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Study of ganglion cell and interstitial cells of Cajal in mice with intestinal aganglionosis undergoing hypoxia and reoxygenation

Grant number: 12/10150-7
Support type:Regular Research Grants
Duration: January 01, 2013 - December 31, 2014
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Jose Luiz Martins
Grantee:Jose Luiz Martins
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


Hirschsprung's disease is characterized by the absence of ganglion cells in the distal colon, and may extend proximally at varying distances. This absence occurs when the neuroblasts stop migrating from the neural crest. The physiopathological basis for the absence of colon peristalsis in Hirschsprung's disease is not yet fully understood. This disease is an ideal model for investigation of the interactions between intestinal ganglion cells and interstitial cells of Cajal, the pacemakers of intestinal motility. Regional differences in the distribution of these cells were found in the healthy human colon, however, in patients with the disease this distribution remains under study. Enterocolitis is the most serious complication associated to Hirschsprung's disease, with expressive morbidity and high mortality rates, between 12% and 30%. In this study it is hypothesized that intestinal lesions triggered by hypoxia could change the density of the interstitial cells of Cajal in the colon of mutant mice with intestinal aganglionosis (Dom mouse - Jackson Laboratory). METHOD: First phase: aims to determine the distribution and density of the ganglion cells and the interstitial cells of Cajal in the colons of mutant mice - heterozygous dominants (Dom mouse) and of mice of the same species, but without aganglionosis (homozygous recessive). Two studies were used in this phase - histological (hematoxylin-eosin coloration) and immunohistochemical (neuron-specific enolase, protein S100 and CD117 - the c-kit, or interstitial cell of Cajal marker). Second phase: aims to study the histopathological and immunohistochemical changes, as described in the first phase, of the colon of mice with intestinal aganglionosis undergoing hypoxia and reoxygenation (Okur model), resulting in intestinal lesion. (AU)