The aim of this study was to investigate the potential anti-inflammatory and anti-oxidant effects of gabapentin (GBP) in mice. The anti-inflammatory and anti-oxidant effects were evaluated using various mediators that induce paw edema, peritonitis model, myeloperoxidase (MPO) activity, proinflammatory cytokine levels, glutathione (GSH) consumption, and malondialdehyde (MDA) production in mice. Pretreatment of mice with GBP (1 mg/kg) significantly reduced carrageenan or dextran-induced paw edema (P<0.05) when compared to vehicle group. Adding to this, GBP (1 mg/kg) significantly inhibited paw edema induced by histamine, serotonin, bradikinin, 48/80 compound, and prostaglandin E2. In the carrageenan-induced peritonitis model, GBP significantly decreased total and differential leukocyte counts and reduced the levels of MPO activity in the plantar tissue and IL-1β and TNF-α concentrations in the peritoneal exudate. The same dose of GBP also decreased the MDA concentration and increased the levels of GSH into the peritoneal fluid. In summary, our results demonstrated that GBP exhibited anti-inflammatory activity in mice by reducing the action of inflammatory mediators, neutrophil migration and proinflammatory cytokine levels, and anti-oxidant properties by decreasing the concentration of MDA and increasing the GSH content. These observations raise the possibility that GBP could be used to improve tissue resistance to damage during inflammatory conditions.

Different data suggest that microglia may participate in the drug addiction process as these cells respond to neurochemical changes induced by the administration of these substances. In order to study the role of microglia in drug abuse, Swiss mice aged 8–9 weeks were treated with the CSF1R inhibitor PLX3397 (40 mg/kg, p.o.) and submitted to behavioral sensitization or conditioned place preference (CPP) induced by cocaine (15 mg/kg, i.p.). Thereafter, brains were used to evaluate the effects of CSF1R inhibition and cocaine administration on morphological, biochemical and molecular changes. CSF1R inhibition attenuated behavioral sensitization, reduced the number of Iba-1+ cells and increased ramification and lengths of the branches in the remaining microglia. Additionally, both cocaine and PLX3397 increased the cell body to total cell size ratio of Iba-1+ cells, as well as CD68+ and GFAP+ stained areas, suggesting an activated pattern of the glial cells. Besides, CSF1R inhibition increased CX3CL1 levels in the striatum, prefrontal cortex and hippocampus, as well as reduced CX3CR1 expression in the hippocampus. In this region, cocaine also reduced BDNF levels, an effect that was enhanced by CSF1R inhibition. In summary, our results suggest that microglia participate in the behavioral and molecular changes induced by cocaine. This study contributes to the understanding of the role of microglia in cocaine addiction.

Cryptococcus gattii (Cg) is one of the agents of cryptococcosis, a severe systemic mycosis with a higher prevalence in men than women, but the influence of the female sex hormone, 17-β-estradiol (E2), on cryptococcosis remains unclear. Our study shows that female mice presented delayed mortality, increased neutrophil recruitment in bronchoalveolar lavage fluid, and reduced fungal load after 24 hr of infection compared to male and ovariectomised female mice (OVX). E2 replacement restored OVX female survival. Female macrophages have more efficient fungicidal activity, which was increased by E2 and reversed by the antagonist of G-protein-coupled oestrogen receptor (GPER), which negatively modulates PI3K activation. Furthermore, E2 induces a reduction in Cg cell diameter, cell charge, and antioxidant peroxidase activity. In conclusion, female mice present improved control of Cg infection, and GPER is important for E2 modulation of the female response. K E Y W O R D S 17-β-estradiol, cryptococcosis, Cryptococcus gattii, GPER

Neuroinflammation seems to be involved in the pathophysiology of Huntington’s Disease (HD), but its specific role on different stages of the disease, especially in later stages, remains to be understood. Here in, we investigated the concentrations of cytokines, chemokines and neurotrophic factors in striatum and frontal cortex of 24-month-old BACHD mice, a murine model of that displays several behavioral and pathological features of human HD. Our results revealed increased concentrations of the chemokine MCP-1 and the neurotrophin NGF in the striatum of BACHD mice alongside a reduction in the levels of the cytokine IL-6 and of the neurotrophin BDNF. In the frontal cortex, we found decreased levels of BDNF and MCP-1. We provide the first evidence that cytokines and neurotrophic factors may contribute to the pathophysiology of advanced HD.

A neotalologia é a ciência, dentro da medicina veterinária, que estuda o período pós-nascimento até o desenvolvimento de certas características de resistência, que para os caninos se dá até a segunda semana de vida. O neonato exige uma abordagem precisa dada às particularidades de sua fisiologia e imunologia extremamente imaturas. O estudo histológico elucida problemas de anormalidade funcional e morfológica, na medida em que proporciona uma análise microscópica e fidedigna. Objetivou-se analisar traqueia e pulmão de neonatos caninos por meio de técnicas de histologia básica. Foram utilizados cinco neonatos, que vieram a óbito pós-parto. Estes foram pesados, medidos e posteriormente dissecados. Procedeu-se a extração da traqueia, brônquios e do pulmão para a submissão destas amostras à rotina histológica. O tecido traqueal apresenta um epitélio pseudoestratificado estereociliado com células caliciformes, pouca quantidade de glândulas na lâmina própria e cartilagem hialina não completamente desenvolvida. Quanto ao tecido dos brônquios, podem-se observar as camadas bem definidas, epitélio pulmonar pseudoestratificado estereociliado com células caliciformes, lâmina própria com vários feixes de músculo liso e espessa camada de tecido conjuntivo vascularizado. Da mesma forma, as placas de cartilagem nos brônquios apresentam-se em desenvolvimento. Os bronquíolos também apresentam o epitélio pulmonar comum e lâmina própria também normal, cercados sem músculo liso. Os sacos alveolares apresentaram células pulmonares típicas. Os tecidos pulmonares de neonatos caninos apresentam-se ainda em estágio de desenvolvimento. É possível entender padrões de histogênese e morfogênese em neonatos caninos.