Thalidomide Attenuates Epileptogenesis and Seizures by Decreasing Brain Inflammation in Lithium Pilocarpine Rat Model

Int J Mol Sci. 2023 Mar 30;24(7):6488. doi: 10.3390/ijms24076488.

Abstract

Thalidomide (TAL) has shown potential therapeutic effects in neurological diseases like epilepsy. Both clinical and preclinical studies show that TAL may act as an antiepileptic drug and as a possible treatment against disease development. However, the evidence for these effects is limited. Therefore, the antiepileptogenic and anti-inflammatory effects of TAL were evaluated herein. Sprague Dawley male rats were randomly allocated to one of five groups (n = 18 per group): control (C); status epilepticus (SE); SE-TAL (25 mg/kg); SE-TAL (50 mg/kg); and SE-topiramate (TOP; 60mg/kg). The lithium-pilocarpine model was used, and one day after SE induction the rats received pharmacological treatment for one week. The brain was obtained, and the hippocampus was micro-dissected 8, 18, and 28 days after SE. TNF-α, IL-6, and IL-1β concentrations were quantified. TOP and TAL (50 mg/kg) increased the latency to the first of many spontaneous recurrent seizures (SRS) and decreased SRS frequency, as well as decreasing TNF-α and IL-1β concentrations in the hippocampus. In conclusion, the results showed that both TAL (50 mg/kg) and TOP have anti-ictogenic and antiepileptogenic effects, possibly by decreasing neuroinflammation.

Keywords: anti-ictogenic; antiepileptogenic; neuroinflammation; temporal lobe epilepsy; thalidomide.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Encephalitis*
  • Epilepsy, Temporal Lobe* / chemically induced
  • Epilepsy, Temporal Lobe* / drug therapy
  • Hippocampus / metabolism
  • Lithium / pharmacology
  • Lithium / therapeutic use
  • Male
  • Pilocarpine / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / chemically induced
  • Seizures / drug therapy
  • Status Epilepticus* / chemically induced
  • Status Epilepticus* / drug therapy
  • Thalidomide / pharmacology
  • Thalidomide / therapeutic use
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Pilocarpine
  • Lithium
  • Thalidomide
  • Tumor Necrosis Factor-alpha

Grants and funding

This study was supported in part by Secretaría de Investigación y Posgrado—Instituto Politécnico Nacional (SIP-IPN 20181089 and SIP-IPN 20190023).