Anticonvulsant and neuroprotective effects of carbamazepine-levetiracetam adjunctive treatment in convulsive status epilepticus rat model: Inhibition of cholinergic transmission

Anticonvulsant and neuroprotective effects of carbamazepine-levetiracetam adjunctive treatment in convulsive status epilepticus rat model: Inhibition of cholinergic transmission

•Carbamazepine (CBZ)-levetiracetam (LEV) treatment delays the onset of convulsion.•Severity of seizure was decreased in LEV, and CBZ -LEV adjunctive treatment.•CBZ-LEV decreased the percentage mortality in status epilepticus (SE) model•CBZ-LEV attenuates hippocampal acetylcholine, malondialdehyde an...

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Published in:Neuroscience letters Vol. 762; p. 136167
Main Authors: Osuntokun, Opeyemi Samson, Abdulwahab, Umar Faruq, Akanji, Nafisat Omolola, Adedokun, Kabiru Isola, Adekomi, Adedayo Damilare, Olayiwola, Gbola
Format: Journal Article
Language:English
Published: Ireland Elsevier B.V 25-09-2021
Subjects:
Acetylcholine
Animals
Anticonvulsants
Anticonvulsants - administration & dosage
Carbamazepine - pharmacology
Disease Models, Animal
Hippocampus - drug effects
Hippocampus - pathology
Levetiracetam - pharmacology
Male
Neuroprotection
Neuroprotective Agents - pharmacology
Neurotransmission
Random Allocation
Rats
Rats, Wistar
Status Epilepticus
Synaptic Transmission - drug effects
Neuroprotection
Anticonvulsants
Status epilepticus
Neurotransmission
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Summary:•Carbamazepine (CBZ)-levetiracetam (LEV) treatment delays the onset of convulsion.•Severity of seizure was decreased in LEV, and CBZ -LEV adjunctive treatment.•CBZ-LEV decreased the percentage mortality in status epilepticus (SE) model•CBZ-LEV attenuates hippocampal acetylcholine, malondialdehyde and TNF in SE model.•Hippocampal astrogliosis due to SE was abrogated across the treatment groups. This study evaluated the anticonvulsant and neuroprotective effects of carbamazepine (CBZ), levetiracetam (LEV), and CBZ + LEV adjunctive treatment in convulsive status epilepticus (CSE) rat model. Twenty-five male Wistar rats were randomized into five groups (n = 5). Groups I and II received 0.2 ml of normal saline intraperitoneally (i.p), while groups III-V received CBZ (25 mg/kg i.p), LEV (50 mg/kg i.p) or combination of sub-therapeutic doses of CBZ (12.5 mg/kg i.p) and LEV (25 mg/kg i.p). Thirty minutes later, seizure was kindled with pilocarpine hydrochloride (350 mg/kg) in group II-V rats. Seizure indices, markers of excitotoxicity, and astroglioses were determined, while the hippocampal morphometry was also evaluated. The data was analysed using descriptive and inferential statistics, while the results were presented as mean ± SEM in graphs or tables, and the level of significance was taken at p < 0.05. The anticonvulsant treatments delayed the inception of seizure indices (p = 0.0006), while the percentage mortality decreased significantly (p = 0.0001) in all the treatment groups. The hippocampal concentrations of acetylcholine, malondialdehyde, and tissue necrotic factor-alpha decreased significantly (p = 0.0077) in all the treated group relative to the positive control. The reactive astrogliosis in the hippocampus (CA 1) increased significantly (p = 0.0001) compared with the control but abrogated in all the treatment groups relative to the positive control. The anticonvulsant and neuroprotective effects are in this order: LEV < CBZ + CBZ < CBZ. The drug efficacy is attributable to the inhibition of cholinergic transmission.
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ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2021.136167