RESUMEN
Sepsis survivors show long-term impairments, including alterations in memory and executive function. Evidence suggests that systemic inflammation contributes to the progression of Alzheimers disease (AD), but the mechanisms involved in this process are still unclear. Boosted (trained) and diminished (tolerant) innate immune memory has been described in peripheral immune cells after sepsis. However, the occurrence of long-term innate immune memory in the post-septic brain is fully unexplored. Here, we demonstrate that sepsis causes long-lasting trained innate immune memory in the mouse brain, leading to an increased susceptibility to Aß oligomers (AßO), central neurotoxins found in AD. Hippocampal microglia from sepsis-surviving mice shift to an amoeboid/phagocytic morphological profile when exposed to low amounts of AßO, and this event was accompanied by the upregulation of several pro-inflammatory proteins (IL-1ß, IL-6, INF-γ and P2X7 receptor) in the mouse hippocampus, suggesting that a trained innate immune memory occurs in the brain after sepsis. Brain exposure to low amounts of AßO increased microglial phagocytic ability against hippocampal synapses. Pharmacological blockage of brain phagocytic cells or microglial depletion, using minocycline and colony stimulating factor 1 receptor inhibitor (PLX3397), respectively, prevents cognitive dysfunction induced by AßO in sepsis-surviving mice. Altogether, our findings suggest that sepsis induces a long-lasting trained innate immune memory in the mouse brain, leading to an increased susceptibility to AßO-induced neurotoxicity and cognitive impairment.
Asunto(s)
Enfermedad de Alzheimer , Sepsis , Péptidos beta-Amiloides/metabolismo , Animales , Hipocampo/metabolismo , Memoria Inmunológica , Ratones , Microglía/metabolismoRESUMEN
INTRODUCTION: Patients with migraine may present a higher quantity of myofascial trigger points (MTrP) and alterations in the cervical muscles when compared to non-migraineurs. The magnetic resonance imaging (MRI) is a robust method for the study of human soft tissues and could be useful to investigate these points. OBJECTIVES: To identify the presence of MTrP in the descending fibers of the trapezius muscle in women with migraine and to quantify the muscle volume by MRI, correlating it with the headache characteristics. METHODS: A cross-sectional analytic study was conducted among 14 women, eight in migraine group, and six in without migraine group. The presence of MTrP was evaluated using Simons' criteria, and linolenic acid capsules subsequently marked the areas. MRI was performed with 1.5T, T1-weighted sequence, and T2 in the axial, sagittal, and coronal planes. The T1-weighted sequences were performed with and without gadolinium contrast. RESULTS: The T1-weighted image analysis with and without gadolinium did not show any signal alteration in the MTrP areas in both groups. The migraine group presented more MTrP in the trapezius muscle (MD [95%CI] = 1[1; 3]; MD [95%CI] = 1[0; 2] right and left side, respectively), and a smaller muscle volume (MD [95%CI] = -198.1[-338.7;-25.6], MD [95%CI] = -149.9[-325.05;-0.13] right and left side, respectively) than non-migraineurs. The migraine frequency presented a negative strong correlation with the trapezius volumes (r = -0.812; p = 0.014). CONCLUSION: Migraineurs present more MTrP and a smaller muscle volume than non-migraineurs. The trapezius volume is negatively correlated with migraine frequency. MRI is not a suitable outcome measure for assessing MTrP.