老年人颅脑外伤后缺血性脑卒中发作特点及治疗

目的探讨老年人颅脑外伤后缺血性脑卒中发作特点及个性化治疗方案。方法针对7例颅脑外伤后急性期出现缺血性脑血管病症状的老年患者，通过脑血管造影检查分析其发病原因并根据不同的脑血管特点决定治疗方案。结果大多数患者（6／7）受伤前已存在不同程度的颅内外血管狭窄、血管壁溃疡以及附壁血栓形成等改变，提示脑缺血发作主要与这些病变为基础的脑血流下降、血栓脱落等因素密切相关。而外伤后脑灌注降低、脑血管痉挛是脑缺血发作的诱发因素。结论老年人外伤后的缺血性脑卒中发作主要与原有的脑血管基础疾病有关，预防和治疗老年人外伤后缺血性脑卒中发作，应基于这些病变特征并选择个体化治疗方案。     

脐带血移植治疗缺氧缺血性脑损伤和缺血性脑卒中的研究进展

人脐带血(human umbilical cord blood, HUCB)富含丰富的未成熟干细胞,这些干细胞具有修复受损组织的潜能.HUCB干细胞移植在动物模型中可以产生多种作用:神经保护、神经再生、抗炎、血管再生等作用.目前HUCB干细胞移植已被用于治疗血液系统疾病,其还可以用于神经系统疾病,并已在基础研究方面取得较大进展.本文简要讨论HUCB移植的治疗机制及在缺氧缺血性脑损伤和缺血性脑卒中的研究进展.     

Salvianolic acid A prevented cerebrovascular endothelial injury caused by acute ischemic stroke through inhibiting the Src signaling pathway

Stroke is an acute cerebrovascular disease caused by ruptured or blocked blood vessels.For the prevention of ischemic stroke,the coagulation state of blood and cerebrovascular protection should be considered.Our previous study has shown that salvianolic acid A(SAA),which is a water-soluble component from the root of Salvia Miltiorrhiza Bge,prevents thrombosis with a mild inhibitory effect on platelet aggregation.In this study we investigated the preventive effects of SAA on cerebrovascular endothelial injury caused by ischemia in vivo and oxygen-glucose deprivation(OGD)in vitro,and explored the underlying mechanisms.An autologous thrombus stroke model was established in SD rats by electrocoagulation.SAA(10 mg/kg)was orally administered twice a day for 5 days before the operation.The rats were sacrificed at 24 h after the operation.We showed that pretreatment with SAA significantly improved the neurological deficits,intracerebral hemorrhage,BBB disruption,and vascular endothelial dysfunction as compared with model group.In human brain microvascular endothelial cells(HBMECs),pretreatment with SAA(10μM)significantly inhibited OGD-induced cell viability reduction and degradation of tight junction proteins(ZO-1,occludin,claudin-5).Furthermore,we found that SAA inhibited the upregulation of Src signaling pathway in vivo and vitro and reversed the increased expression of matrix metalloproteinases(MMPs)after ischemic stroke.In conclusion,our results suggest that SAA protects cerebrovascular endothelial cells against ischemia and OGD injury via suppressing Src signaling pathway.These findings show that pretreatment with SAA is a potential therapeutic strategy for the prevention of ischemic stroke.     

Modulation of ischemic brain injury and neuroinflammation by adenosine A2A receptors

Over the past 5 years, the adenosine A(2A) receptor (A(2A)R) is emerging as an attractive therapeutic target for modulating brain injury in a variety of animal models of neurological disorders including stroke. The evidence we have to date indicates that both adenosine and A(2A) antagonists are neuroprotective in ischaemic brain injury. From drug development perspective, administering A(2A) antagonists in association with inhibitors of adenosine kinase may represent a novel strategy for treating stroke. Despite the well-documented neuroprotection by A(2A)R antagonists, the mechanism by which A(2A)Rs affect brain injury remains largely unknown. In this section, we also summarize the experimental evidence for A(2A)R modulation of glial function as possible contribution to the modulation of brain injury. In vitro and in vivo studies reveal that in response to local neuroinflammation following brain insults, time-dependent, inflammatory signal-mediated induction of the A(2A)R in glial cells (particularly microglial cells) make this cell type particularly sensitive to A(2A)R modulation of brain injury. Furthermore, in contrast to the generally held view that the A(2A)R exerts predominantly anti-inflammatory effects (based upon studies in peripheral organs), the A(2A)R modulation of neuroinflammation may differentially affect the outcome of brain injury, depending on the nature of brain insults. Thus, in association with their ability to reduce brain injury, inactivation of the A(2A)R in most models and activation of A(2A)R in some cases have been shown to attenuate brain inflammation through control of the proliferation and production of proinflammatory cytokines.     

