Oxidative stress is a well-known common pathological process involved in mediating acute neurological injuries, such as stroke, traumatic brain injury, epilepsy, and hypoglycemia-related neuronal injury. However, effective therapeutic measures aimed at scavenging free reactive oxygen species have shown little success in clinical trials. Recent studies have revealed that NADPH oxidase, a membrane-bound enzyme complex that catalyzes the production of a superoxide free radical, is one of the major sources of cellular reactive oxygen species in acute neurological disorders. Furthermore, several studies, including our previous ones, have shown that the inhibition of NADPH oxidase can reduce subsequent neuronal injury in neurological disease. Moreover, maintaining appropriate levels of NADPH oxidase has also been shown to be associated with proper neurogenesis after neuronal injury. This review aims to present a comprehensive overview of the role of NADPH oxidase in neuronal death and neurogenesis in multiple acute neurological disorders and to explore potential pharmacological strategies targeting the NADPH-related oxidative stress pathways.

Although there have been substantial advances in knowledge regarding the mechanisms of neuron death after stroke, effective therapeutic measures for stroke are still insufficient. Excitatory amino acid carrier 1 (EAAC1) is a type of neuronal glutamate transporter and considered to have an additional action involving the neuronal uptake of cysteine, which acts as a crucial substrate for glutathione synthesis. Previously, our lab demonstrated that genetic deletion of EAAC1 leads to decreased neuronal glutathione synthesis, increased oxidative stress, and subsequent cognitive impairment. Therefore, we hypothesized that reduced neuronal transport of cysteine due to deletion of the EAAC1 gene might exacerbate neuronal injury and impair adult neurogenesis in the hippocampus after transient cerebral ischemia. EAAC1 gene deletion profoundly increased ischemia-induced neuronal death by decreasing the antioxidant capacity. In addition, genetic deletion of EAAC1 also decreased the overall neurogenesis processes, such as cell proliferation, differentiation, and survival, after cerebral ischemia. These studies strongly support our hypothesis that EAAC1 is crucial for the survival of newly generated neurons, as well as mature neurons, in both physiological and pathological conditions. Here, we present a comprehensive review of the role of EAAC1 in neuronal death and neurogenesis induced by ischemic stroke, focusing on its potential cellular and molecular mechanisms.

Oxidative stress has been strongly related with Alzheimer disease pathogenesis. We determined the effects of watermelon powder (WMP) and Lactococcus lactis subsp lactis (LAL) supplementation on the generated Aβ42-induced phenotypes in a Drosophila melanogaster model of AD. Enhanced Aβ42 expression in D. melanogaster neurons can diminish lifespan and flight ability. We have observed longevity methods to assay the effects of WMP and LAL on D. melanogaster survival. Furthermore, flies expressing Aβ42 in their body fed WMP and LAL had up to 90 days, or 35% longer median lifespan than those fed a control diet. In addition, synergistic effect of WMP and LAL improved Aβ42-induced flight impairments in the Drosophila wing tissues. Our microscope experiments revealed that individuals fed synergistic effect of WMP and LAL had ameliorated Aβ42 expression as well as increment of flight ability than Aβ42-induced flies. We propose that WMP is typically rich in L-citrulline and LAL, rich in naturally occurring probiotics and antioxidants, and that it promotes the survival of neurons in brain and wing muscle tissues with increased levels of Aβ42 via a protective cell survival mechanism.

Oxidative stress has been strongly related with Parkinson disease (PD) and Alzheimer disease pathogenesis. We determined the effects of Lactococcus lactis (LAL) supplementation on the generated loss-of-function mutants of PINK1 B9, an AR-JP-linked gene and Aβ42 induced phenotypes in a Drosophila melanogaster model of PD/AD. Enhanced mutant PINK1 B9 and Aβ42 expression in D. melanogaster dopaminergic (DA) neurons can curtail lifespan, flight muscle accompanied by locomotive defects and we have observed longevity methods to assay the effects of LAL on D. melanogaster survival. Furthermore, flies expressing mutant PINK1 B9 and Aβ42 in their brain fed LAL had up to the two weeks, or 25%, greater median lifespan than those fed a standard sucrose diet. In addition, LAL improved mutant PINK1 B9 and Aβ42-induced flight impairments in the Drosophila wing. Our microscopy analyses revealed that individuals fed LAL had improved atypical ommatidia as well as an increased thirteen percentage of flight ability than those fed a control diet. We propose that LAL, rich in naturally occurring probiotics and antioxidants, promotes the survival of neurons in brain and wing muscle tissues with increased levels of mutant PINK1 B9 and Aβ42 via a protective cell survival mechanism.

Background/Introduction The 2019 European Society of Cardiology (ESC) guidelines currently recommend the use of coronary computed tomography angiography (CCTA) as the initial test for diagnosing coronary artery disease (CAD) in symptomatic patients in whom obstructive CAD cannot be excluded by clinical assessment alone. Purpose The purpose of this study is to identify the prevalence of obstructive CAD in patients with stable chest pain, and the correlation between several clinical cardiovascular disease (CVD) risk factors and CCTA findings presented by Coronary Artery Disease Reporting and Data System (CAD-RADS). Methods The present study is a single-center retrospective cross-sectional study. A total of 1,892 patients with stable chest pain who underwent CCTA were enrolled in this study. Diamond-Forrester classification, Framingham risk score (FRS), atherosclerotic CVD (ASCVD) 10-year risk score, coronary artery calcium score (CACS) and CAD-RADS category were obtained from every patient. Results Among 1,892 patients (mean age, 60.5±8.6 years; men, 59.3%), 356 (18.8%) had obstructive CAD according to CCTA. Patients with high and intermediate ASCVD 10-year risk score had 2.59 times (aOR 2.59, 95% CI; 1.58 to 4.23) and 1.66 times (aOR 1.66, 95% CI; 1.04 to 2.65) higher odds of having obstructive CAD than patients with low ASCVD 10-year risk score, respectively (adjusted for Diamond-Forrester classification and CACS group). Higher ASCVD risk scores were significantly associated with higher CAD-RADS category (p<0.001), and patients with CAD-RADS category 3 had ASCVD 10-year risk score of 20.1±12.7. CACS showed the highest discrimination in presence of obstructive CAD, followed by ASCVD 10-year risk score, FRS, and Diamond-Forrester classification (AUC: 0.821 [95% CI; 0.797–0.845]; 0.711 [95% CI; 0.683–0.740]; 0.675 [95% CI; 0.646–0.704]; 0.600 [95% CI; 0.569–0.632], respectively). Conclusion This is the first study of CCTA findings in stable chest pain patients in Korea. The prevalence of obstructive CAD in patients with stable chest pain was 18.8%. Higher ASCVD score is significantly associated with presence of obstructive CAD and higher CAD-RADS category. As coronary stenosis of 50%-69% had a mean ASCVD score of 20.1, we should consider CCTA for identifying obstructive CAD in patients with ASCVD score over 20 with stable chest pain. Funding Acknowledgement Type of funding sources: None.