实验性大鼠大脑皮层梗死后继发丘脑损害与DNA氧化损伤

目的观察大鼠大脑皮层梗死后丘脑腹后外侧核(ventroposterior nucleus of the thalamus,VPN)的继发性损害是否有DNA氧化损伤,并研究抗氧化剂依布硒啉(ebselen,EB)对这种远隔部位损伤是否具有改善作用。方法采用易卒中型肾血管性高血压大鼠(stroke-prone renovascular hypertensive rats,RHRSP),建立大脑中动脉皮层支闭塞(middle cerebral artery occlusion,MCAO)模型后分为:①假手术组,②模型组,③溶剂组,④抗氧化剂EB10mg.kg-1组,⑤抗氧化剂EB30mg.kg-1组,每组5只大鼠。2周后行肢体运动神经功能评估并取VPN后行尼氏染色,免疫组化检测VPN的8-羟基-2-脱氧马苷(8-hydroxy-2-deoxyguanosine,8-ohdG)表达。结果EB10mg.kg-1组和EB30mg.kg-1组神经功能评分优于假手术组(1.80±0.56,1.72±0.48vs2.28±0.33,P<0.05)。尼氏染色可见假手术组同侧VPN细胞形态规整。而梗死同侧VPN神经细胞出现细胞体积变小,胞核固缩,尼氏体退变为萎缩的深色细胞。EB30mg.kg-1组尼氏染色观察到改善作用。溶剂组同侧VPN的8-ohdG阳性细胞数目(0.1mm2)显著增加(146.8±12.1vs108.4±19.2,P<0.05);与溶剂组相比,EB10mg.kg-1组和EB30mg.kg-1组阳性细胞数目显著下降(123.6±14.7,123.4±17.4vs146.8±12.1,P<0.05)。结论实验性大脑皮层梗死后2周,同侧VPN存在DNA氧化性损伤。抗氧化剂EB对VPN的DNA氧化损伤有抑制作用,并可改善神经功能。     

脑创伤致迟发性脑梗死临床分析

目的探讨脑创伤后迟发脑梗死的发生机制,临床诊断及救治措施。方法对32例经影像学证实为颅脑创伤后迟发脑梗死患者的临床资料进行回顾分析。结果出院时按GOS标准评价:恢复良好12例、中残5例、重残4例、植物生存3例,死亡8例,其中非手术治疗20例,存活14例,死亡6例,死亡率30%;手术治疗12例,存活10例,死亡2例,死亡率17%。结论及时诊断与合理有效的治疗是提高脑创伤后迟发性脑梗死的治愈率及提高患者生存质量的关键。     

Functional magnetic resonance imaging based on changes in vascular space occupancy.

During brain activation, local control of oxygen delivery is facilitated through microvascular dilatation and constriction. A new functional MRI (fMRI) methodology is reported that is sensitive to these microvascular adjustments. This contrast is accomplished by eliminating the blood signal in a manner that is independent of blood oxygenation and flow. As a consequence, changes in cerebral blood volume (CBV) can be assessed through changes in the remaining extravascular water signal (i.e., that of parenchymal tissue) without need for exogenous contrast agents or any other invasive procedures. The feasibility of this vascular space occupancy (VASO)-dependent functional MRI (fMRI) approach is demonstrated for visual stimulation, breath-hold (hypercapnia), and hyperventilation (hypocapnia). During visual stimulation and breath-hold, the VASO signal shows an inverse correlation with the stimulus paradigm, consistent with local vasodilatation. This effect is reversed during hyperventilation. Comparison of the hemodynamic responses of VASO-fMRI, cerebral blood flow (CBF)-based fMRI, and blood oxygenation level-dependent (BOLD) fMRI indicates both arteriolar and venular temporal characteristics in VASO. The effect of changes in water exchange rate and partial volume contamination with CSF were calculated to be negligible. At the commonly-used fMRI resolution of 3.75 x 3.75 x 5 mm(3), the contrast-to-noise-ratio (CNR) of VASO-fMRI was comparable to that of CBF-based fMRI, but a factor of 3 lower than for BOLD-fMRI. Arguments supporting a better gray matter localization for the VASO-fMRI approach compared to BOLD are provided.     

局灶脑缺血恢复期半影区小胶质细胞可塑性变化和bFGF表达规律探讨

目的 观察Wistar大鼠大脑中动脉永久性闭塞后不同时段，缺血半影区小胶质细胞和神经元形态学变化及bFGF在皮层和海马的表达规律。方法 将雄性Wistar大鼠48只，随机分为假手术对照组和永久性局灶性脑缺血组，后者再根据缺血时间不同分5个亚组。假手术组：仅暴露大脑中动脉，2h后断头取脑。永久性局灶性脑缺血组：建立大鼠大脑中动脉闭塞模型，分别于缺血后3d、7d、14d、28d、42d断头取脑，行HE和免疫组化染色。观察梗死灶周围半影区的小胶质细胞和神经元的形态学变化和bFGF在皮层及海马部位的表达规律。结果 HE染色可见脑缺血3d时半影区有少量小胶质细胞出现，14d小胶质细胞增多达高峰，42d趋于稳定。脑缺血3d梗死灶周围皮质神经元和胶质细胞开始表达bFGF，7d表达增强，14d达高峰，28d表达开始减弱，42d仍有一定表达，bFGF在海马的表达也有相同规律。结论 小胶质细胞的肥大和增生性变化以及bFGF的表达，不仅发生于脑缺血早期，晚期仍显示持续性变化，表明小胶质细胞活动以及bFGF的表达贯穿于脑缺血的整个病理过程。     