脑外伤严重并发症的预防及护理

目的：探讨颅脑损伤早期严重并发症的预防及护理要点。方法：回顾性分析本院153例重度颅脑损伤患者早期严重并发症治疗及护理的临床资料。结果：本组脑外伤经过并发症的预防、治疗及护理后6个月格拉斯哥结果分级Ⅰ级28例,Ⅱ级5例,Ⅲ17例,Ⅳ级25例,Ⅴ级78例。结论：掌握颅脑外伤早期可能出现的严重并发症,并采取相应的预防措施及护理可以提高患者的生存率,降低患者的伤残率及死亡率。     

二乙基二硫代氨基甲酸钠对沙土鼠脑缺血再灌注损伤的保护作用

蒙古沙土鼠脑缺血６０ｍｉｎ后，脑组织能量物质ＡＴＰ、ＡＤＰ明显下降，且有可检测的次黄嘌呤产生；氧在含量上有趋势。再灌注５ｍｉｎ，氧自由基含量显著增加；灌注３０ｍｉｎ时，ＡＴＰ、ＡＤＰ有所回，ＨＸ降至无法检测ＯＦＲ降于缺血组水平。     

Neurotoxicity of deoxycoformycin: effect of constant infusion on adenosine deaminase,adenosine, 2'-deoxyadenosine and monoamines in the mouse brain

The tight-binding adenosine deaminase inhibitor, 2'-deoxycoformycin (dCF), was continuously infused into mice by intraperitoneal implantation of microosmotic pumps delivering the compound at a rate of 0.16 mg hr^?1 kg^?1 for up to 6 days. The activity of cerebral adenosine deaminase was nearly totally inhibited. The amount of adenosine and 2'-deoxyadenosine was determined in the brain frozen in liquid nitrogen through the intact skull bone. The concentration of adenosine was about 1 $\text{nmol}\text{g}$, and was essentially not altered following treatment with deoxycoformycin. Deoxycoformycin induced a progressive increase in cerebral content of 2'-deoxyadenosine, which after 1 day of treatment equalled the amount of adenosine. The concentrations of serotonin, dopamine and noradrenaline in the brain were not altered.     

半胱氨酰白三烯受体拮抗剂对脑缺血的保护作用

炎症是影响脑缺血急性损伤严重程度以及慢性期恢复的主要因素之一,而半胱氨酰白三烯是体内最重要的炎症介质之一,通过半胱氨酰白三烯受体(CysLT1R和CysLT2R)调节脑缺血后炎症等病变。目前,已证实CysLT1R拮抗剂对脑缺血动物模型急性和亚急性/慢性损伤的保护作用,其神经元保护作用可能是间接通过调节胶质细胞,对星形胶质细胞增殖及胶质疤痕形成则有明确的抑制作用。CysLT2R拮抗剂还有待深入研究,但可能与神经元和星形胶质细胞损伤、小胶质细胞激活等有密切关系。CysLT1R和Cys-LT2R拮抗剂是抗脑缺血损伤潜在的新型治疗药物。     

参麻颈复方对脑缺血损伤小鼠的脑保护作用及其机制研究

目的 观察参麻颈复方颗粒对脑缺血损伤小鼠脑组织的保护作用,并探讨其可能机制。方法 将SPF级C57 BL/6雄性小鼠30只随机分为模型对照组、参麻颈组、尼莫地平组,采用电凝法制备小鼠脑缺血损伤动物模型,给参麻颈组、尼莫地平组小鼠灌胃14 d,应用TTC染色法检测各组小鼠脑梗死体积,提取骨髓内皮祖细胞并测定细胞功能,用蛋白免疫印迹法（Western blot）检测内皮祖细胞中蛋白表达水平。结果 与模型对照组比较,参麻颈组小鼠脑梗死体积明显减少,其内皮祖细胞迁移、黏附以及形成小管的能力显著改善,内皮祖细胞中BDNF蛋白表达水平明显升高。结论 参麻颈复方颗粒对脑缺血损伤小鼠脑组织具有保护作用,可能与调节内皮祖细胞中BDNF的表达,改善骨髓来源内皮祖细胞功能密切相关。     

