关键词： Hemorrhagic transformation (HT)   High mobility group box protein 1 (HMGB1)   Glycyrrhizin   Peroxynitrite (ONOO-)   Tissue plasminogen activator (t-PA)  

摘要： Peroxynitrite (ONOO-) and high mobility group box 1 protein (HMGB1) are important cytotoxic factors contributing to cerebral ischemia-reperfusion injury. However, the roles of ONOO- in mediating HMGB1 expression and its impacts on hemorrhagic transformation (HT) in ischemic brain injury with delayed t-PA treatment remain unclear. In the present study, we tested the hypothesis that ONOO- could directly mediate the activation and release of HMGB1 in ischemic brains with delayed t-PA treatment. With clinical studies, we found that plasma nitrotyrosine (NT, a surrogate marker of ONOO-) was positively correlated with HMGB1 level in acute ischemic stroke patients. Hemorrhagic transformation and t-PA-treated ischemic stroke patients had increased levels of nitrotyrosine and HMGB1 in plasma. In animal experiments, we found that FeTmPyP, a representative ONOO- decomposition catalyst (PDC), significantly reduced the expression of HMGB1 and its receptor TLR2, and inhibited MMP-9 activation, preserved collagen IV and tight junction claudin-5 in ischemic rat brains with delayed t-PA treatment. ONOO- donor SIN-1 directly induced expression of HMGB1 and its receptor TLR2 in naive rat brains in vivo and induced HMGB1 in brain microvascular endothelial ***3 cells in vitro. Those results suggest that ONOO- could activate HMGB1/TLR2/MMP-9 signaling. We then addressed whether glycyrrhizin, a natural HMGB1 inhibitor, could inhibit ONOO- production and the antioxidant properties of glycyrrhizin contribute to the inhibition of HMGB1 and the neuroprotective effects on attenuating hemorrhagic transformation in ischemic stroke with delayed t-PA treatment. Glycyrrhizin treatment downregulated the expressions of NADPH oxidase p47 phox and p67 phox and iNOS, inhibited superoxide and ONOO- production, reduced the expression of HMGB1, TLR2, MMP-9, preserved type IV collagen and claudin-5 in ischemic brains. Furthermore, glycyrrhizin significantly decreased the mortality rate, attenuated hemorrh

关键词： acute ischaemic stroke   early neurological deterioration   nomogram  

摘要： Background and purpose Acute ischaemic stroke (AIS) is a vital cause of mortality and morbidity in China. Many AIS patients develop early neurological deterioration (END). This study aimed to construct a nomogram to predict END in AIS patients. Methods Acute ischaemic stroke patients in Nanjing First Hospital were recruited as the training cohort. Additional patients in Nantong Third People's Hospital were enrolled as the validation cohort. Multivariate logistic regression was utilized to establish the nomogram. Discrimination and calibration performance of the nomogram were tested by concordance index and calibration plots. Decision curve analysis was employed to assess the utility of the nomogram. Results In all, 1889 and 818 patients were recruited in the training and validation cohorts, respectively. Age [odds ratio (OR) 1.075;95% confidence interval (CI) 1.059-1.091], diabetes mellitus (OR 1.673;95% CI 1.181-2.370), atrial fibrillation (OR 3.297;95% CI 2.005-5.421), previous antiplatelet medication (OR 0.473;95% CI 0.301-0.744), hyper-sensitive C-reactive protein (OR 1.049;95% CI 1.036-1.063) and baseline National Institutes of Health Stroke Scale (OR 1.071;95% CI 1.045-1.098) were associated with END and incorporated in the nomogram. The concordance index was 0.826 (95% CI 0.785-0.885) and 0.798 (95% CI 0.749-0.847) in the training and validation cohorts. By decision curve analysis, the model was relevant between thresholds of 0.06 and 0.90 in the training cohort and 0.08 and 0.77 in the validation cohort. Conclusions The nomogram composed of hyper-sensitive C-reactive protein, age, diabetes mellitus, atrial fibrillation, previous antiplatelet medication and baseline National Institutes of Health Stroke Scale may predict the risk of END in AIS patients.

