脑缺血再灌注后大脑皮质环氧化酶-2的表达及川芎嗪的干预作用

目的:探讨环氧化酶-2(COX-2)在脑缺血再灌注损伤后的表达及其作用,为治疗缺血性脑病提供实验依据.方法:以线栓法制作大鼠大脑中动脉阻塞的局灶性脑缺血再灌注模型,采用免疫组织化学和神经行为相结合的方法,观测缺血再灌注侧大脑皮质内 COX-2 表达和神经功能的变化.结果:脑缺血再灌注组 COX-2 免疫阳性神经元在再灌注6 h后较假手术组明显增多,并随着再灌注时间的延长逐渐增加,再灌注24 h后达高峰;与模型组比较,川芎嗪治疗组 COX-2 的表达明显减少.结论:脑缺血再灌注后 COX-2 的表达较正常明显增多,是导致脑缺血再灌注损伤的因素之一,川芎嗪对大鼠脑缺血再灌注损伤有保护作用.     

大鼠脑缺血再灌注后环氧合酶-2促进E-选择素表达增多及灯盏花素的脑保护作用

目的 观察大鼠脑缺血再灌后环氧合酶-2（COX-2）对E-选择素（E-selectin）表达的影响及灯盏花素对COX-2及E-selectin的影响,探讨脑缺血再灌注损伤后, COX-2加重脑损伤的机制及灯盏花素的脑保护作用。 方法 48只清洁级SD大鼠随机分为假手术组、生理盐水组、SC-58125组、灯盏花素治疗组,在缺血2 h再灌注24 h时,神经功能学评分观察大鼠神经行为的变化,2,3,5-氯化三苯四氮唑（TTC）染色观察大鼠脑梗死灶体积的变化;免疫印迹法和酶联免疫吸附测定检测COX-2及E-selectin表达的变化。 结果 SC-58125组和灯盏花素治疗组神经行为学评分明显降低,脑组织梗死体积显著减小,COX-2和E-selectin的表达明显下降。 结论 脑缺血再灌注后,COX-2可能通过促进E-selectin的表达加重缺血区的炎症反应;灯盏花素可能通过抑制COX-2及E-selectin的表达而发挥脑保护作用。     

高血脂大鼠脑缺血再灌注损伤后Bcl-2和Bax的表达变化及灯盏乙素的影响

目的 观察高血脂大鼠缺血侧大脑皮质额叶内B淋巴细胞瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）的表达变化,探讨灯盏乙素对高血脂大鼠脑缺血再灌注损伤的保护作用。 方法 大鼠建立高血脂模型后,线栓法阻塞大脑中动脉建立脑缺血再灌注损伤模型,HE染色观察大脑皮质额叶的病理变化,免疫组织化学和免疫印迹法观察Bcl-2、Bax蛋白的表达变化,同时结合神经行为学评分和2,3,5-氯化三苯基四氮唑（TTC）染色观察大鼠的神经行为及脑梗死灶体积的变化。 结果 与假手术组相比,生理盐水组大鼠脑组织损伤加重,Bcl-2的表达明显减少,Bax的表达明显增高,同时大鼠的神经行为学评分和脑组织梗死灶体积明显增加（P<0.05）。与生理盐水组相比,灯盏乙素治疗组脑组织损伤减轻,Bcl-2的表达明显增多,Bax的表达明显减少,同时大鼠的神经行为学评分和脑组织梗死灶体积明显降低（P<0.05）。 结论 灯盏乙素对高血脂大鼠脑缺血再灌注损伤的保护作用可能是通过促进Bcl-2的表达,抑制Bax的表达实现的。     

