Abstract
BackgroundPrevious studies have shown that seizures can cause cognitive disorders. On the other hand, the Curcuma zedoaria (CZ) has beneficial effects on the nervous system. However, there is little information on the possible effects of the CZ extract on seizures. The aim of this study was to investigate the possible effects of CZ extract on cognitive impairment and oxidative stress induced by epilepsy in rats.MethodsRats were randomly divided into different groups. In all rats (except the sham group), kindling was performed by intraperitoneal injection of pentylenetetrazol (PTZ) at a dose of 35 mg/kg every 48 h for 14 days. Positive group received 2 mg/kg diazepam + PTZ; treatment groups received 100, 200 or 400 mg/kg CZ extract + PTZ; and one group received 0.5 mg/kg flumazenil and CZ extract + PTZ. Shuttle box and Morris Water Maze tests were used to measure memory and learning. On the last day of treatments PTZ injection was at dose of 60 mg/kg, tonic seizure threshold and mortality rate were recorded in each group. After deep anesthesia, blood was drawn from the rats’ hearts and the hippocampus of all rats was removed.ResultsStatistical analysis of the data showed that the CZ extract significantly increased the tonic seizure threshold and reduced the pentylenetetrazol-induced mortality and the extract dose of 400 mg/kg was selected as the most effective dose compared to the other doses. It was also found that flumazenil (a GABAA receptor antagonist) reduced the tonic seizure threshold compared to the effective dose of the extract. The results of shuttle box and Morris water maze behavioral tests showed that memory and learning decreased in the negative control group and the CZ extract treatment improved memory and learning in rats. The CZ extract also increased antioxidant capacity, decreased MDA and NO in the brain and serum of pre-treated groups in compared to the negative control group. Conclusion: It is concluded that the CZ extract has beneficial effects on learning and memory impairment in PTZ-induced epilepsy model, which has been associated with antioxidant effects in the brain or possibly exerts its effects through the GABAergic system.
Highlights
Previous studies have shown that seizures can cause cognitive disorders
Expression of GABAA receptor subunit 4α gene The results show that the expression of GABAA receptor subunit 4α gene was significantly increased in the diazepam group in compared to the negative control group
Studies have shown that PTZ can act by blocking GABAA receptors in the central nervous system neurons [14]
Summary
Previous studies have shown that seizures can cause cognitive disorders. On the other hand, the Curcuma zedoaria (CZ) has beneficial effects on the nervous system. The aim of this study was to investigate the possible effects of CZ extract on cognitive impairment and oxidative stress induced by epilepsy in rats. Excessive neuronal excitability and excessive production of free radicals play an important role in the pathogenesis of a significant range of neurological disorders, including epilepsy. Increased susceptibility of the brain to oxidative damage highlights the importance of understanding the role of oxidative stress in the pathophysiology of seizures and epilepsy [1]. It has been well established that oxidative damage plays an important role in the pathogenesis and complications of other CNS disorders such as learning and memory disorders [2]. Rodent models of temporal lobe epilepsy (TLE) are associated with changes in expression and function of the GABA receptor in the hippocampus [3]
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