Colostomy Delays Cell Loss in the Brain and Improves Juvenile Survival in a Neonatal Rat Model of Hirschsprung’s Disease

Hirschsprung’s disease is a congenital malformation characterized by the absence of enteric ganglia in distal intestine and gut obstruction. Our previous study indicates brain pathology during progression. A subpopulation patients also associated with anomalies central nervous system. In investigation, we studied rat model disease, known as spotting lethal (sl/sl) ETB-/- rats, which carries spontaneous deletion endothelin receptor B (human gene name: EDNRB) manifests similar phenotype humans disease. Homozygous mutant sl/sl rats were successfully rescued from premature death performing colostomy dramatically survived to their juvenile age. By body weight measured, growth was not revealed be significantly different between wildtype ETB+/+ or heterozygous (+/sl) ETB+/- groups while all underwent same colostomy. Cell loss investigated several regions using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay (TUNEL) ETB+/+, ETB-/-, rats. Number TUNEL-positive cells cerebellum hippocampus increased compared that observed molecular layer granular cell layers cerebellum. contrast, no significant difference density cerebral cortex. These results suggest either sl mutation has predominant lasting effects on survival/loss adult findings provide information cellular changes brains due EDNRB well clinically relevant interventions.