脑缺血再灌注对大鼠下丘脑-垂体-肾上腺-胸腺轴的影响

为探讨脑缺血再灌注损伤对大鼠神经-内分泌和免疫功能的影响,本研究采用免疫组织化学和放射免疫等实验技术,从形态、结构和功能三个层次观察了脑缺血再灌注损伤时大鼠下丘脑-垂体-肾上腺-胸腺(HPAT)轴的变化。结果发现:脑缺血后6h、9h组大鼠垂体重量明显减轻;其下丘脑和垂体激素分泌细胞数量减少,体积缩小;脑缺血后血浆CRH、ACTH和CORT浓度呈一致性先短暂升高后持续下降,T细胞增殖能力、T细胞克隆形成率和IL-2活性明显下降,且上述改变缺血9h组重于6h组。当脑缺血恢复再灌注时,缺血3h再灌注组比缺血6h再灌注组恢复快。以上结果表明:①脑缺血再灌注时,HPAT轴先出现一短暂的激活过程,继而很快转入抑制状态;②脑缺血再灌注损伤后大鼠免疫功能受抑制;③缺血后恢复再灌注早,HPAT轴受损轻,恢复快。     

灯盏乙素对高血脂大鼠脑缺血再灌注损伤的影响及机制

目的:研究灯盏乙素对高血脂大鼠脑缺血再灌注损伤的影响,并探讨其机制。方法:喂养高脂饲料建立大鼠高血脂模型,线栓阻塞大脑中动脉复制大鼠脑缺血恢复血流后的再灌注损伤模型,随机分为假手术组、生理盐水对照组和灯盏乙素干预组,灯盏乙素干预组在再灌注开始时及再灌注12 h时由尾静脉注射灯盏乙素注射液(4 ml/kg),同时其他2组注射等剂量的生理盐水。神经功能学评分观察大鼠的神经功能变化,TTC染色观察大鼠的脑坏死灶大小变化,伊文思蓝染色观察大鼠血脑屏障的通透性变化,免疫印迹和RT-PCR观察大鼠大脑皮层内基质金属蛋白酶9(MMP-9)及MMP-9mRNA的表达变化。结果:再灌注24h时,与生理盐水对照组相比,灯盏乙素干预组MMP-9及MMP-9 mRNA的表达水平、神经功能学评分、脑坏死灶大小、血脑屏障的通透性均降低,差异有统计学意义。结论:高血脂脑缺血大鼠恢复血流后的再灌注损伤中,灯盏乙素可通过抑制MMP-9的表达,从而减轻脑组织的再灌注损伤。     

高血脂对大鼠脑缺血再灌注损伤后大脑皮质基质金属蛋白酶9表达的影响

目的:研究高血脂对脑缺血再灌注损伤后大脑皮质基质金属蛋白酶9(MMP-9)表达的影响,探讨高血脂加重脑缺血再灌注损伤的机制。方法:高脂饲料喂养和线栓法分别建立高血脂动物模型和局灶性脑缺血再灌注模型,采用蛋白印迹、TTC染色、EB染色以及神经行为学评分,检测MMP-9的表达和脑梗死体积、血脑屏障通透性及神经行为的变化。结果:与假手术组比较,单纯脑缺血再灌注组和高血脂合并脑缺血再灌注组大脑皮质MMP-9表达增加,再灌注2 h时开始增加,24 h时达高峰,48、72 h时降低。相同再灌注时间点,与单纯脑缺血再灌注组比较,高血脂合并脑缺血再灌注组大脑皮质MMP-9表达明显增加,且脑梗死体积、血脑屏障通透性及神经行为评分均明显升高。结论:高血脂可通过上调大脑皮质MMP-9的表达而加重脑缺血再灌注损伤。     

姜黄素对脑缺血再灌注模型大鼠的神经保护作用及其机制

目的:观察姜黄素对脑缺血再灌注大鼠模型的神经保护作用及其机制。方法:雄性SD大鼠随机分为3组:模型组、姜黄素组和假手术组,模型组采用血管内线栓阻断法制备大鼠局灶性脑缺血再灌注损伤模型,姜黄素组在缺血前1h腹腔注射姜黄素200mg/kg,随后每12h腹腔注射姜黄素60mg/kg(共5次)。再灌注后3h、24h和72h测定脑组织含水量、伊文斯蓝(EB)含量(反映血脑屏障破坏情况),免疫印迹法测定脑组织基质金属蛋白酶-9(MMP-9)表达水平。结果:脑缺血再灌注损伤大鼠脑组织含水量及EB含量增加,MMP-9高表达。姜黄素治疗能够减轻神经功能损伤,降低脑组织含水量和EB含量,并降低MMP-9表达水平(P<0.01)。结论:姜黄素通过降低脑缺血再灌注大鼠MMP-9表达水平及血脑屏障通透性,对脑缺血再灌注损伤起保护作用。     

