丙炔苯丙胺治疗帕金森病的临床研究

目的观察丙炔苯丙胺治疗帕金森病(PD)的临床有效性和安全性。方法采用随机对照的研究方法,对68例PD病人,分别给予丙炔苯丙胺和维生素E或单独维生素E治疗12周。治疗前后对所有PD病人进行统一PD评分量表(UPDRS-Ⅲ)评分、Hoehn-Yahr分级和Hamilton抑郁量表评分以评估药物疗效,同时观察不良反应。结果丙炔苯丙胺治疗组UPDRS-Ⅲ各项评分均较治疗前显著改善。治疗组12周后UPDRS-Ⅲ总分为(20.2±10.8)分与对照组(26.3±11.7)分比较有统计学意义。治疗组12周后总有效率(61.8%)显著高于对照组(14.7%,P<0.01)治疗组Hoehn-Yahr分级减级≥1级者15例(44.1%),与对照组3例(8.9%)相比有统计学意义(P<0.01)。丙炔苯丙胺对PD病人的部分抑郁症状有明显改善(P<0.01)。治疗组副反应的发生率(35.3%)显著高于对照组(5.9%P<0.01),但多数症状轻微,不影响治疗。结论丙炔苯丙胺对PD的主要症状震颤、少动和强直及伴随的抑郁症状有明显疗效,副反应主要为失眠、头晕等主观症状,多数较轻微。     

应用神经示踪技术观察先天性马蹄内翻足大鼠腓肠肌运动神经元的变化

目的观察先天性马蹄内翻足大鼠支配腓肠肌的脊髓运动神经元数量和形态的变化,为先天性马蹄内翻足病因学说中神经肌肉病变学说的研究提供客观依据。方法用全反式维甲酸(alltrans-Retinoicacid,at-RA)诱导大鼠产生先天性马蹄内翻足动物模型,将胎儿外科与显微注射技术相结合,对正常胎鼠和先天性马蹄内翻足胎鼠支配腓肠肌的脊髓运动神经元用荧光金(fluorogold,FG)进行逆行性神经示踪,留取脊髓标本进行冰冻切片,在荧光显微镜下进行FG标记神经元的定量计数和形态观察。结果荧光金标记的神经元主要分布在脊髓前角腹外侧区。RA致畸组中合并神经管发育异常的胎鼠,脊髓冰冻切片未计数到形态正常的FG标记神经元,实验中共有10只胎鼠;未合并神经管发育异常的胎鼠脊髓冰冻切片可观察到FG标记神经元,计数的实验胎鼠数量为25只,其神经元数量比对照组减少、细胞体积较小、突触间联系减少。神经元计数结果为:对照组FG标记神经元数量为(441±222)个;RA致畸组FG标记神经元数量为(266±134)个。结论腰骶段脊髓运动神经元的发育异常可能直接影响其支配部位的肌肉,产生肌肉结构异常和功能障碍,引起肌力不平衡导致足部骨骼形态的改变,最终形成先天性马蹄内翻足畸形的病理改变。     

γ-氨基丁酸对蟾蜍离体脊神经节神经元电活动的影响

在保留坐骨神经（Ｓｃ）和背根（Ｄｒ）的蟾蜍离体脊神经节制备上进行细胞内记录，用刺激Ｓｃ和（或）Ｄｒ的方法，诱发脊神经节（ＤＲＧ）神经元动作电位，观察局部γ 氨基丁酸（ＧＡＢＡ）灌注对该诱发电活动的影响。结果：ＧＡＢＡ灌注使ＤＲＧ神经元动作电位的振幅显著降低，持续期与后超极化显著增强，对刺激频率的跟随能力显著降低。结果提示：ＧＡＢＡ可能通过ＤＲＧ神经元胞体ＧＡＢＡ受体对ＤＲＧ突触传递发挥抑制作用     

Neuropeptide FF in the lateral spinal and lateral cervical nuclei: Evidence of contacts on spinothalamic neurons

Neuropeptide FF (NPFF, F8Famide) is best known for its modulating effect on opioid analgesia and morphine tolerance. However, the exact mode of action of NPFF in sensory transmission is not known. We compared the distribution of NPFF-immunoreactive (ir) fibers and terminal-like thickenings with the retrograde, tracer-filled spinothalamic (ST) neurons in the lateral spinal nucleus (LSN) and lateral cervical nucleus (LCN) of rat, areas where NPFF-containing nerve terminals are abundant. We injected fluorescent latex microspheres into the ventroposterolateral thalamic nucleus and more medial thalamic nuclei, which are innervated by ST neurons. We found NPFF-ir terminal-like thickenings and fibers apposing the tracer-filled neurons in the LSN and LCN. ST neurons filled with the retrograde tracer making contacts with NPFF-ir terminal-like thickenings, were found to terminate not only in the ventroposterolateral thalamic nucleus but also in more medial thalamic nuclei. The highest number of tracer-filled ST neurons having NPFF-ir terminal-like thickenings and fibers in apposition were found at the cervical level. Our results suggest that NPFF-containing systems in the spinal cord of rat are not limited to the substantia gelatinosa, and the sensory functions of NPFF may be mediated at least partly through the modulation of the ST system. NPFF-ir contacts in the LSN and LCN might play an important role in the somatic sensory transmission system. This study shows evidence for the first time that the spinal NPFF-containing system may be involved in mechanisms that control sensory input to the supraspinal levels. Received: 11 March 1997 / Accepted: 10 September 1997     

