Arundic Acid (ONO-2506) Attenuates Neuroinflammation and Prevents Motor Impairment in Rats with Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a severe stroke subtype caused by the rupture of blood vessels within the brain. Increased levels of S100B protein may contribute to neuroinflammation after ICH through activation of astrocytes and resident microglia, with the consequent production of proinflammatory cytokines and reactive oxygen species (ROS). Inhibition of astrocytic synthesis of S100B by arundic acid (AA) has shown beneficial effects in experimental central nervous system disorders. In present study, we administered AA in a collagenase-induced ICH rodent model in order to evaluate its effects on neurological deficits, S100B levels, astrocytic activation, inflammatory, and oxidative parameters. Rats underwent stereotactic surgery for injection of collagenase in the left striatum and AA (2 µg/µl; weight × 0.005) or vehicle in the left lateral ventricle. Neurological deficits were evaluated by the Ladder rung walking and Grip strength tests. Striatal S100B, astrogliosis, and microglial activation were assessed by immunofluorescence analysis. Striatal levels of interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α) were measured by ELISA, and the ROS production was analyzed by dichlorofluorescein (DCF) oxidation. AA treatment prevented motor dysfunction, reduced S100B levels, astrogliosis, and microglial activation in the damaged striatum, thus decreasing the release of proinflammatory cytokines IL-1ß and TNF-α, as well as ROS production. Taken together, present results suggest that AA could be a pharmacological tool to prevent the harmful effects of increased S100B, attenuating neuroinflammation and secondary brain damage after ICH.

Microbiota oral e retal de calitriquídeos (Callithrix sp) em área antropizada de Mata Atlântica, Rio de Janeiro, Brasil / [Oral and rectal microbiota of callitrichids (Callithrix sp) in an anthropized area of the Atlantic Forest in Rio de Janeiro, Brazil]

A proximidade dos primatas não humanos (PNH) com o ser humano pode ser considerada um fator de risco para transmissão de bactérias entre essas duas populações. Neste estudo, foi investigada a microbiota anfibiôntica aeróbica oral e retal de calitriquídeos em um fragmento de Mata Atlântica localizado no Rio de Janeiro, Brasil, e foram realizados testes fenotípicos para detecção de bactérias multirresistentes nos isolados encontrados. Foram capturados 14 calitriquídeos e coletadas 21 amostras (14 de cavidade oral e sete de cavidade retal) em dois pontos da mata próximos às habitações humanas. As espécies mais frequentes, na cavidade oral, foram Klebsiella oxytoca (50,0%), K. pneumoniae (28,6%), Kluyvera ascorbata (21,4%) e Stenotrophomonas maltophilia (21,4%) e, na cavidade retal, K. pneumoniae (85,7%), Escherichia coli (28,6%) e Enterobacter spp. (42,9%). Todos os 48 isolados da família Enterobacteriaceae foram negativos para ESBL (betalactamase de espectro ampliado), mostrando-se não produtores da enzima nos dois métodos utilizados: disco-aproximação e método de detecção automatizado. Na pesquisa de ERC (enterobactérias resistentes a carbapenêmicos), esses mesmos isolados não apresentaram resistência aos antibióticos imipenem, meropenem e ertapenem. Todas as bactérias isoladas apresentam um potencial zoonótico, o que representa um risco à saúde pública e à conservação das espécies.(AU)

