阿替普酶联合阿加曲班对急性缺血性脑卒中患者内皮损伤、血液流变学和神经功能损伤因子的影响

摘要 目的：探讨阿替普酶联合阿加曲班治疗急性缺血性脑卒中（AIS）对患者内皮损伤、血液流变学和神经功能损伤因子的影响。方法：采用随机数字表法,将南方医科大学珠江医院神经内科2019年8月~2021年7月期间收治的94例AIS患者分为对照组（n=47）和研究组（n=47）。对照组患者接受阿替普酶治疗,研究组患者接受阿替普酶联合阿加曲班治疗,对比两组疗效、内皮损伤指标、血液流变学指标、神经功能损伤因子、美国国立卫生研究所卒中量表（NIHSS）评分、Barthel指数（BI）评分和不良反应。结果：与对照组治疗后相比,研究组治疗后的临床总有效率更高（P<0.05）。与对照组治疗后相比,研究组治疗后内皮素-1（ET-1）水平更低,降钙素基因相关肽（CGRP）、一氧化氮（NO）水平更高（P<0.05）。与对照组治疗后相比,研究组治疗后血浆黏度（PV）、全血黏度（WBV）、红细胞压积（HCT）、纤维蛋白原（FIB）水平更低（P<0.05）。与对照组治疗后相比,研究组治疗后神经元特异性烯醇化酶（NSE）、S100β蛋白水平更低（P<0.05）。与对照组治疗后相比,研究组治疗后NIHSS评分更低,BI评分更高（P<0.05）。两组不良反应发生率组间对比无差异（P>0.05）。结论：阿替普酶联合阿加曲班应用于AIS患者,可改善机体血液流变学,减轻内皮功能损伤和神经功能损害。     

Nuclear-translocated Glyceraldehyde-3-phosphate Dehydrogenase Promotes Poly(ADP-ribose) Polymerase-1 Activation during Oxidative/Nitrosative Stress in Stroke

In addition to its role in DNA repair, nuclear poly(ADP-ribose) polymerase-1 (PARP-1) mediates brain damage when it is over-activated by oxidative/nitrosative stress. Nonetheless, it remains unclear how PARP-1 is activated in neuropathological contexts. Here we report that PARP-1 interacts with a pool of glyceradehyde-3-phosphate dehydrogenase (GAPDH) that translocates into the nucleus under oxidative/nitrosative stress both in vitro and in vivo. A well conserved amino acid at the N terminus of GAPDH determines its protein binding with PARP-1. Wild-type (WT) but not mutant GAPDH, that lacks the ability to bind PARP-1, can promote PARP-1 activation. Importantly, disrupting this interaction significantly diminishes PARP-1 overactivation and protects against both brain damage and neurological deficits induced by middle cerebral artery occlusion/reperfusion in a rat stroke model. Together, these findings suggest that nuclear GAPDH is a key regulator of PARP-1 activity, and its signaling underlies the pathology of oxidative/nitrosative stress-induced brain damage including stroke.     

Cardiorespiratory responses to haemolytic anaemia in rainbow trout Oncorhynchus mykiss

To quantify cardiorespiratory response to experimental anaemia in rainbow trout Oncorhynchus mykiss, a 24 h phenylhydrazine treatment was used to reduce haematocrit to almost one third of its initial value over 4–5 days. In response, relative blood velocity in the ventral aorta (an index of cardiac output) progressively increased to more than double to its normocythaemic value and there was no significant change in routine oxygen uptake. Thus, the primary compensatory response to anaemia was an increase in cardiac output.     

