Neuroanatomical Study of In-Vivo Brainstem Abnormalities in Autism Spectrum Disorder and Their Clinical Correlations

Background: Autism Spectrum Disorder (ASD) is typically linked to dysfunction of the brainstem, interfering with sensory treatment and autonomic management. The study aimed at examining the structural changes in the brainstem of a rat model induced by propionic acid (PPA) and focused on neuroanatomy changes within the medulla and pons. Methods: This in vivo study of 6 months (June 2023- December 2023) was carried out in the department of Anatomy at LUMHS Jamshoro. Twenty Wistar male rats were also divided into two groups. control (Group A n = 6) and PPA provoke an autism spectrum disorder (ASD) model (Group B n = 14). The groups were assigned using a random sampling technique. The animals were induced with ASD-like behaviors using oral administration of 250 mg/kg PPA for 5 consecutive days. The open field and social interaction tests were used to conduct behavioral assessments. brainstems were dissected after euthanasia for histopathological analysis, where morphometric evaluation of thickness and densities of the brainstem, and vascular changes were observed. Statistical analysis was run on SPSS version 26, p <0.05 as a significance level(T-test). Results: PPA-treated rats showed significantly reduced brainstem thickness in the pons (1.10 ± 0.06 mm vs. 1.35 ± 0.08 mm, p < 0.001) and medulla (0.98 ± 0.05 mm vs. 1.22 ± 0.07 mm, p < 0.001), with severe neuronal loss (83%) and vascular congestion (91%). Behavioral scores declined, including reduced locomotor activity (392 ± 70 cm vs. 610 ± 85 cm, p < 0.01) and social interaction (3.2 ± 0.9 vs. 7.1 ± 1.0, p < 0.001). Conclusion: This study has demonstrated that PPA-induced ASD triggers structural changes in the brainstem, namely in the medulla and pons, giving hints on the neuroanatomical changes involved in ASD and possible therapeutic options for the medulla and pons.