BackgroundNeuroinflammation (NI) is a key feature in the pathogenesis and progression of infectious and non-infectious neuropathologies, and its amelioration usually improves the patient outcome. Peripheral inflammation may promote NI through microglia and astrocytes activation, an increased expression of inflammatory mediators and vascular permeability that may lead to neurodegeneration. Several anti-inflammatory strategies have been proposed to control peripheral inflammation. Among them, electrical stimulation of the vagus nerve (VNS) recently emerged as an alternative to effectively attenuate peripheral inflammation in a variety of pathological conditions with few side effects.Considering that NI underlies several neurologic pathologies we explored herein the possibility that electrically VNS can also exert anti-inflammatory effects in the brain.MethodsNI was experimentally induced by intraperitoneal injection of bacterial lipopolysaccharide (LPS) in C57BL/6 male mice; VNS with constant voltage (5 Hz, 0.75 mA, 2 ms) was applied for 30 s, 48 or 72 h after lipopolysaccharide injection. Twenty four hours later, pro-inflammatory cytokines (IL-1β, IL-6, TNFα) levels were measured by ELISA in brain and spleen extracts and total brain cells were isolated and microglia and macrophage proliferation and activation was assessed by flow cytometry. The level of ionized calcium binding adaptor molecule (Iba-1) and glial fibrillary acidic protein (GFAP) were estimated in whole brain extracts and in histologic slides by Western blot and immunohistochemistry, respectively.ResultsVNS significantly reduced the central levels of pro-inflammatory cytokines and the percentage of microglia (CD11b/CD45low) and macrophages (CD11b/CD45high), 24 h after the electrical stimulus in LPS stimulated mice. A significantly reduced level of Iba-1 expression was also observed in whole brain extracts and in the hippocampus, suggesting a reduction in activated microglia.ConclusionsVNS is a feasible therapeutic tool to attenuate the NI reaction. Considering that NI accompanies different neuropathologies VNS is a relevant alternative to modulate NI, of particular interest for chronic neurological diseases.
Sepsis occurs when a systemic infection induces an uncontrolled inflammatory response that results in generalized organ dysfunction. The exacerbated peripheral inflammation can induce, in turn, neuroinflammation which may result in severe impairment of the central nervous system (CNS). Indeed, the ensuing blood–brain barrier disruption associated with sepsis promotes glial activation and starts a storm of proinflammatory cytokines in the CNS that leads to brain dysfunction in sepsis survivors. Endotoxic shock induced in mice by peripheral injection of lipopolysaccharides closely resembles the peripheral and central inflammation observed in sepsis. In this review, we provide an overview of the neuroinflammatory features in sepsis and of recent progress toward the development of new anti‐neuroinflammatory therapies seeking to reduce mortality and morbidity in sepsis survivors.
Neuroinflammation is the hallmark of several infectious and neurodegenerative diseases. Synthetic glucocorticoids (GCs) are the first-line immunosuppressive drugs used for controlling neuroinflammation. A delayed diffusion of GCs molecules and the high systemic doses required for brain-specific targeting lead to severe undesirable effects, particularly when lifelong treatment is required. Therefore, there is an urgent need for improving this current therapeutic approach. The intranasal (i.n.) route is being employed increasingly for drug delivery to the brain via the olfactory system. In this study, the i.n. route is compared to the intravenous (i.v.) administration of GCs with respect to their effectiveness in controlling neuroinflammation induced experimentally by systemic lipopolysaccharide (LPS) injection. A statistically significant reduction in interleukin (IL)-6 levels in the central nervous system (CNS) in the percentage of CD45 /CD11b /lymphocyte antigen 6 complex locus G6D [Ly6G and in glial fibrillary acidic protein (GFAP) immunostaining was observed in mice from the i.n.-dexamethasone (DX] group compared to control and i.v.-DX-treated animals. DX treatment did not modify the percentage of microglia and perivascular macrophages as determined by ionized calcium binding adaptor molecule 1 (Iba1) immunostaining of the cortex and hippocampus. The increased accumulation of DX in brain microvasculature in DX-i.n.-treated mice compared with controls and DX-IV-treated animals may underlie the higher effectiveness in controlling neuroinflammation. Altogether, these results indicate that IN-DX administration may offer a more efficient alternative than systemic administration to control neuroinflammation in different neuropathologies.
A retrospective study of our 14-yr records on experimental Taenia crassiceps (ORF(fast) line) cysticercosis (n = 1,198) shows that in 16 of 17 different mice strains, female mice are more frequently infected and carry larger individual parasite loads than males. However, sexual differences in parasite loads significantly varies between strains in relation to their different genetic backgrounds (BALB > C57Bl = OTHERS > C3H). The coefficient of variation in all female mice is significantly smaller than that of all males, an indication of males' more potent, but erratically effective, restraint of cysticercus growth. Similar positive growth bias for female mice is shown by other lines of cysticerci, i.e., HYG(slow) and WFU(slow). These results contravene the usual expectation of female hosts being more resistant than males to parasite infections, and they point to the multiple factors that combined determine sex related differences of mice to experimental cysticercosis infection.
Taenia solium cysticercosis is a parasitic disease frequently affecting human health and the pig industry in many developing countries. A synthetic peptide vaccine (designated S3Pvac) against porcine cysticercosis has been developed previously as an aid to interrupt transmission and has been shown to be effective. The results of the present study support the effectiveness of the vaccine under endemic field conditions. However, given the time-frame of the vaccination trial, no changes in the local levels of transmission were detectable before and after vaccination using sentinel pigs. Thus, this investigation shows the limited usefulness of single vaccination as the sole means of interrupting Taenia solium transmission in an endemic region.
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