脑出血患者尿激酶型纤溶酶原激活物及其受体的变化

目的探讨脑出血患者血浆尿激酶型纤溶酶原激活物(uPA)及其受体(uPAR)的变化及临床意义。方法对64例脑出血患者和30例健康对照组应用酶联免疫吸附双抗体夹心法(ELISA法)定量测定血浆uPA和u-PAR的水平。结果脑出血组uPA含量(2866±788ng/L)和uPAR含量(3645±322ng/L)明显高于正常对照组的uPA含量(1075±244ng/L)和uPAR含量(877±216nP<0.01)。随脑出血患者病情严重程度的加重,血浆uPA和u-PAR的含量增高越明显。结论血浆uPA和uPAR的增高参与了脑出血时继发性损害,与脑出血患者的病情密切相关。     

Thrombolytic therapy with tissue plasminogen activator for prevention of vasospasm in experimental subarachnoid hemorrhage: Its efficacy and problems

Abstract

We investigated the efficacy of two different tissue plasminogen activators (t-PA) for preventing vasospasm after experimental subarachnoid hemorrhage (SAH) in rabbits. Intrathecal injection of Silteplase and Alteplase showed significant preventive action against vasospasm following SAH and thrombolytic effect. The low dose groups with both t-PA showed more preventive action on day 7 than the high dose groups. The data suggest that the determination of optimum dose of t-PA is essential in clinical use of t-PA. [Neurol Res 1996; 18: 342-344]     

水蛭提取液对实验性脑内血肿周围组织tPA、PAI-1的影响

目的探讨水蛭提取液对实验性脑内血肿周围组织组织型纤溶酶原激活物（tPA）、纤溶酶原激活剂抑制物1（PAI-1）的影响。方法采用成组设计的随机对照研究。用定量胶原酶注入大鼠尾状核来建立脑出血模型．酶联免疫吸附法、发色府物法检测血肿周围脑组织生化指标（tPA、PAI-1含量与活性）变化，RT-PCR法观察鼠脑血肿周围脑组织tPA与PAI-1 mRNA的表达，免疫组化法观察鼠脑血肿周围脑组织tPA蛋白的表达。结果水蛭提取液治疗组较生理盐水对照组能增加血肿周围脑组织tPA含量、提高其活性，促进血肿周围脑组织tPA mRNA表达，增强tPA免疫表达．而不影响PAI-1含量与活性或mRNA表达。结论水蛭提取液促进实验性脑内血肿吸收的机制可能为通过对tPA的转录、翻译及合成蛋白的加工修饰来激活内源性纤溶系统，对PAI-1无影响。     

The role of endogenous versus exogenous tPA on edema formation in murine ICH

To minimize the neurotoxic injury by clot-derived substances after intracerebral hemorrhage (ICH) on the surrounding brain tissue, minimally invasive neurosurgical protocols have evolved evacuating the hematoma by stereotaxic injection of a fibrinolytic agent such as recombinant tissue plasminogen activator (rtPA), followed by aspiration of the lysed clot. However, the possible contribution of the presence of exogenous tPA itself to the toxic effects of hematoma-derived factors complicates the rationale and efficacy of this therapeutic approach. To clarify the role of exogenous rtPA on edema development, we examined the extent of edema formation in a murine model of collagenase-induced ICH, which included tPA-deficient (tPA-/-) and wild-type (wt) mice. In 16 (7 tPA-/- and 9 wt mice) out of 32 mice, 1 mg/kg rtPA was injected into the hematoma 5 h after ICH induction followed by aspiration of the liquefied clot 20 min later. In the control group (8 tPA-/- and 8 wt mice), only collagenase was injected. The edema volume was quantified using SPOT software on Luxol Fast Blue and Cresyl violet-stained cross-sections 24 h, 3, and 7 days post surgery. Twenty-four hours after ICH induction, tPA-/- mice had a significantly smaller edema volume (P< 0.01), even when rtPA was administered. Between days 3 and 7 after ICH, exogenous rtPA exerts its edema-promoting effect irrespective of the underlying genotype and exhibits an extensive microglial activation adjacent to the clot. In conclusion, the role of the endogenous tPA appears to be limited to the early phase of edema formation, whereas exogenous rtPA is edema-promoting between days 3 and 7 after ICH.     

