The Impact of Prophylactic Lacosamide on LPS-Induced Neuroinflammation in Aged Rats

Inflammation. 2019 Oct;42(5):1913-1924. doi: 10.1007/s10753-019-01053-7.

Abstract

Sepsis-induced central nervous system damage is called sepsis-associated encephalopathy (SAE). In addition to neuroinflammation, oxidative stress and apoptosis act in the development of SAE. In the current study, we evaluated the protective effects of lacosamide (LCM) on neuroinflammation induced by lipopolysaccharide (LPS). Twenty-four Wistar albino rats were divided into 3 groups as controls, LPS group (5 mg/kg i.p.), and LPS plus LCM group (5 mg/kg i.p and 40 mg/kg i.p, respectively). In the rat brain, LPS-induced tissue damage was revealed histopathologically as hyperemia and microhemorrhages. LCM pretreatment ameliorated these histopathological changes. LPS decreased brain TAS levels and significantly increased MDA, CRP, HSP, IL-1β, and TNF-α expressions in the cortex, hippocampus, and cerebellum. Western analysis revealed increased brain tissue levels of TNF-α, NF-Kβ, and caspase-3 following LPS. Prophylactic LCM treatment reversed these parameters including oxidative stress, inflammation, and apoptosis in the cortex, hippocampus, and cerebellum.

Keywords: LPS; brain; lacosamide; neuroinflammation; oxidative stress; sepsis.

MeSH terms

  • Aging
  • Animals
  • Apoptosis / drug effects
  • Brain / pathology*
  • Cerebellum / drug effects
  • Cerebellum / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Lacosamide / pharmacology*
  • Lacosamide / therapeutic use
  • Lipopolysaccharides
  • Oxidative Stress / drug effects
  • Premedication / methods
  • Protective Agents / pharmacology
  • Rats
  • Sepsis-Associated Encephalopathy / drug therapy
  • Sepsis-Associated Encephalopathy / pathology

Substances

  • Lipopolysaccharides
  • Protective Agents
  • Lacosamide