Diagnostic Value of the Electroencephalogram and Cerebrospinal Fluid in Viral Encephalitis.

BACKGROUND: Electroencephalogram (EEG) and cerebrospinal fluid (CSF) are widely used in the clinical diagnosis of viral encephalitis (VE), but their value in the diagnosis of VE and the detection rate of abnormal indicators need to be further supported by more clinical data. METHODS: In this study, routine laboratory testing, biochemical examinations of cerebrospinal fluid (CSF) and EEG characteristics were performed in patients with VE to guide the diagnosis and treatment of VE in clinical settings. A total of 330 patients with VE were enrolled in the Department of Neurology of the Third Affiliated Hospital of Zunyi Medical University from January 1, 2015 to January 30, 2020. EEG, routine testing and assessment of biochemical indicators of CSF were performed within 10 days after admission, and the results were analyzed by paired χ 2 test to compare the diagnostic value of EEG and CSF for VE. RESULTS: In 330 cases of VE, 283 cases (85.76%) had abnormal EEG, and 189 cases (57.27%) had abnormal CSF indicators. The incidence of EEG abnormalities was higher than that of CSF indicators, and the difference was statistically significant ( P <0.05). CONCLUSIONS: Both the EEG and CSF analysis are valuable indicators in the diagnosis of VE patients. Compared with the CSF examination, the EEG examination had a better diagnostic efficacy for the diagnosis of VE. In addition, a normal EEG or a normal CSF level cannot exclude VE, and it is still necessary to develop new diagnostic indicators to cover all viral encephalitides.

Aberrant TDP-43 phosphorylation: a key wind gap from TDP-43 to TDP-43 proteinopathy.

TDP-43 proteinopathy is a kind of neurodegenerative diseases related to the TAR DNA-binding protein of 43-kDa molecular weight (TDP-43). The typical neurodegenerative diseases include amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), Parkinson's disease (PD) and so on. As the disease process cannot be blocked or slowed down, these patients have poor quality of life and poor prognosis, and bring a huge burden to the family and society. So far, the specific pathogenesis of TDP-43 proteinopathy is not clear, and there is no effective preventive measure and treatment program for this kind of disease. TDP-43 plays an important role in triggering or promoting the occurrence and progression of TDP-43 proteinopathy. The hyperphosphorylation of TDP-43 is undoubtedly an important factor in triggering or promoting the process of TDP-43 proteinopathy. Hyperphosphorylation of TDP-43 can inhibit the degradation of TDP-43, aggravate the aggregation of TDP-43 protein, increase the wrong localization of TDP-43 in cells, and enhance the cytotoxicity of TDP-43. More and more evidences show that the hyperphosphorylation of TDP-43 plays an important role in the pathogenesis of TDP-43 proteinopathy. Inhibition of TDP-43 hyperphosphorylation may be one of the important strategies for the treatment of TDP-43 proteinopathy. Therefore, this article reviews the role of TDP-43 phosphorylation in TDP-43 proteinopathy and the related mechanisms.

Icaritin Improves Memory and Learning Ability by Decreasing BACE-1 Expression and the Bax/Bcl-2 Ratio in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice.

Icaritin (ICT) is the main component in the traditional Chinese herb Epimedium, and it has been shown to have anti-Alzheimer's disease (AD) effects, but its neuroprotective effects and the pharmacological mechanisms are unclear. In the present study, senescence-accelerated mouse prone 8 (SAMP8) mice were randomly divided into a model group and an ICT-treated group. Learning and memory abilities were detected by the Morris water maze assay, and the expression of amyloid beta protein (Aß) and ß-site APP cleavage enzyme 1 (BACE1) was determined by Western blotting and polymerase chain reaction (PCR). Histological changes in CA1 and CA3 were detected by hematoxylin-eosin staining (H&E staining), and the immunohistochemical analysis was used to detect the expression and localization of Bax and Bcl-2. The results showed that compared with the SAMP8 mice, the ICT-treated SAMP8 mice showed improvements in spatial learning and memory retention. In addition, the number of necrotic cells and the morphological changes in CA1 and CA3 areas were significantly alleviated in the group of ICT-treated SAMP8 mice, and the expression of BACE1, Aß 1-42 levels, and the Bax/Bcl-2 ratio in the hippocampus was obviously decreased in the ICT-treated group compared with the control group. The results demonstrated that ICT reduced BACE-1 levels, the contents of Aß 1-42, and the Bax/Bcl-2 ratio, suggesting that ICT might have potential therapeutic benefits by delaying or modifying the progression of AD.

