帕金森病大鼠模型额叶皮质内突触素与神经丝蛋白的表达变化

目的　研究帕金森病 (PD)额叶皮质内突触素 (SYN)与神经丝蛋白 (NF6 0、NF2 0 0 )的表达变化。　方法　大鼠分为模型组 10只和对照组 4只。模型组于 6 羟基多巴 (6 OHDA)毁损后 3～ 5周 ,利用免疫组织化学方法观察大鼠额叶皮质内突触素与神经丝蛋白的染色情况 ,并借助自动图像分析系统对其进行定量分析。　结果　模型组大鼠损毁侧额叶皮质内NF阳性纤维明显减少 ,着色浅淡 ,纤维变短、变细 ,SYN免疫反应物也明显减少 ,分布不均 ,同时两者免疫反应物校正光密度值 (CA)值 )均明显低于对侧和对照组同侧 (P <0 0 1)。　结论　PD大鼠损毁侧额叶皮质内突触素与神经丝蛋白表达显著降低 ,这可能是帕金森病人额叶皮质功能障碍的原因之一。     

皮质下缺血性脑血管病的磁共振波谱研究

目的:检测皮质下缺血性脑血管病(SIVD)患者和正常对照组不同脑区脑组织的代谢水平,探讨其与认知功能损害的关系。方法:采用多体素磁共振波谱(1 H-MRS)技术评测SIVD患者(SIVD组,n=32例)和体检健康人(对照组,n=21)额叶及顶叶皮质、白质的代谢物N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr);计算有关比值NAA/Cr、Cho/Cr,分析有无认知功能损害SIVD患者上述比值的变化。结果:(1)SIVD组额叶皮质、白质及顶叶皮质、白质各体素NAA/Cr比值明显低于对照组(P0.01);(2)SIVD组顶叶皮质及白质的Cho/Cr比值明显高于对照组(P0.01);(3)SIVD组有认知功能损害患者的额叶皮质和顶叶皮质、白质NAA/Cr比值显著低于无认知功能损害者(P值分别0.01、0.01、0.05),Cho/Cr比值的两者间差异无统计学意义(P0.05)。结论:SIVD患者脑组织存在NAA/Cr、Cho/Cr比值改变,且额叶皮质和顶叶皮质、白质NAA/Cr的下降与认知损害有关。     

大鼠额叶皮质损害的脑电功率谱和形态学研究

３５只ＳＤ大鼠随机分成三组：正常组、假损害组和损害组。采用机械抽吸法制作大鼠右侧额叶皮质损害模型。对各组大鼠分别进行脑电功率谱分析和比较．结果发现：正常大鼠和假损害大鼠两侧大脑半球δ、θ、α和β频段相对功率值相近似（Ｐ＞０．０５），ＤＴ／ＡＢ值（即δ＋θ／α＋β的绝对功率值之比）也相似（Ｐ＞０．０５），功率谱曲线两侧基本对称。额叶皮质损害大鼠损害侧δ、θ频段相对功率值较健例显著增高（Ｐ＜０．０５），α、β段相对功率值较健侧显著降低（Ｐ＜０．０５）；ＤＴ／ＡＢ值较健侧显著增加（Ｐ＜０．０５），功率谱曲线两侧明显不对称。额叶皮质损害后３天、２周、４用及８周功率谱分析结果无明显不同。形态学观察证实额叶皮质存在缺损区不因时间延长而自行修复．额叶皮质损害出现的脑功能障碍及损害区形态变化均不能自行修复，表明功能效应和形态结果相一致，提示脑电功率谱分析可作为临床和实验研究中评价脑功能的有效手段。     

