Extrinsic innervation of ileum and pelvic flexure of foals with ileocolonic aganglionosis.

This research investigates the distribution of certain nerve fibers in horse foals with a severe congenital disorder known as lethal white foal syndrome (LWFS). It found abnormal distribution patterns and alterations in nerve pathways, similar to Hirschsprung’s disease in humans.

Understanding Lethal White Foal Syndrome (LWFS)

• LWFS is an severe congenital disorder affecting foals. It is characterized by the failed colonization of neural crest progenitors in the lower part of the small intestine and the entire large intestine. In humans, the equivalent condition is known as Hirschsprung’s disease.
• Symptoms of LWFS include a lack (“aganglionosis”) or scarcity (“hypoganglionosis”) of enteric ganglia, causing intestinal akinesia (loss of muscular function) and colic (pain in the abdomen).

Objective of the research

• Earlier studies on other species with similar conditions have found that fibers originating from outside the affected organ have abnormal distribution patterns. However, the same has not been previously investigated in horses.
• This research aimed to examine the distribution of extrinsic sympathetic and sensory nerve fibers in two foals with LWFS, and compare it with a control subject. The focus was specifically on the ileum (a part of the small intestine) and the pelvic flexure of the colon.

Method and findings

• The sympathetic nerve fibers were identified using markers tyrosine hydroxylase and dopamine beta-hydroxylase. The extrinsic sensory fibers were identified using markers Substance P (SP) and calcitonin gene-related peptide (CGRP).
• Compared to the control, the LWFS affected foals had larger bundles of these fibers, mirroring findings in Hirschsprung’s disease.
• Additionally, altered adrenergic pathways were observed, particularly in the pelvic flexure. This suggests disruption in the regulation of key physiological mechanisms.
• The numbers of SP- and CGRP-immunoreactive fibers in the muscular part of the intestine, where enteric neurons operate, were significantly reduced.
• However, fibers thought to be extrinsic sensory axons were found to persist around submucosal blood vessels. The numbers of these fibers were reduced in the mucosa, which highlights a potential disruption in the intestine’s ability to sense and respond to stimuli.

Implications of the study

• This research suggests that in LWFS, not only is the intrinsic innervation of the gut affected, but also the extrinsic innervation, which helps to modulate gut functions.
• More insights into these neural alterations can contribute to a better understanding of LWFS, and its human equivalent, Hirschsprung’s disease. It can potentially inform new therapeutic strategies and diagnostic methods for these conditions.