Icariin improves cognitive deficits by reducing the deposition of ß-amyloid peptide and inhibition of neurons apoptosis in SAMP8 mice.

Effective therapeutic drugs for prevent or reverse the pathobiology of Alzheimer's disease (AD) have not been developed. Icariin (ICA), a prenylated flavonol glycoside derived from the traditional Chinese herb Epimedium sagittatum, exerts a variety of pharmacological activities and shows promise in the treatment and prevention of AD. This study investigated the neuroprotective effects of ICA in SAMP8 mice model of aspects of early AD and explored potential underlying mechanisms. Our results showed that intragastric administration of ICA could reverse the learning and memory impairment of SAMP8 mice in the Morris water maze. Western blot of hippocampal specimens revealed that ICA down-regulated the expression of BACE1 to reduce the expression of cytotoxic Aß1-42. Furthermore, ICA siginificantly increase the Bcl-2/Bax ratio by increasing the expression of anti-apoptotic protein Bcl-2, and decreasing the expression of pro-apoptotic protein Bax, and thus inhibit neurons apoptosis. These findings indicate that ICA could improve cognitive deficits by reducing the deposition of ß1-42 and inhibition of neurons apoptosis and provide further evidence for the clinical efficacy of ICA in the treatment of AD.

Diabetes mellitus and Alzheimer's disease: GSK-3ß as a potential link.

It is well known that Alzheimer's disease (AD) is closely related to diabetes mellitus (DM), and AD is also regarded as Type 3 diabetes (T3D). However, the exact link between AD and DM is still unclear. Recently, more and more evidence has shown that glycogen synthase kinase-3ß (GSK-3ß) may be the potential link between DM and AD. In DM, GSK-3ß is the crucial enzyme of glycogen synthesis, which plays a key role in regulating blood glucose. More importantly, GSK-3ß is one of the key factors leading to insulin deficiency and insulin resistance, and insulin resistance is an important hallmark of the occurrence and development of DM. In AD, GSK-3ß plays an important role in hyperphosphorylation of microtubule-associated protein tau (tau), which is one of the pathological features in AD. GSK-3ß is one of the important kinases of tau phosphorylation and is involved in the insulin/phosphoinositide 3-kinase/protein kinase B (insulin/PI3K/Akt) signaling pathway. Dysfunction of the insulin/PI3K/Akt signaling pathway, which regulates glucose metabolism in the brain, can lead to tau hyperphosphorylation in the brain of AD patents. Additionally, insulin resistance in DM may cause ß-amyloid (Aß) deposition, which will be cleared by tau, but excessive phosphorylation of tau will further aggravate the neurotoxicity; then damage the brain and affect the cognitive function. GSK-3ß is considered as a common kinase in insulin signaling transduction and tau protein phosphorylation, so we have reasons to believe that GSK-3ß is a potential link between DM and AD.

TLR4 is a link between diabetes and Alzheimer's disease.

Recently, more and more studies have shown that there is an essential link between diabetes mellitus (DM) and Alzheimer's disease (AD). In addition, innate immunity plays an important role in the occurrence and development of DM and AD, which increase the risk of developing type 2 diabetes (T2D) and AD. Although the pathogenesis of those diseases is still a matter of debate, the important role of Toll-like receptor 4 (TLR4) in the two diseases has been receiving much attention at present. TLR4 and insulin resistance do have close ties, and chronic TLR4 activation may contribute to the insulin resistance. Aside from this, TLR4-mediated chronic inflammation also causes many DM complications such as diabetic nephropathy, diabetic retinopathy and diabetic neuropathy and has a profound impact on the internal environment of the body and brain's microenvironment. In parallel, TLR4 is widely distributed in the brain and also has an important role in the central nervous system (CNS) via regulation of neuroinflammation. The cerebrum under the circumstances of insulin resistance may lead to mitochondrial dysfunction in neurons. Interestingly, in the initial stage, the activation of TLR4 has a useful scavenging effect on amyloid beta (Aß), but chronic long-term activation leads to Aß deposition in the brain. Therefore we speculate that the TLR4 signaling pathway may be a potential link between DM and AD.