Proximity of nonhuman primates (NHP) to humans can be considered a risk factor for transmission of pathogens between these two populations. This study investigated the oral and rectal aerobic bacterial microbiota of marmosets in an anthropized area of the Atlantic Forest located in Rio de Janeiro, Brazil, and performed phenotypic tests for detection of multidrug-resistant bacteria. Twenty-one samples (14 from the oral cavity and seven from the rectum) were collected from 14 Callithrix sp. captured in two sites of the forest near human dwellings. The most frequent species identified from the oral cavity swabs were Klebsiella oxytoca (50.0%), K. pneumoniae (28.6%), Kluyvera ascorbata (21.4%) and Stenotrophomonas maltophilia (21.4%), whereas the species most commonly identified from the rectum swabs were K. pneumoniae (85.7%), Enterobacter spp. (42.9%) and Escherichia coli (28.6%). All isolates of family Enterobacteriaceae showed no extended spectrum ß-lactamase production by disk-diffusion and automated detection tests. In the search for carbapenem-resistant enterobacteriaceae these isolates presented no resistance to the imipenem, meropenem and ertapenem antibiotics. The isolate of Staphylococcus aureus was susceptible to oxacillin and the isolate of Enterococcus was susceptible to vancomycin. All isolated bacteria showed zoonotic potential, thus posing a risk to species conservation and public health.(AU)

Arundic Acid (ONO-2506), an Inhibitor of S100B Protein Synthesis, Prevents Neurological Deficits and Brain Tissue Damage Following Intracerebral Hemorrhage in Male Wistar Rats.

Stroke is one of the leading causes of mortality and neurological morbidity. Intracerebral hemorrhage (ICH) has the poorest prognosis among all stroke subtypes and no treatment has been effective in improving outcomes. Following ICH, the observed high levels of S100B protein have been associated with worsening of injury and neurological deficits. Arundic acid (AA) exerts neuroprotective effects through inhibition of astrocytic synthesis of S100B in some models of experimental brain injury; however, it has not been studied in ICH. The aim of this study was to evaluate the effects of intracerebroventricular (ICV) administration of AA in male Wistar rats submitted to ICH model assessing the following variables: reactive astrogliosis, S100B levels, antioxidant defenses, cell death, lesion extension and neurological function. Firstly, AA was injected at different doses (0.02, 0.2, 2 and 20 µg/µl) in the left lateral ventricle in order to observe which dose would decrease GFAP and S100B striatal levels in non-injured rats. Following determination of the effective dose, ICH damage was induced by IV-S collagenase intrastrial injection and 2 µg/µl AA was injected through ICV route immediately before injury. AA treatment prevented ICH-induced neurological deficits and tissue damage, inhibited excessive astrocytic activation and cellular apoptosis, reduced peripheral and central S100B levels (in striatum, serum and cerebrospinal fluid), improved neuronal survival and enhanced the antioxidant defences after injury. Altogether, these results suggest that S100B is a viable target for treating ICH and highlight AA as an interesting strategy for improving neurological outcome after experimental brain hemorrhage.

Prenatal and Early Postnatal Environmental Enrichment Reduce Acute Cell Death and Prevent Neurodevelopment and Memory Impairments in Rats Submitted to Neonatal Hypoxia Ischemia.

Environmental enrichment (EE) is an experimental strategy to attenuate the negative effects of different neurological conditions including neonatal hypoxia ischemia encephalopathy (HIE). The aim of the present study was to investigate the influence of prenatal and early postnatal EE in animals submitted to neonatal HIE model at postnatal day (PND) 3. Wistar rats were housed in EE or standard conditions (SC) during pregnancy and lactation periods. Pups of both sexes were assigned to one of four experimental groups, considering the early environmental conditions and the injury: SC-Sham, SC-HIE, EE-sham, and EE-HIE. The offspring were euthanized at two different time points: 48 h after HIE for biochemical analyses or at PND 67 for histological analyses. Behavioral tests were performed at PND 7, 14, 21, and 60. Offspring from EE mothers had better performance in neurodevelopmental and spatial memory tests when compared to the SC groups. HIE animals showed a reduction of IGF-1 and VEGF in the parietal cortex, but no differences in BDNF and TrkB levels were found. EE-HIE animals showed reduction in cell death, lower astrocyte reactivity, and an increase in AKTp levels in the hippocampus and parietal cortex. In addition, the EE was also able to prevent the hippocampus tissue loss. Altogether, present findings point to the protective potential of the prenatal and early postnatal EE in attenuating molecular and histological damage, as well as the neurodevelopmental impairments and the cognitive deficit, caused by HIE insult at PND 3.