Functional improvement by electro-acupuncture after transient middle cerebral artery occlusion in rats

Abstract

Functional recovery by the application of electro-acupuncture (EA) on different acupoints was investigated using a transient middle cerebral artery occlusion (MCAO) model in rat. Acupoints were Baihui (D20) plus Renzhong (D26) (MCAO + D group), and Hanyan (G4), Xuanlu (G5), Xuanli (G6), plus Qubin (G7) (MCAP + G group). Animals with EA treatment showed significant functional improvements from 12 days after the reperfusion against those without EA treatment. Among EA treated groups, MCAO + G showed a more significant recovery than MCAO + D. Infarct volume revealed the significant reduction in the EA treated groups especially in MCAO + G at 30 days. Immunohistochemical study showed a remarkable induction of vascular endothelial growth factor (VEGF) in astrocytes of the peri-infarct area at 30 days, more in EA treated groups than in groups treated with MCAO alone. These results suggest that the acupoints applied in this study are effective for the functional recovery, and an enhanced expression of VEGF may play a certain role in recovery process after stroke.     

Human serum paraoxonase gene polymorphisms,Q192R and L55M,are not associated with the risk of cerebral infarction in Chinese Han population

Abstract

Objectives: It has been reported that human serum paraoxonase (PON1) gene is associated with coronary heart disease (CHD) and diabetes mellitus (DM). However, little is known about the role of PON1 gene polymorphism in cerebral infarction (CI). For this, we have investigated the relationship between PON1 gene polymorphisms, Q192R and L55M, and CI in Chinese Han population.

Methods: The PON1 genotypes, Q192R and L55M, from 153 CI patients and 153 healthy individuals, were determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Their allele frequencies were then determined. The association of the PON1 gene polymorphism with the risk of CI was analysed by statistical analysis software.

Results: The frequencies of PON1-Q192R genotypes in CI and control group are 13.7 and 9.8% (QQ), 51.6 and 53.6% (QR), 34.6 and 36.6% (RR) respectively. There is no significant difference in PON1-Q192R genotype (p=0.566) and allele frequencies (p=0.505) between CI patients and controls. The frequencies of PON1-55 genotypes in the CI and control group are 96.7 and 93.5% (LL), 3.3 and 6.5% (LM) respectively. No MM genotype was found in both CI and control group. No significant difference in genotype (p=0.289) and allele (p=0.296) distribution between CI patients and controls was observed.

Discussion: Our results suggest that the human serum paraoxonase polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in Chinese Han population.     

Neuroprotective effects of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), an antioxidant in middle cerebral artery occlusion induced focal cerebral ischemia in rats

Abstract

Objectives: In the present study, we have investigated the neuroprotective potential of 6hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), in middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia.

Methods: Sprague–Dawley rats were subjected to 2 hours of MCAO followed by 22 or 70 hours of reperfusion. After reperfusion, rats were evaluated for neurological deficits and cerebral infarction. Brain malondialdehyde (MDA) level and in situ terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) were also estimated.

Results: Focal cerebral ischemia produced a significant infarct volume and neurological scores as compared with sham-operated animals. Cerebral ischemia reperfusion injury was associated with an increase in lipid peroxidation in ipsilateral and contralateral hemisphere of brain along with an increase in TUNEL positive cells in ipsilateral hemisphere of brain sections indicating oxidative stress and DNA fragmentation, respectively. Trolox (10 and 30 mg/kg, i.p.) treatment significantly decreased neurological damage which was evident from the reduction in infarct volume and neurological score. Trolox (30 mg/kg) also attenuated oxidative stress and DNA fragmentation.

Discussion: Oxidative stress-induced neuronal damage is implicated in the pathophysiology of cerebral ischemia. Our study suggests that Trolox is a potent neuroprotective agent in focal cerebral ischemia and its neuroprotective effects may be attributed to the reduction of lipid peroxidation and DNA fragmentation.     

Application of non-invasive cerebral electrical impedance measurement on brain edema in patients with cerebral infarction

Abstract

Objective: To investigate the change of brain edema in patients with cerebral infarction by non-invasive cerebral electrical impedance (CEI) measurements.