移植间充质干细胞治疗帕金森病大鼠

目的移植骨髓间充质干细胞(MSCs)治疗大鼠帕金森病(PD)。方法将BrdU标记的MSCs移植到单侧注射6-OHDA制备的PD大鼠模型损毁侧纹状体内,由阿朴吗啡诱导大鼠的旋转行为,用免疫组化和免疫荧光法检测大鼠黑质TH的表达和移植细胞的存活、迁移和分化,用1H-MRS检测大鼠双侧纹状体N-乙酰门冬氨酸(NAA)、胆碱类化合物(Cho)、肌酸(Cr)的信号强度。结果骨髓MSCs定向移植术后8周,PD大鼠的旋转行为较术前明显改善,损毁侧黑质TH阳性细胞数较术前增加;BrdU阳性细胞散在分布于移植侧脑组织内,可表达神经胶质纤维酸性蛋白(GFAP)和微管相关蛋白2(MAP-2);PD大鼠损毁侧纹状体NAA/Cr较术前升高(P<0.05),Cho/Cr下降(P<0.05)。结论植入纹状体内骨髓MSCs能够存活并对PD模型大鼠有治疗作用。     

益精养血方对帕金森病大鼠多巴胺能神经元凋亡的影响

目的:研究益精养血方对帕金森病(Parkinson disease,PD)大鼠多巴胺能神经元凋亡的影响。方法:采用6-羟多巴胺制备的大鼠PD模型,实验分为模型组、实验(中药)组和正常组。正常组和模型组大鼠生理盐水灌胃,实验组大鼠益精养血方灌胃,各30 d。灌胃结束2周后行行为学检测,免疫组织化学方法观测黑质酪氨酸羟化酶(TH)、Bcl- 2、Caspase-3的表达,免疫电镜技术观察黑质多巴胺能神经元结构变化。结果:实验组大鼠的旋转圈数比治疗前明显减少;实验组损毁侧与健侧黑质TH阳性细胞数量较模型组显著提高;实验组损毁侧黑质Caspase-3表达的D值比模型组显著降低,而Bcl-2的表达与Caspase-3相反;免疫电镜观察TH免疫反应产物表达于黑质DA能神经元高尔基复合体质膜面及胞质内,电子密度较高,在正常组中多见,实验组较少,而模型组很少见。结论:益精养血方对PD大鼠多巴胺能神经元凋亡有明显抑制作用。     

大鼠中缝背核一氧化氮合酶神经元投射纤维在大脑皮质微血管的分布

目的：研究通过损毁脑干中缝背核(DR)，探讨中缝背核NOS阳性神经元是否投射分布于大脑皮质微血管。方法：将16只SD雄性成年大鼠分为实验组与对照组。对实验组大鼠中缝背核微量注射喹啉酸，饲养1w，灌注固定，然后将大脑及脑干作冠状冰冻切片，NADPH—d组化染色。结果：实验组大鼠的中缝背核被有效损毁，其NOS阳性神经元的数量减少了59．1％(P＜0．001)。额、顶叶皮质NOS阳性纤维终末减少了32．1％(P＜0．05)，其中附着于皮质微血管的NOS阳性纤维终未了减少了37．8％(P＜0．01)。而枕额叶皮质NOS阳性纤维终末也减少了32．8％(P＜0．05)，其中附着于皮质微血管的阳性纤维终末减少了39．4％(P＜0．01)。结论：位于中缝背核的NOS阳性神经元投射分布于大脑皮质微血管，可能参与大脑皮质血流量的调节。     

视觉诱发电位和1H磁共振波谱在枕叶癫痫的应用价值

目的：通过对枕叶癫痫患者进行视觉诱发电位（PVEP）和氢质子波谱分析（1HMRS）检查，分析二者在枕叶癫痫的应用价值。方法：19例患者进行PVEP、1HMRS和MRI检查。VEP检查分析其P100潜伏期和波幅；1HMRs测量双侧枕叶N-乙酰天门冬氨酸（NAA）、肌酸（Cr）和胆碱（Cho），得出NAA／Cr、NAA／Cho和NAA／（Cr＋Cho）的比值。选取年龄相应的健康人15例作为对照组，同样进行PVEP和1HMRS检查。分析患者组与对照组的P100潜伏期和波幅、NAA／Cr、NAA／Cho和NAA／（Cr＋Cho）比值的差异；分析P100潜伏期与NAA／（Cr＋Cho）比值的相关关系。结果：患者组NAA／Cr、NAA／Cho和NAA／（cr＋Cho）的比值与对照组比较有显著差异；P100潜伏期和波幅与对照组比较有显著差异；P100潜伏期延长与NAA／（Cr＋Cho）比值降低呈负相关。结论：PVEP和1HMRS检查联合应用可以提高枕叶癫痫诊断的可靠性，还可帮助定位，为MRI无可见病灶者行外科治疗提供依据；1HMRS在枕叶癫痫定位诊断方面较MRI更敏感；PVEP和1HMRS检查有较高的一致性。     

