Dysregulation of neural tube vascular development as an aetiological factor in autism spectrum disorder: Insights from valproic acid exposure

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.