基于动脉自旋标记技术的内侧颞叶癫痫病人脑血流灌注成像研究北大核心CSCD

基于动脉自旋标记(arterial spin labeling,ASL)技术,分析内侧颞叶癫痫(mesialtemporal lobe epilepsy,mTLE)患者大脑血流灌注(perfusion)的改变情况。在静息态下,采集了30例内侧颞叶癫痫伴单侧海马硬化发作间期患者(其中左侧16例,右侧14例)及22例健康志愿者的ASL数据,并通过计算获取其相对脑血流量(relative CBF,rCBF)及灌注不对称率(asymmetric index,AI)。癫痫病人与正常人的比较结果表明:左侧mTLE患者在两侧海马旁回、梭状回、额叶、颞叶和患侧海马回及岛叶,右侧mTLE患者在两侧海马回、海马旁回、额叶、颞叶和患侧杏仁核及岛叶,rCBF均有所下降,且患侧的下降程度和范围均大于对侧。说明mTLE患者的海马硬化可能导致了痫灶区功能异常,并通过癫痫的发作影响到全脑。     

十二井穴刺络放血联合亚低温治疗对颅脑创伤急性期大鼠脑水肿的影响

目的:探讨十二井穴刺络放血联合亚低温对颅脑创伤(TBI)大鼠急性期脑水肿的影响。方法:将75只健康成年雄性SD大鼠随机分为5组(n=15):假手术组(Sham)、颅脑创伤组(TBI)、放血组(BL)、亚低温组(MIH)、放血联合亚低温组(BL+MIH)。采用电子脑皮质损伤撞击仪(eCCI)建立大鼠TBI模型,BL组于伤后即刻行十二井穴刺络放血,每日2次;MIH组在伤后即刻采用亚低温冰毯使体温降至32℃,持续干预6 h。伤后48 h分别采用核磁共振成像技术(MRI)观察脑水肿变化(n=3)、神经功能缺损评分(m NSS)观察行为学改变及干/湿重法测定脑含水量(n=8)、伊文思蓝染色(EB)检测血脑屏障通透性(BBB)(n=4)。结果:MRI显示,TBI组脑水肿及血肿明显,中线明显偏移;而干预组较TBI组水肿明显减轻,中线居中。与TBI组比较,各干预组m NSS评分均明显改善(P0.05),而且BL+MIH组优于单独BL和MIH组(均P0.01);各干预组脑含水量也有不同程度降低(P0.05),尤以MIH组和BL+MIH组降低最为显著(P0.01);各干预组血脑屏障通透性均有明显改善(均P0.01),而且MIH组和BL+MIH组显著优于单独BL组(P0.05,P0.01)。结论:十二井穴刺络放血和亚低温均可以降低神经功能缺陷评分,减轻脑水肿,降低血脑屏障通透性,对创伤性大鼠脑组织有保护作用,且二者联合治疗效果更加明显。     

低氧适应对家兔脑血流调节的影响

本实验用电磁血流量法观察了低氧适应对家兔脑血流(CBF)调节的影响。结果表明,高CO_2和低O_2高CO_2时,适应组CBF改变不明显,对照组CBF明显增加(p<0.01)。两组脑脊液pH(pH_(CSF))均明显降低(p<0.05和p<0.01)。对照组低O_2高CO_2时的CBF比单独高CO_2增加更多。低CO_2、低O_2低CO_2及低O_2时,CBF和pH_(CSF)均接近于安静值。以低pH值脑脊液(CSF)脑内灌注,对照组CBF趋于增加,适应组不增加。将CO_2饱和的人工CSF用于局部脑表面,适应组脑膜微血管无明显扩张,对照组明显扩张(p<0.01)。该结果提示,低氧适应家兔脑血管和CBF对脑细胞外液H~ 和/或对低O_2的反应降低。     