关键词： COVID-19   meningitis   neurological symptoms  

摘要： There has been a global outbreak of coronavirus disease 2019 (COVID-19) since December 2019. In clinical practice, not only fever and respiratory tract symptoms but also multiple organ symptoms are observed in patients diagnosed with COVID-19. Herein, we report a rare case of a patient diagnosed with COVID-19 who manifested with concomitant neurological symptoms. The patient developed fever and respiratory symptoms at disease onset, followed by muscle soreness, and subsequently altered consciousness and psychiatric symptoms, with positive signs based on neurological examination. The patient tested positive for the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) nucleic acid (throat swab). Further, chest computed tomography (CT) revealed typical COVID-19 findings, and head CT did not reveal significant abnormalities. The patient recovered after treatment and was discharged. This rare case indicates that SARS-CoV-2 can invade the central nervous system, thus causing neurological symptoms and signs. This article is protected by copyright. All rights reserved.

关键词： endocannabinoid system   neurological diseases   cardiac functions   metabolic diseases   immune functions  

摘要： The identification of the human cannabinoid receptors and their roles in health and disease, has been one of the most significant biochemical and pharmacological advancements to have occurred in the past few decades. In spite of the major strides made in furthering endocannabinoid research, therapeutic exploitation of the endocannabinoid system has often been a challenging task. An impaired endocannabinoid tone often manifests as changes in expression and/or functions of type 1 and/or type 2 cannabinoid receptors. It becomes important to understand how alterations in cannabinoid receptor cellular signaling can lead to disruptions in major physiological and biological functions, as they are often associated with the pathogenesis of several neurological, cardiovascular, metabolic, and inflammatory diseases. This review focusses mostly on the pathophysiological roles of type 1 and type 2 cannabinoid receptors, and it attempts to integrate both cellular and physiological functions of the cannabinoid receptors. Apart from an updated review of pre-clinical and clinical studies, the adequacy/inadequacy of cannabinoid-based therapeutics in various pathological conditions is also highlighted. Finally, alternative strategies to modulate endocannabinoid tone, and future directions are also emphasized.

关键词： Biomarkers   Mortality   Neurological recovery   Perforin-2   Sudden cardiac arrest  

摘要： Background: Biomarkers involved in inflammation and stress response were implicated in patients who were successfully resuscitated from out of hospital cardiac arrest (sR-OHCA). Here we report that macrophage-expressed gene, perforin-2, an evolutionarily conserved protein with membrane attack domain, is associated with poor neurological outcomes and mortality after sR-OHCA. Objectives: To examine the association between circulating perforin-2 protein measured within 6-h of sR-OHCA, mortality and neurological outcomes. Methods: We prospectively enrolled 144 sR-OHCA patients from 4 different tertiary care centers. We measured perforin-2 and other conventional clinical biomarkers and compared between survivors vs. non-survivors. The neurological outcomes were dichotomized as poor- or good-according to the cereberal performance score. Results: At the end of the hospital stay, 45% of the patients had died and 46% had poor neurological outcomes. Serum perforin-2 levels were significantly higher in patients with poor neurological recovery, compared to the ones with goodneurological recovery (ng/mL, 13.7 +/- 45.9 vs. 1.2 +/- 7.0, p = 0.01). There were no differences in other routinely measured biomarkers and left ventricular ejection fraction. On multivariate logistic regression, elevated perforin-2 (OR: 12.78, 95% CI: 1.0-17.8, p = 0.02), comatose on presentation (OR: 27.82, 95% CI: 0.2-19.5, p = 0.02) and non-shockable rhythm (OR: 17.04, 95% CI: 0.7-15.7, p = 0.01) were the significant predictors of poor neurological outcome. Conclusions: This study reports a novel macrophage-expressed circulating biomarker perforin-2 to be strongly associated with reduced survival and poor neurological outcomes in sR-OHCA. These data can guide clinicians to prognosticate survival and neurological outcomes in sR-OHCA, and also form the basis for future therapeutic approaches.

