Hirschsprung's disease--immunohistochemical findings

Abstract

Hirschsprung's disease (HSCR) is characterized by a non-propulsive distal intestinal segment (usually colon) leading to a functional obstruction. An absence of ganglia in the affected segment explains the synonymous term "aganglionosis coli". The lack of peristalsis is partly due to a deficient intestinal smooth muscle relaxation based on an absence of non-adrenergic, non-cholinergic (NANC) inhibitory innervation. Morphological studies using conventional microscopy, immunohistochemistry and immunochemistry against general neuronal markers and neuropeptides have been used to characterize the disturbed NANC innervation in HSCR. An increased cholinergic and adrenergic innervation is registered in the aganglionic segment in spite of the lack of neuronal cell bodies: Neuropeptides like vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), gastrin-releasing peptide (GRP), calcitonin gene-related peptide (CGRP), substance P (SP), enkephalins and galanin immunoreactive nerve fibres are all reduced in number in the aganglionic segment. In contrast, neuropeptide Y (NPY)-containing nerve fibres are increased in number in the diseased segment, probably reflecting the adrenergic hyperinnervation. General neuronal markers including chromogranins have been used to map the neuronal network in the HSCR intestine and also to investigate the endocrine cell system in the intestinal mucosa. Nitric oxide is a potent component of the NANC inhibitory innervation and its synthesizing enzyme, nitric oxide synthase (NOS), is shown to be almost absent in the neuronal system in aganglionic intestine.