4.1 Article

Resveratrol prevents brain edema, blood-brain barrier permeability, and altered aquaporin profile in autism animal model

期刊

出版社

WILEY
DOI: 10.1002/jdn.10137

关键词

aquaporin; autism spectrum disorder; blood-brain barrier; resveratrol; valproic acid; water content

资金

  1. Instituto Nacional de Ciencia e Tecnologia em Neuroimunomodulacao (INCT-NIM), Rio de Janeiro, Brazil [465489/2014-1]
  2. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
  3. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
  4. Fundo de Incentivo a Pesquisa e Eventos do Hospital de Clinicas de Porto Alegre (FIPE-HCPA) [13-0047]

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The study evaluated various physiological indicators related to the brain in an animal model of autism spectrum disorder, demonstrating significant changes in blood-brain barrier permeability and brain water content. Resveratrol was found to have an impact on these indicators and could prevent some of the alterations, providing insights into the pathophysiology of autism spectrum disorder.
Autism spectrum disorder can present a plethora of clinical conditions associated with the disorder, such as greater brain volume in the first years of life in a significant percentage of patients. We aimed to evaluate the brain water content, the blood-brain barrier permeability, and the expression of aquaporin 1 and 4, and GFAP in a valproic acid-animal model, assessing the effect of resveratrol. On postnatal day 30, Wistar rats of the valproic acid group showed greater permeability of the blood-brain barrier to the Evans blue dye and a higher proportion of brain water volume, prevented both by resveratrol. Prenatal exposition to valproic acid diminished aquaporin 1 in the choroid plexus, in the primary somatosensory area, in the amygdala region, and in the medial prefrontal cortex, reduced aquaporin 4 in medial prefrontal cortex and increased aquaporin 4 levels in primary somatosensory area (with resveratrol prevention). Valproic acid exposition also increased the number of astrocytes and GFAP fluorescence in both primary somatosensory area and medial prefrontal cortex. In medial prefrontal cortex, resveratrol prevented the increased fluorescence. Finally, there was an effect of resveratrol per se on the number of astrocytes and GFAP fluorescence in the amygdala region and in the hippocampus. Thus, this work demonstrates significant changes in blood-brain barrier permeability, edema formation, distribution of aquaporin 1 and 4, in addition to astrocytes profile in the animal model of autism, as well as the use of resveratrol as a tool to investigate the mechanisms involved in the pathophysiology of autism spectrum disorder.

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