关键词： NIH funding   NIH funding gender disparity   Gender   Neurological surgery   Women in neurosurgery   Gender disparity  

摘要： Research productivity is a vital component to an academic neurosurgeon's career. We sought to evaluate gender differences in NIH funding among faculty in neurological surgery departments. NIH funding awarded to PIs of neurological surgery departments from 2014 to 2019 were obtained and analyzed for gender differences in funding trends, with attention to terminal degree and academic rank, as well as publication range in length of years and h-index. 79.4% of all NIH grants were awarded to male PIs, with the remaining 20.5% given to their female counterparts. Mean of the total NIH grants awarded to men was significantly higher at $1,796,684 (+/- Standard Error of Mean (SEM) $155,849, IQR: $1,759,250) compared to women at $1,151,968 (+/- SEM $137,914, IQR: $1,388,538) (P = 0.022). Mean NIH funding per grant for men was $365,760 (+/- SEM: $39,592, IQR: $189,692) and for women was $292,912 (+/- SEM: 28,239, IQR: $283,177). Differences in mean NIH funding per grant approached but did not reach statistical significance between men and women (P = 0.122). When stratified for academic rank, there was a significant difference in mean NIH funding per grant between men and women on the associate professor level (p < 0.005), with women exceeding men in funding at this academic level, with other academic ranks remaining non-significant. Overall, male neurosurgeons receive significantly more total NIH grant funding than their female counterparts, except at the level of associate professor where women were found to surpass men. (C) 2020 Elsevier Ltd. All rights reserved.

关键词： Extracellular-regulated protein kinases (ERK)   Erythropoietin (EPO)   Autophagy   Spinal cord injury (SCI)  

摘要： The objective of this study was to explore the neuroprotective molecular mechanisms of erythropoietin (EPO) in rats following spinal cord injury (SCI). First, a standard SCI model was established. After drug or saline treatment was administered, locomotor function was evaluated in rats using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. H&E, Nissl, and TUNEL staining were performed to assess the ratio of cavities, number of motor neurons, and apoptotic cells in the damaged area. The relative protein and mRNA expressions were examined using western blot and qRT-PCR analyses, and the inflammatory markers, axon special protein, and neuromuscular junctions (NMJs) were detected by immunofluorescence. Both doses of EPO notably improved locomotor function, but high-dose EPO was more effective than low-dose EPO. Moreover, EPO reduced the cavity ratio, cell apoptosis, and motor neuron loss in the damaged area, but enhanced the autophagy level and extracellular-regulated protein kinase (ERK) activity. Treatment with an ERK inhibitor significantly prevented the effect of EPO on SCI, and an activator mimicked the benefits of EPO. Further investigation revealed that EPO promoted SCI-induced autophagy via the ERK signaling pathway. EPO activates autophagy to promote locomotor function recovery in rats with SCI via the ERK signaling pathway.

摘要： Dreams are experiences that occur during sleep, while we are disconnected from the environment. Thanks to recent progress in neuroimaging techniques, it is now becoming possible to relate dream features to specific patterns of brain activity. Some conditions occurring in patients with neurological disorders, such as lucid dreams and parasomnias, not only have diagnostic value, but also offer a window into the dream process. They show that dreaming is reflected in physiological signals, behaviours, and brain activity patterns, and that the body can enact dream content Yet, the dream body can also be distinct from the real body;in their dreams, patients with congenital paraplegia can walk, those with sleep apnoea rarely suffocate, and phantom limb pain can disappear. These conditions provide valuable models for future studies investigating the mechanisms that underlie oneiric experiences.