N-Acetyl cysteine amide and cerium oxide nanoparticles as a drug delivery for ischemic stroke treatment: Inflammation and oxidative stress crosstalk.

BACKGROUND: Inflammation and oxidative stress crosstalk is involved in the ischemic stroke(IS) pathogenesis and the new therapeutic options should be offered based on the targets that are critical in the golden hour of IS. YKL-40 and total antioxidant capacity(TAC), the inflammation and oxidative stress biomarkers, provide us with clues for proper intervention targets. N-acetyl cysteine amide (NACA), a lipophilic antioxidant, with a nanoparticle-based drug delivery system is permeable enough to penetrate blood-brain barrier (BBB) and was proposed as a new treatment option for IS. In this study, we evaluated the YKL-40 and TAC levels in the sera of IS patients to elucidate the best intervention target. A rat tissue model is used to assess the NACA efficiency. The microbiology tests performed to figure out the potential NACA and antibiotics interactions. MATERIAL AND METHODS: The YKL-40 and TAC were measured in the serum of IS patients by ELISA and FRAP methods, respectively. The serum samples were obtained 12 h after the patient's admission and meantime other laboratory findings and NIHSS-based prognosis were recorded. In the animal study, the brain cortex, liver, kidney, adipose, and the heart of healthy rats were dissected and then incubated in DMEM cell culture media containing 50 micrograms/milliliter of nanoparticles; the nanoparticles were titanium dioxide nanoparticles (TiO2 NPs), copper oxide nanoparticles (CuO NPs) and cerium dioxide nanoparticles (CeO2 NPs). Olive oil and human serum albumin solution were exposed to the nanoparticles with and without NACA. TAC was measured in the supernatant culture media. With similar concentrations and settings, we evaluated the NACA, nanoparticle, and antibiotics interactions on pseudomonas aeruginosa. RESULTS: There was a nonparametric correlation between YKL-40 levels and post stroke serum TAC levels. Nonsmokers had higher YKL-40 and TAC levels than smokers. A new calculated variable, urea*lymphocyte/age, predicts a poor prognosis with an acceptable AUC (0.708). Exposing to the nanoparticles, the liver, kidney, and brain had a significantly higher TAC than adipose and cardiac tissue. The NACA had an ameliorative effect against TiO2 NPs in the brain. This effectiveness of NACA was also observed against CuO NPs treatment. However, the CeO2 NPs exert a strong antioxidant property by reducing the TAC in the brain tissue but not the others. Albumin showed antioxidant properties by itself, but olive oil had an inert behavior. NACA had no interaction with the action of routine antibiotics. CONCLUSION: Oxidative stress but not inflammation is the best point for intervention in IS patients because YKL-40 has not a relationship with NIHSS score. The CeO2 NPs and NACA combination are eligible option to develop antioxidant-based drug for the treatment of IS. As a complementary finding, the urea*lymphocyte/age is proposed as a NIHSS-based prognosis biomarker.

Pre-treatment or post-treatment with hydroxychloroquine demonstrates neuroprotective effects in cerebral ischemia/reperfusion.

Stroke is a serious life-threatening medical condition and is one of the principal reasons for death and disabilities worldwide. The aim of the present study was to determine the neuroprotective effects of hydroxychloroquine (HCQ) and the timing of its administration in cerebral ischemia/reperfusion (I/R) in rats. A global I/R model was used, and HCQ was administered in either pre- or post-treatment doses of 25 and 50 mg/kg. Effects of HCQ on infarct size, histological changes, oxidative stress, and learning and memory were evaluated. Phospho-AMPK and SQSTM1/p62 protein levels were also measured to elucidate the possible mechanisms involved. HCQ in both pre- (at doses of 25 and 50 mg/kg) or post-treatment (at a dose of 50 mg/kg) protocols reduces brain infarct size and histopathological changes and improves learning and memory after cerebral I/R. Pre-treatment with HCQ reduced AMPK activity with no significant effect on SQSTM1/p62 increment. Post-treatment with HCQ increased AMPK activity and SQSTM1/p62 protein levels. Our results show the neuroprotective effects of HCQ on cerebral I/R through the reduction in infarct size, histopathological changes, and improvement in memory and learning functions. Moreover, AMPK and autophagy may play a role in this protective effect.

Causes of mortality in patients after first-ever stroke: A retrospective population-based study.

