Interstitial cells of cajal: key players in gastrointestinal motor disorders
- Autores: Natalia Zarate Lopez
- Directores de la Tesis: Jan D. Huizinga (dir. tes.), Juan Ramón Malagelada Benaprés (codir. tes.)
- Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2008
- Idioma: español
- Tribunal Calificador de la Tesis: Miquel Vilardell Tarrés (presid.), Marcel Jiménez Farrerons (secret.), Josep Maria Piqué Badia (voc.), Miguel Mínguez Pérez (voc.)
- Materias:
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- Resumen
ICC have moved from neglected cells to principal actors in the neurogastroenterology arena. Their ubiquitous presence in the gastrointestinal motility. This will be followed by a comprehensive understanding of the altered motor patterns and sensory functions in the gut in the absence of functional ICC. Their fate in different gastrointestinal motor disorders has started to be explored only recently. The objectives of the studies included in this thesis were:
1. To determine the fate of the different ICC subypes in various clinical conditions, namely achalasia, gastroparesis and Crohn's disease, characterized among other pathological abnormalities by neuronal damage and/or degeneration and impaired motor function of the revelant region.
2. To determine the relation between ICC injury and nitregic neuronal degeneration in achalasia.
3. To determine the relation between ICC and immune cells, particularly mast cells which share the c-kit receptor with ICC and possess the ability to influence survival of neighbouring cells.
4. To determine the role of damage to ICC in the gastroparesis associated with exposure to whole body irradiation using an animal model.
In order to achieve the first 3 objectives surgical samples from the lower esophageal sphincter from patients with achalasia, terminal ileum from immunohistochemistry techniques and electron microscopy. Results were compared with those obtained in appropiate control specimen. In order to answer the objective of the forth study, mice were radiated or sham radiated and gastric specimen were also studied morphologically. Rate of gastric emptying and antro-duodenal persitalsis were assessed with the aid of fluoroscopy and building spatio-temporal maps. Gastric accommodation and mechanical properties of muscle strips were also assessed.
The results of the study showed that:
1. Interstitial cells of Cajal are decreased in number and exhibit ultrastructural damage in achalasia, Crohn's disease and idiopathic gastroparesis.
2. ICC establish intimate membrane to membrane contacts with mast cells in achalasia and Crohn's disease; the nature of this relation and its influence in ICC survival warrants further investigation.
3. ICC are decreased in number in conditions associated with neuronal degeneration or damage, including achalasia, Crohn's disease and idiopathic gastroparesis.
4. Damage to ICC in achalasia and Crohn's disease was not related with the duration of the disease. Taking into account the chronic nature of these conditions, this finding suggests the capacity of these cells to regenerate.
5. An animal model of acute gastric stasis following exposure to whole body irradiation evidenced that the enteric nervous system and ICC were affected. Nitric oxide could also contribute to the impaired gastric motor function.
6. Damage to ICC likely contributes to dysmotility of the affected organ.
