Intranasal Dexamethasone Reduces Mortality and Brain Damage in a Mouse Experimental Ischemic Stroke Model

Neuroinflammation triggered by the expression of damaged-associated molecular patterns released from dying cells plays a critical role in the pathogenesis of ischemic stroke. However, the benefits from the control of neuroinflammation in the clinical outcome have not been established. In this study, the effectiveness of intranasal, a highly efficient route to reach the central nervous system, and intraperitoneal dexamethasone administration in the treatment of neuroinflammation was evaluated in a 60-min middle cerebral artery occlusion (MCAO) model in C57BL/6 male mice. We performed a side-by-side comparison using intranasal versus intraperitoneal dexamethasone, a timecourse including immediate (0 h) or 4 or 12 h poststroke intranasal administration, as well as 4 intranasal doses of dexamethasone beginning 12 h after the MCAO versus a single dose at 12 h to identify the most effective conditions to treat neuroinflammation in MCAO mice. The best results were obtained 12 h after MCAO and when mice received a single dose of dexamethasone (0.25 mg/kg) intranasally. This treatment significantly reduced mortality, neurological deficits, infarct volume size, blood–brain barrier permeability in the somatosensory cortex, inflammatory cell infiltration, and glial activation. Our results demonstrate that a single low dose of intranasal dexamethasone has neuroprotective therapeutic effects in the MCAO model, showing a better clinical outcome than the intraperitoneal administration. Based on these results, we propose a new therapeutic approach for the treatment of the damage process that accompanies ischemic stroke.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00884-9) contains supplementary material, which is available to authorized users.     

Virtual Crossmatching in Kidney Transplantation: The Wait Is Over

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补阳还五汤对大鼠缺血性脑中风损伤后轴突再生的影响

目的:探索补阳还五汤促进缺血性脑中风大鼠轴突再生和神经康复的作用。方法:SD大鼠共180只,建立大脑中动脉梗死(MCAO)模型,选取造模成功的大鼠随机分成模型组、补阳还五汤组(12 g·kg~(-1))和尼莫地平组(20 mg·kg~(-1)),另设假手术组,每组28只。连续灌胃给药7 d后,断头取脑,通过TTC染色检测脑梗死率,测定脑含水量检测脑水肿程度,改良银染法观察轴突变性,免疫荧光染色观察神经微丝蛋白-200(NF-200)的表达,实时荧光定量PCR(Real-time PCR)检测排斥性导向分子a(RGMa),Ras同源酶(Rho),Rho激酶(ROCK)和脑衰反应调节蛋白2(CRMP2)的mRNA表达,并通过改良神经功能评分观察神经功能恢复情况。结果:与假手术组比较,模型组的脑梗死体积和脑含水量显著上升(P0.01),神经功能显著下降(P0.01),轴突变性和神经纤维损伤严重,轴突生长相关蛋白的mRNA表达异常(P0.01);与模型组比较,补阳还五汤组和尼莫地平组的脑损伤程度明显降低,表现为脑梗死率和脑含水量显著降低(P0.01),轴突变性减少;NF-200阳性染色增多;RGMa,Rho和ROCK的mRNA表达明显降低(P0.05),CRMP2的mRNA表达显著升高(P0.01),神经功能明显提高(P0.05)。结论:补阳还五汤可通过调节轴突生长相关蛋白的mRNA表达促进缺血性脑中风损伤后轴突再生,从而改善神经功能。     

SWIM技术治疗后循环大血管闭塞所致急性缺血性卒中的有效性和安全性观察

目的 观察SWIM技术治疗后循环大血管闭塞所致急性缺血性卒中的有效性及安全性。 方法 回顾性分析2017年2月-2018年11月于大连市中心医院采用SWIM技术治疗的后循环大血管闭 塞所致急性缺血性卒中患者的临床资料，评价该技术的疗效和安全性，并分析影响患者预后的因素。 观察指标为术后即刻成功再通（mTICI≥2b）、90 d良好预后（mRS评分≤2分），以及术后24 h任何颅内 出血、90 d全因死亡。 结果 共纳入35例患者，平均年龄66.1±12.1岁，男性26例（74.3%），基线NIHSS评分22（15～34）分。 术后即刻成功再通率为94.3%（33/35），90 d良好预后率为45.7%（16/35），24 h颅内出血率为17.1% （6/35），90 d全因死亡率为37.1%（13/35）。单因素分析显示，基线NIHSS评分较低（P =0.001）、基 线后循环ASPECTS评分较高（P =0.016）、发病至到院时间较短（P =0.039）、发病至再通时间较短 （P =0.047）、血管成功再通率较高（P =0.036）以及饮酒比例较低（P =0.042）与良好预后相关。 结论 使用SWIM技术治疗后循环急性缺血性卒中相对安全、有效。     