厄贝沙坦对脑损伤大鼠神经细胞凋亡的影响

目的:研究血管紧张素I受体(AT1)抑制剂厄贝沙坦对侧位液压脑损伤模型大鼠神经细胞凋亡的影响。方法:利用改良的侧位液压损伤装置建立大鼠颅脑损伤(TBI)模型,术前及术后给予厄贝沙坦治疗,用激光多普勒测定局部脑区血流(r CBF)的变化,术前及术后1、3、5和7d利用神经功能评分评估大鼠神经功能损伤,利用TUNEL染色检测大鼠脑细胞凋亡情况,利用Western Blot检测大鼠脑组织损伤周围区域活性caspase 3的表达。结果:与正常值相比,TBI手术后损伤局部脑区r CBF下降至30%(P0.05),神经功能评分显著降低(P0.05),损伤区周围脑组织TUNEL阳性细胞明显增多,活性caspase 3的表达显著增加(P0.05)。厄贝沙坦治疗组大鼠r CBF显著高于单纯TBI组,梗死区面积显著缩小,神经功能得到明显改善,损伤区周围脑组织TUNEL阳性细胞和活性caspase 3表达下降(P均0.05)。结论:厄贝沙坦预处理能够通过抑制凋亡发挥神经保护作用。     

CT灌注评价高碳酸血症模型下正常大鼠脑组织血流动力学变化

目的探讨CT灌注评价高碳酸血症模型下正常大鼠脑组织血流动力学变化的可行性;研究大鼠CT灌注参数变化率与α-SMA表达之间的相关性。方法 10只雄性SD大鼠,体质量250～300g,在吸入空气和吸入高浓度CO2混合气体(10%CO2和90%空气组成)后15min,分别使用GE16层Light Speed CT扫描仪对大鼠脑尾状核层面进行CT灌注扫描,原始图像经GE ADW4.2工作站Perfusion3.0脑部灌注软件处理后产生灌注曲线及伪彩图像,两次扫描前均测定大鼠的血液CO2分压、pH值等血气分析指标。检查结束后24h内,大鼠取脑固定,在尾状核中心层面切片,进行脑组织HE染色及鼠特异性SMA抗体免疫组化染色。应用SPSS11.5统计学软件进行分析:采用配对t检验,比较正常大鼠右侧尾状核在吸入空气和吸入高浓度CO2混合气体后CT灌注参数脑血容量(CBV)、脑血流量(CBF)、血管表面通透性(PS)和平均透过时间(MTT)的变化有无差异;采用Pearson相关分析分别检测大鼠右侧尾状核的SMA阳性血管染色计数与灌注参数CBV和CBF在CO2分压升高前后的变化率相关性。结果所有大鼠在吸入含10%CO2和90%空气的混合气体15min后,动脉血CO2分压均明显升高(t=9.39,P0.001),血浆pH值降低(t=13.49,P0.001)。正常SD大鼠右侧基底节区CBV、CBF、PS每100g组织分别为(10.28±4.01)mL、(304.95±88.77)mL/min、(0.26±0.37)mL/min,MTT值为(1.48±0.07)s;吸入10%CO2和90%空气的混合气体后右侧基底节区CBV、CBF值明显增加,每100g组织分别为(19.25±8.42)mL(t=4.92,P=0.001)和(507.33±167.94)mL/min(t=6.75,P0.001);吸入混合气体前后CBV、CBF增加百分比分别为(87.14±46.45)%、(65.75±22.05)%;PS及MTT变化不显著(P均0.05)。大鼠脑组织α-SMA阳性染色血管计数为(12.7±3.23)条/高倍视野。Pearson相关分析显示,正常脑组织的CBV和CBF变化率与其α-SMA阳性计数之间呈显著相关(r分别为0.652和0.890,P均0.05)。结论 CT灌注技术在改变血液CO2分压的条件下可以反映脑组织血流动力学变化;大鼠正常脑组织高碳酸血症前后CT灌注参数变化率与成熟血管数量相关。     

