Chagasic megacolon: enteric neurons and related structures

Abstract

Megacolon, the irreversible dilation of a colonic segment, is a structural sign associated with various gastrointestinal disorders. In its hereditary, secondary form (e.g. in Hirschsprung’s disease), dilation occurs in an originally healthy colonic segment due to an anally located, aganglionic zone. In contrast, in chronic Chagas’ disease, the dilated segment itself displays pathohistological changes, and the earliest and most prominent being found was massive loss of myenteric neurons. This neuron loss was partial and selective, i.e. some neurons containing neuronal nitric oxide synthase and/or vasoactive intestinal peptide (VIP) were spared from neuron death. This disproportionate survival of inhibitory neurons, however, did not completely correlate with the calibre change along the surgically removed, megacolonic segments. A better correlation was observed as to potentially contractile muscle tissue elements and the interstitial cells of Cajal. Therefore, the decreased densities of α-smooth muscle actin- and c-kit-immunoreactive profiles were estimated along resected megacolonic segments. Their lowest values were observed in the megacolonic zones itself, whereas less pronounced decreases were found in the non-dilated, transitional zones (oral and anal to dilation). In contrast to the myenteric plexus, the submucosal plexus displayed only a moderate neuron loss. Neurons co-immunoreactive for VIP and calretinin survived disproportionately. As a consequence, these neurons may have contributed to maintain the epithelial barrier and allowed the chagasic patients to survive for decades, despite their severe disturbance of colonic motility. Due to its neuroprotective and neuroeffectory functions, VIP may play a key role in the development and duration of chagasic megacolon.

Trypanosoma cruziparasites fight for control of the JAK-STAT pathway by disarming their host

“…Although Chagas' disease is the main cause of heart failure among people living in poverty in Latin America, it is generally regarded as a neglected tropical disease with an immense socio-economic burden. [2][3][4] At present, no vaccination against T. cruzi is available and chemotherapeutic intervention is limited and may cause severe side effects.…”

Nitrergic Myenteric Neurons are Spared in Experimental Chagasic Megacolon

“…Acquired enteric neurodegeneration of an originally healthy (normal ganglionic) segment is an important manifestation of at least 20% of patients suffering from Chagas' . During its chronic phase, myenteric neuron loss and irreversible dilation occur in the affected gut segment and the consequent dilation is termed as primary megacolon [7].…”

“…The tissue infection and the intense parasitism of acute phase affect neuronal integrity [11,12]. However, the relative absence of parasite and the very discreet inflammatory process of chronic phase probably indicate a progressive injury mechanism, suggested to involve autoimmunity [7] which needs to be better understood in the context of the changes in TGI associated to the megacolons.…”

“…Although one of these studies have addressed the differential loss of neuronal subclasses in human megacolon [7], the importance of reproducing this finding in a suitable model of murine megacolon is indiscutible and would provide a unique perspective to study the intrinsic mechanisms of the neural lesions in intestinal Chagas disease.…”

Síntese e avaliação biológica de sulfonil-hidrazonas análogos do nitrofural como candidatos a antichagásicos

“…Conhecida como forma digestiva da doença, os "megas", ocorrem resultante da ação de anticorpos do indivíduo infectado, seguido de lesões inflamatórias nas fibras do músculo liso do sistema digestivo e dos nervos autonômicos entéricos, findando no aumento desses órgãos (JABARI et al, 2014, TEIXEIRA, NASCIMENTO, STURM, 2006MONCAYO, YANINE, 2006). Nessa fase há comprometimento do sistema nervoso autônomo, levando à falta de coordenação motora; ocorre também a hipertrofia muscular e a dilatação desses órgãos.…”