Ketamine, at low dose, decrease behavioural alterations in epileptic diseases induced by pilocarpine in mice

Int J Neurosci. 2020 Nov;130(11):1118-1124. doi: 10.1080/00207454.2020.1730363. Epub 2020 Feb 19.

Abstract

Objective: The objective of the present study was to evaluate the effect of low-dose of ketamine, in short-term, on behavioral impairment and acute neuronal death in the cerebral cortex during the acute phase in a model of epileptic mouse induced by pilocarpine.Methods:Ketamine was administrated (10 mg/kg) intraperitoneally, 30 min before pilocarpine injection (100 mg/kg) in the first group. The second group received the same dose of ketamine 30 min after pilocarpine injection. The effect of ketamine on behavioral disorders and cerebral neuronal integrity in epileptic mice was evaluated.Results:Clinical observations and behavioural tests relate a reduction in behavioural dysfunctions in mice treated with ketamine. Interestingly, treatment of mice with low dose of ketamine decreased the clinical symptoms (movements of the vibrios, nods of the head, and movements of the whiskers), especially when administered before epilepsy induction. Furthermore, the administration of ketamine limits oedema in the hippocampus, neuronal degeneration and gliosis in the different cortical layers. These results could be explained by NMDA receptors inhibition by ketamine.Conclusion:Therefore, it appears that ketamine is endowed with a potential neuroprotective effect and can reduce the severity of neurodegeneration, especially when administrated before Status Epilepticus (SE) installation.

Keywords: Temporal lobe epilepsy; acute phase; behavioral study; cerebral histology; ketamine; pilocarpine.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Brain Edema / prevention & control*
  • Cerebral Cortex / drug effects*
  • Disease Models, Animal
  • Epilepsy / chemically induced
  • Epilepsy / drug therapy*
  • Epilepsy / pathology*
  • Gliosis / prevention & control*
  • Hippocampus / drug effects
  • Injections, Intraperitoneal
  • Ketamine / administration & dosage
  • Ketamine / pharmacology*
  • Mice
  • Nerve Degeneration / prevention & control*
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Pilocarpine / pharmacology
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*

Substances

  • Neuroprotective Agents
  • Receptors, N-Methyl-D-Aspartate
  • Pilocarpine
  • Ketamine