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

Neurosci Lett. 2021 Sep 25:762:136167. doi: 10.1016/j.neulet.2021.136167. Epub 2021 Aug 11.

Abstract

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.

Keywords: Anticonvulsants; Neuroprotection; Neurotransmission; Status epilepticus.

MeSH terms

  • Acetylcholine
  • Animals
  • Anticonvulsants / administration & dosage*
  • Carbamazepine / pharmacology*
  • Disease Models, Animal
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Levetiracetam / pharmacology*
  • Male
  • Neuroprotective Agents / pharmacology
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Status Epilepticus*
  • Synaptic Transmission / drug effects

Substances

  • Anticonvulsants
  • Neuroprotective Agents
  • Carbamazepine
  • Levetiracetam
  • Acetylcholine