HIRSCHSPRUNGS-DISEASE - IMMUNOHISTOCHEMICAL FINDINGS

Hirschsprung's disease (HSCR) is characterized by a non-propulsive dis tal intestinal segment (usually colon) leading to a functional obstruc tion. An absence of ganglia in the affected segment explains the synon ymous term <<aganglionosis coli>>. The lack of peristalsis is partly d ue to a deficient intestinal smooth muscle relaxation based on an abse nce of non-adrenergic, non-cholinergic (NANC) inhibitory innervation. Morphological studies using conventional microscopy, immunohistochemis try and immunochemistry against general neuronal markers and neuropept ides have been used to characterize the disturbed NANC innervation in HSCR. An increased cholinergic and adrenergic innervation is registere d in the aganglionic segment in spite of the lack of neuronal cell bod ies: Neuropeptides like vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), gastrin-releasing p eptide (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 segm ent, probably reflecting the adrenergic hyper-innervation. General neu ronal markers including chromogranins have been used to map the neuron al network in the HSCR intestine and also to investigate the endocrine cell system in the intestinal mucosa. Nitric oxide is a potent compon ent of the NANC inhibitory innervation and its synthesizing enzyme, ni tric oxide synthase (NOS), is shown to be almost absent in the neurona l system in aganglionic intestine.