Objective . To investigate the protective effect of laminarin on PC12 cells damaged by oxygen glucose deprivation/reoxygenation (OGD/R) and its molecular mechanism. Methods . PC12 cells in the logarithmic phase were randomly divided into the control group, OGD/R group, and OGD/R+laminarin (0.5, 2.5, and 5  μ g/ml) group. CCK-8 activity assay kit was used to detect cell viability. ELISA kit was performed to examine the levels of proinflammatory factors (TNF- α , IL-1 β , and IL-6) and oxidative stress markers (ROS, LDH, and MPO). In addition, flow cytometry was employed to determine cell cycle and apoptosis. The expression of cell proliferation-related proteins (PCNA and Ki67), apoptosis-related proteins (Bcl-2, Bax, and Caspase-3), and PTEN/PI3K/AKT pathway-related proteins was evaluated by Western blot. Results . Compared with the control group, the cell viability was decreased significantly in the OGD/R group. CCK-8 results showed that laminarin could attenuate the damage of PC12 cell viability induced by OGD/R in a concentration-dependent manner. Meanwhile, the highest concentration of 5  μ g/ml laminarin could significantly promote the viability of PC12 cells and the expression of PCNA and Ki67 than the OGD/R group. Additionally, ELISA assays showed that laminarin significantly inhibited the expression of proinflammatory factors (TNF- α , IL-1 β , and IL-6) and the levels of oxidative stress markers (ROS, LDH, and MPO). Flow cytometry results demonstrated that laminarin promoted the cell cycle. And laminin upregulated the expression of apoptotic protein Bcl-2, while downregulated the expression of apoptotic proteins Bax and Caspase-3. Finally, laminarin significantly suppressed the expression of PTEN and facilitated the expression of PI3K and p-AKT compared to the OGD/R group. Conclusion . Laminarin could alleviate the OGD/R-induced PC12 cell neuronal injury via promoting cell activity and cycle and inhibiting inflammation, oxidative stress, and apoptosis. The mechanism may be related to the downregulation of PTEN protein and the activation of the PI3K/AKT pathway.

AIMS:This study investigated the safety and efficacy of remote ischemic conditioning (RIC) on ameliorating the sequelae of ischemic moyamoya disease (iMMD).METHODS:A total of 30 iMMD patients underwent long-term RIC and were followed up at 0.5, 1, and 2 years for clinical outcomes, including frequency of stroke recurrence, Patient Global Impression of Change (PGIC) scale, peak systolic velocities (PSV), and cerebral perfusion.RESULTS:During the whole RIC treatment process, no RIC-related adverse event occurred. Only one of 30 patients suffered a onetime infarction (3.3%), and the ratios of acceptable PGIC were 88.2%, 64.3%, and 92.3% at 0.5, 1, and 2 years follow-up. Kaplan-Meier analysis showed the frequency of stroke recurrence was significantly reduced after RIC (P = .013). The frequency of TIA per week was 1.1 (0.6, 2.8) prior to RIC and 0.1 (0.0, 0.5) post-RIC (P < .01). Compared to baseline, PSV values were significantly reduced after RIC treatment (P = .002 at 0.5, P = .331 at 1, and P = .006 at 2 years). In patients undergoing perfusion studies, 75% obtained improvement on followed-up SPECT and 95% on followed-up PET maps.CONCLUSIONS:Remote ischemic conditioning may be beneficial on controlling iMMD-induced ischemic events, relieving symptoms, and improving cerebral perfusion, without incidence of complications in this case series.

Hypoxic preconditioning (HPC) elicits resistance to more drastic subsequent insults, which potentially provide neuroprotective therapeutic strategy, but the underlying mechanisms remain to be fully elucidated. Here, we examined the effects of HPC on synaptic ultrastructure in olfactory bulb of mice. Mice underwent up to five cycles of repeated HPC treatments, and hypoxic tolerance was assessed with a standard gasp reflex assay. As expected, HPC induced an increase in tolerance time. To assess synaptic responses, Western blots were used to quantify protein levels of representative markers for glia, neuron, and synapse, and transmission electron microscopy was used to examine synaptic ultrastructure and mitochondrial density. HPC did not significantly alter the protein levels of astroglial marker (GFAP), neuron-specific markers (GAP43, Tuj-1, and OMP), synaptic number markers (synaptophysin and SNAP25) or the percentage of excitatory synapses versus inhibitory synapses. However, HPC significantly affected synaptic curvature and the percentage of synapses with presynaptic mitochondria, which showed concomitant change pattern. These findings demonstrate that HPC is associated with changes in synaptic ultrastructure. (C) 2014 Wiley Periodicals, Inc.