Thrombolysis for intraventricular hemorrhage after endovascular aneurysmal coiling

Objective and Importance: Current applications of lytic therapy for intraventricular hemorrhage (IVH) rely on exclusion of vascular abnormalities as etiology. Its use in patients with recently coiled aneurysms remains far from considered safe. We report a patient with subara chnoid hemorrhage (SAH) and massive IVH from aneurysmal rupture, which was safely treated with intraventricular recombinant tissue plasminogen activator (rt-PA) after endovascular coiling. We also review two other similar cases reported in the literature. Clinical Presentation: A 61-year-old man presented with a ruptured anterior communicating artery aneurysm causing SAH and IVH (Hunt & Hess grade IV, Fisher grade III with IVH). During coiling of the aneurysm, extravasation of contrast was noted on fluoroscopy. Follow-up head computed tomography (CT) scan showed casted ventricles. Once in the intensive care unit, the patient progressed to coma, which did not improve with external ventricular drainage alone. Intervention: After endovascular coiling of the aneurysm, intraventricular rt-PA was administered. Isovolemic injections of 2 mg rt-PA every 12 hours were performed for a total of four doses. No clinical or radiological evidence of worsening SAH/IVH was documented. At the time of discharge, the patient was awake but requiring assistance with activities of daily living. Conclusion: We report the safe administration of intraventricular rt-PA after endovascular coiling of a ruptured cerebral aneurysm. Two other similar cases were found in the literature and are reviewed. Hindrance of aneurysmal cavity thrombosis by early administration of rt-PA (increasing the risk of rerupture) remains a widespread concern. The lack of such instances should therefore be acknowledged. We propose that inclusion of such patients in trials assessing safety/efficacy of thrombolytic theray in the treatment of patients with intracranial hemorrhage should be carefully considered.     

静脉应用rt-PA联合亚低温治疗对急性脑梗死患者NIHSS评分、颅内压和血清SOD、MDA水平的影响

目的 探讨静脉应用rt-PA联合亚低温治疗对急性脑梗死患者NIHSS评分、颅内压和血清SOD、MDA水平的影响。方法 选取本院50例急性脑梗死患者并随机分为2组,每组各25例,其中对照组采用rt-PA静脉溶栓,观察组采用rt-PA静脉溶栓联合亚低温全身治疗1 d,观察时间分别为治疗1、3、7 d; 记录2组患者治疗前后的NIHSS评分、颅内压和血清SOD、MDA水平。结果 经过7 d的治疗后观察组患者的NIHSS评分、颅内压和血清MDA水平均显著低于对照组(P均<0.05); 观察组患者血清SOD水平显著高于对照组(P<0.05)。结论 静脉应用rt-PA联合亚低温治疗可能通过减轻患者的氧化应激反应而有利于急性脑梗死患者的预后。     

甲基强的松龙对急性脊髓损伤神经元保护作用的实验研究

目的探讨甲基强的松龙对急性脊髓损伤(ASCI)后神经元是否具有保护作用。方法大鼠随机分为2组，即模型组和正常对照组(N组)，模型组建立脊髓半横断损伤模型后又分两组，即激素治疗组(M组)，腹腔注射甲基强的松龙(MP)；模型对照组(B组)术后不做处理。每组大鼠观察损伤后3d、7d、15d和30d。取脊髓损伤部位标本做光镜病理组织学检查，观察正常神经元和变性神经元的数量变化。结果(1)B组在ASCI早期脊髓损伤区的灰白质被明显的破坏，有出血及坏死，可见多量空泡状细胞和溃变的神经纤维，部分组织液化。在损伤灶内见正常神经元及神经纤维的数量稀少，多数神经元呈现不同程度的变性乃至坏死。随着时间的延长，神经元数量进一步减少，胶质细胞增生形成疤痕，或者液化形成囊腔。病变常常累及对侧组织，而M组的脊髓损伤区组织结构的变化与B组基本相同。(2)在ASCI后3d，M组的正常神经元数量少于B组，变性神经元数量与B组相近；在损伤7d以后，随着时间的延长，B组的变性神经元数量减少的同时，正常神经元的数量稍有减少，而M组的变性神经元数量减少的同时，正常神经元数量有所增加。结论(1)MP对ASCI后的继发性组织结构破坏无明显的改善作用；(2)MP在ASCI早期能促使神经元的死亡，但在后期能增加正常神经元的数量，其机理有待于进一步研究。     

