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Evaluation of hypothalamic impairment in vasopressin secretion during sepsis

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Luís Henrique Angenendt da Costa
Total Authors: 1
Document type: Master's Dissertation
Press: Ribeirão Preto.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
Defense date:
Examining board members:
Maria Jose Alves da Rocha; Rafael Simone Saia; Angelita Maria Stabile
Advisor: Maria Jose Alves da Rocha

Sepsis and its complications (severe sepsis and septic shock) remain as the main cause of death in intensive care units worldwide. Clinical and experimental studies have shown that in the early phase of sepsis the plasma concentration of arginine vasopressin (AVP) is increased. However, during the pathophysiological process the plasma levels remain inadequately low, despite of persistent hypotension. One of the hypothesis suggested for this relative deficiency is the apoptosis of vasopressinergic neurons. Our objective was to identify elements involved in the hypothalamic cellular death and evaluate the modifications of glial cells and blood-brain-barrier (BBB) during sepsis. Wistar rats were submitted to sepsis by cecal ligation and puncture (CLP) or non-manipulated (naïve), as control and then divided in two groups. In the first one, they were perfused and brains were collected for immunohistochemistry. In another one they were decapitated for blood collection and further plasma interferongama (IFN-?) analysis by ELISA. Brain was also collected for apoptosis-related proteins expression analysis in the hypothalamus or in the supraoptic (SON) and paraventricular (PVN) nuclei. A third set was separated for the investigation of BBB permeability. Despite of increased immunostaining for CD8 and MHC-I in the SON of septic animals, we did not find evidence of cell death mediated by immune cells. In the SON and PVN of septic animals, the expression of proteins involved in the activation of the extrinsic apoptosis pathway (tBID, cleaved caspase-8) was not altered, whereas anti-apoptotic factors related to the intrinsic pathway (BCL-2, BCLxL) were decreased. In the SON of these animals, microglia assumed a morphology related to its activation, associated with the increase of plasma IFN-?. There was a transitory breakdown of BBB in hypothalamus after 6 hours following CLP. The results indicate that the intrinsic apoptosis pathway seems to be responsible for the cell death observed in vasopressinergic nuclei and this condition is temporally associated with microglial activation and BBB leaking (AU)

FAPESP's process: 13/03723-3 - Evaluation of hypotalamic neuronal impairment in vasopressin secretion during sepsis
Grantee:Luís Henrique Angenendt da Costa
Support type: Scholarships in Brazil - Master