大鼠脑缺血再灌注后诱导型环氧合酶和丙二醛的表达及川芎嗪的干预作用

目的 探讨脑缺血再灌注损伤后诱导型环氧合酶(COX-2)和丙二醛(MDA)的表达及其意义,为治疗缺血性脑病提供实验依据。 方法 以线栓法制作大鼠大脑中动脉阻塞的局灶性脑缺血再灌注模型,采用免疫印迹法和硫代巴比妥酸法以及与神经行为相结合的方法,观测缺血再灌注侧大脑皮质内COX-2和MDA的表达和神经功能的变化,2,3,5氯化二苯四氮唑(TTC)染色观测脑梗死体积的变化 结果 MDA与COX-2的表达呈正相关(r=0.910,P＜0.01)。COX-2和MDA在假手术组含量均较低,I 2h/R 6h两者均有明显升高,并随再灌注时间延长逐渐升高,在I 2h/R 24h达高峰,I 2h/R 48h 略有下降,但仍维持在较高水平;与I 2h/R 24h模型组比较,川芎嗪治疗组的脑梗死体积明显减小（P＜0.01),MDA含量明显降低（P＜0.01）。 结论 脑缺血再灌注后,COX-2和MDA的表达较正常组明显增多,是导致脑缺血再灌注损伤的因素之一。川芎嗪对大鼠脑缺血再灌注损伤有保护作用。     

普罗布考通过TGF-β1/Smad 2/3通路减轻大鼠脑缺血再灌注损伤

目的:探讨普罗布考对大鼠脑缺血再灌注(I/R)的影响及其可能机制。方法:线栓法建立大鼠大脑中动脉栓塞(MCAO)模型,用1.5、3 mg/kg普罗布考进行干预,将200只大鼠分为假手术组、I/R组、溶剂组、小剂量组(1.5 mg/kg)及大剂量组(3mg/kg)。术后15 min腹腔注射药物,于1、3、5 d和7 d取材。观察普罗布考对脑缺血再灌注炎性损伤急性期及恢复早期神经功能评分、梗死灶体积、脑组织水含量的影响,并用ELISA检测脑组织匀浆环氧酶(COX-2)和5脂氧酶(5-LOX)活性变化,免疫印迹检测各组TGF-β1和p-Smad2/3蛋白表达量的变化。结果:与假手术组比较,MCAO术后小鼠出现严重的神经功能障碍、脑水肿和脑梗死,COX-2和5-LOX蛋白表达显著升高,而TGF-β1和p-Smad2/3蛋白表达明显降低;与手术组比较,经普罗布考干预后,小鼠神经功能评分、脑水肿和脑梗死情况明显改善,COX-2和5-LOX蛋白表达明显降低,而TGF-β1和p-Smad2/3蛋白表达明显升高,且大剂量组优于小剂量组。结论:普罗布考能缓解大鼠脑缺血再灌注炎性损伤,其机制可能与激活TGF-β1/Smad2/3信号通路,抑制脑内COX-2与5-LOX的活性有关。     

川芎嗪对大鼠脑缺血再灌注损伤后大脑皮质Bc1-2表达的影响

目的:研究川芎嗪对大鼠脑缺血再灌注损伤后Bcl-2表达的影响.方法:以线栓法制作大鼠大脑中动脉阻塞的局灶性脑缺血再灌注模型,采用免疫印迹、2, 3, 5-氯化三苯四氮唑(TTC)、 H-E染色和神经行为相结合的方法,观测缺血再灌注侧大脑皮质内Bcl-2的表达、脑梗塞体积、脑组织结构及神经功能的变化.结果:与缺血再灌注组(I 2h/R24h)比较,川芎嗪组的Bcl-2表达明显增高,脑梗塞体明显缩小,脑组织的病理损伤和神经异常行为明显减轻.结论:川芎嗪可通过上调Bcl-2的表达,缩小脑梗塞的体积和减轻脑缺血区组织结构的损伤以及明显改善神经症状,对脑缺血再灌注损伤有保护作用.     