大鼠脑出血后脑血流和脑水分含量变化的研究

研究大鼠脑出血后局部脑血流量（ｒＣＢＦ）与脑水分变化的规律及影响因素。用立体定向法自体血回注建立大鼠脑尾状核出血模型，分别在２４ｈ内不同时限用氢清除法测定ｒＣＢＦ，干湿重法测定脑水分含量，发现出血后１０ｍｉｎ同侧ｒＣＢＦ即下降，１ｈ达最低水平，出血量大时对侧半球也有明显下降；双侧脑水分含量均明显增加，其高峰期晚于ｒＣＢＦ的下降。说明脑出血后迅速出现广泛的低灌注和脑水肿     

实验性大鼠脑出血后TNF-α、ICAM-1的表达和脑水肿的研究

目的:探讨TNF-α、ICAM-1在大鼠脑出血后脑水肿中的表达及意义。方法:利用立体定向技术建立中等 量大鼠自体尾动脉血脑出血模型(50μl),于脑出血后6h、24h、48h、72h处死大鼠,进行脑含水量测定,并于脑出血后3h、 6h、12h、24h、48h、72h、7d处死大鼠,进行TNF-α、IGAM-1的免疫组化染色,并对结果进行统计处理。结果:大鼠脑出血 后脑水肿于48h达到高峰;大鼠脑组织表达TNF-α也于48h达到高峰,高于假手术组,分别为58．4±6．19和2±1．12,P <0．01;ICAM-1表达72h达高峰,与假手术组比较存在显著性差异,分别为7．8±0．84和0．8±0．84,P<0．01。结论: TNF-α、ICAM-1在大鼠脑出血后血肿周围表达的高峰与脑水肿高峰存在时间上的相关性,提示高表达的TNF-α、ICAM- 1可能参与了脑水肿形成。     

水蛭素对大鼠实验性脑出血神经组织的保护作用

目的通过实验性大鼠脑出血模型研究水蛭素对脑出血后神经组织的保护作用。方法自体动脉血注入法建立实验性脑出血动物模型,而后实验组注入100U水蛭素,对照组注入生理盐水。于术后2d、3d和5d处死动物。分别行HE染色、caspase-3免疫组化染色和TUNEL染色。结果水蛭素干预组与对照组比较,血肿周围的细胞坏死和组织水肿明显减轻。各时间点caspase-3和TUNEL阳性细胞数均明显减少。结论脑出血后局部应用水蛭素可以减轻脑出血后的组织水肿,抑制神经细胞凋亡,对血肿周围的神经组织具有保护作用。     

Neural plasticity after spinal cord injury

Plasticity changes of uninjured nerves can result in a novel neural circuit after spinal cord injury, which can restore sensory and motor functions to different degrees. Although processes of neural plasticity have been studied, the mechanism and treatment to effectively improve neural plasticity changes remain controversial. The present study reviewed studies regarding plasticity of the central nervous system and methods for promoting plasticity to improve repair of injured central nerves. The results showed that synaptic reorganization, axonal sprouting, and neurogenesis are critical factors for neural circuit reconstruction. Directed functional exercise, neurotrophic factor and transplantation of nerve-derived and non-nerve-derived tissues and cells can effectively ameliorate functional disturbances caused by spinal cord injury and improve quality of life for patients.     

The effect of direct current field polarity on recovery after acute experimental spinal cord injury

Recent evidence indicates that direct current (DC) fields promote recovery of acutely injured central and peripheral nervous system axons. The polarity of the applied DC field may play an important role in modulating these effects. In the present study, the effect of DC field polarity on recovery of injured spinal cord axons was examined anatomically, electrophysiologically and behaviourly in a rat model. After a 53 g clip compression injury of the cord at T1, 30 adult rats were randomly and blindly allocated to one of three groups (n = 10 each): one group received implantation of a DC stimulator (14 microA) with the cathode caudal to the injury site; the second group received implantation of a similar stimulator with the cathode rostral to the injury site; and the third group received a sham (O microA) stimulator. Clinical neurological function was assessed by the inclined plane technique and axonal function was assessed by motor- and somatosensory-evoked potentials (MEP and SSEP). A quantitative assessment of axonal integrity was performed by counting neurons in the brain retrogradely labelled by the axonal tracer horseradish peroxidase (HRP) and by counting axons at the injury site. The inclined plane scores (P less than 0.0001), MEP amplitude (P less than 0.02), counts of neurons retrogradely labelled by HRP (P less than 0.0001), and axon counts at the injury site (P less than 0.01) were significantly greater in the group treated with a DC field with the cathode caudal to the lesion than in the other two groups. Conversely, the cathode rostral DC field caused a decrease in the number of neurons retrogradely labelled by HRP (P less than 0.05) compared to the sham and cathode caudal groups. These data confirm our previous finding that DC fields promote recovery of acutely injured spinal cord axons. Furthermore, the polarity of the applied field is of critical importance to this effect.     

