Combined melatonin and adrenocorticotropic hormone treatment attenuates N-methyl-d-aspartate-induced infantile spasms in a rat model by regulating activation of the HPA axis

source extracted confidence: high 2026-04-09
#adrenocorticotropic-hormone #animals #animals-newborn #anticonvulsants #disease-models-animal

Combined melatonin and adrenocorticotropic hormone treatment attenuates N-methyl-d-aspartate-induced infantile spasms in a rat model by regulating activation of the HPA axis

Wan et al., 2021 | Neurosci Lett | Other

Citation

Wan Lin, Yang Guang, ... Wang Jing. Combined melatonin and adrenocorticotropic hormone treatment attenuates N-methyl-d-aspartate-induced infantile spasms in a rat model by regulating activation of the HPA axis. Neurosci Lett. 2021-Mar-23;748:135713. doi:10.1016/j.neulet.2021.135713

Abstract

Infantile spasms (IS) is a serious epileptic syndrome that frequently occurs in infancy. Adrenocorticotropic hormone (ACTH) is generally the first-line treatment for IS; however, side effects limit its application. Melatonin (MT) has been used in clinical treatment for sleep disorders with only minor side effects. Further, MT was shown to be a powerful anticonvulsant in an animal model of epilepsy. In this research, we aimed to compare the anticonvulsant efficacy of ACTH and/or MT for treatment of IS and explore the mechanisms underlying the anticonvulsant activity of MT, using an N-methyl-d-aspartate (NMDA)-induced IS model in neonatal rats following exposure to prenatal stress. Latency to the onset of spasms and the total number of spasms were recorded to assess spasm severity. Treatment with ACTH and/or MT significantly reduced the number of spasms and prolonged the latency period. Additionally, expression of GR-α, HDAC2, BNDF, TrkB, and C-Cbl were significantly increased by induction with NMDA, and this effect was reversed by ACTH and/or MT treatment. Hence, our data suggest that combined ACTH and MT treatment is effective for reducing the number of spasms and increasing the latency period in NMDA rats, by restoring dysregulation of the HPA axis. These findings have the potential to provide a new strategy for the treatment of IS.

Key Findings

These findings have the potential to provide a new strategy for the treatment of IS.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition sleep

MeSH Terms

  • Adrenocorticotropic Hormone
  • Animals
  • Animals, Newborn
  • Anticonvulsants
  • Disease Models, Animal
  • Humans
  • Hypothalamo-Hypophyseal System
  • Infant
  • Melatonin
  • N-Methylaspartate
  • Pituitary-Adrenal System
  • Rats, Sprague-Dawley
  • Spasms, Infantile
  • Rats

Evidence Classification

  • Level: Other
  • Publication Types: Journal Article, Research Support, Non-U.S. Gov't
  • Vertical: d-aspartic-acid

Provenance

Source extracted via PubMed E-utilities API on 2026-04-12