Asymmetry of the internal connections of the striate cortex of the cat in the projection zone of the center of the field of vision

Studies were carried out on the organization of the internal connections of the striate cortex in cats in the projection zone of the center (0–5°) of the field of vision by microintophoretic application of horseradish peroxidase to electrophysiologically identified orientational columns. The area containing neurons showing retrograde labeling in most cases extended in the mediolateral direction. Labeled cells were located in the upper (II, III) and lower (V, VI) layers of the cortex, and the shapes and orientations of the areas containing labeled neurons in these layers coincided. Spatial asymmetry was detected in the distribution of labeled neurons relative to the orientational column studied. Labeled cells were located predominantly medial to the columns, regardless of the distance from the projection of the area centralis. Considering the visuotopical map of field 17, the asymmetry detected here provides evidence that neurons in orientational columns have more extensive connections with neurons of the peripheral part of the cortex. An asymmetrical distribution of “silent” zones around the receptive fields of neurons in orientational columns is suggested, and that these appear to receive influences from the periphery of the visual field. Laboratory of Visual Physiology and Laboratory of Central Nervous System Morphology, I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Makarov Bank, 199034 St. Petersburg, Russia. Translated from Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 82, No. 12, pp. 23–29, December, 1996.     

Effects of the lesion of the postcommissural part of the septum on the behavior of the rat.

The effects of the lesion of the postcommissural part of the septum on behavior of the rat has been studied. Results may be summarized as follows. An increase in the exploratory behavior in the open field which decreases rapidly; a decrease in the number of defecations in this test and a decrease in time leaving a dark environment for exploration. In the shuttle box test, no facilitation of the acquisition, but a permanent and quite significant increase in the intertrial activity has been found. We conclude that the lesions tend to decrease the emotivity of the subjects. An interpretation on the basis of the species -- specific defensive reactions explains the transitory and permanent effects of the lesions on the spontaneous activity.     

Counterpointing the functional role of the forebrain and of the brainstem in the control of the sleep-waking system

