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Embryonic stem cell (ESC)-derived products have emerged as a promising cell source for neuroregeneration. C17.2 neural precursor cells were noted to express genes of neurotrophins and neuroprotective factors and to be enable to enhance proliferation, neuritogenesis, and differentiation of SH-SY5Y and SK-N-AS neuroblasts, suggesting their neurotrophic potential. We used C17.2 cells as neurotrophic chaperones to induce ESCs, D3, and E14TG2a into neural lineage cells. Significantly greater numbers of Sox-2(+), Musashi-1(+), and nestin(+) neurospheres developed in noncontact cocultures than in cultures of ESCs without C17.2 support or with 50% conditioned medium after 8 days. Immunoreactivity of the neuronal, astrocytic and oligodendrocytic markers was evident in cultures further differentiated for 10 days. Expression of Pax-6, Otx-1, and Nurr-1 genes suggested neuroectodermal precursors in products encompassing neural stem cells, dopaminergic neurons, astrocytes, and oligodendrocytes. Alpha-fetoprotein, GATA-4, Brachyury, Nkx-2.5, and Myf-5 genes were not detected, indicating any mesodermal and endodermal cells. However, weak expression of Oct-4 was noted. Behavioral assessment of ischemic mice 2 weeks after transplantation revealed significant improvement in cognitive function compared with that in ischemic sham-operated mice. Tracking bromodeoxyuridine-labeled products demonstrated that mostly implanted cells were localized along the needle track of the injection in the brain parenchyma, whereas some migrated to the striatum, cortex, nerve fiber bundle of the corpus callosum, and hippocampus in the ipsilateral hemisphere. One episode (of 22) of teratoma development was noted. Data from this study suggest a paradigm of trophism of neural progenitor cells for induction of ESCs into neural lineage cells.  相似文献
中国急性缺血性脑卒中治疗现状   总被引:18,自引:1,他引:17  
目的 按照国家和国际治疗指南,评估中国缺血性脑卒中急性期患者的治疗状况.方法 2006年7月1日至11月30日在全国62家医院前瞻性地收集诊断为新发急性脑卒中(脑梗死和脑出血)的所有成人(≥15岁)病例的治疗用药数据.结果 筛查了13 038例患者,其中符合入组标准的6416例,缺血性脑卒中74.5%(4783例),缺血性脑卒中患者从发病到医院时间平均为20.0 h(3.8~59.0 h),发病3 h内到医院的有1019例(21.3%),溶栓治疗只有1.9%(91/4783例),用神经保护剂和中药治疗的分别为75.9%和83.1%,抗血小板治疗的有80.5%,23.5%的脑卒中患者既未得到溶栓治疗,也未得到阿司匹林治疗.结论 目前中国缺血性脑卒中治疗现状喜忧参半:阿司匹林的应用虽然与指南存在差距,但是基本达到西方的应用水平;临床过多使用神经保护剂和中药,而确实有效的溶栓治疗却远远不够,脑卒中发生以后到医院的时间明显长于国外.  相似文献
To elucidate whether vascular endothelial growth factor (VEGF) improves stroke-induced striatal neurogenesis, we intraventricularly injected human VEGF(165)-expressive plasmid (phVEGF) mixed with liposome into adult rats after a transient middle cerebral artery occlusion (MCAO). The results showed that EGFP, a reporter protein, positive cells appeared at 2 hr, further enhanced at 4 hr, reached the maximum at 3 days and still remained at 14 days after a single injection. Treatment with phVEGF increased angiogenesis, as indicated by double staining of vWF, a marker of endothelial cells, and 5'-bromodeoxyuridine (BrdU), a marker of cell proliferation. The phVEGF treatment dose-dependently reduced infarct volume of brain at 2 weeks after MCAO. The neuroprotection by VEGF could be obtained when the plasmid was injected within 2 hr after stroke. Moreover, VEGF overexpression significantly increased cell proliferation in the ipsilateral SVZ and the numbers of BrdU(+)-CRMP-4(+) and BrdU(+)-Tuj1(+), two markers of immature newborn neurons, and BrdU(+)-MAP-2(+), a marker of mature newborn neurons, cells in the ipsilateral striatum to MCAO. Present results show that VEGF plasmid treatment after stroke can significantly reduce infarct volume and enhance striatal neurogenesis in adult rat brain. This suggests that VEGF overexpression acquires significant functions of neuronal protection and repair in the injured brain, which provides a possibility to develop a novel therapeutic strategy for the patients with stroke.  相似文献
肠内营养支持对急性重症脑卒中患者预后的影响   总被引:13,自引:1,他引:12  