Methods: An invariable secure current at a frequency of 50 kHz and an intensity of 0.1 mA was given into a person's brain. CEI values of the bilateral hemisphere of 200 healthy volunteers and 107 patients with cerebral infarction were measured by non-invasive brain edema monitor. The results of perturbative index (PI) converted from CEI were compared with the volumes of brain edema, which were calculated by an image analysing system according to magnetic resonance imaging or computed tomography.

Results: (1) In the healthy volunteers, PI values in the left and right hemisphere were 7·98 ± 0·95 and 8·02 ± 0·71 respectively, and there was no significant difference between the two sides (p>0·05). Age, gender and different measuring times did not obviously affect PI values (p>0·05). (2) In the cerebral infarction group, CEI measurements were more sensitive to the volumes of lesion, which were more than 20 ml. The positive ratio of PI was higher when the volumes of infarction were >20 ml (80·0%): the ratio of PI was 75·9% when the volumes of infarction were 20–50 ml and it was 83·3% when the volumes of lesion were more than 50 ml. PI was lower when the volumes were less than 20 ml. (3) PI of the infarction side increased obviously 3–5 days after onset; the difference of two sides was the most significant. There was a positive correlation between PI of the infarction side and volume of infarction.

Conclusions: PI may be a sensitive parameter for non-invasive monitoring of the change of brain edema in patients with cerebral infarction. CEI is a valuable method for the early detection of brain edema.     

大鼠脑梗死后神经前体细胞的增殖及电针作用的实验研究

目的　研究脑梗死病灶周围及海马处神经前体细胞增殖水平的动态变化及电针治疗对其的影响。方法　采用易卒中型肾性高血压大鼠 (RHRSP) ,电凝法凝闭大脑中动脉 (MCAO)。用Garcia等的综合评分法评定大鼠的神经行为学功能 ,免疫组化观察梗死灶边缘、对侧镜区及双侧海马 5 溴脱氧尿核苷 (Bromodeoxyuridine,BrdU)标记细胞的变化。结果　MCAO后大鼠轻偏瘫 ,5天时神经行为学功能恢复正常。MCAO后梗死灶边缘、双侧镜区及双侧海马均有BrdU阳性细胞分布 ,且病灶侧多于病灶对侧 ,病灶周围分布密集。电针治疗促使梗死灶边缘BrdU阳性细胞增多 ,随着治疗时间增加细胞增多更明显。结论　脑梗死可诱导病灶周边及海马神经前体细胞增殖水平上调 ,2周内神经前体细胞随着电针治疗时间的增加而增多。神经前体细胞可能是脑梗死康复的重要物质基础。     

The plasticity of posterior communicating artery influences on the outcome of white matter injury induced by chronic cerebral hypoperfusion in rats

Abstract

Objective: This study was performed to identify which factors are involved in the development of white matter lesions induced by chronic cerebral hypoperfusion in rats.

Methods: Male Wistar and Sprague–Dawley (SD) rats (250–270 g) were subjected to the permanent occlusion of bilateral common carotid arteries (BCCAO). The regional cerebral blood flow (rCBF) was measured by laser Doppler flowmetry and the plasticity of the posterior communicating artery (PcomA) was visualized by transcardiac perfusion of latex solution. For the histological examination, Klüver–Barrera staining was used to evaluate white matter damage.

Results: When compared with SD rats, Wistar rats showed lower rCBF after BCCAO, as well as thinner PcomAs. Moreover, 21 days after BCCAO, Wistar rats showed marked vacuolation of white matter in the optic tract, whereas SD rats had an almost intact optic tract.

Discussion: These results suggest that the plasticity of the PcomA and the reduction of rCBF in Wistar rats are important factors in the development of BCCAO-induced white matter lesions.     