CT灌注成像与大鼠C6胶质瘤CD105表达的相关性

目的研究大鼠脑C6胶质瘤CT灌注参数的变化特征,分析CT灌注参数在评价C6胶质瘤血管生成中的价值。方法 20只雄性SD大鼠,随机分为肿瘤组和对照组。对照组通过立体定向仪于鼠脑右侧尾状核区注射10μL生理盐水,肿瘤组于鼠脑右侧尾状核区种植C6胶质瘤细胞复制大鼠脑胶质瘤模型,3周后两组大鼠分别在脑尾状核层面进行CT灌注扫描,大鼠脑组织进行HE染色及FVIII抗体和CD105单抗免疫组化染色。应用SPSS11.5统计学软件进行数据分析,P〈0.05有统计学意义。结果大鼠胶质瘤的CBV、CBF、PS及MTT值分别为（17.35±6.73）mL/100 g、（508.66±158.88）mL/min.100 g、（13.92±8.96）mL/min.100 g、（1.79±0.44）s;对照组大鼠右侧基底节CBV、CBF、PS及MTT值分别为（均数±标准差）分别为（10.28±4.01）mL/100 g、（304.95±88.77）mL/100 g.min、（0.26±0.34）mL/100 g.min、（1.48±0.07）s,两组CBV、CBF、PS值差异有显著性,胶质瘤组呈现明显的高灌注特征,MTT差异无显著性。胶质瘤FVIII和CD105计数分别为（34.7±7.13）条/高倍视野、（16.6±4.12）条/高倍视野;对照组FVIII计数为（17.31±5.62）条/高倍视野,对照组无明显CD105染色阳性血管。肿瘤实质区的CBV、PS与免疫组化的FVIII-MVD和CD105-MVD计数之间明显相关（P均〈0.05）,CBF与CD105-MVD计数之间相关（P〈0.05）,MTT与免疫组化MVD计数之间均无显著相关性。结论 CT灌注参数CBV、CBF及PS与CD105-MVD表达正相关,CT灌注成像有助于胶质瘤血管生成的研究。     

磁共振灌注加权成像与弥散加权成像在脑胶质瘤分级诊断中的应用

目的:探讨磁共振灌注加权成像(perfusion weighted imaging,PWI)与弥散加权成像(diffusion weighted imaging,DWI)在脑胶质瘤分级诊断中的应用价值。方法:选取2012年1月-2017年6月在我院就诊并经病理证实为脑胶质瘤患者100例,其中高、低级别胶质瘤患者各44、56例。对所有患者行PWI、DWI检查,比较肿瘤不同区域表观扩散系数(apparent diffusion coefficient,ADC)、局部脑血流量(regional cerebral blood flow,rCBF),不同级别肿瘤实质区、瘤周水肿区rADC、rrCBF,根据ROC曲线分析rADC、rrCBF对不同级别胶质瘤的诊断阈值、敏感性、特异性。结果:与对侧相应正常脑实质比较,瘤周水肿区及肿瘤实质区ADC、rCBF均显著升高(P0.05);与瘤周水肿区比较,肿瘤实质区ADC、rCBF均显著升高(P0.05)。高级别肿瘤实质区rADC显著低于低级别肿瘤实质区(P0.05),rrCBF显著高于肿瘤实质区(P0.05)。高级别瘤周水肿区与低级别瘤周水肿区rADC间无显著差异(P0.05),高级别瘤周水肿区rrCBF显著高于低级别瘤周水肿区(P0.05)。在对高、低级别脑胶质瘤的分级中,rADC、rrCBF的曲线下面积(under the receiver operating characteristic curve,AUC)分别为0.957、0.978,均0.9。rADC诊断不同分级胶质瘤的敏感度是90.12%,特异度是95.26%,诊断阈值是13.12;rrCBF诊断不同分级胶质瘤的敏感度是92.31%,特异度是98.57%,诊断阈值是2.62。rADC与rrCBF诊断不同分级胶质瘤敏感度、特异度间无显著差异(P0.05)。结论:PWI、DWI能够为脑胶质瘤的分级诊断提供参考依据。     

正常大鼠脑CT灌注成像的可重复性研究

目的:评价多层螺旋CT灌注成像对正常大鼠脑血流动力学观测结果的可重复性.方法:分别对10只健康Wistar大鼠间隔2d进行CT灌注扫描,两组原始灌注数据由2名放射科医师分别进行5次后处理得出CBF、CBV和MTT值.分析观察者内和观察者间观测结果的可重复性,以及对同一组研究对象间隔2d两次检查结果的一致性.结果:多层螺旋CT对Wistar大鼠脑所采集的灌注原始数据在观察者内和观察者间观测结果均无统计学差别(P＞0.05),并具有很好的线性(CBF和CBV值)或等级(MTT值)正相关(P＜0.01).对同一组研究对象间隔2d的两次CT灌注成像结果也存在同样好的重复性.结论:多层螺旋CT灌注成像对于Wistar大鼠脑部血流动力学观测具有很高的精密度和准确性,完全适于小型动物模型脑部血流动力学的研究.     