阿哌沙班预防心房颤动患者的卒中

阿哌沙班是激活Ⅹ因子(Ⅹa)抑制剂,具有快速吸收、线性药代动力学、较少药物相互作用的特点。在不适合接受华法林治疗的心房颤动人群中所进行的随机对照试验证实,阿哌沙班在减少卒中和系统栓塞方面的疗效优于阿司匹林,安全性相似;在至少有1个危险因素的心房颤动人群中进行的与华法林的对照试验中,阿哌沙班可减少卒中和栓塞事件,主要是减少出血性卒中,同时减少重要出血和全因死亡。     

3-硝基丙酸预处理诱导沙土鼠脑缺血耐受与海马星形胶质细胞的激活

目的：探讨海马区星形胶质细胞的激活与3－硝基丙酸（3－NPA）预处理诱导脑缺血耐受的关系。方法：阻断沙土鼠双侧颈总动脉造成前脑缺血模型，通过HE染色和免疫组化观察海马锥体细胞死亡和星形胶质细胞的反应。结果：对照组海马CA1区已失去正常结构，锥体细胞大部分丧失，存活神经元计数显低于假手术组。3－NPA预处理组存活神经元减少，但高于对照组，假手术组海马CA1区仅见少量胶质原纤维酸性蛋白（GFAP）阳性细胞，染色较弱，突起不明显，对照组海马CA1区GFAP阳性细胞增多，多为弱阳性。3－NPA预处理组海马CA1区GFAP阳性细胞数目明显增多，染色较深，突起增粗。结论：星形胶质细胞形态和机能的改变可能与3－硝基丙酸预处理诱导脑缺血耐受有关。     

二十二碳六烯酸乙酯对脑缺血再灌注氧化损伤及脑水肿的影响

目的 研究二十二碳六烯酸乙酯(ethyl docosahexaenoate，E-DHA)对沙土鼠脑缺血再灌注引起的氧化损伤和脑水肿的保护作用。方法 采用沙土鼠双侧颈总动脉阻断法制作全脑缺血再灌注损伤模型。检测E-DHA对缺血再灌注后脑中丙二醛(MDA)和谷胱甘肽(GSH)含量；谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、ATP酶活性；水及Na^ 、Ca^2 含量的影响．并进行了病理检查。结果 缺血前E-DHA预防给药10周有效阻止了脑缺血再灌注引起的MDA升高，GsH降低，GsH-Px、CAT活性降低．ATP酶活性降低，水及Ca^2 、Na^ 含量升高。结论 E-DHA对沙土鼠脑缺血再灌注具有保护作用，其机理与清除自由基和减轻脑水肿有关。     

后颅窝注血法建立大鼠蛛网膜下腔出血后早期脑损伤模型

目的建立一种微创、有效、简单、重复性好的大鼠蛛网膜下腔出血后早期脑损伤动物模型。方法健康SD大鼠30只,随机分成正常对照组、假手术组和SAH组。采用后颅窝注血法建立蛛网膜下腔出血后早期脑损伤动物模型,记录一般情况、死亡率和神经行为学评分,24h后处死大鼠,开颅取脑观察大体标本,取大鼠脑干行HE染色,观察基底动脉的直径、血管壁厚度及病理结构变化。结果与正常对照组及假手术组比较,SAH组大鼠神经行为学评分明显降低（F=47.087,P〈0.05）,蛛网膜下腔可见弥漫性分布的血液或血凝块,主要分布于基底池及颅底蛛网膜下腔,基底动脉直径较正常对照组和假手术组明显减小（F=55.417,P〈0.05）,壁厚明显增大（F=18.341,P〈0.05）。结论采用后颅窝注血法可成功建立大鼠蛛网膜下腔出血后早期脑损伤模型。     