黎芦碱对分离的大鼠神经细胞内游离钙的影响

用Ｆｕｒａ－２双波长荧光法测得分离的大鼠神经细胞静息胞内游离钙浓度（［Ｃａ２＋］ｉ）为１１９．４±９．１ｎｍｏｌ·Ｌ－１（ｎ＝８）．藜芦碱（１０－４ｍｏｌ·Ｌ－１）可显著促进Ｃａ２＋内流而使［Ｃａ２＋］ｉ升高（Ｐ＜０．０１，ｎ＝８）；尼莫地平对静息［Ｃａ２＋］ｉ无影响．但能浓度依赖性地对抗藜芦碱所致［Ｃａ２＋］ｉ的升高。提示藜芦碱诱发的［Ｃａ２＋］ｉ升高由存在于神经细胞膜上的Ｌ型电压依赖性钙通道介导；尼莫地平可用以间接地保护神经细胞免受藜芦碱的兴奋毒性。     

Effects of modulators of Ca2+-activated, intermediate-conductance potassium channels on motility of the rat small intestine, in vivo

The movements of the intestine shift between different motor patterns, including between propulsion and mixing, but there is little information concerning mechanisms that may lead to changes in the patterns of motility. We have investigated the influence on intestinal motility of drugs that affect the after-hyperpolarization potential (AHP) of intrinsic primary afferent neurons (IPANs). The current of the AHP is carried by the intermediate conductance, calcium-activated, potassium (IK) channel. In anaesthetized rats, the IK channel blocker, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (0.05-1 mg kg(-1), i.v.) disrupted the regular propulsive pressure waves that occur in the small intestine and reduced propulsion of the contents (after 1 mg kg(-1), the fluid propelled was <25% of control). If the propulsion in the intestine was regular, the IK channel opener, 5,6-dichloro-1-ethyl-2-benzimidazolinone (DC-EBIO, 0.1 mg kg(-1) h(-1)) had no effect. DC-EBIO (0.1 mg kg(-1) h(-1)) restored propulsive activity after the nitric oxide synthase inhibitor, Nomega-nitro-l-arginine had changed motility to a mixing pattern. We suggest that the AHP determines the synchrony of action potential firing in synaptically coupled IPANs, and that this synchrony influences the patterns of firing of muscle motor neurons, and hence the pattern of contraction of the muscle and whether the pattern is predominantly propulsive or predominantly mixing.     

Calcium-binding proteins are concentrated in the CA2 field of the monkey hippocampus: a possible key to this region's resistance to epileptic damage

Summary Previous immunocytochemical studies have shown a heterogeneous distribution of parvalbumin (PA) and calbindin (CB) in the rat hippocampal formation. The results of the present study showed a heterogeneous distribution of PA and CB in primate Ammon's horn. The density and intensity of immunoreactivity for both of these calcium-binding proteins was greatest in CA2 as compared to CA1 and CA3. CB-immunoreactivity was localized to the cell bodies, dendrites, and axon initial segments of pyramidal cells whereas PA-immunostaining was found in the axon terminals, dendrites and cell bodies of interneurons that have features similar to GABAergic inhibitory neurons. Based on previous studies that have shown a protective role of calcium-binding proteins in neurons exposed to hyperstimulation, these results suggest that the resistance of CA2 pyramidal cells in temporal lobe epilepsy is due to the high concentration of CB and PA in this region of Ammon's horn.     

Mirror Movements of Hind Limbs of the Rat with Experimentally Induced Lumbosacral Agenesis

Abstract Neuropathological and electrophysiological studies were designed to clarify the pathomechanism of motor disturbance in the hind limbs of rats with sacral agenesis. The model animals were obtained from mother rats which had been treated with trypan blue on day 8 of gestation. Mirror movements in the hind limbs were observed in 7 out of 56 rats with lumbosacral agenesis. The conus medullaris in rats with lumbosacral agenesis ended at the level between Th13-L1 vertebra, whereas that in normal cases terminated between L3-4. The spinal cord of the lumbosacral region was hypoplastic and dysplastic particularly in the ventral half. Anterior horn cells were sporadic and there were no apparent median fissure in the spinal cord of the lumbosacral region. On the other hand, any abnormality was not found in the brain, the brain stem, and the spinal cord of the cervicothoracic region. Horseradish peroxidase (HRP) was injected into the unilateral hind limbs. In segments of the anomalous spinal cord, HRP-labeled neurons in the anterior horn were found not only on the injected side but also on the other side. In electrophysiological examination, F' wave was recorded on the non-stimulated side with longer latency and duration compared with that of the stimulated side. These morphological and physiological findings indicated that the mirror movements in the hind limbs of the model animals may arise from developmental errors of motor nervous pathway, with some deficient inhibitory mechanism in the upper neural system.     

出生后大鼠螺旋神经节神经元形态学研究

目的 证实出生后第2周是大鼠耳蜗螺旋神经节神经元发育的关键时刻。方法 选用60只出生后1—49d(postnatal day 1 to 49，PND l—49)的SD大鼠(分为10组)和6只成年(4月龄)SD大鼠。取平行蜗轴的中轴切片，光镜下观察螺旋神经节神经元形态；通过形态学测量神经元细胞面积、细胞核面积、Rosenthal隧道截面积并计数神经元，计算核浆比和细胞密度。结果 PND l—14大鼠神经元细胞面积逐渐增大；PND l—3大鼠细胞核面积较小，此后无明显变化趋势；PND 7大鼠细胞密度和核浆比明显下降，PND l4大鼠核浆比有明显下降。发育最早从钩回开始，逐渐向顶回发展。结论 出生后第2周是大鼠耳蜗螺旋神经节神经元发育的重要阶段。