冠状动脉狭窄程度和药物对频域心电图的影响

本实验在于阐明频域心电图(FCG)可以反映冠状动脉血流量(CBF)。狗的冠状动脉(CA)左前降支予以轻度狭窄,R_x、R_(xy)、F_(min)值都增大,说明FCG这些参数的变化比由CA左旋支狭窄引起的变化提前出现(左旋支在中度狭窄时才出现FCG的变化)。当狭窄程度达到中度或重度时,除了R_y在中度狭窄不发生明显变化外,其余指标都显著增大(p<0.05),F_(min)和R_(xy)增大程度尤其明显(p<0.01),心率(HR)和CBF显著下降,主动脉平均压(P_a)轻度下降。 在CBF减少的情况下,通过CA灌注硝酸甘油(8μg/min)10min后,HR、CBF、R_x、R_y、R_(xy),和F_(min)没有明显变化,而小冠状动脉远端平均压(P_c)降低(p<0.01),p_x、P_y也降低(p<0.05)。在相同情况下,灌注烟浪丁,HR和P_a几乎不变,P_c和CBF明显上升;除F_(min)外,FCG所有的指标都增大(p<0.05)。在CA狭窄的情况下,麦角新碱可诱发血管收缩,反映在P_a、HR和CBF轻度下降和P_c、P_x、P_y、R_x、F_(min)、R_y和R_(xy)显著上升,CA灌注麦角新碱(0.2μg/min)后,FCG的指标随着缺血程度的改变而变化。     

脉冲式及伪连续式动脉自旋标记技术静息态脑灌注对比研究北大核心CSCD

比较研究了脉冲式动脉自旋标记(pulsed arterial spin labeling,PASL)和伪连续式动脉自旋标记(pseudo continuous arterial spin labeling,pCASL)两种磁共振成像技术在静息态脑灌注中的应用。在静息态下,采用两种动脉自旋标记技术采集了10例健康志愿者的脑灌注数据,并计算脑血流量。两种技术的测量结果均显示,人脑默认网络中的楔前叶、角回、岛叶和后扣带回的相对脑血流量高于全脑平均灌注,而pCASL更敏感。在白质、额叶、顶叶、小脑和小脑蚓区域,pCASL和PASL测量得到的灌注值有显著性差异,除枕叶、小脑和小脑蚓外,PASL测量得到的灌注量小于pCASL。在全脑范围内,pCASL的信噪比明显高于PASL,且负灌注量很少。实验表明,pCASL可以提供比PASL更准确的测量结果。     

Brain abscess due to Nocardia

Cerebral Nocardiosis is a rare disease, usually occurring in immunocompromised hosts. We report here two cases of brain abscess due to Nocardia species-one due to usual N. asteroides and other by uncommon N. caviae. N. asteroides affected the brain in a post renal transplant patient, whereas N. caviae caused infection of brain in an apparently healthy individual. To the best of our knowledge, all the previous cases of brain abscess due to Nocardia caviae have been reported in compromised hosts. Agar dilution antimicrobial testing showed relatively higher resistant pattern in N. asteroides. In spite of antimicrobial therapy, both the patients succumbed, one within 4 days and other after an initial improvement for four weeks due to drainage of abscess.The technical assistance of Mr. R.K. Sapra and Mr. Pawan Kumar is greatfully acknowledged.     

