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.
journal_name
Inflammopharmacologyjournal_title
Inflammopharmacologyauthors
Bojja SL,Medhi B,Anand S,Bhatia A,Joshi R,Minz RWdoi
10.1007/s10787-020-00782-8subject
Has Abstractpub_date
2021-01-01 00:00:00eissn
0925-4692issn
1568-5608pii
10.1007/s10787-020-00782-8pub_type
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journal_title:Inflammopharmacology
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pub_type: 杂志文章,评审
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journal_title:Inflammopharmacology
pub_type: 杂志文章
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journal_title:Inflammopharmacology
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journal_title:Inflammopharmacology
pub_type: 杂志文章
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更新日期:2013-12-01 00:00:00
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journal_title:Inflammopharmacology
pub_type: 杂志文章,评审
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journal_title:Inflammopharmacology
pub_type: 杂志文章
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journal_title:Inflammopharmacology
pub_type: 杂志文章
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