亚低温对缺血性脑卒中小鼠血脑屏障损伤保护作用

目的 探讨亚低温对缺血性脑卒中小鼠血脑屏障的保护作用,寻找亚低温发挥保护作用的机制。方法 选取由南通大学实验动物中心提供的SPF级别雄性C57/BL6小鼠54只,分为假手术组（n=18）和卒中组（n=36）,卒中组分为亚低温组（n=18）和常温组（n=18）。卒中组在行大脑中动脉阻塞手术后对亚低温组小鼠予以亚低温处理,在口腔温度监测下维持小鼠温度为（34±0.5）℃,其他组术后均置于保温毯上正常复温。术后每日对各组神经功能进行评分,同时使用错步时间检测卒中后小鼠行为运动功能。于术后第3天处死小鼠,取梗死脑区行蛋白质印迹法（Western blotting）检测血脑屏障黏附分子紧密连接蛋白（ZO-1）,紧密连接跨膜蛋白（Claudin-5）的蛋白表达以判断血脑屏障损伤的程度。结果 假手术组、亚低温组、常温组小鼠存活率分别为100%(18/18),94.44%(17/18),88.89%(16/18)。三组存活率比较,差异无统计学意义（χ2=53.72, P=0.122）。卒中组小鼠术后第1、2、3天神经功能评分[（2.8±0.2）、（2.6±0.3）、（2.4±0.3）分]明显高于假手术...     

Role of angiotensin II receptor subtype activation in cognitive function and ischaemic brain damage

Recent clinical studies have demonstrated that angiotensin II type 1 (AT(1) ) receptor blockers (ARBs) reduce the onset of stroke, stroke severity and the incidence and progression of Alzheimer's disease and dementia. We can expect that ARBs exert these effects by both AT(1) receptor blockade and angiotensin II type 2 (AT(2) ) receptor stimulation. Moreover, recent experimental results support the notion that AT(2) receptor stimulation with AT(1) receptor blockade could contribute to protection against ischaemic brain damage at least partly due to an increase in cerebral blood flow and decrease in oxidative stress, and prevent cognitive decline. Cellular therapy has been focused on as a new therapeutic approach to restore injured neurons. In this context, it has been reported that AT(2) receptor stimulation enhances neurite outgrowth and decreases neural damage, thereby enhancing neurogenesis. Moreover, additional beneficial effects of ARBs with an AT(1) receptor blocking action with a partial peroxisome proliferator-activated receptor (PPAR)-γ agonistic effect have been reported, and interaction of AT(2) receptor activation and PPAR-γ might be involved in these ARBs' effects. This article reviews the effects of regulation of activation of angiotensin II receptor subtypes on ischaemic brain damage and cognitive function, focusing on the effects of AT(2) receptor stimulation.     

多肽类药物在新生儿缺氧缺血性脑损伤中的研究进展

新生儿缺氧缺血性脑损伤是新生儿死亡和婴幼儿神经系统功能障碍的主要原因,目前唯一公认有效的治疗方法是亚低温治疗.近年来,随着新技术的发展,多肽类药物由于具有高选择性、高效性、耐受性好、制备简单、成本低等优点,得到了广泛关注.利用新生儿缺氧缺血性脑损伤模型的研究发现,多种多肽类药物可直接作用或通过与细胞穿膜肽结合进入神经细...     

脊髓腺苷受体介导侧脑室吗啡预处理对大鼠缺血后心肌的保护作用

目的探讨脊髓腺苷受体在侧脑室吗啡预处理对大鼠心肌缺血/再灌注损伤的保护作用中的介导作用以及与心肌缺血/再灌注损伤所引起的炎症反应的关系。方法健康♂SD大鼠54只,随机分为假手术组(Sham组)、对照组(CON组)、吗啡预处理组(MPC)、腺苷体阻断剂茶碱(theophylline,THE)+吗啡预处理组(MPC+THE组)、另设茶碱自身对照组,除茶碱自身对照组(6只)外,其他每组12只。每组观察指标包括:平均动脉压(MAP)、心率(HR),计算平均动脉压和心率乘积(RPP);心肌缺血危险区(AAR)、梗死区(IS)的体积,心肌梗死面积以IS/AAR表示;免疫组化测定心肌组织细胞间黏附分子(ICAM-1)的表达水平。结果与CON组相比,MPC组的IS和IS/AAR均明显下降(P<0.01),MPC+THE组分别明显低于CON组(P<0.01),高于MPC组(P<0.01),THE自身对照组与CON组相比差异无显著性(P>0.05);CON组心肌中的ICAM-1的表达水平明显高于Sham组(P<0.01),MPC组心肌组织中的ICAM-1的表达水平明显低于CON组(P<0.01),而MPC+THE组心肌组织中的ICAM-1的表达水平高于MPC组(P<0.01),低于CON组(P<0.01)。结论侧脑室吗啡预处理可以上调大鼠脊髓腺苷受体的激动水平,后者通过抑制心肌缺血/再灌注损伤的炎症反应,部分介导了侧脑室吗啡预处理对大鼠心肌缺血/再灌注损伤的保护作用。     

Prostaglandin EP1 receptor contributes to excitotoxicity and focal ischemic brain damage.