力源精纯溶栓酶治疗急慢性脑梗死临床研究

目的　探讨力源精纯溶栓酶治疗急慢性脑梗死不同时期不同阶段的溶栓疗效。　方法　用力源精纯溶栓酶治疗脑梗死 50例 (急性期 3 1例 ,慢性期 1 9例 )为实验组 ,急、慢性期用药剂量不同 ;用川芎嗪治疗脑梗死 3 2例为对照组 ,进行疗效评定。　结果　基本治愈和总有效率 ,实验组分别为 2 1例 ( 42 %)和 4 3例 ( 86%) ,对照组分别为 9例 ( 2 8.1 3 %)和 2 1例 ( 65.63 %)。两组总有效率比较有显著性差异 ( P<0 .0 5)。急性期总有效率 80 .65%,慢性期总有效率 94 .74 %,急、慢性期疗效比较无差异 ( P >0 .0 5)。1例原有肝功能轻度损害病人用药后有出血倾向终止治疗。 1例原有乙肝病史病人用药 1 4天后出现一过性肝功能损害。凝血机制检查显示力源精纯溶栓酶可显著降低血纤维蛋白原 ,对血小板、凝血酶原时间延长影响甚微。　结论　力源精纯溶栓酶治疗急慢性脑梗死均有明显疗效 ,副作用少。肝肾功能异常者慎用或不用。该药是预防和治疗急慢性脑梗死快速、有效、安全的药物。     

TGF-β1基因SNPs与长沙汉族人群 脑卒中的相关性研究

目的:通过对长沙汉族人群TGFB1的多态分布规律的研究,从遗传流行病学的角度探讨TGFB1SNPs（单核甘酸多态性）与长沙汉族人群脑卒中的关系.方法:应用PCR、RFLP及DNA直接测序等方法对研究人群进行-509C＞T及+869T＞C基因分型.研究对象包括:脑梗死(CI)患者186例,脑出血(CH)患者202例,正常...     

Effect of Selective Brain Hypothermia on Regional Cerebral Blood Flow and Tissue Metabolism Using Brain Thermo-Regulator in Spontaneously Hypertensive Rats

To investigate the effect of selective hypothermia of the brain (brain cooling) on regional cerebral blood flow and tissue metabolism, we have developed a brain thermo-regulator. Brain temperature was modulated by a water-cooled metallic plate placed on the surface of the rats' scalp to get the appropriate brain temperature precisely with ease. Regional cerebral blood flow and brain temperature were measured simultaneously using a Teflon-coated platinum electrode and thermocouple probe inserted stereotaxically into the parietal cortex and thalamus in spontaneously hypertensive rats. Experimental forebrain ischemia was induced by the occlusion of bilateral common carotid artery under normo- and hypothermic brain condition, and the supratentorial brain tissue metabolites were measured enzymatically after 60 min of forebrain ischemia. When cortical temperature was set to hypothermia, cortical blood flow was significantly lowered by 40% at 30°C and 20% at 33°C as compared with that at 36°C (p < 0.0001 and p < 0.05, respectively). Thalamic blood flow was also significantly reduced by 20% when cortical temperature was set to 30°C as compared with 36°C (p < 0.05). There were no significant differences in arterial blood pressure and gas parameters throughout these experiments. In the rats with selective brain hypothermia (30°C) immediately after the induction of cerebral ischemia, the level of brain ATP concentration after 60 min of ischemia was significantly higher than that in normothermia rats (36°C) (p < 0.05). Our findings indicate that: 1) the metallic plate brain thermo-regulator is useful in small animal experiments; 2) regional brain temperature regulates regional cerebral blood flow; and 3) selective brain hypothermia, even started after the forebrain ischemia, ameliorates the derangement of brain metabolism, suggesting its effectiveness as a cytoprotective strategy.     

The role of thrombin and thrombin receptors in ischemic,hemorrhagic and traumatic brain injury: deleterious or protective?

In the last two decades it has become apparent that thrombin has many extravascular effects that are mediated by a family of protease-activated receptors (PARs). PAR-1, -3 and -4 are activated via cleavage by thrombin. The importance of extravascular thrombin in modulating ischemic, hemorrhagic and traumatic injury in brain has recently become clear. Thus, in vitro, thrombin at low concentration protects neurons and astrocytes from cell death caused by a number of different insults. In vivo, pretreating the brain with a low dose of thrombin (thrombin preconditioning), attenuates the brain injury induced by a large dose of thrombin, an intracerebral hemorrhage or by focal cerebral ischemia. Thrombin may also be an important mediator of ischemic preconditioning. In contrast, high doses of thrombin kill neurons and astrocytes in vitro and cause disruption of the blood-brain barrier, brain edema and seizures in vivo. This review examines the role of thrombin in brain injury and the molecular mechanisms and signaling cascades involved.     