电针对急性脑梗死大鼠皮层神经蛋白聚糖表达的影响

目的 探讨电针治疗对脑梗死后不同时间点神经蛋白聚糖(neurocan)表达的影响.方法 将90只SD大鼠采用随机数字表分为假手术组、大脑中动脉闭塞(MCAO)模型组、电针治疗组.用电凝法建立MCAO模型,选取内关、外关、足三里、三阴交四穴给予电针刺激,连续治疗4周.选取1、2、4周三个时间点用免疫荧光检测neurocan蛋白的分布,应用实时荧光定量RT-PCR、Western blot方法 检测neurocan tuRNA、neurocan蛋白的表达情况. 结果 neurocan主要分布于梗死灶周同区域的胶质细胞及细胞间隙.MCAO模型组neurocanmRNA表达在梗死后1周明显增高,且梗死后2周(0.806±0.224)表达达峰值,持续至梗死后4周仍表达仍增多;电针治疗组neurocanmRNA表达在电针治疗后1周明显降低,而后逐渐下降,至4周(0.031±0.018)达最低值.MCAO模型组neurocan蛋白表达明显增高.且有逐渐升高趋势,术后4周(0.878±0.049)达最高值;电针治疗组neurocan蛋白表达在电针治疗后2周明显降低,而后逐渐下降,至4周(0.292±0.042)达最低.以上差异均有统计学意义(P均<0.05). 结论 电针对脑梗死后neurocan的表达增加起抑制作用,这可能是电针抑制胶质瘢痕形成的机制之一.     

Post-operative changes of cerebral circulation and metabolism in the acute stage of low-grade aneurysmal subarachnoid hemorrhage

Abstract

Objective: Pre- and post-operative cerebral circulation and metabolism were evaluated in patients with low-grade acute aneurysmal subarachnoid hemorrhage (SAH) who underwent early surgery to investigate the effects on brain dysfunction.

Methods: Positron emission tomography (PET) was performed to measure the regional cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO₂), oxygen extraction fraction (OEF) and cerebral blood volume in four patients (one male and three females, mean age: 60.3 years) with low-grade SAH within 30 hours of onset. Post-operative PET was performed on the seventh post-operative day. No patient suffered clinical deterioration during the study. Pre-operative PET scans demonstrated significant global reduction of CBF and CMRO₂, compared to 16 normal control subjects, and no significant change in OEF. CBF and CMRO₂ reduction post-operatively improved to the normal control values. Post-operative OEF was significantly increased compared to the normal control value.

Conclusions: Patients with low-grade SAH have impairment of cerebral circulation and metabolism in the acute period, which improves after surgery. Early surgery for low-grade SAH, necessary to avoid rerupture of the aneurysm, did not worsen the impairment of cerebral circulation and metabolism. However, measures to protect the brain from perioperative damage are necessary to achieve the optimum outcome.     

高同型半胱氨酸血症对急性脑梗死近期预后的影响

目的:探讨高同型半胱氨酸血症(Hhcy)对急性脑梗死近期预后的影响,以期为脑梗死干预治疗奠定理论基础。方法:测定121例急性脑梗死患者和52例健康对照者空腹血浆总同型半胱氨酸,以此结果将患者分为Hhcy组和非Hhcy组,对两组患者神经功能缺损和日常生活能力进行追踪观察。结果:Hhcy和非Hhcy组患者发病3天内神经功能缺损和发病第7、14天神经功能缺损和日常生活能力评分无显著差异(P>0.05);发病第30、90、180天,Hhcy组神经功能缺损评分显著高于非Hhcy组,而日常生活能力评分显著低于非Hhcy组(P<0.05)。结论:Hhcy不利于急性脑梗死患者近期康复。     

脑梗死大鼠神经前体细胞增殖水平的研究

目的研究脑梗死病灶周围及海马处神经前体细胞增殖水平的动态变化。方法采用易卒中型肾性高血压大鼠(RHRSP)，电凝大脑中动脉(MCA)主干制成脑梗死(MCAO)模型。行大鼠神经功能评定，免疫组化观察并计数梗死灶边缘、对侧镜区及双侧海马5-溴脱氧尿核苷(Bromodeoxyuridine，BrdU)标记的细胞。结果MCAO后大鼠神经功能评分减低，5d时恢复正常。MCAO后梗死灶边缘、对侧镜区及双侧海马均有BrdU阳性细胞分布，且病灶侧多于病灶对侧，集中分布于病灶周围。结论脑缺血可诱导神经前体细胞增殖并移向病灶，可能成为脑梗死恢复的重要物质基础。     