视觉诱发电位和1H磁共振波谱在枕叶癫的应用价值

目的：通过对枕叶癫痫患者进行视觉诱发电位（PVEP）和氢质子波谱分析（1HMRS）检查，分析二者在枕叶癫痫的应用价值。方法：19例患者进行PVEP、1HMRS和MRI检查。VEP检查分析其P100潜伏期和波幅；1HMRs测量双侧枕叶N-乙酰天门冬氨酸（NAA）、肌酸（Cr）和胆碱（Cho），得出NAA／Cr、NAA／Cho和NAA／（Cr＋Cho）的比值。选取年龄相应的健康人15例作为对照组，同样进行PVEP和1HMRS检查。分析患者组与对照组的P100潜伏期和波幅、NAA／Cr、NAA／Cho和NAA／（Cr＋Cho）比值的差异；分析P100潜伏期与NAA／（Cr＋Cho）比值的相关关系。结果：患者组NAA／Cr、NAA／Cho和NAA／（cr＋Cho）的比值与对照组比较有显著差异；P100潜伏期和波幅与对照组比较有显著差异；P100潜伏期延长与NAA／（Cr＋Cho）比值降低呈负相关。结论：PVEP和1HMRS检查联合应用可以提高枕叶癫痫诊断的可靠性，还可帮助定位，为MRI无可见病灶者行外科治疗提供依据；1HMRS在枕叶癫痫定位诊断方面较MRI更敏感；PVEP和1HMRS检查有较高的一致性。     

Mrh-aFGF对帕金森病大鼠中脑腹侧被盖区神经元的保护

目的探讨重组人改构体酸性成纤维细胞生长因子(Mrh-a FGF)对帕金森病(PD)大鼠中脑腹侧被盖区神经元病变的影响。方法将54只SPF级雄性SD大鼠随机分为对照组、模型组和治疗组,每组18只。6-羟基多巴胺(6-OHDA)分别注入大鼠左侧黑质和中脑腹侧被盖区后建立PD模型,侧脑室内注射Mrh-a FGF,用阿扑吗啡诱导旋转行为;Nissl染色法观察大鼠中脑腹侧被盖区神经元病理学改变;电子显微镜观察中脑腹侧被盖区神经元及突触超微结构的变化。结果模型组大鼠损毁侧中脑腹侧被盖区神经元数目较健侧明显减少(P0.05);治疗组术后1周、2周、4周损毁侧神经元数目均较模型组明显增加(P0.05);模型组大鼠中脑腹侧被盖区神经元超微结构明显受损,出现核固缩,粗面内质网扩张、脱颗粒,线粒体肿胀、嵴消失,以及突触前后膜肿胀、突触间隙消失,治疗组中脑腹侧被盖区神经元超微结构有明显改善。结论 Mrh-a FGF能减少PD大鼠中脑腹侧被盖区神经元的丢失,并改善其神经元的超微结构。     

猫丘脑中央外侧核内脊丘系终末与丘脑-皮质投射神经元之间的突触联系

本实验应用顺行溃变和HRP逆行追踪相结合的方法，首次在电镜水平对猫丘脑中央外侧核内脊丘系终末与丘脑-皮质投射神经元之间的突触联系进行了研究．在脊髓第4颈段刀切损毁一侧侧索和前索后，将HRP注射于同侧大脑前上薛氏回和中上薛氏回前端。在电镜下于损毁同侧中央外侧核内可见下列突触连结：（1）溃变的脊丘系轴突终末与标记树突形成的轴-树突触；（2）溃变的脊丘系轴突终末与非标记树突形成的轴-树突触，个别非标记树突含有突触小泡；（3）正常的轴突终末与HRP标记树突和胞体形成的轴-树突触和轮一体突触；（4）正常的两个轴突终末与HRP标记树突形成的轴-轴-树连续性突触；（5）非标记的含突触小泡的突触前树突与HRP标记树突形成的树-树突触。同时可见大量汇聚型突触复合体。本文首次报道在丘脑中央外侧核内，脊丘系终末与丘脑-皮质投射神经元之间存在着直接的突触联系。     