This paper reviews the lifetime contributions of the author to the field of sleep-wakefulness (S-W), reinterprets results of the early studies, and suggests new conclusions and perspectives. Long-term cats with mesencephalic transection show behavioral/polygraphic rapid eye movement sleep (REMS), including the typical oculo-pupillary behavior, even when the section is performed in kittens prior to S-W maturation. REMS can be induced as a reflex. Typical non-rapid eye movement S (NREMS) is absent and full W/arousal is present only after a precollicular section. The isolated forebrain (IF) rostral to the transection exhibits all features of W/arousal and NREMS [with electroencephalographic (EEG) spindles and delta waves], arousal to olfactory stimuli, and including the appropriate oculo-pupillary behaviors. These features also mature normally after neonatal transection. REMS is absent from the IF. After deprivation there is NREMS pressure and rebound in the IF, but the decerebrate cat only shows pressure for REMS. Most IF reactions to pharmacologic agents are within expectations, except for the tolerance/withdrawal effects of long-term morphine use which are absent. In contrast, these effects are supported by the brainstem (i.e. seen in the decerebrate cat). In cats with ablation of the telencephalon, or diencephalic cats, delta waves are absent in the thalamus. EEG thalamic spindle waves are seen triggering S for only 4-5 days after ablation. Therefore, true NREMS is absent in chronic diencephalic cats although pre- and postsomniac behaviors persist. These animals are hyperactive and show a pronounced, permanent insomnia; however, a low dose of barbiturate triggers a dramatic REMS/atypical NREMS rebound. Cats without the thalamus (athalamic cats), initially show a dissociation between behavioral hyperactivity/insomnia and the neocortical EEG, which for 15-20 days exhibits only delta and slower oscillations. Fast, low-voltage W rhythms appear later on, first during REMS, but spindle waves and S postures are absent from the start, such that these cats also display only atypical NREMS. Athalamic cats also show barbiturate-sensitive insomnia. Cats with ablation of the frontal cortices or the caudate nuclei remain permanently hyperactive. They also show a mild, but significant hyposomnia, which is permanent in afrontal cats, but lasts for about a month in acaudates. The polygraphic/behavioral features of their S-W states remain normal. We conclude and propose that: (a) the control of the S-W system is highly complex and distributed, but is organized hierarchically in a well-defined rostro-caudal manner; the rostral-most or highest level (telencephalon), is the most functionally complex/adaptative and regulates the lower levels; the diencephalic/basal forebrain, or middle level, has a pivotal role in inducing switching between S and W and in coordinating the lowest (brainstem) and highest levels; (b) W can occur independently in both the forebrain and brainstem, but true NREMS- and REMS-generating mechanisms exist exclusively in the forebrain and brainstem, respectively; (c) forebrain and brainstem S-W processes can operate independently from each other and are preprogrammed at birth; this helps understanding normal and abnormal polygraphic/behavioral dissociations in humans and normal dissociations/splitting in aquatic mammals; (d) NREMS homeostasis is present in the IF, but only REMS pressure after deprivation persists in the decerebrate cat; (e) the thalamus engages in both NREMS and W; (f) insomnia in diencephalic cats is the result of an imbalance between antagonistic W- and S-promoting cellular groups in the ventral brain (normally modulated by the telencephalon); (g) the EEG waves, which are signature for each S-W state, appear to truly drive the concomitant behaviors, e.g. a hypothetical human IF could alternate between behavioral NREMS and W/arousal/awareness; (h) a role for REMS is to keep the individual sleeping at the end of the self-limiting NREMS periods. The need for accelerating research on telencephaling NREMS periods. The need for accelerating research on telencephalic S-W processes and downstream control of the lower S-W system levels is emphasized.     

Topical organization of the projections of neurons of the substantia nigra and the ventral field of the tegmentum of the midbrain to the head of the caudate nucleus of the cat

Neuroscience and Behavioral Physiology -     

Ultrastructure of the endothelium of the drainage system of the eye

The endothelium of the ocular drainage system (Schlemm’s canal, collector tubules, and aqueous veins) in primary juvenile glaucoma undergoes degenerative dystrophic changes with compensatory hypertrophy and proliferation at the initial stages of the glaucomatous process and atrophy and desquamation at advanced and terminal stages. Progressive decrease in the pinocytous function of endotheliocytes, reduction of the protein-synthesizing and mitochondrial compartments of the cytoplasm, and formation of autophagosomes reflect the process of endotheliocyte degeneration in general. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 5, pp. 574–577, May, 2008     

The development of the ligament of the head of the femur

The hip joints of 30 human male and female fetuses and stillborns between 20 mm and 350 mm crown-rump length were studied by light microscopy. The ligament of the head of the femur developed in situ as a condensation of mesenchyme at the end of the second month of intra-uterine life (IUL), and was vascularized by branches of acetabular vessels early in the fourth month. In the majority of fetuses older than 5.5 months IUL, vessels in the ligament passed a short way into the femoral head within cartilage canals, to supply a small region around the fovea capitis. The remainder of the head was supplied by vessels in canals from around the upper part of the neck. The ligament changed from predominantly cellular to fibrous during the last 4 months of IUL. This increase in strength suggested significant mechanical functions in utero: limitation of adduction-flexion and opposition to postero-superior dislocation were the most likely.     

Involvement of the striatum in the central regulation of the hormonal functions of the gonads

Studies reported here show that intrastriatal administration of corticoliberin to rats decreases the blood testosterone level. However, in conditions of chemical deficiency of dopaminergic transmission in the dorsal striatum induced by injection of 6-hydroxydopamine, the effect of this neurohormone did not appear. It is concluded that extrahypothalamic corticoliberin is involved in regulating the hormonal reproductive system acting via dopaminergic mechanisms. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 85, No. 4, pp. 594–597, April, 1999.