Hand preference in a captive island group of chimpanzees (Pan troglodytes)

Morphological cerebral asymmetries in chimpanzee brains, similar to those found in humans, in whom they are associated with speech and handedness, suggest the possibility of functional lateralization in the chimpanzee. This possibility was investigated by examining hand preferences in an island group of five chimpanzees on a series of unimanual and bimanual tasks that are diagnostic of human hand and cerebral dominance. Each subject was tested in a double compartment cage on three unimanual nonsequential, three unimanual sequential, and three bimanual coordination tasks. One of the three unimanual sequential tasks was a bar-press task that is analogous to the commonly used human finger-tapping task. For the unimanual tasks, exclusive of the bar-press, the chimpanzees showed a highly individualistic pattern of hand preference that did not change as a function of task complexity. On the bar-press task, four of five subjects produced higher rates with one hand compared to the other; however, relative hand performance on this task was unrelated to hand preference on the other unimanual tasks. For the group of subjects, performance rates did not differ between the left and right hands; however, a practice effect was observed for the right hand in all subjects. The bimanual tasks also revealed a complex pattern of individual handedness, with no trends apparent for the group as a whole. Consistent with previous findings, the results from these tests on this group of five chimpanzees suggest that cerebral morphological asymmetries in the chimpanzee are not associated with motor dominance as reflected in handedness.     

A natural coumarin derivative esculetin offers neuroprotection on cerebral ischemia/reperfusion injury in mice

Previous studies have demonstrated that a natural coumarin compound esculetin (Esc) possesses antioxidant, anti-tumor, and anti-inflammation activities and rescues cultured primary neurons from NMDA toxicity. In this study, we investigated the neuroprotective effects of Esc on cerebral ischemia/reperfusion (I/R) injury in a middle cerebral artery occlusion model in mice. Esc (20 μg) was administered intracerebroventricularly at 30 min before ischemia. We found that Esc significantly reduced infarct volume and decreased neurological deficit scores after 75 min of ischemia and 24 h of reperfusion. Post-treatment of Esc still provided neuroprotection even when Esc was administered after 4 h of reperfusion. Our data also indicated that intraperitoneal administration of Esc showed protective effects on cerebral I/R injury in a dose-dependent manner. We further explored the protective mechanisms of Esc on cerebral I/R injury and found that Esc decreased cleaved caspase 3 level, a marker of apoptosis. Finally, our data demonstrated that Esc exerted its anti-apoptotic activity by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax, two apoptosis-related proteins. Because of its clinical use as an anticoagulant and its safety profile, Esc may have a therapeutic potential for the treatment of stroke in the future clinical trials.     

In vivo tracer studies of glucose metabolism,cerebral blood flow,and protein synthesis in naloxone precipitated morphine withdrawal

Quantitative autoradiography of [¹⁴C]deoxyglucose, [¹⁴C]iodoantipyrine, and [¹⁴C]leucine was used to estimate regional cerebral glucose metabolism, cerebral blood flow, and cerebral protein synthesis, respectively, in rats during morphine dependence and withdrawal. Glucose metabolism was elevated in 19 of 26 selected brain regions; the elevations in glucose metabolism were similar when data were expressed as either optical density ratios or as calculated rate values of mol/100 gm/min. Restraining the rats produced heterogeneous effects on glucose metabolism during morphine withdrawal (MW). Neither estimated cerebral blood flow nor cerebral protein synthesis were affected by morphine and/or naloxone treatments in either naive or morphine-dependent rats. The data demonstrate that changes in regional cerebral glucose utilization occur independently of blood flow changes and exclude the possibility that regional changes in glucose utilization occur as a consequence of large regional changes in protein synthesis rates in brain. These data confirm the utility of 2-deoxyglucose measures of MW as objective biochemical indices of opiate agonist and antagonist effects in vivo.