Resveratrol prevents brain edema, blood–brain barrier permeability, and altered aquaporin profile in autism animal model,International Journal of Developmental Neuroscience

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Resveratrol prevents brain edema, blood–brain barrier permeability, and altered aquaporin profile in autism animal model
International Journal of Developmental Neuroscience ( IF 1.7 ) Pub Date : 2021-07-01 , DOI: 10.1002/jdn.10137
Iohanna Deckmann _{1,

2,

3,

4} , Júlio Santos-Terra _{1,

2,

3,

4} , Mellanie Fontes-Dutra _{1,

2,

3,

4} , Marília Körbes-Rockenbach _{1,

2,

3} , Guilherme Bauer-Negrini _{1,

2,

3,

4} , Gustavo Brum Schwingel _{1,

2,

3,

4} , Rudimar Riesgo _{1,

3,

4,

5} , Victorio Bambini-Junior _{1,

3,

4,

6} , Carmem Gottfried _{1,

2,

3,

4}

Affiliation

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.

中文翻译：

白藜芦醇可防止自闭症动物模型中的脑水肿、血脑屏障通透性和水通道蛋白谱改变

自闭症谱系障碍可能会出现大量与该障碍相关的临床状况，例如很大一部分患者在生命的头几年脑容量更大。我们的目的是在丙戊酸-动物模型中评估脑含水量、血脑屏障通透性、水通道蛋白 1 和 4 以及 GFAP 的表达，以评估白藜芦醇的作用。在出生后第 30 天，丙戊酸组的 Wistar 大鼠表现出对伊文思蓝染料的血脑屏障渗透性更高，脑水量比例更高，白藜芦醇可以防止两者。产前暴露于丙戊酸会减少脉络丛、初级体感区、杏仁核区和内侧前额叶皮层中的水通道蛋白 1，减少内侧前额叶皮层的水通道蛋白 4，增加初级体感区的水通道蛋白 4 水平（预防白藜芦醇）。丙戊酸暴露也增加了初级体感区和内侧前额叶皮层中星形胶质细胞的数量和 GFAP 荧光。在内侧前额叶皮质中，白藜芦醇阻止了荧光的增加。最后，还有白藜芦醇的作用本身关于杏仁核区域和海马中星形胶质细胞和 GFAP 荧光的数量。因此，这项工作证明了血脑屏障通透性、水肿形成、水通道蛋白 1 和 4 的分布以及自闭症动物模型中的星形胶质细胞分布以及使用白藜芦醇作为研究机制的工具的显着变化参与自闭症谱系障碍的病理生理学。

更新日期：2021-07-01

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