Adequate nutrient intake mitigate the toxic effects of bromate on the rotifer Brachionus calyciflorus.

Bromate is receiving increased attention as a typical disinfection by-product in aquatic environments, but bromate toxicity tests on invertebrate such as Brachionus calyciflorus rotifer are inadequate. In the present study, the long-term toxicity tests on B. calyciflorus were performed during 21 days under the exposure of different bromate concentrations and two algal density conditions. Furthermore, we evaluated the feeding behaviors of the rotifers under the impact of bromate. The maximum population density of rotifers was significantly reduced at 100 and 200 mg/L bromate exposure at the two algal density conditions. However, we observed that the maximum population density and population growth rate of rotifers were higher at 3.0 × 106 cells/mL algal density than those at 1.0 × 106 cells/mL under the same conditions of bromate exposure. These results suggest that higher food density may have alleviated the negative effects of bromate on rotifers. Meanwhile, the ingestion rate at an algal density of 3.0 × 106 cells/mL was higher than that at 1.0 × 106 cells/mL. The present study provides a basic reference to comprehensively evaluate the toxic effects of bromate on aquatic organisms.

The Apelin/APJ system modulates seizure activity and endocytosis of the NMDA receptor GluN2B subunit.

In the central nervous system (CNS), the apelin/APJ system is broadly expressed. According to some studies, activation of this system protects against excitotoxicity mediated by N-methyl-D-aspartate (NMDA) receptors and exerts neuroprotective effects. However, the role of this system in epilepsy remains unclear. In the present study, immunofluorescence staining and western blotting were used to assess APJ localization and expression in the brains of mice with recurrent spontaneous seizures induced by kainic acid (KA). Behavior and local field potentials (LFPs) were assessed in mice with KA-induced seizures. Susceptibility to seizures was assessed in a pentylenetetrazole (PTZ)-induced seizure model. Whole-cell patch-clamp recordings were used to evaluate the role of the apelin/APJ system in regulating synaptic transmission in brain slices from mice in which Mg2+-free medium was used to induce seizures. NMDA receptor GluN2B subunit expression and phosphorylation of GluN2B at Ser1480 were measured in the mouse hippocampus. APJ was primarily localized in neurons, and its expression was upregulated in the epileptic brain. APJ activation after KA-induced status epilepticus (SE) reduced epileptic activity, whereas APJ inhibition aggravated epileptic activity. In the PTZ model, APJ activation reduced and APJ inhibition increased susceptibility to seizures. The apelin/APJ system affected NMDA receptor-mediated postsynaptic currents in patch-clamp recordings. Moreover, APJ regulated the levels of GluN2B phosphorylated at Ser1480 and the abundance of cell-surface GluN2B in neurons. Furthermore, endocytosis of the NMDA receptor GluN2B subunit was regulated by the apelin/APJ system. Together, our findings indicate that the apelin/APJ system modulates seizure activity and may be a novel therapeutic target for epilepsy.

GSDMD knockdown exacerbates hippocampal damage and seizure susceptibility by crosstalk between pyroptosis and apoptosis in kainic acid-induced temporal lobe epilepsy.

