Bisphenol A (BPA), a ubiquitous environmental contaminant, has been shown to cause developmental toxicity and carcinogenic effects. BPA may have physiological activity through estrogen receptor (ER) -α and -β, which are expressed in the central nervous system. We previously found that exposure of BPA to immature mice resulted in behavioral alternation, suggesting that overexposure of BPA could be neurotoxic. In this study, we further investigated the molecular neurotoxic mechanisms of BPA. BPA increased vulnerability (decrease of cell viability and differentiation, and increase of apoptotic cell death) of undifferentiated PC12 cells and cortical neuronal cells isolated from gestation 18 day rat embryos in a concentration-dependent manner (more than 50 µM). The ER antagonists, ICI 182,780, and tamoxifen, did not block these effects. The cell vulnerability against BPA was not significantly different in the PC12 cells overexpressing ER-α and ER-β compared with PC12 cells expressing vector alone. In addition, there was no difference observed between BPA and 17-β estradiol, a well-known agonist of ER receptor in the induction of neurotoxic responses. Further study of the mechanism showed that BPA significantly activated extracellular signal-regulated kinase (ERK) but inhibited anti-apoptotic nuclear factor kappa B (NF-κB) activation. In addition, ERK-specific inhibitor, PD 98,059, reversed BPA-induced cell death and restored NF-κB activity. This study demonstrated that exposure to BPA can cause neuronal cell death which may eventually be related with behavioral alternation in vivo. However, this neurotoxic effect may not be directly mediated through an ER receptor, as an ERK/NF-κB pathway may be more closely involved in BPA-induced neuronal toxicity.
The diagnosis of hypersomnia may be changed by the repeated multiple sleep latency test (MSLT). We investigated the long-term reliability of MSLT in the diagnosis of narcolepsy type 1(NT1) and 2 (NT2). Methods: We reviewed the data of patients with NT1 and NT2 who underwent MSLT at least twice between 2008 and 2020. The clinical information and polysomnography/MSLT data were thoroughly assessed, and two sleep experts evaluated the consistency and reliability of diagnosis independently. Results: Eighty patients (38 with NT1 and 42 with NT2 as a final diagnosis) were included in this study. Of the 80 patients, 20 (nine with NT1 and 11 with NT2) underwent the 3rd MSLT. No significant differences were found in the sleep data and Epworth Sleepiness Scale at baseline. During the 2nd MSLT, 18.4% (n=7) patients with NT1 and 47.6% (n=20) patients with NT2 did not satisfy the diagnosis of narcolepsy. At the 3rd MSLT, six out of nine patients with NT1 and seven of 11 patients with NT2 were not suitable for narcolepsy. Two of the initial NT1 (5.2%) and 10 of the initial NT2 (23.8%) patients were found to be normal. Three patients who were confirmed to have NT1 through consecutive MSLTs had significantly shorter sleep latency and more number of sleep-onset rapid eye movements than the other patients. Conclusions: The reliability of MSLT were not robust in the diagnosis of NT1 and NT2 in this long-term follow-up study. The MSLT results should be interpreted with careful consideration based on elaborate preparations.
Objective Focal cortical dysplasia (FCD) represents a heterogeneous group of disorders of the cortical formation and is one of the most common causes of epilepsy. Magnetic resonance imaging (MRI) is the modality of choice for detecting structural lesions, and the surgical prognosis in patients with MR lesions is favorable. However, the surgical prognosis of patients with MR-negative FCD is unknown. We aimed to evaluate the long-term surgical outcomes and prognostic factors in MR-negative FCD patients through comprehensive presurgical data. Methods We retrospectively reviewed data from 719 drug-resistant epilepsy patients who underwent resective surgery and selected cases in which surgical specimens were pathologically confirmed as FCD Type I or II. If the epileptogenic focus and surgical specimens were obtained from brain areas with a normal MRI appearance, they were classified as MR-negative FCD. Surgical outcomes were evaluated at 2 and 5 years, and clinical, neurophysiological, and neuroimaging data of MR-negative FCD were compared to those of MR-positive FCD. Results Finally, 47 MR-negative and 34 MR-positive FCD patients were enrolled in the study. The seizure-free rate after surgery (Engel classification I) at postoperative 2 year was 59.5% and 64.7% in the MR-negative and positive FCD groups, respectively (p = 0.81). This rate decreased to 57.5% and 44.4% in the MR-negative and positive FCD groups (p = 0.43) at postoperative 5 years. MR-negative FCD showed a higher proportion of FCD type I (87.2% vs. 50.0%, p = 0.001) than MR-positive FCD. Unilobar cerebral perfusion distribution (odds ratio, OR 5.41) and concordance of interictal epileptiform discharges (OR 5.10) were significantly associated with good surgical outcomes in MR-negative FCD. Conclusion In this study, MR-negative and positive FCD patients had a comparable surgical prognosis, suggesting that comprehensive presurgical evaluations, including multimodal neuroimaging studies, are crucial for obtaining excellent surgical outcomes even in epilepsy patients with MR-negative FCD.
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