61 research outputs found
Resolvin D1 Halts Remote Neuroinflammation and Improves Functional Recovery after Focal Brain Damage Via ALX/FPR2 Receptor-Regulated MicroRNAs
Remote damage is a secondary phenomenon that usually occurs after a primary brain damage in regions that are distant, yet functionally connected, and that is critical for determining the outcomes of several CNS pathologies, including traumatic brain and spinal cord injuries. The understanding of remote damage-associated mechanisms has been mostly achieved in several models of focal brain injury such as the hemicerebellectomy (HCb) experimental paradigm, which helped to identify the involvement of many key players, such as inflammation, oxidative stress, apoptosis and autophagy. Currently, few interventions have been shown to successfully limit the progression of secondary damage events and there is still an unmet need for new therapeutic options. Given the emergence of the novel concept of resolution of inflammation, mediated by the newly identified ω3-derived specialized pro-resolving lipid mediators, such as resolvins, we reported a reduced ability of HCb-injured animals to produce resolvin D1 (RvD1) and an increased expression of its target receptor ALX/FPR2 in remote brain regions. The in vivo administration of RvD1 promoted functional recovery and neuroprotection by reducing the activation of Iba-1+ microglia and GFAP+ astrocytes as well as by impairing inflammatory-induced neuronal cell death in remote regions. These effects were counteracted by intracerebroventricular neutralization of ALX/FPR2, whose activation by RvD1 also down-regulated miR-146b and miR-219a-1-dependent inflammatory markers. In conclusion, we propose that innovative therapies based on RvD1-ALX/ FPR2 axis could be exploited to curtail remote damage and enable neuroprotective effects after acute focal brain damage
Intermittent theta-burst stimulation rescues dopamine-dependent corticostriatal synaptic plasticity and motor behavior in experimental parkinsonism. Possible role of glial activity.
Background: Recent studies support the therapeutic utility of repetitive transcranial magnetic stimulation in Parkinson's disease (PD), whose progression is correlated with loss of corticostriatal long-term potentiation and long-term depression. Glial cell activation is also a feature of PD that is gaining increasing attention in the field because astrocytes play a role in chronic neuroinflammatory responses but are also able to manage dopamine (DA) levels.
Methods: Intermittent theta-burst stimulation protocol was applied to study the effect of therapeutic neuromodulation on striatal DA levels measured by means of in vivo microdialysis in 6-hydroxydopamine-hemilesioned rats. Effects on corticostriatal synaptic plasticity were studied through in vitro intracellular and whole-cell patch clamp recordings while stepping test and CatWalk were used to test motor behavior. Immunohistochemical analyses were performed to analyze morphological changes in neurons and glial cells.
Results: Acute theta-burst stimulation induced an increase in striatal DA levels in hemiparkinsonian rats, 80 minutes post-treatment, correlated with full recovery of plasticity and amelioration of motor performances. With the same timing, immediate early gene activation was restricted to striatal spiny neurons. Intense astrocytic and microglial responses were also significantly reduced 80 minutes following theta-burst stimulation.
Conclusion: Taken together, these results provide a first glimpse on physiological adaptations that occur in the parkinsonian striatum following intermittent theta-burst stimulation and may help to disclose the real potential of this technique in treating PD and preventing DA replacement therapy-associated disturbances
Modulation of apoptosis by caprine herpesvirus 1 infection in a neuronal cell line
Caprine herpesvirus type 1 (CpHV-1), like other members of the alpha subfamily of herpesviruses, establishes latent infections in trigeminal ganglion neurons. Our groups previously demonstrated that CpHV-1 induces apoptosis in goat peripheral blood mononuclear cells and in an epithelial bovine cell line, but the ability of CpHV-1 to induce apoptosis in neuronal cells remains unexplored. In this report, the susceptibility of Neuro 2A cells to infection by CpHV-1 was examined. Following infection of cultured cells with CpHV-1, expression of cell death genes was evaluated using real-time PCR and Western blot assays. Analysis of virus-infected cells revealed activation of caspase-8, a marker for the extrinsic pathway of apoptosis, and caspase-9, a marker for the intrinsic pathway of apoptosis at 12 and 24 h post-infection. Significant increase in the levels of cleaved caspase-3 was also observed at the acme of cytopathic effect at 24 h post-infection. In particular, at 3 and 6 h post-infection, several proapototic genes were under-expressed. At 12 h post-infection several proapototic genes such as caspases, TNF, Cd70, and Traf1 were over expressed while Bcl2a1a, Fadd, and TNF genes were underexpressed. In conclusion, the simultaneous activation of caspase-8 and caspase-9 suggests that CpHV-1 can trigger the death-receptor pathway and the mitochondrial pathway separately and in parallel. Our findings are significant because this is the first published study showing the effect of CpHV-1 infection in neuronal cells in terms of gene expression and apoptosis modulation
Prognostic Role of CSF β-amyloid 1-42/1-40 Ratio in Patients Affected by Amyotrophic Lateral Sclerosis
