Evaluation of the effects of the Zika Virus-Immunoglobulin G+ complex on murine microglial cells.

After the Zika virus (ZIKV) epidemic in Brazil, ZIKV infections were linked to damage to the central nervous system (CNS) and congenital anomalies. Due to the virus's ability to cross the placenta and reach brain tissue, its effects become severe, leading to Congenital Zika Syndrome (CZS) and resulting in neuroinflammation, microglial activation, and secretion of neurotoxic factors. The presence of ZIKV triggers an inadequate fetal immune response, as the fetus only has the protection of maternal antibodies of the Immunoglobulin G (IgG) class, which are the only antibodies capable of crossing the placenta. Because of limited understanding regarding the long term consequences of ZIKV infection and the involvement of maternal antibodies, this study sought to assess the impact of the ZIKV + IgG⁺complex on murine microglial cells. The cells were exposed to ZIKV, IgG antibodies, and the ZIKV + IgG⁺complex for 24 and 72 h. Treatment-induced cytotoxic effects were evaluated using the cell viability assay, oxidative stress, and mitochondrial membrane potential. The findings indicated that IgG antibodies exhibit cytotoxic effects on microglia, whether alone or in the presence of ZIKV, leading to compromised cell viability, disrupted mitochondrial membrane potential, and heightened oxidative damage. Our conclusion is that IgG antibodies exert detrimental effects on microglia, triggering their activation and potentially disrupting the creation of a neurotoxic environment. Moreover, the presence of antibodies may correlate with an elevated risk of ZIKV-induced neuroinflammation, contributing to long-term CNS damage.

Influence of Zika virus on the cytotoxicity, cell adhesion, apoptosis and inflammatory markers of glioblastoma cells.

Glioblastoma (GBM) is one of the most common types of brain tumor in adults. Despite the availability of treatments for this disease, GBM remains one of the most lethal and difficult types of tumors to treat, and thus, a majority of patients die within 2 years of diagnosis. Infection with Zika virus (ZIKV) inhibits cell proliferation and induces apoptosis, particularly in developing neuronal cells, and thus could potentially be considered an alternative for GBM treatment. In the present study, two GBM cell lines (U-138 and U-251) were infected with ZIKV at different multiplicities of infection (0.1, 0.01 and 0.001), and cell viability, migration, adhesion, induction of apoptosis, interleukin levels and CD14/CD73 cell surface marker expression were analyzed. The present study demonstrated that ZIKV infection promoted loss of cell viability and increased apoptosis in U-138 cells, as measured by MTT and triplex assay, respectively. Changes in cell migration, as determined by wound healing assay, were not observed; however, the GBM cell lines exhibited an increase in cell adhesion when compared with non-tumoral cells (Vero). The Luminex immunoassay showed a significant increase in the expression levels of IL-4 specifically in U-251 cells (MOI 0.001) following exposure to ZIKV. There was no significant change in the expression levels of IFN-γ upon ZIKV infection in the cell lines tested. Furthermore, a marked increase in the percentage of cells expressing the CD14 surface marker was observed in both GBM cell lines compared with in Vero cells; and significantly increased CD73 expression was observed particularly in U-251 cells, when compared with uninfected cells. These findings indicate that ZIKV infection could lead to reduced cell viability, elevated CD73 expression, improved cellular adherence, and higher rates of apoptosis in glioblastoma cells. Further studies are required to explore the potential use of ZIKV in the treatment of GBM.

Guillain-Barré syndrome associated with COVID-19: A systematic review.

With the outbreak of coronavirus disease 2019 (COVID-19), the whole world was impacted by a pandemic. With the passage of time and knowledge about the dynamics and viral propagation of this disease, the short-, medium- and long-term repercussions are still being discovered. During this period, it has been learned that various manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect the nervous system. In recent months, a variety of studies and case reports have proposed an association between COVID-19 and Guillain-Barré syndrome (GBS). The present work aims to systematically review the publications available to date to verify the relationship between these two pathologies and the characteristics of post-COVID GBS. There were 156 studies included in this work, resulting in a total of 436 patients. The findings show a mean age of the patients of 61,38 years and a male majority. The GBS symptoms began on average 19 days after the onset of COVID-19 infection. Regarding GBS, the main manifestations found included generalized weakness, reflex reduction, facial paresis/paralysis and hypoesthesia. As expected, the most common result in cerebrospinal fluid (CSF) analysis was albuminocytological dissociation. A pattern of blood analysis findings common to all patients was not observed due to non-standardization of case reports. Regarding electrodiagnostic studies, acute inflammatory demyelinating polyneuropathy (AIDP) appeared as the most common subtype of GBS in this study. There have been reports, to a lesser extent, of acute motor axonal neuropathy (AMAN), acute sensorimotor axonal neuropathy (AMSAN), the pharyngeal-cervical-brachial variant (PCB), and Miller-Fisher syndrome (MFS). The GBS treatment used was mainly intravenous immunoglobulin (IVIG) and plasma exchange (PLEX). Therefore, the present study reports a high prevalence of hospitalization and intensive care units ICU admissions, conjecturing a relationship between the development of GBS and the severity of COVID-19. Despite the severity, most patients showed improvement in GBS symptoms after treatment, and their residual symptoms did not include motor involvement. Therefore, the development of GBS seems to be related to COVID-19 infection, as reported by the present systematic review.

Depression comorbidity in epileptic rats is related to brain glucose hypometabolism and hypersynchronicity in the metabolic network architecture.

OBJECTIVE: Temporal lobe epilepsy (TLE) is one of the most common types of epilepsy syndromes in the world. Depression is an important comorbidity of epilepsy, which has been reported in patients with TLE and in different experimental models of epilepsy. However, there is no established consensus on which brain regions are associated with the manifestation of depression in epilepsy. Here, we investigated the alterations in cerebral glucose metabolism and the metabolic network in the pilocarpine-induced rat model of epilepsy and correlated it with depressive behavior during the chronic phase of epilepsy. METHODS: Fluorodeoxyglucose (18 F-FDG) was used to investigate the cerebral metabolism, and a cross-correlation matrix was used to examine the metabolic network in chronically epileptic rats using micro-positron emission tomography (microPET) imaging. An experimental model of epilepsy was induced by pilocarpine injection (320 mg/kg, ip). Forced swim test (FST), sucrose preference test (SPT), and eating-related depression test (ERDT) were used to evaluate depression-like behavior. RESULTS: Our results show an association between epilepsy and depression comorbidity based on changes in both cerebral glucose metabolism and the functional metabolic network. In addition, we have identified a significant correlation between brain glucose hypometabolism and depressive-like behavior in chronically epileptic rats. Furthermore, we found that the epileptic depressed group presents a hypersynchronous brain metabolic network in relation to the epileptic nondepressed group. SIGNIFICANCE: This study revealed relevant alterations in glucose metabolism and the metabolic network among the brain regions of interest for both epilepsy and depression pathologies. Thus it seems that depression in epileptic animals is associated with a more diffuse hypometabolism and altered metabolic network architecture and plays an important role in chronic epilepsy.