Easson, K. | Search bioRxiv

bioRxiv2025

Reduced cerebrovascular reactivity is more pronounced in female than male youth with complex congenital heart defects

AimsCongenital heart defects (CHD) are the most common neonatal malformations. Neonates with complex CHD present with cerebrovascular dysfunction, including deficits in cerebrovascular reactivity (CVR), a measure of vascular reserve. However, it is unknown whether these deficits persist beyond the perioperative period. Methods and ResultsHere, we compared CVR between 53 youth with CHD and 54 age-matched controls without CHD. CVR was derived using a novel approach based on resting state blood oxygen-level dependent magnetic resonance imaging. We found that youth with CHD present with relative CVR deficits in the whole gray matter and in the anterior cerebral artery territory when compared to controls. Sex differences were identified in the middle cerebral artery territory, with females having lower relative CVR than males in the CHD group. Greater CVR deficits were observed in individuals with single-ventricle as compared to participants with a two-ventricle physiology. Finally, in the CHD group, a lower CVR was found to be associated with reduced performance on the Metacognitive Abilities Index of the BRIEF-A. ConclusionThese results indicate that cerebrovascular deficits in CHD survivors persistent into young adulthood and that CVR offers great promise as a biomarker of cerebrovascular health which could be targeted in future interventions.

neuroscience↗

bioRxiv2021

Examining the effect of chronic intranasal oxytocin administration on the neuroanatomy and behavior of three autism-related mouse models

1Although initially showing great potential, oxytocin treatment has encountered a translational hurdle in its promise of treating the social deficits of autism. Some debate surrounds the ability of oxytocin to successfully enter the brain, and therefore modify neuroanatomy. Moreover, given the heterogeneous nature of autism, treatment will only amerliorate symptoms in a subset of patients. Therefore, to determine whether oxytocin changes brain circuitry, and whether it does so variably, depending on genotype, we implemented a large randomized, blinded, placebo-controlled, preclinical study on chronic intranasal oxytocin treatment in three different mouse models related to autism with a focus on using neuroanatomical phenotypes to assess and subset treatment response. Intranasal oxytocin (0.6IU) was administered daily, for 28 days, starting at 5 weeks of age to the 16p11.2 deletion, Shank3 (exon 4-9) knockout, and Fmr1 knockout mouse models. Given the sensitivity of structural magnetic resonance imaging (MRI) to the neurological effects of interventions like drugs, along with many other advantages, the mice underwent in vivo longitudinal and high-resolution ex vivo imaging with MRI. The scans included three in vivo T1-weighted, 90um isotropic resolution scans and a T2-weighted, 3D fast spin echo with 40um isotropic resolution ex vivo scan to assess the changes in neuroanatomy using established automated image registration and deformation based morphometry approaches in response to oxytocin treatment. The behavior of the mice was assessed in multiple domains, including social behaviours and repetitive behaviours, among others. Treatment effect on the neuroanatomy did not reach significance, although the pattern of trending effects was promising. No significant effect of treatment was found on social behavior in any of the strains, although a significant effect of treatment was found in the Fmr1 mouse, with treatment normalizing a grooming deficit. No other treatment effect on behavior was observed that survived multiple comparisons correction. Overall, chronic treatment with oxytocin had limited effects on the three mouse models related to autism, and no promising pattern of response susceptibility emerged.

developmental biology↗