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Enteric ganglia specific cell type reactions to intestinal ischemia

Grant number: 08/05718-9
Support type:Scholarships abroad - Research
Effective date (Start): January 01, 2009
Effective date (End): March 31, 2009
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Patricia Castelucci
Grantee:Patricia Castelucci
Host: John B. Furness
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : University of Melbourne, Australia  


The work we have done on the consequences of inflammation induced by TNBS in enteric neurons over the last few years, using electrophysiological methods and measures of second messenger activation, has demonstrated changes in specific classes of neurons (Nurgali et al. 2007; Poole et al. 2007). The fact that specific classes of neuron are affected probably influences the outcome of inflammation on overall functions (motility, secretion),controlled by enteric neurons. There is evidence that ischemia/reperfusion injury also damages enteric neurons (Piao et al. 1999; Lindeström and Ekblad 2004; Silva et al. 2007; Ventura-Martinez et al. 2007), and there is one paper that indicates that some neurons might be selectively affected (Calcina et al. 2005). The numbers of neurons that were immunoreactive for nitric oxide synthase (NOS) and vasoactive intestinal peptide (VIP) were increased, and tachykinin-IR fibres were decreased 24 hr after a 1 hr vascular occlusion in the rat (Calcina et al. 2005). The paper by Calcina et al. only investigated a small sample of the neuron types (inhibitory motor neurons with NOS and VIP immunoreactivity, although this could have also included some interneurons), and the endings of excitatory motor neurons, with tachykinin (SP) immunoreactivity. The rat is not the best place to begin, as the chemical coding of all neuron types is not known. However, in the guinea-pig there is a thorough knowledge of all neuron types and their chemical coding (Furness 2006).The studies that have been published concentrate on the myenteric plexus, while it would be expected that submucosal neurons would also be affected.The process of tissue damage by periods of restricted blood flow followed by reperfusion is complex. In addition, it might be anticipated that the large, ovoid, Type II neurons would be affected. These neurons have about 4x the mitochondrial density of other enteric neurons (Pompolo and Furness 1988), which suggests that they are energy-demanding. These neurons uniquely express a volume regulatory channel, the intermediate-conductance calcium-dependent potassium (IKCa) channel (Furness et al. 2003; Nguyen et al. 2007). Type II neurons also express KATP channels that are opened when cells are metabolically compromised. The additional effect of KATP opening may accentuate the effects of IKCa channel opening on cell volume. The proposal is that you consider the project in two parts, (1) an analysis of the changes in specific cell types in the guinea-pig small intestine that is subject to local ischemia and (2) an investigation of the effects of neuroprotective agents on neuronal changes. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PONTELL, LOUISE; CASTELUCCI, PATRICIA; BAGYANSZKI, MARIA; JOVIC, TANJA; THACKER, MICHELLE; NURGALI, KULMIRA; BRON, ROMKE; FURNESS, JOHN B. Structural changes in the epithelium of the small intestine and immune cell infiltration of enteric ganglia following acute mucosal damage and local inflammation. Virchows Archiv, v. 455, n. 1, p. 55-65, JUL 2009. Web of Science Citations: 29.

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