目的 探讨肠内营养支持对急性重症脑卒中患者预后的影响.方法 将54例急性重症脑卒中患者随机分为营养支持组(30例)和对照组(24例),在常规治疗的基础上,分别给予能全力高能营养素合剂及普通流汁鼻饲.住院第1 d、10 d和21 d分别检测两组患者血红蛋白、血清白蛋白、三酰什油水平、美国国立卫生院卒中量表(NIHSS)评分,统计感染发生率;入院30 d时进行日常生活能力量表(ADL)评定和分级.结果 住院第10 d、21 d两组患者各项营养指标均下降,对照组下降更为明显(均P<0.05);对照组第10d、21 d低蛋白血症发生率及感染发生率显著升高(均P<0.05);营养支持组第10 d、21 d感染发生率显著低于对照组(均P<0.05).第21 d两组NIHSS评分均有明显改善,营养支持组较对照组同期改善更为显著(均P<0.05),第30 d时临床痊愈率(ADL Ⅰ,23%)及与日常生活自理率(ADL Ⅰ~Ⅲ,86%)显著高于对照组(12%,66%,)(均P<0.05).结论 早期肠内营养支持可明显改善重症脑卒中患者的营养状况,降低感染的发生率,改善预后.  相似文献
Kim SU 《Brain & development》2007,29(4):193-201
Neural stem cells (NSCs)of the central nervous system (CNS) have recently received a great deal of attention and interest for their therapeutic potential for neurological disorders. NSCs are defined as CNS progenitor cells that have the capacity for self-renewal and multipotent potential to become neurons or glial cells. Recent studies have shown that NSCs isolated from mammalian CNS including human can be propagated in vitro and then implanted into the brain of animal models of human neurological disorders. Recently, we have generated clonally derived immortalized human NSC cell lines via a retroviral vector encoded with v-myc oncogene. One of the human NSC lines, HB1.F3, was utilized in stem-cell based therapy in animal models of human neurological disorders. When F3 human NSCs were implanted into the brain of murine models of lysosomal storage diseases, stroke, Parkinson disease, Huntington disease or stroke, implanted F3 NSCs were found to migrate to the lesion sites, differentiate into neurons and glial cells, and restore functional deficits found in these neurological disorders. In animal models of brain tumors, F3 NSCs could deliver a bioactive therapeutically relevant molecules to effect a significant anti-tumor response intracranial tumor mass. Since these genetically engineered human NSCs are immortalized and continuously multiplying, there would be limitless supply of human neurons for treatment for patients suffering from neurological disorders including stroke, Parkinson disease, Huntington disease, ALS, multiple sclerosis and spinal cord injury. The promising field of stem cell research as it applies to regenerative medicine is still in infancy, but its potential appears limitless, and we are blessed to be involved in this exciting realm of research.  相似文献
Pneumonia constitutes a serious medical complication and major cause of death in patients after cerebral stroke. In a mouse model of cerebral ischemia (MCAO), we have recently demonstrated that stroke animals spontaneously develop severe bacterial pneumonia which is preceded by a stress-mediated suppression of cellular immune responses in primary and secondary lymphoid organs. However, little is known about the mechanisms leading to impaired pulmonary antimicrobial immune response after cerebral ischemia. In this study, we demonstrate a rapid up-regulation of the immunomodulatory neuropeptide alpha-melanocyte-stimulating hormone (MSH) in the lung within 24 h after cerebral ischemia. Systemic administration of the naturally occurring alpha-MSH receptor-1 (MC-1R) antagonist agouti immediately after MCAO significantly reduced pulmonary bacterial burden at 72 h. In contrast, administration of recombinant alpha-MSH further increased bacterial load in lungs of MCAO animals. In addition, cerebral ischemia resulted in a strong modulation of local pulmonary immunity with increased production of IL-10 by lung macrophages, reduced pulmonary lymphocyte counts, as well as decreased lymphocytic IFN-gamma but increased IL-4 production. However, alpha-MSH blockade by administration of agouti did not prevent changes in lung immune cell numbers or cytokine production suggesting that suppression of cellular immune responses is not the primary mechanism of alpha-MSH mediated inhibition of pulmonary antibacterial defenses. This study indicates an important role of alpha-MSH for the increased infectious susceptibility after cerebral ischemia and may provide new therapeutic strategies to prevent post-stroke infectious complications.  相似文献