The clinical side effects associated with the inhibition of cyclooxygenase enzymes under pathologic conditions have recently raised concerns. A better understanding of neuroinflammatory mechanisms and neuronal survival requires knowledge of cyclooxygenase downstream pathways, especially PGE2 and its G-protein-coupled receptors. In this study, we postulate that EP1 receptor is one of the mechanisms that propagate neurotoxicity and could be a therapeutic target in brain injury. This hypothesis was tested by pretreating C57BL/6 wildtype mice with the EP1 receptor selective agonist ONO-DI-004 and the selective antagonist ONO-8713, followed by striatal unilateral NMDA injection. Results revealed that ONO-DI-004 increased NMDA-induced lesion volume up to 128.7 +/- 12.0%, while ONO-8713 significantly decreased lesion volume to 71.3 +/- 10.9%, as compared to the NMDA-control group. Neurotoxic EP1 receptor properties were also studied using C57BL/6 EP1 receptor knockout (EP1-/-) mice, which revealed a significant decrease to 74.5 +/- 8.2%, as compared to wildtype controls. The protective effect of the antagonist ONO-8713 was also tested in the EP1-/- mice, revealing no additional protection in these mice. Together, these results support the selectivity of ONO-8713 toward EP1 receptor and suggest the neurotoxic role of EP1 receptor. Furthermore, the EP1 receptor role in ischemic brain damage was investigated using a model of middle cerebral artery occlusion (MCAO) and reperfusion. The infarct volume was significantly reduced to 56.9 +/- 11.5% in EP1-/- mice, as compared to wildtype controls. This is the first study that demonstrates that EP1 receptor aggravates neurotoxicity and that modulation of this receptor can determine the outcomes in both excitotoxic and focal ischemic neuronal damage.     

丹参对肾缺血再灌注损伤细胞色素C氧化酶活性的影响

目的：研究丹参对大鼠肾缺血再灌注损伤细胞色素C氧化酶活性的影响。方法：复制大鼠肾缺血再灌注损伤模型，用丹参保护，观察分组织病理变化；测定血清MDA、BUN、CREA、SOD含量和分组织SOD、MDA含量和COX活力。结果：IRI组舌组织COX活力最低，与CON组、DS组及RI组比较均有非常显著性差异(P＜0．01)；CON组、DS组及RI组之间无差异(P＞0．05)。结论；应用丹参后肾缺血再灌注损伤细胞色素C氧化酶活性增高，脂质过氧化反应残轻，对肾缺血再灌注操作有保护作用。     

Stimulation of nucleoside efflux and inhibition of adenosine kinase by A1 adenosine receptor activation

Adenosine is produced intracellularly during conditions of metabolic stress and is an endogenous agonist for four subtypes of G-protein linked receptors. Nucleoside transporters are membrane-bound carrier proteins that transfer adenosine, and other nucleosides, across biological membranes. We investigated whether adenosine receptor activation could modulate transporter-mediated adenosine efflux from metabolically stressed cells. DDT1 MF-2 smooth muscle cells were incubated with 10 microM [3H]adenine to label adenine nucleotide pools. Metabolic stress with the glycolytic inhibitor iodoacetic acid (1AA, 5 mM) increased tritium release by 63% (P < 0.01), relative to cells treated with buffer alone. The IAA-induced increase was blocked by the nucleoside transport inhibitor nitrobenzylthioinosine (1 microM), indicating that the increased tritium release was primarily a purine nucleoside. HPLC verified this to be [3H]adenosine. The adenosine A1 receptor selective agonist N6-cyclohexyladenosine (CHA, 300 nM) increased the release of [3H]purine nucleoside induced by IAA treatment by 39% (P < 0.05). This increase was blocked by the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (10 microM). Treatment of cells with UTP (100 microM), histamine (100 microM), or phorbol-12-myristate-13-acetate (PMA, 10 microM) also increased [3H]purine nucleoside release. The protein kinase C inhibitor chelerythrine chloride (500 nM) inhibited the increase in [3H]purine nucleoside efflux induced by CHA or PMA treatment. The adenosine kinase activity of cells treated with CHA or PMA was found to be decreased significantly compared with buffer-treated cells. These data indicated that adenosine A1 receptor activation increased nucleoside efflux from metabolically stressed DDT1 MF-2 cells by a PKC-dependent inhibition of adenosine kinase activity.