The involvement of β-amyloid (Aβ) in the pathogenesis of amyotrophic lateral sclerosis (ALS) has been widely discussed and its role in the disease is still a matter of debate. Aβ accumulates in the cortex and the anterior horn neurons of ALS patients and seems to affect their survival. To clarify the role of cerebrospinal fluid (CSF) Aβ 1-42 and Aβ 42/40 ratios as a potential prognostic biomarker for ALS, we performed a retrospective observational study on a cohort of ALS patients who underwent a lumbar puncture at the time of the diagnosis. CSF Aβ 1-40 and Aβ 1-42 ratios were detected by chemiluminescence immunoassay and their values were correlated with clinical features. We found a significant correlation of the Aβ 42/40 ratio with age at onset and Mini Mental State Examination (MMSE) scores. No significant correlation of Aβ 1-42 or Aβ 42/40 ratios to the rate of progression of the disease were found. Furthermore, when we stratified patients according to Aβ 1-42 concentration and the Aβ 42/40 ratio, we found that patients with a lower Aβ 42/40 ratio showed a shorter survival. Our results support the hypothesis that Aβ 1-42 could be involved in some pathogenic mechanism of ALS and we suggest the Aβ 42/40 ratio as a potential prognostic biomarker
T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells
Effective cancer immunotherapy requires overcoming immunosuppressive tumor microenvironments. We\ua0found that local nitric oxide (NO) production by tumor-infiltrating myeloid cells is important for adoptively transferred CD8(+) cytotoxic T\ua0cells to destroy tumors. These myeloid cells are phenotypically similar to inducible nitric oxide synthase (NOS2)- and tumor necrosis factor (TNF)-producing dendritic cells (DC), or Tip-DCs. Depletion of immunosuppressive, colony stimulating factor 1 receptor (CSF-1R)-dependent arginase 1(+) myeloid cells enhanced NO-dependent tumor killing. Tumor elimination via NOS2 required the CD40-CD40L pathway. We also uncovered a strong correlation between survival of colorectal cancer patients and NOS2, CD40, and TNF expression in their tumors. Our results identify a network of pro-tumor factors that can be targeted to boost cancer immunotherapies
Predicting needlestick and sharps injuries in nursing students: Development of the SNNIP scale
© 2020 The Authors. Nursing Open published by John Wiley & Sons Ltd. Aim: To develop an instrument to investigate knowledge and predictive factors of needlestick and sharps injuries (NSIs) in nursing students during clinical placements. Design: Instrument development and cross-sectional study for psychometric testing. Methods: A self-administered instrument including demographic data, injury epidemiology and predictive factors of NSIs was developed between October 2018–January 2019. Content validity was assessed by a panel of experts. The instrument's factor structure and discriminant validity were explored using principal components analysis. The STROBE guidelines were followed. Results: Evidence of content validity was found (S-CVI 0.75; I-CVI 0.50–1.00). A three-factor structure was shown by exploratory factor analysis. Of the 238 participants, 39% had been injured at least once, of which 67.3% in the second year. Higher perceptions of “personal exposure” (4.06, SD 3.78) were reported by third-year students. Higher scores for “perceived benefits” of preventive behaviours (13.6, SD 1.46) were reported by second-year students
Predicting needlestick and sharps injuries in nursing students: Development of the SNNIP scale
Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?
BACKGROUND:
As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years.
METHODS:
Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients.
RESULTS:
Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients 64aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446).
CONCLUSIONS:
The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged 6470 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor
Relationship between asymmetric nostril use and human emotional odours in cats
Abstract Cat social behaviour and cognition has received a growing interest during the last decades. Recent studies reported that cats efficiently engage in interspecific communication with humans and suggest that cats are sensitive to human emotional visual and auditory cues. To date, there is no evidence on the social and informative role of human emotional odours, which may affect human-cat communication. In this study, we presented cats with human odours collected in different emotional contexts (fear, happiness, physical stress and neutral) and evaluated the animals’ behavioural responses. We found that “fear” odours elicited higher stress levels than “physical stress” and “neutral”, suggesting that cats perceived the valence of the information conveyed by “fear” olfactory signals and regulate their behaviour accordingly. Moreover, the prevalent use of the right nostril (right hemisphere activation) with the increase of stress levels, particularly in response to “fear” odours, provides first evidence of lateralized emotional functions of olfactory pathways in cats
Por una ciencia en ambientes no formales como reconocimiento a las pluralidades epistémicas de la diversidad cultural cordobesa: Elaboración de videos educativos para difusión en redes sociales y página web del Centro de Zoología Aplicada
Se presenta una experiencia educativa en el marco de la asignatura Práctica de la Enseñanza del Profesorado en Ciencias Biológicas de la Facultad de Ciencias Exactas, Físicas y Naturales de la Universidad Nacional de Córdoba, Argentina. Las prácticas se desarrollaron en interacción con el Centro de Zoología Aplicada, dependiente de la misma facultad. Se sustentó en tres ejes: educación no formal, aportes a la educación formal y TIC. Se plantearon como propósitos: facilitar la interacción entre los ciudadanos y el manejo de información atendiendo al contexto cultural, social y económico de la comunidad cordobesa. Se implementó en dos fases: diagnóstico, en el cual se acordaron las acciones y ejecución, en la que se concretaron. Como resultado se produjeron tres videos educativos en formato mp4 para subir a la web y a las redes sociales. Esta experiencia ha sido enriquecedora para fortalecer la enseñanza de las ciencias
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