Manzo Jorge, Hernández-Aguilar María Elena, Toledo-Cárdenas María Rebeca, Herrera-Covarrubias Deissy, Coria-Avila Genaro A
Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa Ver, México.
J Physiol. 2025 Jan 2. doi: 10.1113/JP286899.
Autism spectrum disorder (ASD) is a prevalent neurodevelopmental condition affecting a substantial number of children globally, characterized by diverse aetiologies, including genetic and environmental factors. Emerging research suggests that neurovascular dysregulation during development could significantly contribute to autism. This review synthesizes the potential role of vascular abnormalities in the pathogenesis of ASD and explores insights from studies on valproic acid (VPA) exposure during neural tube development. VPA, a widely used antiepileptic drug and mood stabilizer, crosses the placental barrier and impacts the developing fetal brain. Studies indicate that VPA disrupts normal angiogenesis by reducing the expression levels of vascular endothelial growth factor A (VEGFA) and its receptors, and purinergic signalling, which are crucial for both vascular and neural development. Such disruptions may lead to abnormalities in neuronal migration and pathfinding, potentially contributing to the neural and behavioural manifestations of ASD. Thus despite the relatively limited findings, improper vascularization of the neural tube appears to be a contributing factor in the pathogenesis of ASD, as also suggested by VPA studies. Integrating these insights, it is hypothesized that vascular factors should be considered in the aetiological analysis of idiopathic autism.
自闭症谱系障碍（ASD）是一种普遍存在的神经发育疾病，全球大量儿童受其影响，其病因多样，包括遗传和环境因素。新出现的研究表明，发育过程中的神经血管调节异常可能对自闭症有显著影响。本综述综合了血管异常在ASD发病机制中的潜在作用，并探讨了神经管发育期间丙戊酸（VPA）暴露研究的相关见解。VPA是一种广泛使用的抗癫痫药物和情绪稳定剂，可穿过胎盘屏障并影响发育中的胎儿大脑。研究表明，VPA通过降低血管内皮生长因子A（VEGFA）及其受体的表达水平以及嘌呤能信号传导来破坏正常的血管生成，而这两者对血管和神经发育都至关重要。这种破坏可能导致神经元迁移和寻路异常，可能导致ASD的神经和行为表现。因此，尽管研究结果相对有限，但神经管血管化异常似乎是ASD发病机制中的一个促成因素，VPA研究也表明了这一点。综合这些见解，推测在特发性自闭症的病因分析中应考虑血管因素。