高同型半胱氨酸血症对急性脑梗死短期预后的影响

目的探讨高同型半胱氨酸血症(HHcy)与急性脑梗死患者短期预后之间的关系。方法测定165例急性脑梗死患者空腹血浆Hcy浓度,将患者分为HHcy组和非HHcy组,并在其入院时和治疗14d后进行改良Rankin量表(MRS)评分。结果入院时非HHcy组和HHcy组患者MRS评分中生活自理(MRS评分≤2分)人数和不能自理(MRS评分≥3分)人数的百分比之间无统计学差异(P>0.05),经相同药物治疗14d后,非HHcy组患者中生活自理人数的百分比较HHcy组患者显著升高(P<0.01),不能自理人数的百分比较HHcy组患者显著降低(P<0.01),非HHcy组患者中生活不能自理得到改善人数的百分比较HHcy组患者也显著升高(P<0.01)。结论HHcy组急性脑梗死患者的短期预后比非HHcy组差,降低HHcy对于缺血性脑血管病具有重要的预防和治疗意义。     

Failure to improve the effect of thrombolysis by memantine in a rat embolic stroke model

Abstract

Objectives: Partial and delayed recanalization is a regular finding after thrombolysis in stroke patients who may benefit from additional therapy with neuroprotectants. To translate this scenario into an experiment, memantine was combined with thrombolysis in an embolic stroke model and tissue outcome was assessed in terms of complete and incomplete damage.

Methods: Tissue plasminogen activator (tPA, 5 mg/kg, b.w.) was administered 1.5 or 3.5 hours after embolic middle cerebral artery (MCA) occlusion in rats. In both groups, rats were assigned to additional therapy with memantine (10 mg/kg, i.p.) or saline injection. Ischemia and eventual reperfusion were continuously monitored by laser-Doppler flowmetry. Reperfusion was defined as a lasting increase in post-thrombolytic cerebral blood flow to >60% of baseline (complete) or to a lesser degree (partial). Experiments were terminated 6 hours post-occlusion to obtain quantitative histopathology.

Results: tPA induced complete or partial recanalization in 54% of treated animals. Successful reperfusion reduced total ischemic lesion volume by 42% compared with non-reperfused animals (p<0.05), but increased significantly the percentage of scattered neuronal injury from 25.6 (non-reperfusion) to 36.3% (reperfusion, p<0.05). Memantine did not improve the effect of tPA-induced recanalization on infarct morphology whether applied at 1.5 or 3.5 hours post-occlusion.

Discussion: We conclude from our experiments that add-on therapy with memantine did not alter the effect of thrombolysis in an embolic stroke model. Recanalization appears to be a prerequisite to confer neuroprotective effects.     

对照研究无症状性脑梗塞对抑郁症的影响

目的旨在探讨无症状性脑梗塞（ＳＣＩ）对原发抑郁症的影响。方法以３１例反复发作的抑郁症患者在合并ＳＣＩ后作为观察组，配对选择未合并ＳＣＩ的抑郁症患者作为对照组，并进行对照研究。结果观察组的焦虑激越、疑病、胃肠道症状、晨重夕轻、躯体不适等症状均显著比对照组多见（Ｐ＜０．０５）；而且入院和出院ＧＡＳ评分显著比对照组低（Ｐ＜０．０５）；好转、住院天数也显著延长（Ｐ＜０．０５）。结论观察组的抑郁症状严重，治疗困难     

急性脑梗死的基础性治疗

目的 研究急性脑梗死规范化的基础治疗.方法 将发病24h内183例急性脑梗死患者随机分为规范组、非规范组;规范组按一般治疗、特殊治疗、护理规范处理; 非规范组是除规范组外其它方法,疗效判定指标为：近期疗效、远期疗效、病死率、住院天数、住院费用和并发症发生率.结果 在近期疗效,住院天数和住院费用,病死率和并发症发生率,规范组优于非规范组,远期疗效无显著差异.结论 对急性脑梗死进行规范化的基础治疗是有必要的.     