对比不同类型干细胞对于缺血性脑卒中治疗的研究进展

成人中枢神经系统存在着一定量的神经干细胞,其具有两大关键能力;自我更新和多向分化潜能。缺血性脑卒中是一种由于由脑血流的缺失或减少引起的脑动脉闭塞,进而导致脑组织梗死的脑血管疾病。虽然对于脑损伤的药物治疗已经取得了一定的成果,但目前以干细胞为基础的治疗方法仍成为了研究热点。无论是内源性神经干细胞还是外源性神经干细胞移植均可在脑损伤后向远端损伤区迁移并分化成新的神经细胞,从而在中枢神经系统疾病尤其是脑梗死后进行组织修复和功能恢复。因此在这篇综述中,我们主要探讨不同类型的干细胞对脑梗死介导的脑损伤的应用潜能,对比不同类型干细胞对缺血性脑卒中的治疗优缺点。     

Proteomic signatures of serum albumin-bound proteins from stroke patients with and without endovascular closure of PFO are significantly different and suggest a novel mechanism for cholesterol efflux

Background

The anatomy of PFO suggests that it can allow thrombi and potentially harmful circulatory factors to travel directly from the venous to the arterial circulation – altering circulatory phenotype. Our previous publication using high-resolution LC-MS/MS to profile protein and peptide expression patterns in plasma showed that albumin was relatively increased in donor samples from PFO-related than other types of ischemic strokes. Since albumin binds a host of molecules and acts as a carrier for lipoproteins, small molecules and drugs, we decided to investigate the albumin-bound proteins (in a similar sample cohort) in an effort to unravel biological changes and potentially discover biomarkers related to PFO-related stroke and PFO endovascular closure.

Methods

The method used in this study combined albumin immuno-enrichment with high resolution LC-MS in order to specifically capture and quantify the albumin-bound proteins. Subsequently, we measured cholesterol and HDL in a larger, separate cohort of PFO stroke patients, pre and post closure.

Results

The results demonstrated that a number of proteins were specifically associated with albumin in samples with and without endovascular closure of the PFO, and that the protein profiles were very different. Eight proteins, typically associated with HDL were common to both sample sets and quantitatively differently abundant. Pathway analysis of the MS results suggested that enhanced cholesterol efflux and reduced lipid oxidation were associated with PFO closure. Measurement of total cholesterol and HDL in a larger cohort of PFO closure samples using a colorimetric assay was consistent with the proteomic predictions.

Conclusions

The collective data presented in this study demonstrate that analysis of albumin-bound proteins could provide a valuable tool for biomarker discovery on the effects of PFO endovascular closure. In addition, the results suggest that PFO endovascular closure can potentially have effects on HDL, cholesterol and albumin-bound ApoA-I abundance, therefore possibly providing benefits in cardioprotective functions.

Electronic supplementary material

The online version of this article (doi:10.1186/1559-0275-12-2) contains supplementary material, which is available to authorized users.     

Cystathionine β-Synthase Inhibition Is a Potential Therapeutic Approach to Treatment of Ischemic Injury

Hydrogen sulfide (H₂S) has been reported to exacerbate stroke outcome in experimental models. Cystathionine β-synthase (CBS) has been implicated as the predominant H₂S-producing enzyme in central nervous system. When SH-SY5Y cells were transfected to overexpress CBS, these cells were able to synthesize H₂S when exposed to high levels of enzyme substrates but not substrate concentrations that may reflect normal physiological conditions. At the same time, these cells demonstrated exacerbated cell death when subjected to oxygen and glucose deprivation (OGD) together with high substrate concentrations, indicating that H₂S production has a detrimental effect on cell survival. This effect could be abolished by CBS inhibition. The same effect was observed with primary astrocytes exposed to OGD and high substrates or sodium hydrosulfide. In addition, CBS was upregulated and activated by truncation in primary astrocytes subjected to OGD. When rats were subjected to permanent middle cerebral artery occlusion, CBS activation was also observed. These results imply that in acute ischemic conditions, CBS is upregulated and activated by truncation causing an increased production of H₂S, which exacerbate the ischemic injuries. Therefore, CBS inhibition may be a viable approach to stroke treatment.     