BACKGROUND: Neuronal loss is a vital pathological feature of temporal lobe epilepsy (TLE). However, the exact mechanism of neuronal loss in TLE is not fully understood. Pyroptosis, a novel form of programmed cell death (PCD), has been considered a contributor to the pathogenesis of TLE. However, recent studies have implicated extensive molecular crosstalk among pyroptosis, apoptosis, and necroptosis in various diseases, and they can be transformed to each other according to different contexts. This study aimed to investigate whether gasdermin D (GSDMD)-mediated pyroptosis is involved in the pathogenesis of TLE and whether crosstalk exists in the process of the modulation of pyroptosis. METHODS: The TLE model was established by intra-amygdala injection of kainic acid. The Racine score and local field potential (LFP) recordings were used to assess seizure severity. Western blotting and immunofluorescence were applied to detect the levels and cellular localization of GSDMD. The neuronal loss and type of neuronal death in the bilateral hippocampus were assessed by Nissl staining and flow cytometry analysis. The underlying crosstalk among pyroptosis, apoptosis, and necroptosis was explored by western blot and verified by VX765. RESULTS: GSDMD was significantly upregulated and mainly expressed within the neurons of the hippocampus in the TLE model. Inhibition of pyroptosis by GSDMD knockdown triggered caspase-3-mediated apoptosis, leading to excess neuronal loss and deterioration of epileptic behaviors. Blocking caspase-1 markedly inhibited caspase-3-mediated apoptosis and improved epileptic behaviors under GSDMD knockdown. CONCLUSIONS: Our results demonstrate that GSDMD-mediated pyroptosis is involved in the pathogenesis of TLE. However, inhibition of GSDMD triggers caspase-1-mediated crosstalk between pyroptosis and apoptosis, which exacerbates neuronal loss and seizure susceptibility. Therefore, the complex crosstalk among different forms of PCD should be considered when a potential molecular target in the single PCD pathway is modulated. On the other hand, along with further studies of molecular crosstalk among the PCD pathways, taking advantage of crosstalk to attenuate neuronal loss may provide new insight for the clinical therapy of TLE.

Levetiracetam induces severe psychiatric symptoms in people with epilepsy.

BACKGROUND: Drug-induced psychiatric symptoms are an important cause of treatment failure. Worldwide, levetiracetam has been widely used to treat epilepsy; however, associated psychobehavioral abnormalities have been observed . This study aimed to characterize levetiracetam-induced severe psychiatric symptoms and to propose preventive and therapeutic measures. METHODS: In this retrospective cluster sampling study, psychiatric symptoms of patients who had taken levetiracetam for at least 1 month were analyzed. RESULTS: 111(7.8%) of the 1,412 included patients exhibited severe psychiatric symptoms. Hallucinations, delusions, aggressive behavior, and agitation were the most common manifestations . Some patients also showed suicidal and self-harm behaviors. These symptoms were mainly controlled by reducing the dose of levetiracetam, stopping the drug, or adding antipsychotic drugs to the treatment regimen. CONCLUSION: The severe psychiatric symptoms caused by levetiracetam require special attention.

SAPAP3 regulates epileptic seizures involving GluN2A in post-synaptic densities.

Aberrantly synchronized neuronal discharges in the brain lead to epilepsy, a devastating neurological disease whose pathogenesis and mechanism are unclear. SAPAP3, a cytoskeletal protein expressed at high levels in the postsynaptic density (PSD) of excitatory synapses, has been well studied in the striatum, but the role of SAPAP3 in epilepsy remains elusive. In this study, we sought to investigate the molecular, cellular, electrophysiological and behavioral consequences of SAPAP3 perturbations in the mouse hippocampus. We identified a significant increase in the SAPAP3 levels in patients with temporal lobe epilepsy (TLE) and in mouse models of epilepsy. In addition, behavioral studies showed that the downregulation of SAPAP3 by shRNA decreased the seizure severity and that the overexpression of SAPAP3 by recombinant SAPAP3 yielded the opposite effect. Moreover, SAPAP3 affected action potentials (APs), miniature excitatory postsynaptic currents (mEPSCs) and N-methyl-D-aspartate receptor (NMDAR)-mediated currents in the CA1 region, which indicated that SAPAP3 plays an important role in excitatory synaptic transmission. Additionally, the levels of the GluN2A protein, which is involved in synaptic function, were perturbed in the hippocampal PSD, and this perturbation was accompanied by ultrastructural morphological changes. These results revealed a previously unknown function of SAPAP3 in epileptogenesis and showed that SAPAP3 may represent a novel target for the treatment of epilepsy.

Clinical analysis of 103 cases of tuberculous meningitis complicated with hyponatremia in adults.