磁共振波谱评价大脑半球代谢物的偏侧优势

为了利用无创性的磁共振波谱成像技术研究大脑半球代谢物的非对称性,本研究对56例正常成年人行磁共振波谱成像,主要对双侧大脑半球的4个解剖区域:额叶、颞叶、枕叶及顶叶的代谢物天门冬氨酸(NAA)、肌酸(Cr)、胆碱(Cho)进行测量,并以Cr为内参照物比较NAA和Cho相对含量(NAA/Cr、Cho/Cr)的侧别差异。结果表明:双侧额叶之间的NAA/Cr存在显著性差异,而Cho/Cr无显著性差异;在双侧颞叶之间,这2种比值均存在显著性差异;双侧枕叶之间Cho/Cr存在显著性差异,而NAA/Cr无显著性差异;双侧顶叶之间的NAA/Cr存在显著性差异,而Cho/Cr无显著性差异。本研究结果提示双侧大脑半球的代谢物存在偏侧优势。     

Sequential proton MRS study of brain metabolite changes monitored during a complete pathological cycle of demyelination and remyelination in a lysophosphatidyl choline (LPC)-induced experimental demyelinating lesion model

Metabolite changes in rat brain internal capsule (ic) area were monitored using volume localized in vivo proton MR spectroscopy (MRS) in a lysophosphatidyl choline (LPC)-induced experimental demyelinating lesion model of multiple sclerosis (MS), during the early phase (pre-acute) as well as during the complete pathological cycle of de- and re-myelination processes. The N-acetyl aspartate (NAA) peak showed reduction during the early phase of the lesion progression (demyelination) until day 10 and increased thereafter during remyelination. However, choline (Cho) and lipid resonances showed increased signal intensity during the early phase and decreased during remyelination. A progressive reduction of the NAA/Cr metabolite ratio in lesioned rats was observed during demyelination (up to day 10) compared with before lesion (control), and the value increased thereafter during remyelination (from day 15). During this period, however, the Cho/Cr ratio was a higher until day 10 and subsequently declined and was close to that calculated before lesion creation. The changes in NAA/Cr and Cho/Cr metabolite ratios correspond to changes in the individual metabolite peaks such as NAA and Cho. The increase in the intensity of the choline resonance during the early phase is indicative of the onset of an inflammatory demyelination process, and its rapid decrease thereafter is due to reduction in the inflammatory process associated with remyelination. Similarly, the increase in the intensity of lipids during the pre-acute stage of the lesion is attributed to active demyelination, which significantly decreased during remyelination. These MR results correlate well with the histology data obtained.     

MRI and 1H-MRS detects volumetric and metabolic abnormalities of hippocampal sclerosis in temporal lobe epilepsy

Objective:To further investigate the ability of MRI and 1H-MRS techniques for presurgical evaluation of hippocampal sclerosis. Methods:MRI and 1H-MRS were performed on 30 healthy subjects to determine the confidence levels. Eight patients who were pathologically confirmed hippocampal sclerosis were then studied using the same protocols. The difference of hippocampal formation (DHF) was used to determine atrophy of hippocampus. Areas under the peak of N-acetylaspartate(NAA) ,Creatine(Cr) and Choline (Cho) were measured, and the ratios of NAA/Cr, Cho/Cr, and NAA/Cr+Cho were calculated. NAA/Cr+Cho value was applied to localize the seizure focus. Results:Two patients showed hippocampal atrophy according to DHF value. NAA/Cr ratio decreased significantly in ipsilateral hippocampus compared to that in contralateral hippocampus and control subjects(P＜0.01). Cho/Cr value increased in both ipsi-and contralateral hippocampus in comparison with that in control subjects(P＜0.01). NAA/Cr+Cho ratio, however, significantly reduced in both ipsi-and contralateral hippocampus(P＜0.01) with lowest NAA/Cr+Cho ratio in seizure foci. Six patients could be lateralized by reduced and/or asymmetric NAA/Cr+Cho value. Conclusion:1H-MRS should be a promising diagnostic tool to detect neuron abnormality.1H-MRS and MRI complement each other hi presurgical lateralization of epileptogenic lesion in epilepsy patients.     

