This paper addresses how hormesis, a biphasic dose response, can protect and affect performance of neural systems. Particular attention is directed to the potential role of hormesis in mitigating age-related neurodegenerative diseases, genetically based neurological diseases, as well as stroke, traumatic brain injury, seizure, and stress-related conditions. The hormetic dose response is of particular significance since it mediates the magnitude and range of neuroprotective processes. Consideration of hormetic dose-response concepts can also enhance the quality of study designs, including sample size/statistical power strategies, selection of treatment groups, dose spacing, and temporal/repeat measures' features.

BACKGROUND AND PURPOSE: Ischemic brain injury induces both functional and structural disarray affecting the blood–brain barrier (BBB) which in return aggravates stroke outcomes. Complement system and its bioactive proteins are important molecular responders to ischemia. C5a protein along with its receptor C5a receptor 1 is a key component of this system with potent pro-inflammatory and chemoattractant properties. The purpose of this study is to investigate the role of C5a protein and its receptor which are believed to participate in the inflammatory response that follows ischemic insult. MATERIALS AND METHODS: To mimic an ischemic in vivo event in which C5a may contact brain endothelial cells after injury, we studied oxygen-glucose deprivation (OGD) followed by reperfusion in brain microvascular endothelial cells (b.End. 3) by only added C5a at the time of reperfusion. Cell death and viability were estimated by trypan blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, respectively. Tight junction protein zonula occluden (ZO-1) levels were analyzed by Western blot analysis, and nitric oxide (NO) was assessed using the Griess reagent. RESULTS: Brain-derived endothelial cell was susceptible to OGD-induced injury in a duration-dependent manner as was the presence of ZO-1 protein. However, the addition of C5a protein had no notable effects even when used at high concentrations up to 100 nM. While OGD led to reduction in ZO-1 protein levels, no change was seen following the addition of C5a. Finally, OGD led unexpectedly to small decreases in NO generation, but this was again unaltered by C5a. CONCLUSIONS: Our study suggests that complement system protein C5a may not have a direct role in the disruption of BBB, following brain ischemia. This is in contrary with previous literature that suggests a possible role of this protein in the inflammatory response to ischemia.

OBJECTIVES: We have previously shown the neuroprotective function of microRNA-99a-5p in experimental stroke. Here, we explore its diagnostic potential for acute stroke patients. MATERIALS AND METHODS: MiR-99a-5p levels in circulating from acute stroke patients and control were measured by real-time polymerase chain reaction. Pearson's correlation and receiver operator characteristic (ROC) curves were used to analyze clinical significance of miR-99a-5p and its sensitivity and specificity for stroke diagnosis. RESULTS: We demonstrated that miR-99a-5p expression was upregulated in neutrophils of both ischemic stroke and hemorrhage patients, while was only increased in the lymphocytes of hemorrhage patients. ROC analysis revealed that the miR-99a-5p level in neutrophils and lymphocytes had a moderate diagnostic value for stroke. Moreover, a positive correlation existed between plasma miR-99a-5p levels and neutrophil numbers or neutrophil/lymphocyte ratio. Meanwhile, miR-99a-5p levels in neutrophils were negatively correlated with thrombin time, while positively correlated with D-dimer and urea levels. Lymphocytic miR-99a-5p levels were positively correlated with platelet mean volume and distribution width. CONCLUSION: This study demonstrated that miR-99a-5p levels in circulating immune cells might facilitate the diagnosis of ischemic stroke.

OBJECTIVE: This prospective study was planned to formulate and evaluate a predictive score for in-hospital mortality in cases of acute ischemic stroke. MATERIALS AND METHODS: In this study, 188 consecutive patients of ischemic stroke were included over 19 months. Only patients with renal failure and malignancy were excluded from the study. All patients were subjected to clinical evaluation along with Glasgow Coma Scale (GCS), National Institute of Health Science scale (NIHSS) score, and modified Rankin score (mRS). Investigations total leukocyte count (TLC), capillary blood sugar at admission, high-sensitivity C-reactive protein (HS-CRP), and troponin I, electrocardiogram, and neuroimaging were performed. The patients were followed up till their outcome in the hospital, and patients who expired were grouped as “mortality group” and the rest as “discharged group.” One-way anova analysis was carried out among the significant parameters to identify independent predictors of mortality in cases of ischemic stroke. RESULTS: After statistical analysis, it was found that late presentation to the hospital, pyrexia (temperature >99F), low diastolic blood pressure at the time of admission, hypoxia (saturation of oxygen <94%), NIHSS score >15, mRS >3, GCS <8, hyperglycemia (random blood sugar >200 mg/dL), raised TLC, and HS-CRP (>10 mg/L) are positive predictive factors of mortality in cases of ischemic stroke. Based on the above findings, a simple and easily applicable mortality in ischemic stroke (MIS) score is developed. CONCLUSION: This MIS score system will help the clinicians in better management of the patient and improved counseling the relatives of patients with ischemic stroke.

PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is a frequently encountered clinical condition in clinical practice, particularly in obese and diabetic patients. Carotid atherosclerosis is regarded as surrogate marker of coronary atherosclerosis. We aimed to know whether evaluation for carotid atherosclerosis should be done in all patients of NAFLD. MATERIALS AND METHODS: A total of 200 NAFLD patients and 100 age- and sex-matched controls were enrolled into the study. Ultrasound was done to document fatty liver and carotid intimal thickness, and relation between these two was observed. RESULTS: Grade 1 fatty liver was seen in 36% patients while Grade 2 fatty liver was found in 39% and Grade 3 fatty liver in 25%. Patients with Grade 1 fatty liver had left intima-media thickness (IMT) in the range of 0.4–0.6 mm (mean IMT - 0.69 mm) and had right IMT in the range of 0.5–0.8 mm (mean IMT - 0.71 mm). In patients with Grade 2 fatty liver, left IMT was in the range of 0.6–1.0 mm (mean IMT - 0.80 mm) and right IMT in the range of 0.7–1.0 mm (mean IMT - 0.84 mm), while in patients with Grade 3 fatty liver, left IMT was in the range of 0.8–1.2 mm (mean IMT - 0.93 mm) and right IMT in the range of 0.9–1.4 mm (mean IMT - 0.99 mm). Among controls, the mean left IMT was 0.579 mm and mean right IMT was 0.575 mm. CONCLUSION: The level of carotid intimomedial thickness was more in cases than in controls and progressively increased with the grade of fatty liver which was statistically significant.