平肝定眩汤治疗肝阳上亢型后循环缺血性眩晕60例临床观察

目的:观察平肝定眩汤对肝阳上亢型后循环缺血性眩晕的疗效。方法:选取2017年6月-2018年10月烟台业达医院收治的后循环缺血性眩晕的患者120例,按随机数字表法分为治疗组和对照组。治疗组和对照组各60例,两组一般的资料经统计学方法,差异无统计学意义(P>0.05),具有可比性。两组均给予改善循环,控制血压、血糖,调节血脂,抗血小板聚集等基础治疗。治疗组给予平肝定眩汤,对照组给予平眩胶囊。两组疗程均为4周,观察两组患者治疗前后总体症状,脑血流速度、血脂、血糖等指标改善情况。采用SPSS 11.0统计学软件进行计算。结果:治疗组总有效率91.7%(55/60),对照组总有效率61.6%(37/60),两组疗效比较有统计学意义(P<0.05)。治疗组三酰甘油(Triglyceride,TG)、血清总胆固醇(Serum Total Cholesterol,TC)、HDL-C、LDL-C治疗后显著改善,与治疗前比较,差异有统计学意义(P<0.05);对照组TG及TC治疗前后差异有统计学意义(P<0.05),高密度脂蛋白胆固醇(High Density Liptein Cholesterol,HDL-C)及低密度脂蛋白胆固醇(Low Density Liptein Cholesterol,LDL-C)治疗前后比较,差异无统计学意义(P>0.05)。两组治疗后TC比较,差异有统计学意义(P<0.05)。两组治疗后空腹血糖(Fasting Plasma Glucose,GLU)明显降低(P<0.05),两组间的治疗后比较,差异无统计学意义(P>0.05)。治疗组治疗后椎动脉(Vertebral Artery,VA)、基底动脉(Basilarartery,BA)平均血流速度(Mean Blood Flow Velocity,VM)明显提高,与对照组治疗后相比较,差异具有统计学意义(P<0.05)。结论:平肝定眩汤治疗后循环缺血性眩晕在改善患者症状、降低血液黏稠度,改善脑血流状况方面疗效显著。     

Mesenchymal stem cell therapy alleviates the neuroinflammation associated with acquired brain injury

Ischemic stroke and traumatic brain injury (TBI) comprise two particularly prevalent and costly examples of acquired brain injury (ABI). Following stroke or TBI, primary cell death and secondary cell death closely model disease progression and worsen outcomes. Mounting evidence indicates that long‐term neuroinflammation extensively exacerbates the secondary deterioration of brain structure and function. Due to their immunomodulatory and regenerative properties, mesenchymal stem cell transplants have emerged as a promising approach to treating this facet of stroke and TBI pathology. In this review, we summarize the classification of cell death in ABI and discuss the prominent role of inflammation. We then consider the efficacy of bone marrow–derived mesenchymal stem/stromal cell (BM‐MSC) transplantation as a therapy for these injuries. Finally, we examine recent laboratory and clinical studies utilizing transplanted BM‐MSCs as antiinflammatory and neurorestorative treatments for stroke and TBI. Clinical trials of BM‐MSC transplants for stroke and TBI support their promising protective and regenerative properties. Future research is needed to allow for better comparison among trials and to elaborate on the emerging area of cell‐based combination treatments.     