实验性脑出血后大鼠行为学和血肿周围组织病理学的研究

目的观察大鼠脑出血后不同时间点神经行为学和血肿周围脑组织病理学的特点。方法将成年SD大鼠随机分为假手术组和脑出血组;脑出血组大鼠通过立体定向术向脑内注入VII型胶原酶制成脑尾状核出血模型,并按不同时间点（1、3、7、14、28d）分为5个亚组。采用神经功能评分和HE染色分别观察脑出血大鼠神经行为学和脑组织形态学的改变。结果与假手术组相比,脑出血组大鼠的神经行为学评分3d时最明显[3d与1、7d无明显差异（P〉0.05）;与14d和28d有显著差异（P〈0.05）]。脑出血后1d在尾壳核区域可见血肿形成,呈椭圆形或不规则形;3d时脑水肿明显;7d时血肿周围脑组织有胶质细胞增生;14d时血肿区逐渐形成不规则囊腔;28d时囊腔仍然存在,出血周边区见胶质细胞进一步增多。结论脑出血后神经行为学的改变、血肿及囊腔的形成与出血时间有关。     

静脉低剂量重组组织型纤溶酶原激活物治疗短暂性脑缺血发作的临床对照研究

目的观察短暂性脑缺血发作(TIA)患者采用静脉低剂量重组组织型纤溶酶原激活物(rt-PA)治疗后血浆t-PA、PAI-1在不同时间点的变化特点,评价其疗效及安全性。方法纳入试验的TIA住院患者42例,根据患者是否接受静脉低剂量rt-PA治疗分为rt-PA治疗组和阿司匹林对照组(每组21人),治疗组患者入院第1 d、2 d、3 d给予rt-PA 20 mg,静滴,1次/d,3 d后改为阿司匹林100 mg,口服,1次/d;对照组患者入院后即给予阿司匹林100 mg,口服,1次/d。两组患者均住院观察2周,有卒中危险因素者给予相应治疗。结果(1)治疗组与对照组患者血浆t-PA水平均高于正常,但治疗组患者的t-PA在第1 d和第3 d明显高于入院时水平和对照组,差别均有显著性意义(P＜0．05);治疗组与对照组血浆PAI-1水平间差别无显著性意义,但均高于正常水平。(2)治疗组患者第1 d TIA发作控制率为80．96%,对照组为66．67%。治疗组有效控制率为95．24%,对照组为90．48%。(3)治疗组未见主要不良事件发生。结论(1)静脉低剂量rt-PA治疗TIA可有效提高纤溶系统活性,抑制血栓形成;(2)静脉应用低剂量rt-PA是控制TIA急性发作的有效方法之一,且起效快、副作用小、安全性高。     

Decompression of the spinal cord improves recovery after acute experimental spinal cord compression injury

The value of decompression after spinal cord injury in patients is still an unresolved issue. It has previously been shown in our laboratory that functional recovery in rats after cord compression varied with both the force and time until decompression. However, the longest duration studied was only 15 minutes, which is far less than that usually encountered in clinical practice, and therefore, the present study was undertaken to determine the value of decompression after more prolonged periods of compression. A factorially designed experiment with five rats per cell was used with the clip compression injury model. Forces of 2.3, 16.9 or 53.0 gms were applied at C7-T1 until decompression was performed after 15, 60, 120, or 240 minutes of compression. Functional recovery was assessed weekly for 8 weeks using the inclined plane technique. Maximum and minimum performance limits were established in normal rats and rats with cord transection, respectively. Univariate analysis and multiple comparison tests were used to analyse the data. The major determinant of recovery was the force of the injury. For example, the animals injured by the 2.3 gm clip performed significantly better than those injured at higher forces for all times until decompression (p less than 0.0001), and there was a significant difference in recovery between the groups injured by the 16.9 and 53.0 gm clips, although only for the 15 minutes until decompression group (p less than 0.05). The time until decompression also affected recovery, but only for the lighter compression forces (2.3 and 16.9 gm). For example, animals decompressed after 60 minutes of 2.3 gm compression recovered significantly better than those decompressed after 240 minutes (p less than 0.05). Thus, if the initial injury force is small, decompression is beneficial even after prolonged injury.     