Reduced brain glutamate in patients with Parkinson's disease

An understanding of the role played by glutamate (Glu) in idiopathic Parkinson's disease (PD) has remained somewhat elusive. Animal models of PD suggest that over-activity of Glu receptors complicates the motor symptoms of PD and that Glu blockade may be a pharmacologic target in PD, whereas patient autopsy studies have proved less convincing for changes in Glu. No previous 1H MRS patient studies have documented changes in glutamate. All but one of these previous studies were performed at 1.5 T. We performed 3 T 1H MRS of the posterior cingulate gyrus in 12 non-demented patients with PD and 12 age-matched, neurologically normal control participants. Glu, N-acetylaspartate (NAA) and choline-containing compounds (Cho) measured in reference to creatine + phosphocreatine (Cr) were determined from single-voxel proton MR spectra measured by PRESS at TE of 80 ms. The results show that the Glu/Cr ratio was reduced in patients with PD compared with controls (t = 2.54; P = 0.019), whereas no differences were observed in NAA/Cr or Cho/Cr ratios. These findings suggest that a reduction in Glu occurs in the cerebral cortex of patients with PD. (1)H MRS at 3 T should be investigated in future studies as a means of tracking the course of metabolic brain changes in association with progression of disease in patients with PD.     

Metabolite alterations in autistic children: a 1H MR spectroscopy study

PurposeThe purpose of this study was to assess the role of proton magnetic resonance spectroscopy (1H MRS) in the detection of changes in cerebral metabolite levels in autistic children.Material and methodsStudy group consisted of 12 children, aged 8–15 years, who were under the care of Pediatric Neurology Department and Pediatric Rehabilitation Department of Medical University of Bialystok. The diagnosis of autism was established by neurologist, psychiatrist and psychologist in every case. All patients matched the clinical criteria of the disease according to International Statistical Classification of Diseases and Related Health Problems (ICD-10). The control group included 16 healthy children aged 7–17. ¹H MRS was performed with a single-voxel method (TE-36, TR-1500, NEX-192). The volume of interest (VOI) was located in the frontal lobe regions, separately on each side.ResultsWe showed lower N-acetylaspartate/creatine (NAA/Cr), γ-aminobutyric acid /creatine (GABA/Cr) and glutamate/creatine (Glx/Cr) in the frontal lobes in the study group comparing with healthy controls. The ratio of myoinositol/creatine (mI/Cr) was increased in autistic children. No differences in choline/creatine (Cho/Cr) ratio in study group and controls were found. There was a correlation between age and NAA/Cr in autistic children (R=0.593 p=0.041). No significant differences in metabolite ratios between right and left hemisphere in ASD and controls were found.Conclusions¹H MRS can provide important information regarding abnormal brain metabolism. Differences in NAA/Cr, GABA/Cr, Glx/Cr and mI/Cr may contribute to the pathogenesis of autism.     

