Quantitative analysis of neuronal innervation in the aganglionic bowel of patients with Hirschsprung's disease

Although there is marked proliferation of nerve fibers in the aganglionic bowel of patients with Hirschsprung's disease (HD), controversy exists as to whether these fibers terminate in the cells of the bowel wall. This study quantitates biochemically the synaptic vesicle proteins and neurofilaments in the aganglionic bowel of HD patients. The bowel specimens obtained from 12 patients with HD (mean age, 4.6 months) and nine age-matched controls were analyzed by Western blot analysis using monoclonal antibody 171B5 against the synaptic vesicle 38,000-d protein (SVP38), and the specific band obtained was quantitated by densitometry. Similarly, using monoclonal antibody NF70K for detecting the 70,000-d component of neurofilament (NF70), nerve fibers were quantitated. In the aganglionic HD bowel, the quantity of SVP38, representing a proportion of synapses, was significantly lower than that in the normoganglionic bowel (P < .001). The quantity of NF70, representing a proportion of nerve fibers, was significantly greater than that in the normoganglionic bowel (P < .05). These findings suggest that the nerve fibers in the aganglionic bowel of HD patients have much less developed connections with the cells of the bowel wall, indicating overall poor innervation, despite marked proliferation of the nerve fibers.