ABSTRACT
Kainic acid (KA) was recently identified as an epileptogenic and neuroexcitotoxic agent that is responsible for inducing learning and memory deficits in various neurodegenerative diseases, such as Alzheimer's disease (AD). However, the mechanism by which KA acts upon AD remains unclear. To this end, we presently investigated the roles of KA in processing amyloid-ß protein precursor (AßPP) and amyloid-ß protein (Aß) loads during the course of AD development and progression. Specifically, KA treatment clearly caused the upregulation of tumor necrosis factor α (TNF-α) via activation of the PI3-K/AKT, ERK1/2, and p65 pathways in glial cells. TNF-α secreted from glial cells was then found to be responsible for stimulating the expression of BACE-1 and PS1/2, which resulted in the production and deposition of Aß in neurons. Finally, the accumulation and aggregation of Aß lead to the cognitive decline of APP23 mice. These results indicate that KA accelerates the progression of AD by inducing the crosstalk between glial cells and neurons.
Subject(s)
Amyloid beta-Peptides/metabolism , Brain/metabolism , Excitatory Amino Acid Agonists/toxicity , Kainic Acid/toxicity , Memory Disorders , Tumor Necrosis Factor-alpha/metabolism , Amyloid Precursor Protein Secretases/metabolism , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Animals , Aspartic Acid Endopeptidases/metabolism , Disease Models, Animal , Enzyme Inhibitors/pharmacology , Gene Expression Regulation/drug effects , Gene Expression Regulation/genetics , Maze Learning/drug effects , Memory Disorders/chemically induced , Memory Disorders/genetics , Memory Disorders/pathology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neurons/drug effects , Neurons/metabolism , Oligopeptides/metabolism , RNA, Messenger/metabolism , Signal Transduction/drug effects , Signal Transduction/geneticsABSTRACT
PURPOSE: The purpose of this study was to investigate the prevalence of incidental pulmonary embolism (IPE) in suspected stroke patients receiving carotid computed tomography angiography (CTA) and its characteristics. MATERIALS AND METHODS: A total of 4873 cases receiving carotid CTA between January 2013 and December 2016 were retrospectively reassessed by one radiologist. Patients with previous or suspected PE were excluded. The remaining prior contrast-enhanced carotid CTA studies were regarded as a "potentially incidental" IPE when a filling defect was found in one or more pulmonary arteries and subjected to the other two thoracic radiologists independently for reviewing and assessing for characteristics of the IPE and the image quality of the PE. The differences were noted between inpatients and outpatients in prevalence of IPE. Characteristics of the patients with IPE were also studied in terms of gender, age, as well as clinical indication. RESULTS: The prevalence of IPE among these suspected stroke patients was 0.8% on carotid CT angiography, and 24 (96%) of all IPEs had not been previously diagnosed by the original reporting radiologists. Most of the IPEs were at the lobar or segmental levels, single and in right upper lobe of pulmonary arteries. In most of the cases, the reviewing radiologists judged the contrast bolus as good. The outpatient group had a lower percentage of patients with IPE when compared with the inpatient counterpart (p = 0.024). The prevalence of IPE in patients with suspected stroke was higher with the increasing of age (p = 0.013). CONCLUSIONS: IPE can occur in suspected stroke patients on carotid CT angiography, and most of them have been previously neglected in clinical practice. Radiologists should check the higher pulmonary arterial vasculature carefully on the contrast-enhanced carotid CTA scans.