BACKGROUND: Stroke is the third most common cause of death in developed countries and it is the most common cause of disability in the adult population of Iran. In this study, we aimed to evaluate the effects of age, sex, and other predisposing risk factors on mortality after stroke. METHODS: We studied 1572 patients with first-ever stroke during a 7-year period from January 2008 to December 2014. Patients' medical records including demographic information, past medical history, physical examination, and laboratory testing were reviewed. We analyzed the correlation of qualitative and quantitative variables with sex and mortality. RESULTS: Of all patients, 252 (16%) died during the hospital stay and of the remaining 1320 patients, 453 (34.3%) died during the follow-up period. There was no significant correlation between mortality and sex (p = .508). Descriptively, the number of women was higher in all age groups except in the age group 55-64 years. No significant correlation was observed between sex and age group (p = .748). We also observed a significant association between age group and mortality (p < .001). Hypertension is the most prevalent disease in both men and women. Higher levels of creatinine, urea, fasting blood sugar, neutrophils, cholesterol, and LDL significantly increase and higher levels of lymphocytes, platelets, RBCs, hemoglobin, and triglyceride significantly decrease the mortality. CONCLUSION: There are no sex differences in mortality after first-ever stroke. Elderly patients need more support and attention due to greater stroke mortality. Complete blood count, lipid profile and blood levels of urea, creatinine, and fasting blood sugar may be useful in predicting mortality after first-ever stroke.

Investigating the relationship between interleukin-6 serum levels and outcome in acute ischemic CVA.

INTRODUCTION: Interleukin-6 (IL-6) is among the inflammatory mediators exhibiting elevated levels in ischemic stroke (IS) patients. The present study set out to evaluate the relationship between serum levels of interleukin-6 with long-term and at-hospital outcomes of acute ischemic stroke in patients hospitalized at Imam Khomeini Hospital, Urmia, Iran, from 2017 to 2018. METHOD AND MATERIALS: This cross-sectional descriptive study enrolled 29 and 31 acute stroke patients for long-term and at-hospital observation, respectively. Evaluation of stroke severity was performed using the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) on days 1, 5, and 90. Serum IL-6 level was measured via enzyme-linked immunosorbent assay (ELISA) on days one and five. RESULTS: In the present cohort study, the following population were enrolled: for long-term evaluation, 11 (38%) men and 18 (63%) women with a mean age of 64.5 ± 14.9 years, and for at-hospital evaluation: 11 (37.5%) men and 20 (64.5%) with a mean age of 65.25 ± 14.37 years. A significant positive correlation was observed between IL-6 levels with NIHSS and mRS scores of the patients from time of admission until the end of the follow-up period (long-term: p < .001; at-hospital: 0.022). CONCLUSION: The evidence from the present study suggests that IL-6 contributes to the determination of the severity of ischemic strokes and may be useful in predicting prognosis. However, larger scale studies are required to further establish these finds.

Application of Texture Analysis in Diagnosis of Multiple Sclerosis by Magnetic Resonance Imaging.

INTRODUCTION: Visual inspection by magnetic resonance (MR) images cannot detect microscopic tissue changes occurring in MS in normal appearing white matter (NAWM) and may be perceived by the human eye as having the same texture as normal white matter (NWM). The aim of the study was to evaluate computer aided diagnosis (CAD) system using texture analysis (TA) in MR images to improve accuracy in identification of subtle differences in brain tissue structure. MATERIAL & METHODS: The MR image database comprised 50 MS patients and 50 healthy subjects. Up to 270 statistical texture features extract as descriptors for each region of interest. The feature reduction methods used were the Fisher method, the lowest probability of classification error and average correlation coefficients (POE+ACC) method and the fusion Fisher plus the POE+ACC (FFPA) to select the best, most effective features to differentiate between MS lesions, NWM and NAWM. The features parameters were used for texture analysis with principle component analysis (PCA) and linear discriminant analysis (LDA). Then first nearest-neighbour (1-NN) classifier was used for features resulting from PCA and LDA. Receiver operating characteristic (ROC) curve analysis was used to examine the performance of TA methods. RESULTS: The highest performance for discrimination between MS lesions, NAWM and NWM was recorded for FFPA feature parameters using LDA; this method showed 100% sensitivity, specificity and accuracy and an area of Az=1 under the ROC curve. CONCLUSION: TA is a reliable method with the potential for effective use in MR imaging for the diagnosis and prediction of MS.