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Abstract

The Neuroprotective Effect of Erythropoietin in Rat Hippocampus in an Endotoxic Shock Model

VOLUME 68 - NUMBER 6 / November - December (Original articles)

Luis Javier Ramírez-Jirano, Laboratory of Neuroimmunomodulation, Centro de Investigación Biomédica de Occidente, CIBO, IMSS, Guadalajara, Jal., Mexico
Tania Zenteno-Savín, Programa de Planeación Ambiental y Conservación, Centro de Investigaciones Biológicas del Noroeste S.C., CIBNOR, La Paz, B.C.S.
Ramón Gaxiola-Robles, Programa de Planeación Ambiental y Conservación, Centro de Investigaciones Biológicas del Noroeste S.C., CIBNOR, La Paz, B.C.S. and Hospital General de Zona No. 1, Instituto Mexicano del Seguro Social, La Paz, B.C.S., Mexico
Elsy Janeth Ramos-González, Laboratory of Neuroimmunomodulation, Centro de Investigación Biomédica de Occidente, CIBO, IMSS, Guadalajara, Jal., Mexico
Blanca Miriam Torres-Mendoza, Neurosciences Division, Centro de Investigación Biomédica de Occidente, CIBO, IMSS, Guadalajara, Jal., Mexico
Oscar Kurt Bitzer-Quintero, Laboratory of Neuroimmunomodulation, Centro de Investigación Biomédica de Occidente, CIBO, IMSS, Guadalajara, Jal., Mexico

Background: Sepsis is characterized by an early systemic inflammation in response to infection. In the brain, inflammation is associated with expression of pro-inflammatory cytokines (e.g. tumor necrosis factor-α, interleukin-1β and interleukin-6, among others) that may induce an overproduction of reactive oxygen and nitrogen species. The constitutive expression of cytokines in the brain is low, but may be induced by various stimuli, including lipopolysaccharide, which causes neuronal damage. Erythropoietin, among other effects, acts as a multifunctional neurotrophic factor implicated in neurogenesis, angiogenesis, vascular permeability, and immune regulation in the central nervous system. In an experimental model of endotoxic shock, we studied the neuroprotective capacity of erythropoietin in the rat hippocampus and compared with melatonin, a neurohormone with an important antioxidant and immunomodulatory effect. Methods: In 21-day-old male Wistar rats divided into eight groups, we administered by intraperitoneal injection lipopolysaccharide, erythropoietin, melatonin, or combinations thereof. The hippocampus was dissected and morphological (histological analysis) and biochemical (cytokine levels) studies were conducted. Results: The number of dead neuronal cells in histological sections in groups treated with lipopolysaccharide was higher compared to the erythropoietin group. There was a greater decrease (70%) in interleukin-1β concentrations in rats with endotoxic shock that received erythropoietin compared to the lipopolysaccharide group. Conclusions: The neuronal cell loss caused by endotoxic shock and interleukin-1β levels were reduced by the administration of the hematopoietic cytokine erythropoietin in this experimental model.

Keywords: Erythropoietin. Endotoxic shock. Neuroimmunology. Neuroinflammation. Oxidative stress.

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