Symptomatic intracranial arterial stenosis (SIAS) is very common in octo- and nonagenarians, especially in the Chinese population, and is likely the most common cause of stroke recurrence worldwide. Clinical trials demonstrate that endovascular treatment, such as stenting, may not be suitable for octogenarians with systemic diseases. Hence, less invasive methods for the octogenarian patients are urgently needed. Our previous study (unique identifier: NCT01321749) showed that repetitive bilateral arm ischemic preconditioning (BAIPC) reduced the incidence of stroke recurrence by improving cerebral perfusion (confirmed by single photon emission computed tomography and transcranial Doppler sonography) in patients younger than 80 years of age; however, the safety and effectiveness of BAIPC on stroke prevention in octo- and nonagenarians with SIAS are still unclear. The objective of this study was to evaluate the safety and effectiveness of BAIPC in reducing stroke recurrence in octo- and nonagenarian patients with SIAS. Fifty-eight patients with SIAS were enrolled in this randomized controlled prospective study for 180 consecutive days. All patients enrolled in the study received standard medical management. Patients in the BAIPC group (n = 30) underwent 5 cycles consisting of bilateral arm ischemia followed by reperfusion for 5 min each twice daily. Those in the control group (n = 28) underwent sham-BAIPC twice daily. Blood pressure, heart rate, local skin status, plasma myoglobin, and plasma levels of thrombotic and inflammatory markers were documented in both groups before beginning the study and for the first 30 days. Finally, the incidences of stroke recurrence and magnetic resonance imaging during the 180 days of treatment were compared. Compared with the control, BAIPC had no adverse effects on blood pressure, heart rate, local skin integrity, or plasma myoglobin, and did not induce cerebral hemorrhage in the studied cohort. BAIPC reduced plasma high sensitive C-reactive protein, interleukin-6, plasminogen activator inhibitor-1, leukocyte count, and platelet aggregation rate and elevated plasma tissue plasminogen activator (all p < 0.01). In 180 days, 2 infarctions and 7 transient ischemic attacks were observed in the BAIPC group compared with 8 infarctions and 11 transient ischemic attacks in the sham BAIPC group (p < 0.05). BAIPC may safely inhibit stroke recurrence, protect against brain ischemia, and ameliorate plasma biomarkers of inflammation and coagulation in octo- and nonagenarians with SIAS. A multicenter trial is ongoing.

Objective To analyze the significance of brain-heart syndrome on evaluating clinical outcome in patients with acute ischemic stroke. Methods The prognosis of the total of 504 patients with acute ischemic stroke in our hospital from January 2008 to December 2012 were analyzed retrospectively. Patients were divided into two groups according to the ischemic volume: lacunar infarction and large artery atherosclerosis occlusion,incidences of the brain-heart syndrome among the two groups were compared. And also,patients were divided into two groups according to the evolution of clinical process: deteriorating infarction or non-deteriorating infarction. Incidences of the brain-heart syndrome between the two groups were compared. Moreover,patients were divided into four groups according to the location of the ischemic brain lesion: brainstem,cortex lobes,basal ganglia and cerebellum. Incidences of the brain-heart syndrome among the groups were compared. Results Incidence of brain-heart syndrome was relevant with the subtype of the ischemic stroke,high incidence was in the large artery atherosclerosis occlusion group( 76. 74%) rather than in the lacunar infarction group( 5. 54%),P < 0. 01. A high incidence of brain- heart syndrome( 87. 72%) was seen in the group of patients with deteriorating infarction rather than in the infarction group without deteriorating( 72. 78%),P < 0. 05. Meanwhile,infarctions located in brainstem may have the highest incidence of brain-heart syndrome among the four subgroups( 73. 53% of brainstem,48. 99% of cortex lobes, 22. 22% of basal ganglia,and 17. 24% of cerebellum),P < 0. 01. Conclusion The type and the location of ischemic lesions were relevant with the incidence of brain-heart syndrome. Brain-heart syndrome may predict the ischemic lesion involve brainstem or make a deterioration.

