in the kainate-induced temporal epilepsy model.Methods : NAC was dissolved in physiological saline and administered intraperitoneally at 50 mg/kg and 100 mg/kg dosage, starting from one week prior to surgery and one day following the surgery. Status epilepticus (SE) was induced by i.c.v. injection of kainic acid (KA). KA (0.8 μg in 1.0 μl saline) was injected at a speed of 0.2 μl/min. The KA-treated rats were behaviorally monitored for 3 h after recovery from anesthesia. Seizures were rated according to Racine s scale. Three days later, animals were sacrificed. Their brain sections were then stained with %1 Cresyl violet to count the number of surviving neurons in the CA3 and hilar regions. Live cells were quantified at 400× magnification.Results : There was no significant difference between the KA and KA+NAC groups for seizure intensities, this could imply that the NAC had no anticonvulsive effect at least at this dosages. However, a significant difference in the latency to the onset of seizure activity was shown after treatment with NAC (50 & 100 mg/kg).The histological analysis showed that NAC can significantly reduce the number of necrotic and degenerating neurons in CA3 and Hilar areas at 50 & 100 mg/kg dosages.Conclusion : This study demonstrates that NAC has protective effects against KA-induced status epilepticus in rat. NAC was also effective in retarding the onset of seizure activity, although it could not attenuate seizure severity. It minimized neuronal loss in hippocampus and probably would be effective in improve of memory impairment in epilepsy.

کلیدواژه ها:

N-acetyl cystein ، epilepsy ، hippocamp