Aerobic Fitness and the Brain: Increased N-Acetyl-Aspartate and Choline Concentrations in Endurance-Trained Middle-Aged Adults

Engagement in regular aerobic exercise is associated with cognitive benefits, but information on the mechanisms governing these changes in humans is limited. The goal of the current study was to compare neurometabolite concentrations relating to cellular metabolism, structure, and viability in endurance-trained and sedentary middle-aged adults. Twenty-eight endurance-trained and 27 sedentary adults, aged 40–65 years, underwent general health assessment, cardiorespiratory fitness measurement, neuropsychological testing, and proton magnetic resonance spectroscopy (¹H MRS). ¹H MRS was used to examine N-acetyl-aspartate (NAA), creatine (Cr), myo-inositol (mI), choline (Cho), and glutamate (Glu) concentrations in frontal and occipitoparietal grey matter. Group differences in concentrations of NAA, Cho, mI, and Glu, calculated as ratios over Cr, were explored using ANOVA. There were no significant differences in global cognitive function, memory, and executive function performance between the groups. In comparison to sedentary adults, the endurance-trained group displayed significantly higher NAA/Cr in the frontal grey matter (F(1, 53) = 5.367, p = 0.024) and higher Cho/Cr in the occipitoparietal grey matter (F(1, 53) = 5.138, p = 0.028). Within our middle-aged sample, endurance-trained adults demonstrated higher levels of NAA/Cr in the frontal grey matter and higher Cho/Cr in the occipitoparietal grey matter. Higher levels of NAA may indicate greater neuronal integrity and higher cerebral metabolic efficiency in association with cardiorespiratory fitness, whereas increased Cho may represent increased phospholipid levels secondary to neural plasticity.     

Metabolic alterations in the visual pathway of retinitis pigmentosa rats: A longitudinal multimodal magnetic resonance imaging study with histopathological validation

Because retinitis pigmentosa (RP) has been shown to cause degenerative changes in the entire visual pathway, there is an urgent need to perform longitudinal assessments of RP-induced degeneration and identify imaging protocols to detect this degeneration as early as possible. In this study, we assessed a transgenic rat model of RP by using complementary noninvasive magnetic resonance imaging techniques, namely, proton magnetic resonance spectroscopy (¹H-MRS), to investigate the metabolic changes in RP. Our study demonstrated decreased concentrations and ratios to creatine (Cr) of N-acetylaspartate (NAA), glutamate (Glu), γ-aminobutyric acid (GABA), and taurine (Tau), whereas myo-inositol (Ins) and choline (Cho) were increased in the visual cortex of Royal College of Surgeons (RCS) rats compared with control rats (p < 0.05). Furthermore, with the progression of RP, the concentrations of NAA, Glu, GABA, and Tau, and the ratios of GABA/Cr and Tau/Cr significantly decreased over time, whereas the concentrations of Ins and Cho and the ratio of Ins/Cr significantly increased over time (p < 0.05). In addition, in RCS rats, NAA/Cr decreased significantly from 3 to 4 months postnatal (p < 0.001), and Cho/Cr increased significantly from 4 to 5 months postnatal (p = 0.005). Meanwhile, the ¹H-MRS indicators in 5-month postnatal RCS rats could be confirmed by immunohistochemical staining. In conclusion, with the progression of RP, the metabolic alterations in the visual cortex indicated progressive reprogramming with the decrease of neurons and axons, accompanied by the proliferation of gliocytes.     

Decreased frontal lobe ratio of N-acetyl aspartate to choline in familial schizophrenia: a proton magnetic resonance spectroscopy study

Neuropathological and neuroimaging studies suggest neuronal dysfunction in schizophrenia. N-acetyl aspartate (NAA) is a useful marker of neuronal dysfunction that can be measured with magnetic resonance spectroscopy (MRS). In the present study NAA, choline (Cho), phospho-creatine ((P)Cr), inositol containing compounds and glutamine/glutamate (Glx) were assessed in the left frontal lobe and basal ganglia of subjects with familial schizophrenia, family members with mixed psychiatric diagnoses, unaffected family members, and community controls. Concentrations of metabolites were analyzed and expressed as ratios. NAA/Cho, NAA/(P)Cr and Glx containing compounds showed a negative correlation with age in the frontal lobe. After covarying for age, subjects with schizophrenia had a significant reduction in the left frontal lobe NAA/Cho ratio compared with unaffected family members (P=0.018) as well as with community non-familial (P=0.037) controls. These MRS observations support the hypothesis of a disease-related neuronal deficit in the frontal lobe of schizophrenic patients, and relatively normal basal ganglia.