Metformin ameliorates the status epilepticus- induced hippocampal pathology through possible mTOR modulation

Sree Lalitha Bojja, Bikash Medhi, Shashi Anand, Alka Bhatia, Rupa Joshi, Ranjana W. Minz

Research output: Contribution to journalArticlepeer-review

Abstract

The initial precipitating injury such as SE progresses to chronic epilepsy through multiple epileptogenic processes. Early epileptogenic events are generally characterized by neuroinflammation, neurodegeneration and abnormal neurogenesis in the hippocampus. Metformin has exhibited anti-inflammatory and neuroprotective properties in numerous studies. The current study attempts to investigate the effect of metformin on seizure-induced inflammation and neuronal degeneration, and the involvement of the mTOR pathway. Status epilepticus (SE) was induced in male Wistar rats with systemic administration of Lithium (127 mg/kg) and Pilocarpine (30 mg/kg). In test rats, Metformin 100 mg/kg or 200 mg/kg was administered orally for 7 days, followed by SE induction. Results indicate that metformin did not alter the SE profile significantly which was evident by the behavioural scoring and electroencephalogram (EEG) recordings. However, metformin 200 mg/kg attenuated the SE-induced glial activation (p < 0.01), up regulated mRNA levels of proinflammatory cytokines (p < 0.001) and chemokines (p < 0.001) and enhanced BBB permeability (p < 0.05). In addition, metformin ameliorated the insult-induced region-specific neuronal damage (p < 0.01) and restored the hippocampal neuronal density. Metformin significantly inhibited phosphorylated S6 ribosomal protein (phospho-S6rp) (p < 0.05), thus demonstrating that the beneficial effects might be partly mediated by the mTOR pathway. The study thus reiterates that mTOR signalling is one of the mechanisms involved in inflammation and neurodegeneration in early epileptogenesis following SE.

Original languageEnglish
Pages (from-to)137-151
Number of pages15
JournalInflammopharmacology
Volume29
Issue number1
DOIs
Publication statusPublished - 02-2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology
  • Pharmacology (medical)

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