目的探讨动脉溶栓联合血管成形术治疗急性重症缺血性卒中的临床疗效及安全性。方法 2009年9月—2013年4月,首都医科大学宣武医院对单纯动脉溶栓后（尿激酶）再通不良的16例重症急性缺血性卒中[美国国立卫生院卒中量表评分中位数（NIHSS）18（14～21）分;改良Rankin评分（mRS）中位数4（3～5）分]患者行血管成形术治疗。对其中6例行球囊扩张术,3例行支架置入术,7例行球囊扩张联合支架置入术。结果①16例患者术前血流灌注（TIMI）分级0级14例（87.5%）,1级2例（12.5%）。术后14例血管再通,总再通率为87.5%。其中11例（68.8%）完全再通,3例（12.5%）部分再通。行球囊扩张联合支架置入术的7例,均为完全再通;单纯支架置入术的3例,完全再通2例,部分再通1例;单纯球囊扩张术的6例,完全再通2例,部分再通2例,未再通（TIMI分级由0级变为1级）2例。②术后2例（12.5%）死亡,1例于术后第5天死于小脑及脑干出血,另1例于术后第6天死于蛛网膜下腔出血。③生存的14例患者,术后2周NIHSS评分和mRS评分均较术前明显改善;术后3个月,NIHSS和mRS评分较术后2周进一步改善。差异均有统计学意义,P＜0.01或P＜0.05。采用超声随访14例患者,随访时间中位数19.5（3～46）个月,仅行球囊扩张术后的1例患者出现再狭窄。结论单纯动脉溶栓后再通不良的重症急性缺血性卒中,联合血管成形术可能会提高血管再通率,改善临床预后。其中联合支架置入术可能较单纯联合球囊扩张术具有更高的再通率。

<正>脑卒中是一类高发病率、高致残率、高死亡率疾病,中老年人多发,是当今世界三大致死疾病之一,是危及我国人民健康的头号杀手,不仅影响患者的生活质量,也给家庭和社会带来了沉重的经济负担[1]。大部分脑卒中患者一旦发病,其病理生理过程很难逆转,有效的治疗方法不多。最近,美国有研究表明,如果每个人都得到合理预防,脑卒中发生率将减少31%、平均

<正>缺血性脑损伤(卒中)的研究始于20世纪70年代,在早期,通过对卒中发病机制和调节介质的研究,提示神经保护药是潜在、有效的干预和治疗药物。此后,大量研究采用动物模型来探讨缺血后脑内生化和分子生物学的改变,证实部分药物确实具有一定神经保护作用,为神经保护药物在临床中的应用提供了依据。通过MEDLINE检索引擎(PubMed)以"neuropro-

Around the world, stroke is the second most common cause of death and a major cause of disability. The main direct cause of stroke is the occlusion of intracranial artery, which leads to cell death in the core suffered region, or cell functional impairment surrounding the dead core (termed ischemic penumbra). Opening the occluded artery to save the ischemic penumbra is the aim of thrombolysis therapy. But the reperfusion induced injury counteracts the potential profit by thrombolysis. Herein, we assume that gradual reperfusion can reduce the reperfusion injury by reducing the production of free radicals during reperfusion. The reason is: free radicals are critical in the reperfusion injury; free radicals come from the penumbra during reperfusion; the respiratory chain is the main source of free radical; the enzyme activity of the respiratory chain is upgraded during ischemia; once reperfused, the activity upgraded enzymes in the respiratory chain meet normal amount of oxygen and glucose, which produces exceeding intermediates (free radicals); while gradual reperfusion reduces the production of free radicals, because it can confine the amount of oxygen and glucose.

组织型纤溶酶原激活剂(tissue plasminogen activator,t-PA)静脉溶栓是美国食品药品监督管理局(FDA)认证的缺血性卒中急性期唯一有效的治疗手段.但t-PA静脉溶栓时间窗较短(≤4.5 h),对颈内动脉及大脑中动脉等大血管闭塞的溶栓效果较差,限制了其应用范围[1].有关研究报道,近端血管闭塞的缺血性卒中患者应用静脉溶栓治疗的再通率较低[2].针对这些问题,逐渐研发出多模式血管内介入治疗方法,包括动脉溶栓、机械碎栓、机械取栓、血栓抽吸、球囊扩张及支架置入术等.我们现将目前血管内治疗急性缺血性卒中的策略与技术的新进展综述如下.