Poster abstracts
Poster number 52 submitted by Ana Leon-Rodriguez
Primed microglia and increased hypothalamic neuroinflammation after acute stress in traumatic brain injured-mice
Ana Leon-Rodriguez (Departamento de Biologia Celular, Genetica y Fisiologia de la Universidad de Malaga, Spain-Area de Fisiologia Animal; IBIMA-Plataforma BIONAND), Lynde Wangler, Ethan Goodman, Jonathan Packer, Amara Davis (Department of Neuroscience at The Ohio State University Columbus, Ohio, USA), John Sheridan (Department of Neuroscience at The Ohio State University, Columbus, Ohio, USA; Institute for Behavioral Medicine, Wexner Medical Center; Chronic Brain Injury Program), Jesus M. Grondona (Departamento de Biologia Celular, Genetica y Fisiologia de la Universidad de Malaga, Spain-Area de Fisiologia Animal; IBIMA-Plataforma BIONAND), Jonathan Godbout (Department of Neuroscience at The Ohio State University, Columbus, Ohio, USA; Institute for Behavioral Medicine, Wexner Medical Center; Chronic Brain Injury Program), Maria Dolores Lopez-Avalos (Departamento de Biologia Celular, Genetica y Fisiologia de la Universidad de Malaga, Spain-Area de Fisiologia Animal; IBIMA-Plataforma BIONAND)
Abstract:
Microglia are activated by neuroinflammatory insults, and this activation is usually tightly controlled and transient in duration. Following traumatic brain injury (TBI), however, microglia can become “primed.” Functionally priming is characterized by an exacerbated inflammatory response to secondary stimulus that augments cognitive and behavioral deficits. Psychological stress is one stimulus that may enhance the reactivity of primed microglia. Thus, the objective of this study was to determine the degree to which TBI-induced microglial priming resulted in enhanced neuroinflammatory and neuroendocrine responses to Acute Social Defeat (ASD) stress. Here adult (2 month of age) male C57BL/6 mice were subjected to TBI induced by a midline fluid percussion injury. 14 days later, control and TBI mice were exposed to a 2-hour cycle of ASD. IBA-1 and GFAP immunohistological analysis were performed to determine the number and mark intensity of microglia and astrocyte, and to evaluate the morphology of microglia within the paraventricular nucleus of the hypothalamus (PVN). Morphological analysis of hypothalamic microglia showed a main effect of TBI, which was increased in mice that also received the ASD compared to non-stressed mice. ASD caused exacerbated neuroinflammatory pathways in the hypothalamus of mice that received TBI compared to controls. For example, transcriptional analysis revealed increased expression of key cytokines and chemokines (IL1B, IL6, CXCL1 and CCL2), protein receptors (TLR4) and neurohormones (AVP and OXT) within the third-ventricle paraventricular tissue of the hypothalamus. ASD produced increased corticosterone levels in the serum of mice, although no effect of TBI was found. Overall, these data provide evidence of primed microglia in the hypothalamus after diffuse TBI that resulted in an amplified neuroinflammatory response to an acute stressor.
Keywords: TBI, Priming, Microglia