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Neuroendocrine alterations during experimental sepsis induced by cecal ligation and puncture

Abstract

Despite considerable technological advances, systemic infections, including sepsis and its complications (septic shock and multiple organ dysfunction) still are the major cause of death in Intensive Care Units all over the world. The high morbidity and associated mortality rates of sepsis and its different clinical stages represent a major challenge to medical doctors, especially since current treatments are merely those of support. Important progress in the comprehension of the pathophysiology of sepsis has been made through experiments, but many more studies are still needed to come to a more profound understanding of the alterations caused by this disease. The experimental sepsis induced by cecal ligation and puncture (CLP) is the model that better mimic gut derived-sepsis because it shows a septic focus and more complex inflammatory response. However, the late phase of polymicrobial sepsis is also characterized by an inappropriate low level of vasopressin (AVP) and there are several hypotheses for such inappropriate secretion. Recently, we have investigated some of these hypotheses and found that a reduction in autonomic nervous system activity causes the impairment of baroreflex and the iNOS-derived NO prevents hypothalamic activation that may contribute to the reduction of vasopressin plasma levels in the late phase of severe sepsis. Nevertherless, is not yet clear whether the deficiency in the hormone secretion is due to changes in the synthesis of AVP or caused by nitric oxide apoptosis-induced in vasopressinergic neurons of hypothalamic nuclei. This current project intends to investigate other options for inappropriate low level of vasopressin (AVP) secretion in the late phase of sepsis, such as changes in hormone synthesis and apoptosis in hypothalamic nuclei of animals with polymicrobial sepsis induced by cecal ligtion and puncture. (AU)

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Scientific publications (4)
(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)
OLIVEIRA-PELEGRIN, GABRIELA RAVANELLI; DE AZEVEDO, SERGIO VICENTE; YAO, SONG TIENG; MURPHY, DAVID; ALVES ROCHA, MARIA JOSE. Central NOS inhibition differentially affects vasopressin gene expression in hypothalamic nuclei in septic rats. Journal of Neuroimmunology, v. 227, n. 1-2, p. 80-86, OCT 8 2010. Web of Science Citations: 14.
OLIVEIRA-PELEGRIN, GABRIELA RAVANELLI; AGUILA, FABIO ALVES; BASSO, PAULO JOSE; ALVES ROCHA, MARIA JOSE. Role of central NO-cGMP pathway in vasopressin and oxytocin gene expression during sepsis. Peptides, v. 31, n. 10, p. 1847-1852, OCT 2010. Web of Science Citations: 19.
OLIVEIRA-PELEGRIN, G. R.; BRANCO, L. G. S.; ROCHA, M. J. A. Central NO-cGMP pathway in thermoregulation and survival rate during polymicrobial sepsis. Canadian Journal of Physiology and Pharmacology, v. 88, n. 2, SI, p. 113-120, FEB 2010. Web of Science Citations: 1.
PASCOTI BRUHN, FERNANDO HENRIQUE; FARIAS CORREA, POLLYANNA BARBOSA; OLIVEIRA-PELEGRIN, GABRIELA RAVANELLI; ALVES ROCHA, MARIA JOSE. Blocking systemic nitric oxide production alters neuronal activation in brain structures involved in cardiovascular regulation during polymicrobial sepsis. Neuroscience Letters, v. 453, n. 3, p. 141-146, APR 10 2009. Web of Science Citations: 8.

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