脑卒中患者吞咽障碍及康复效果影像学研究

目的探讨电视X线透视吞咽功能检查（videofluoroscopic swallowing study,VFSS）在脑卒中患者吞咽功能评估中的应用价值,观察脑卒中后吞咽障碍发生情况,康复前后患者吞咽功能变化.方法脑卒中患者70例及健康成人80名分别作为研究组与对照组均进行VFSS,比较两组误吸等VFSS异常征象的发生情况.对发现误吸患者进行吞咽功能康复训练4周,训练后复查VFSS,比较训练前后吞咽异常的发生情况变化.结果对照组渗透或误吸、口腔滞留、咽腔滞留的发生率为5.0%,13.4%,25.3%.主要为轻度渗透及口咽腔滞留.研究组渗透或误吸、口腔滞留、咽腔滞留发生率为45.0%,46.5%,48.9%,主要为重度渗透或误吸,中重度口咽腔滞留.其中隐匿性误吸为10次（占总误吸的24.4%）.误吸患者康复治疗后渗透或误吸发生率较康复治疗前减少（P＜0.05）.结论脑卒中后吞咽障碍在康复期仍较为常见,可表现为多种影像学异常.VFSS可确切诊断吞咽异常,进行针对性康复训练,使患者吞咽功能提高.     

栓线法大鼠局灶性脑缺血模型的研究

采用颈部旁侧手术入路，结扎右侧颈总动脉、颈外动脉及其分支后颈内动脉栓线法制作大鼠大脑中动脉闭塞再灌流损伤模型。闭塞成功率９４．１％，动物偏瘫症状评分在缺血２ｈ再灌流３ｄ后趋于稳定，病理改变以尾壳核损害最重。再灌流７ｄ脑梗塞体积为９７．８±９．４ｍｍ３，动物死亡率５９．４％。缺血２ｈ后再灌流先出现过渡灌注，而后呈持续性低灌注。本文模型勿需开颅，缺血效果可靠，对局灶性脑缺血的研究具有实用价值。     

Developmental spectrum of the excitotoxic cascade induced by ibotenate: a model of hypoxic insults in fetuses and neonates

Ibotenate, a glutamatergic agonist, was used to study the spectrum of excitoxic disturbances at different ages of cerebral development. Cultures of whole mouse embryo were submitted to ibotenate at E8 for 20 h: during the phase of early premigratory differentiation; ibotenate did not induce any detectable histological lesion. During migration of supragranular neurons, newborn hamsters intracerebrally injected at P0 with ibotenate display neuronal migration disorders graded from nodular heterotopias to extensive laminar heterotopias mimicking some aspects of lissencephalic and double-cortex syndromes. After completion of neuronal layer V, P0 mice injected with ibotenate exhibit laminar neuronal depopulation of layer V-VIa mimicking human micro-gyria. At P5 in mouse, after completion of neuronal migration of the cortical plate, ibotenate induces neuronal loss in all cortical layers and the formation of porencephalic cysts. This study emphasizes the dramatic role played by glutamate in brain development, in the occurrence of neuronal migration disorders in the cortex. and in grey and white matter damage.     

Effect of amyloid peptides on the increase in TrkA receptor expression induced by nicotine in vitro and in vivo

The ability of nicotine to induce a cytoprotective or neuroprotective action occurs through several down-stream mechanisms. One possibility is that the drug increases the expression of tyrosine kinase A (TrkA) nerve growth factor (NGF) receptors. Certain β-amyloid peptides (e.g., Aβ1–42) have been shown to bind with high affinity to α7 nicotinic receptors and thus interfere with a potentially neurotrophic influence. Treatment of differentiated PC-12 cells with nicotine produced a concentration-dependent increase in cell-surface TrkA receptors that occurred concomitantly with cytoprotection. The effect of nicotine was blocked by either of the α7 receptor antagonists α-bungarotoxin (α-BTX) or methyllycaconatine. The cytoprotective action of nicotine also was inhibited by pretreatment with 10–100 nM Aβ1–42. Nicotine also was administered (four injections of 30 μg, spaced evenly over 24 h) to rats by direct injection into a lateral cerebral ventricle. Brain TrkA expression was increased significantly in hippocampus and entorhinal cortex (up to 32% above control), with no changes found in cerebral cortex or hypothalamus. The nicotine-induced increases in TrKA expression in hippocampus and entorhinal cortex were significantly inhibited by 10 μg α-BTX or by 10 nmol Aβ1–42. Therefore, physiologically relevant concentrations of Aβ1–42 can prevent nicotine-induced TrkA receptor expression in brain regions containing cholinergic neurons susceptible to the neurotoxicity associated with Alzheimer’s disease.     

Primary gastrointestinal lymphomas in Turkey: a retrospective analysis of clinical features and results of treatment.

Thirty-three patients with primary gastrointestinal lymphoma (GIL) followed at Ankara University Medical School have been evaluated. The most frequent locations of the disease are the small intestine (48.4%) and the stomach (39.3%). The intermediate and high grade lymphomas constitute 84.8% of the cases. The mean age of the patients with small intestinal lymphoma is 28.7 years and 47.1 years for those with gastric lymphoma. The patients treated with surgery and chemotherapy (S+CT) have a longer survival than those treated with chemotherapy (CT) alone. In conclusion: 1) Small intestinal lymphoma occurs more frequently than gastric lymphoma in our study. 2) The median age of the Turkish patients with primary GIL is approximately 10 years less than those in the Western countries. 3) The therapeutic results of S+CT are superior to those of CT in the early stages of the disease.