急性脑梗死的基础性治疗

目的研究急性脑梗死规范化的基础治疗。方法将发病24h内183例急性脑梗死患者随机分为规范组、非规范组;规范组按一般治疗、特殊治疗、护理规范处理;非规范组是除规范组外其它方法,疗效判定指标为:近期疗效、远期疗效、病死率、住院天数、住院费用和并发症发生率。结果在近期疗效、住院天数和住院费用、病死率和并发症发生率,规范组优于非规范组,远期疗效无显著差异。结论对急性脑梗死进行规范化的基础治疗是有必要的。     

影响急性脑梗死患者治疗效果的相关因素分析

目的 探讨影响急性脑梗死患者治疗效果的相关因素.方法 对360例急性脑梗死患者予以卒中单元规范化治疗;在治疗前、治疗14 d时进行美国国立卫生研究院卒中量表(NIHSS)评分,以及检测有关血常规、生化指标.采用多因素Logistic回归分析对与患者治疗后NIHSS评分相关的指标进行分析.结果 与治疗前比较,脑梗死各亚组的血浆脂蛋白[Lp(a)]、尿酸、D-二聚体(D-D)、超敏C反应蛋白(hs-CRP)水平明显降低;轻、中度亚组血糖及中、重度亚组直接胆红素水平明显降低;中度亚组三酰甘油、低密度脂蛋白(LDL)及重度亚组总胆红素水平明显降低(均P＜0.05).重度亚组治疗前的血同型半胱氨酸(Hcy)水平明显高于轻、中度亚组(均P ＜0.05).多因素Logistic回归分析显示,治疗后NIHSS评分与血糖、hs-CRP、Hcy、尿酸、D-D、LDL、Lp(a)水平相关(OR=1.235～4.042,P＜0.05～0.001).结论 血糖、hs-CRP、Hcy、尿酸、D-D、LDL和Lp(a)为影响急性脑梗死患者治疗效果的相关因素.     

重症脑梗死脑血流动力学的动态观察

目的:动态观察重症脑梗死脑血流动力学变化的特征和规律。方法:对42例急性重症脑梗死患者进行连续7天的TCD检测,20例正常人TCD检测数据作为正常组。结果:急性重症脑梗死患者脑血流速度减慢。血管阻力参数值(Pl、Rl)增大,病程的3～5天各指标变化达高峰。结论:根据脑血流动力学的特征性改变,表明重症脑梗死在病程早期就有不同程度的缺血性脑水肿发生,进展迅速,多在病程的3—5天达高峰:TCD用于床旁连续监测,可通过动态观察TCD参数变化,评价颅内压变化、判断预后。     

氢溴酸樟柳碱注射液对急性脑梗死患者NIHSS评分、改良Barthel指数和CTP参数的影响

目的 观察氢溴酸樟柳碱注射液治疗急性脑梗死的临床疗效。方法 将86例符合急性脑梗死诊断标准的患者随机分为治疗组和对照组,各43例,对照组仅采用常规治疗,治疗组在常规治疗的基础上加用樟柳碱注射液进行治疗,连用2周; 于治疗前及治疗后14 d依据美国国立卫生院脑卒中量表(NIHSS评分)对2组患者神经功能缺损程度进行评价,在治疗后14、30、90 d采用改良 Barthel 指数(MBI)对患者进行日常生活活动能力(ADL)进行评分,同时采用CT灌注成像(CTP)分析治疗前及治疗后14 d梗死区rCBF(局部脑血流量)、rCBV(局部脑血容量)、TTP(达峰时间)和MTT(平均通过时间)指标水平的变化。结果(1)在治疗后的14 d 2组患者NIHSS评分相比治疗前均下降,但治疗组显著优于对照组(P<0.05);(2)治疗后14 d治疗组较对照组rCBV、rCBF均增加,TTP、MTT均缩短(P<0.05);(3)在治疗后30 d、90 d 2组患者改良Barthel 指数(MBI)相比治疗前均呈现好转,但治疗组效果显著优于对照组(P<0.05)。结论 氢溴酸樟柳碱序贯治疗急性脑梗死能明显改善神经功能缺损症状,且安全有效。     

急性脑梗死溶栓治疗方案

抢救缺血半暗带是急性脑梗死现代治疗的主要目标。尽管在急性脑梗死早期，病变中心部位很快即出现坏死，但若及时恢复血流和改善脑组织代谢仍可避免梗死灶周围仅有功能改变的缺血半暗带组织发生坏死。缺血半暗带和中心坏死区是一个动态的病理生理过程，随着缺血程度的加重和缺血