Accumulating data suggest that matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9, are deleterious after acute ischaemic stroke. A beneficial effect of MMPs in the repairing phases of cerebral ischaemia has also been proposed. This study investigated the relationship between MMP-2 and MMP-9 and stroke subtypes, clinical recovery and haemorrhagic transformation (HT). We measured MMP-9 and MMP-2 plasma levels in 29 patients with ischaemic stroke at days one and seven. MMP-2 levels increased only in lacunar strokes, whilst MMP-9 increased only in patients with more severe stroke. Basal MMP-2 levels were higher in patients with stable or recovering symptoms whilst MMP-9 values at day seven were correlated with worse clinical outcome. No differences related to the presence of HT were found. This study sustains a different behaviour of MMPs after ischaemic stroke. MMP-2 seems to be expressed early and related to better outcome, whilst MMP-9 seems to be late and related to more severe stroke.  相似文献
中国七城市卒中患者急诊溶栓情况分析   总被引:9,自引:2,他引:7  
目的超早期重组组织型纤溶酶原激活剂(recombinant tissue plasminogen activator,rt-PA)溶栓治疗是缺血性卒中有效的治疗方法,但目前缺血性卒中救治过程中存在溶栓率偏低的问题,本调查的目的在于了解实际溶栓状况及未溶栓原因。方法本调查在中国的7个城市51家中心展开前瞻性调查,调查采用标准的登记数据,内容包括患者的一般人口学信息、院前卒中急救信息、院前院内关键延误时间、溶栓信息等。结果在研究期间,共有1091例患者确诊符合入选标准,其中754例(69.6%)急性缺血性卒中患者中共有20例(2.7%)患者溶栓,其中静脉rt-PA15例、动脉rt-PA2例、静脉尿激酶(Urokinase,UK)5例。在静脉rt—PA中,93.5%(14/15)存在方案违背。大部分病例(17/20)在2呐就到达了医院,院前延迟平均中位时间为1.17h。急诊接诊到获得检查(CT或磁共振)平均中位时间为0.67h。未进行溶栓的主要原因除年龄(〉80岁或〈18岁)(28.9%)、卒中症状太轻(24.0%)、病情迅速恢复(16.5%)、CT影像已有病灶(15.7%)、时间〉5h(15.7%)、卒中症状太重(7.4%)等因素外,患者/家属主观拒绝仍占了18.2%。结论急性缺血性卒中溶栓比例偏低,溶栓药物使用不规范且存在方案违背,存在院前延迟问题,亟待整合院前急救中心与医院间医疗资源,规范院前转运途径,缩短延误时间,提高溶栓率。  相似文献
OBJECTIVE: Carotid endarterectomy (CEA) is the gold-standard procedure for the majority of patients with high-grade symptomatic internal carotid artery stenosis and also for specified high-grade asymptomatic stenoses; however, a proportion of patients are treated with carotid endovascular therapy. We aimed to document medium-term clinical and neurosonographical outcome after carotid artery stenting (CAS). METHODS: 53 patients (mean age: 65 +/- 8 years) with high-grade (> or = 70 % by means of duplex sonography) carotid artery stenosis were enrolled into the study. Nineteen patients had asymptomatic, 34 patients had symptomatic stenoses. All patients had a pre-interventional CT, Doppler and duplex sonography, and digital subtraction angiography (DSA) or magnetic resonance angiography (MRA) prior to the procedural DSA. All patients were offered CEA as the gold-standard procedure and as an alternative to CAS. Both clinical and Duplex sonographical follow-up was obtained at day 1 and 7, month 1, month 3, month 6, month 12, and every subsequent 6 months after the procedure. Mean follow-up time was 22 +/- 1.6 months (+/- SEM). RESULTS: 2/53 patients suffered from stroke. A further 2 patients suffered from carotid artery occlusion shortly after CAS. The cumulative rate of restenosis during follow-up was 24.5 % (13/53). Four of these (7.5 %) were of high-grade and led to further interventional or surgical therapy. CONCLUSIONS: A high rate of restenosis was found during follow-up after CAS. Our analysis of non-selected patients emphasizes that CEA remains the gold-standard procedure for the treatment of symptomatic internal carotid artery stenosis. The frequently performed endovascular treatment of carotid stenosis outside the setting of a randomized controlled trial is not supported by our data.  相似文献
立体定向神经干细胞移植治疗脑出血后遗症疗效分析   总被引:9,自引:3,他引:6  
目的观察应用神经干细胞移植治疗脑出血后遗症的临床疗效。方法2000年6月至2006年12月我们对16例脑出血患者采用立体定向技术,选取病变侧基底节区作为靶点进行神经干细胞移植术,于治疗前、治疗后1月、6月进行神经功能评分,应用国际通用的功能独立性测量评定其运动及生活能力。结果接受神经干细胞移植的脑出血患者无严重手术并发症。手术后6个月内临床症状改善有效率达81.25%(13例/16例),本组16例术前FIM评分为90.21±2.32,术后1个月为92.76±1.89,术后6个月为96.37±3.83,差异有显著性意义。治疗1个月后功能独立性评分高于治疗前(P〈0.05),而治疗6个月后高于1个月(P〈0.05)。结论神经千细胞移植治疗可以一定程度地改善脑出血患者的后遗症,可提高脑出血患者的运动功能,提高患者生活质量,但其长期疗效仍需进一步观察。  相似文献
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