Expecting the Holistic Regulation from Chinese Medicine Based on the "Solar System" Hypothesis of Ischemic Heart Disease

Stenosis of the coronary artery has been considered as an essential component of ischemic heart disease (IHD). Consequently, revascularization [e.g., percutaneous coronary intervention (PCI) and coronary artery bypass] has been the primary therapeutic approach to IHD. Such strategy has indeed revolutionized the management of IHD patients. However, not all patients with myocardial ischemia have visible coronary stenosis. Moreover, cardiovascular events occur in nearly 20% patients with stable coronary artery disease who have undergone PCI. The recently proposed “solar system” hypothesis of IHD postulates that coronary stenosis is only one (albeit important) of its features. Mechanistic contribution and clinical implication of multiple pathophysiological processes beyond coronary stenosis are highlighted in this hypothesis. On the basis of a holistic regulation and individualized medicine, Chinese medicine (CM) has been used in the real-world setting to manage a variety of diseases, including IHD, for more than two thousands years. In this article, we summarize the evidence of CM that supports the “solar system” IHD hypothesis, and argue for a comprehensive approach to IHD. At the theoretical level, the central features of this approach include a holistic view of disease and human subjects, as well as individualized medicine. At the practical level, this approach emphasizes anoxia-tolerance and self-healing.     

Epileptogenic modulation index and synchronization in hypsarrhythmia of West syndrome secondary to perinatal arterial ischemic stroke

ObjectivePerinatal arterial ischemic stroke (PAIS) is associated with epileptic spasms of West syndrome (WS) and long term Focal epilepsy (FE). The mechanism of epileptogenic network generation causing hypsarrhythmia of WS is unknown. We hypothesized that Modulation index (MI) [strength of phase-amplitude coupling] and Synchronization likelihood (SL) [degree of connectivity] could interrogate the epileptogenic network in hypsarrhythmia of WS secondary to PAIS.MethodsWe analyzed interictal scalp electroencephalography (EEG) in 10 WS and 11 FE patients with unilateral PAIS. MI between gamma (30–70 Hz) and slow waves (3–4 Hz) was calculated to measure phase-amplitude coupling. SL between electrode pairs was analyzed in 9-frequency bands (5-delta, theta, alpha, beta, gamma) to examine inter- and intra-hemispheric connectivity.ResultsMI was higher in affected hemispheres in WS (p = 0.006); no differences observed in FE. Inter-hemispheric SL of 3-delta, theta, alpha, beta, gamma bands was significantly higher in WS (p < 0.001). In WS, modified Z-Score of intra-hemispheric SL values in 3-delta, theta, alpha, beta and gamma in the affected hemispheres were significantly higher than those in the unaffected hemispheres (p < 0.001) as well as 0.5–4 Hz (p = 0.004).ConclusionsThe significantly higher modulation in affected hemisphere and stronger inter- and intra-hemispheric connectivity generate hypsarrhythmia of WS secondary to PAIS.SignificanceEpileptogenic cortical-subcortical transcallosal networks from affected hemisphere post-PAIS provokes infantile spasms.     

Japanese Versus Non-Japanese Patients with Transient Ischemic Attack or Minor Stroke: Subanalysis of TIA registry.org

BackgroundTIAregistry.org is an international cohort of patients with transient ischemic attack (TIA) or minor stroke within 7 days before enrollment in the registry. Main analyses of 1-year follow-up data have been reported.⁵ We conducted subanalysis on the baseline and 1-year follow-up data of Japanese patients.MethodsThe patients were classified into 2 groups based on Japanese ethnicity, Japanese (345) and non-Japanese (3238), and their baseline data and 1-year event rates were compared. We also determined risk factors and predictors of 1-year stroke.ResultsCurrent smoking, regular alcohol drinking, intracranial arterial stenosis, and small vessel occlusion; and hypertension, dyslipidemia, coronary artery disease, and extracranial arterial stenosis were more and less common among Japanese patients, respectively. Stroke risk was higher and TIA risk was lower at 1-year follow-up among Japanese patients. The baseline risk factors for recurrent stroke were diabetes, alcohol drinking, and large artery atherosclerosis. Independent predictors of 1-year stroke risk were prior congestive heart failure and alcohol consumption.ConclusionsThe two populations of patients featured differences in risk factors, stroke subtypes, and outcome events. Predictors of recurrent stroke among Japanese patients included congestive heart failure and regular alcohol drinking. Strategies to attenuate residual risk of stroke aside from adherence to current guidelines should take our Japanese-patient specific findings into account.