血栓通配合康复训练对缺血性脑卒中恢复期患者肢体康复的疗效

目的:探究血栓通配合康复训练对缺血性脑卒中(cerebral arterial thrombosis,CAT)恢复期患者肢体康复的疗效情况。方法:选取2011年3月-2013年3月我院收治的84例CAT患者按数字表法随机分为观察组和对照组,各42例。对照组单纯采用康复训练治疗,观察组在对照组康复训练的基础上服用血栓通配合治疗,分别观察治疗前、治疗后1个月、3个月、6个月的各项基本指标并对比研究。结果:两组患者治疗前和治疗1月后Barthel评分无明显差异(P0.05);观察组治疗后3、6个月Barthel评分显著高于对照组,差异有统计学意义(P0.05),两组患者治疗前和治疗1月后肢体Fugl-Meyer评分无明显差异(P0.05);观察组治疗后3、6个月肢体Fugl-Meyer评分显著高于对照组,差异有统计学意义(P0.05),且对照组出院时上肢依然未完全恢复。通过对对照组和观察组患者的生活质量评分比较,观察组生活质量的各项评分均明显高于对照组,两组比较差异有统计学意义(P0.05)。结论:对缺血性脑卒中恢复期患者采用血栓通药物配合适当的康复训练疗效较好,术后肢体恢复理想,值得作为治疗CAT的首选方法在临床上推广应用。     

Is Female Visual Signaling to Male Song Socially Regulated in Brown‐headed Cowbirds?

This research focused on how adult female brown‐headed cowbirds, Molothrus ater, regulate social feedback on a group level to shape the development of male song. Specifically, females produce rapid wing movements in response to male song, termed ‘wing strokes,’ which have been shown to shape male song and predict song quality. These effects have been documented in captive dyads and triads, but not in more naturalistic flocks, where song development actually occurs. Here, we studied wing stroking in small seminatural flocks of differing female‐to‐male ratios. Despite differences in the number of females and their social selectivity, the same pattern of female feedback emerged in seven of eight flocks: One female produced the majority of wing strokes to male song, making her the primary wing stroker in her flock. Previous studies on large flocks have demonstrated females to facilitate male song improvisation and development if they exhibited higher social selectivity by approaching immature males less. Here, we found that primary wing strokers were indeed more socially selective than non‐primary wing strokers. This research is the first to document social stimulation being facilitated at the group level to ensure that more highly selective females deliver the most feedback.     

Creatinyl amino acids—new hybrid compounds with neuroprotective activity

Prolonged oral creatine administration resulted in remarkable neuroprotection in experimental models of brain stroke. However, because of its polar nature creatine has poor ability to penetrate the blood–brain barrier (BBB) without specific creatine transporter (CRT). Thus, synthesis of hydrophobic derivatives capable of crossing the BBB by alternative pathway is of great importance for the treatment of acute and chronic neurological diseases including stroke, traumatic brain injury and hereditary CRT deficiency. Here we describe synthesis of new hybrid compounds—creatinyl amino acids, their neuroprotective activity in vivo and stability to degradation in different media. The title compounds were synthesized by guanidinylation of corresponding sarcosyl peptides or direct creatine attachment using isobutyl chloroformate method. Addition of lipophilic counterion (p‐toluenesulfonate) ensures efficient creatine dissolution in DMF with simultaneous protection of guanidino group towards intramolecular cyclization. It excludes the application of expensive guanidinylating reagents, permits to simplify synthetic procedure and adapt it to large‐scale production. The biological activity of creatinyl amino acids was tested in vivo on ischemic stroke and NaNO₂‐induced hypoxia models. One of the most effective compounds—creatinyl‐glycine ethyl ester increases life span of experimental animals more than two times in hypoxia model and has neuroprotective action in brain stroke model when applied both before and after ischemia. These data evidenced that creatinyl amino acids can represent promising candidates for the development of new drugs useful in stroke treatment. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.