Neural and endocrine alterations in experimental sepsis surviving animals submitted to behavioral tests

• Grant number: 11/05821-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2011
• End date: June 30, 2013
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria José Alves da Rocha
• Grantee: Tatiana Tocchini Felippotti
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Sepsis and its consequences, septic shock and organic dysfunction represent a serious problem of public health. Besides the monetary costs, it causes a high mortality rate and the surviving patients may leave the hospital with cognitive alterations resulting in future admissions, burdening even more the national public health system. In Brazil, the mortality rate for sepsis is 57.3% (Ilas, 2010), or the other way round, 42.7% of the patients are able to survive. Nevertheless, there are no studies done until now aiming these patients after they leave the hospital. Impairment of memory, attention, concentration and/or loss of general cognitive functions are some of the alterations reported in such patients. Memory formation and behavior are facilitated by the endogenous modulatory system, mediated by the liberation of hormones during stress, and organized by multiple brain structures, amongst these the hypothalamus, hippocampus, amygdala and locus coeruleus. During sepsis, cytokines, prostaglandins, leukotrienes, nitric oxide, and other compounds are liberated, which may contribute to the cognitive alterations observed in some patients during and/or after the treatment of the disease. These substances may also be responsible for the hormonal alterations that occur during sepsis. In this laboratory we have been investigated mainly vasopressin secretion, this showing an increase in the early phase and an impairment despite persistent hypotension during the late phase of sepsis. Moreover, we recently observed that there was an increase in apoptosis markers, such as cleaved caspase 3, HIF-1, BAX, and cytochrome C in the hypothalamus of rats in the late phase of sepsis induced by cecal ligation and puncture. The cell death may also be responsible for some of the hormonal alterations. However, it is not known yet whether such hormonal alterations persist in rats that survive sepsis, and also, if we can observe neuronal death in rats that survive sepsis Therefore, we expect that investigations on the brain and hormonal alterations in such survivors can provide information that could be useful for clinical handling of the patients. That information could also help health professionals to become aware of the importance of medical monitoring of these patients after their hospital discharge. The aims of this study are: a) investigating hormonal (vasopressin, oxytocin, prolactin, ACTH and corticosterone) and neuronal alterations (c-fos and Neu-N expression) in sepsis surviving animals submitted to stressors, such as immobilization, footshock and social defeat; b) investigating the above mentioned neuronal alterations (c-fos and Neu-N expression) in sepsis survivors submitted to inhibitory avoidance as a means to evaluate aversive memory. (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)

BIAGIONI, AUDREY FRANCISCO; DOS ANJOS-GARCIA, TAYLLON; ULLAH, FARHAD; FISHER, ISAAC RENE; FALCONI-SOBRINHO, LUIZ LUCIANO; DE FREITAS, RENATO LEONARDO; FELIPPOTTI, TATIANA TOCCHINI; COIMBRA, NORBERTO CYSNE. Neuroethological validation of an experimental apparatus to evaluate oriented and non-oriented escape behaviours: Comparison between the polygonal arena with a burrow and the circular enclosure of an open-field test. Behavioural Brain Research, v. 298, n. B, p. 65-77, FEB 1 2016. (14/10742-7, 08/08955-1, 11/05821-7, 07/01174-1, 12/03798-0, 09/17258-5, 13/10984-8, 11/06036-1)

BIAGIONI, AUDREY FRANCISCO; DOS ANJOS-GARCIA, TAYLLON; ULLAH, FARHAD; FISHER, ISAAC RENE; FALCONI-SOBRINHO, LUIZ LUCIANO; DE FREITAS, RENATO LEONARDO; FELIPPOTTI, TATIANA TOCCHINI; COIMBRA, NORBERTO CYSNE. Neuroethological validation of an experimental apparatus to evaluate oriented and non-oriented escape behaviours: Comparison between the polygonal arena with a burrow and the circular enclosure of an open-field test. Behavioural Brain Research, v. 298, p. 13-pg., 2016-02-01. (14/10742-7, 12/03798-0, 13/10984-8, 09/17258-5, 08/08955-1, 11/06036-1, 11/05821-7, 07/01174-1)