OBJECTIVE: Tuberculous meningitis (TBM) is a common infection of the central nervous system. TBM with hyponatremia is very common. If hyponatremia is not treated properly, it might affect the outcome of TBM patients. METHODS: We included 226 patients diagnosed with TBM who were admitted from August 2010 to August 2015 and retrospectively analyzed the clinical data of patients with and without hyponatremia. RESULTS: In total, 45.6% (103/226) patients had hyponatremia and 54.4% (123/226) patients did not have hyponatremia. Serum sodium and severity of TBM were independent prediction factors of poor outcomes in TBM. The prognosis of patients with hyponatremia was worse than that of patients without hyponatremia. The mortality was 3.9% (4/103) in the hyponatremia group, while 0% (0/123) in the non-hyponatremia group. The degree of hyponatremia was related to imaging, cerebrospinal fluid (CSF) cell count and protein, severity of TBM, time to correct hyponatremia, and prognosis. We analyzed the causes of hyponatremia and found syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was the most common cause (77.7%, 80/103), followed by cerebral salt wasting (CSW) (17.5%, 18/103). Comparing SIADH and CSW, there was a significant difference in mean blood pressure, albumin, and hematocrit, and no significant difference in demographic characteristics, imaging, CSF cell count and protein, severity, occurrence and correction time of hyponatremia, or prognosis. CONCLUSION: TBM with hyponatremia was dominated by moderate hyponatremia, which often manifested as SIADH. The more severe hyponatremia was, the longer the correction time of hyponatremia, which will affect the prognosis of TBM patients.

Intestinal Klebsiella pneumoniae infection enhances susceptibility to epileptic seizure which can be reduced by microglia activation.

Epilepsy is a common nervous system disease, and the existing theory does not fully clarify its pathogenesis. Recent research suggests that intestinal microbes may be involved in the development of epilepsy, but which microbe is involved remains unclear. We used 16s rRNA sequencing to identify the most relevant gut microbe. To determine the relationship between this microbe and epilepsy, we used an animal model. In addition, western blotting and immunofluorescence, as well as inhibitor studies, were used to evaluate and confirm the role of microglia in this process. In this study, we first report an increase in gut Klebsiella pneumoniae in patients with epilepsy. Subsequently, animal studies revealed that Klebsiella pneumoniae in the intestinal tract affects seizure susceptibility and activates microglial cells to release inflammatory factors. Furthermore, the inflammatory response of microglial cells plays a protective role in the seizure susceptibility caused by an increased abundance of Klebsiella pneumoniae. Our results suggest that gut disruption may be involved in seizure regulation and microglia protect the brain against seizure under this condition. These findings provide a new perspective for research on the pathogenesis and prevention of epilepsy.

Relapsed Primary Central Nervous System Lymphoma: Current Advances.

Primary central nervous system lymphoma is an invasive malignant lymphoma confined to the central nervous system. Although patients undergoing first-line treatment can achieve complete response, most of them still relapse within two years. Relapsed lymphoma is derived from occult lymphoma cells, and B cell receptor pathway activation and immune escape are the key mechanisms for the pathogenesis of PCNSL. Most relapses are in the central nervous system, a small number of relapses are isolated systemic relapses, and clinical symptoms occur early and vary. Current treatments for relapse include high-dose methotrexate rechallenge and other regimens of chemotherapy, whole-brain radiation therapy, hematopoietic stem-cell transplantation, targeted therapy and immunotherapy, which have become promising treatments. The overall prognosis of relapsed PCNSL is very poor, although it is affected by many factors. This article summarizes the mechanisms, related factors, clinical features, follow-up, treatment and prognosis of relapsed primary central nervous system lymphoma.

The comorbidity of epilepsy and depression: diagnosis and treatment.

INTRODUCTION: Depression can seriously affect the quality of life of epileptic patients and can even lead to suicide. Understanding the regularity, prevention and treatment of depression in patients with epilepsy (PWE) contributes to the improvement of their quality of life. Areas covered: In this paper, we retrospectively analyzed the relevant literature on the pathogenesis, related factors, clinical characteristics, diagnosis and treatment of depression in PWE. A literature search utilized the PubMed, Embase and Google Scholar databases. Expert commentary: PWE often have depression, which can be the result of seizures, antiepileptic drugs (AEDs) or social-demographic factors. It needs to be better understood, and the diagnosis should be more comprehensive for early treatment.