Diagnostics,treatment and secondary prevention of ischemic stroke in the Silesian Province,Poland between 2009 and 2015

Background

The available data on diagnostics and treatment of ischemic stroke (IS) in Poland come mainly from non-representative cohorts or are outdated.

重组组织型纤溶酶原激活剂静脉治疗轻型缺血性卒中患者的疗效分析

目的 观察轻型缺血性卒中患者重组组织型纤溶酶原激活剂（recombinant tissue plasminogen activator,rt-PA）静脉溶栓治疗的疗效及安全性。      

Prior use of 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase inhibitor, simvastatin fails to improve outcome after experimental intracerebral hemorrhage

Objective

Contrary to some clinical belief, there were quite a few studies regarding animal models of intracerebral hemorrhage (ICH) in vivo suggesting that prior use of statins may improve outcome after ICH. This study reports the effect of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor, simvastatin given before experimental ICH.

Methods

Fifty-one rats were subjected to collagenase-induced ICH, subdivided in 3 groups according to simvastatin treatment modality, and behavioral tests were done. Hematoma volume, brain water content and hemispheric atrophy were analyzed. Immunohistochemical staining for microglia (OX-42) and endothelial nitric oxide synthase (eNOS) was performed and caspase-3 activity was also measured.

Results

Pre-simvastatin therapy decreased inflammatory reaction and perihematomal cell death, but resulted in no significant reduction of brain edema and no eNOS expression in the perihematomal region. Finally, prior use of simvastatin showed less significant improvement of neurological outcome after experimental ICH when compared to post-simvastatin therapy.

Conclusion

The present study suggests that statins therapy after ICH improves neurological outcome, but prior use of statins before ICH might provide only histological improvement, providing no significant impact on neurological outcome against ICH.     

Neuroprotective effects of infliximab in experimental spinal cord ischemic injury

Reactive oxygen species (ROS) have been implicated in the pathogenesis of spinal cord injury after both ischemia–reperfusion (I/R) and trauma. This experimental study was designed to investigate the potential effects of infliximab, an anti-tumor necrosis factor-α agent, on I/R injury of the rabbit spinal cord. Eighteen New Zealand white rabbits were divided into three groups, each consisting of six rabbits: sham (no I/R), I/R, and infliximab (I/R + infliximab). Spinal cord ischemia was induced by applying an infrarenal aortic cross clamp for 30 minutes. At 48 hours after ischemia, animals were functionally evaluated using the Tarlov score. Changes in the spinal cord were observed by measuring tissue levels of malondialdehyde (MDA), glutathione (GSH), advanced oxidation protein products (AOPP), and superoxide dismutase (SOD) and by evaluating hematoxylin–eosin-stained sections. At 48 hours after ischemia, the Tarlov scores in the infliximab group were higher than those of the I/R group, MDA and AOPP levels in the I/R group were significantly higher than those in the sham and infliximab groups (p < 0.05), and SOD levels in the infliximab group were significantly higher than those in the I/R and sham groups (p < 0.05). The sham group had higher GSH levels than the infliximab group; however, the difference was not statistically significant (p > 0.05). Histological examination revealed that the infliximab group had significantly less vascular proliferation, edema, and neuron loss than the I/R group. These results indicate that infliximab may protect the spinal cord against injury in a rabbit I/R model.     

Relationship between preoperative status of the fibrinolytic system and occurrence of deep vein thrombosis after major abdominal surgery

This study comprised 50 patients subjected to major abdominal surgery, of which 13 developed deep vein thrombosis (DVT) according to the 125I-fibrinogen test. Plasma was sampled preoperatively, for the specific analysis of tissue plasminogen activator (t-PA) before and during venous occlusion. The recently described fast t-PA inhibitor and plasmin alpha 2-antiplasmin complex (PAP) were also measured. The result of the laboratory analyses were correlated to the development of DVT. From the data obtained it is concluded that the evaluation of t-PA release during venous occlusion is a poor predictive factor for the occurrence of DVT after major abdominal surgery. The level of the t-PA inhibitor appears to be raised in these patients, but the values obtained in this material were not related to the development of postoperative DVT. Patients with elevated PAP levels, as shown previously, have a lesser tendency to develop postoperative DVT.