Microglia and astrocyte activation in vasopressinergic nuclei in severe sepsis

Abstract

Sepsis is a potentially fatal condition that occurs when the body produces an inflammatory response to an infectious agent (bacteria, fungi, parasites or viruses) that can lead to multiple organ failure, shock and death. In the pathophysiological process of sepsis excessive production and release of inflammatory mediators may directly or indirectly activate the central nervous system. In the brain, glial cells (astrocytes and microglia) are the main responsible for the central production of these inflammatory mediators, especially IL-1², TNF-a and nitric oxide (NO). Initially, these products are synthesized in order to combat the infection, but when overstimulated glial cells can lead to damage in nervous tissue. One of the physiological systems affected in sepsis is the neuroendocrine. A hormone that has been studied during sepsis in our laboratory is vasopressin (AVP). AVP is a nonapeptide synthesized in the magnocellular neurons of supraoptic (SON) and paraventricular (PVN) nuclei of hypothalamus, playing an important role in electrolyte and fluid homeostasis and in the maintenance of blood pressure. During sepsis there is a biphasic response in the secretion of this hormone: in the initial phase there is an increase in the concentration of plasma AVP in an attempt to maintain blood pressure and tissue perfusion, but in the late phase the release of this hormone is basal, despite persistent hypotension, which contributes to general organ dysfunction. One hypothesis to explain this phenomenon is apoptosis in vasopressinergic neurons, leading to impairment in AVP synthesis. In the late phase of sepsis it is observed high expression of inducible nitric-oxide synthase (iNOS) in the SON and PVN, as well as cytokines like IL-1² and TNF-a, which can lead to programmed cell death. Considering the role of glial cells in the production of these inflammatory mediators, our objective will be to investigate whether the production of these cytokines would be due to the activation of microglia and astrocytes in the vasopressinergic neurons during the late phase of sepsis. (AU)