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      An aqueous extract of Khaya senegalensis (Desv.) A. Juss. (Meliaceae) prevents seizures and reduces anxiety in kainate-treated rats: modulation of GABA neurotransmission, oxidative stress, and neuronal loss in the hippocampus

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          Abstract

          Ethnopharmacological relevance

          Temporal lobe epilepsy is the most common form of drug-resistant epilepsy. Therefore, medicinal plants provide an alternative source for the discovery of new antiepileptic drugs.

          Aim of the study

          This study was aimed at investigating the antiepileptic- and anxiolytic-like effects of an aqueous extract of Khaya senegalensis ( K. senegalensis) in kainate-treated rats.

          Methods

          Seventy-two rats received a single dose of kainate (12 mg/kg) intraperitoneally. Those that exhibited two hours of status epilepticus were selected and monitored for the first spontaneous seizure. Then, animals that developed seizures were divided into 6 groups of 8 rats each and treated twice daily for 14 days as follows: negative control group received per os ( p.o.) distilled water (10 ml/kg); two positive control groups received either sodium valproate (300 mg/kg, p.o.) or phenobarbital (20 mg/kg, p.o.); and three test groups received different doses of the extract (50, 100, and 200 mg/kg, p.o.). In addition, a group of 8 normal rats (normal control group) received distilled water (10 ml/kg, p.o.). During the treatment period, the animals were video-monitored 12 h/day for behavioral seizures. At the end of the treatment period, animals were subjected to elevated plus-maze and open field tests. Thereafter, rats were euthanized for the analysis of γ-aminobutyric acid (GABA) concentration, oxidative stress status, and neuronal loss in the hippocampus.

          Results

          The aqueous extract of K. senegalensis significantly reduced spontaneous recurrent seizures (generalized tonic-clonic seizures) and anxiety-like behavior compared to the negative control group. These effects were more marked than those of sodium valproate or phenobarbital. Furthermore, the extract significantly increased GABA concentration, alleviated oxidative stress, and mitigated neuronal loss in the dentate gyrus of the hippocampus.

          Conclusion

          These findings suggest that the aqueous extract of K. senegalensis possesses antiepileptic- and anxiolytic-like effects. These effects were greater than those of sodium valproate or phenobarbital, standard antiepileptic drugs. Furthermore, these effects are accompanied by neuromodulatory and antioxidant activities that may be related to their behavioral effects. These data justify further studies to identify the bioactive molecules present in the extract for possible future therapeutic development and to unravel their mechanisms of action.

          Abstract

          Temporal lobe epilepsy, anxiety, GABA, oxidative stress, Khaya senegalensis.

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          Most cited references120

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          Tissue sulfhydryl groups

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            ILAE official report: a practical clinical definition of epilepsy.

            Epilepsy was defined conceptually in 2005 as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. This definition is usually practically applied as having two unprovoked seizures >24 h apart. The International League Against Epilepsy (ILAE) accepted recommendations of a task force altering the practical definition for special circumstances that do not meet the two unprovoked seizures criteria. The task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring >24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals who either had an age-dependent epilepsy syndrome but are now past the applicable age or who have remained seizure-free for the last 10 years and off antiseizure medicines for at least the last 5 years. "Resolved" is not necessarily identical to the conventional view of "remission or "cure." Different practical definitions may be formed and used for various specific purposes. This revised definition of epilepsy brings the term in concordance with common use. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.
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              The use of the elevated plus maze as an assay of anxiety-related behavior in rodents.

              The elevated plus maze is a widely used behavioral assay for rodents and it has been validated to assess the anti-anxiety effects of pharmacological agents and steroid hormones, and to define brain regions and mechanisms underlying anxiety-related behavior. Briefly, rats or mice are placed at the junction of the four arms of the maze, facing an open arm, and entries/duration in each arm are recorded by a video-tracking system and observer simultaneously for 5 min. Other ethological parameters (i.e., rears, head dips and stretched-attend postures) can also be observed. An increase in open arm activity (duration and/or entries) reflects anti-anxiety behavior. In our laboratory, rats or mice are exposed to the plus maze on one occasion; thus, results can be obtained in 5 min per rodent.
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                Author and article information

                Contributors
                Journal
                Heliyon
                Heliyon
                Heliyon
                Elsevier
                2405-8440
                26 May 2022
                May 2022
                26 May 2022
                : 8
                : 5
                : e09549
                Affiliations
                [a ]Department of Animal Biology and Physiology, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon
                [b ]Department of Pharmacy, University of Mountains, P.O. Box 208, Banganté, Cameroon
                Author notes
                []Corresponding author. kandedakavaye@ 123456yahoo.fr
                [†]

                Just deceased.

                Article
                S2405-8440(22)00837-4 e09549
                10.1016/j.heliyon.2022.e09549
                9160348
                35663738
                7e933ce1-65b7-4d54-ad56-d5b3ab3fb3a9
                © 2022 Published by Elsevier Ltd.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 25 January 2022
                : 28 March 2022
                : 23 May 2022
                Categories
                Research Article

                temporal lobe epilepsy,anxiety,gaba,oxidative stress,khaya senegalensis

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