下丘脑内基因转染对大鼠颞叶癫痫海马病理变化的影响

目的 探讨下丘脑过度兴奋对于颞叶癫痫海马病理变化的影响。方法 利用仙台病毒(HVJ)-脂质体转染法在下丘脑的乳头体内转染兴奋性氨基酸受体亚基GluR2Q，研究其对于海人酸(kainic acid，KA)致痫鼠海马病理变化的影响。结果 GluR2Q能加重KA引起的海马齿状回损伤，但是对CA1及CA3区神经元损伤有一定程度的改善作用。结论 GluR2Q可以使下丘脑兴奋性增强，通过对海马齿状回的抑制解除作用促进癫痫波在海马内的传播。     

下丘脑内基因转染对大鼠癫痫行为的影响

目的探讨下丘脑过度兴奋对于颞叶癫痫行为学变化的影响，从而进一步阐明下丘脑与颢叶癫痫的关系以及谷氨酸受体2亚基Q型(glutamate receptor 2Q，GluR2Q)在癫痫发病中的作用机制。方法20只Wistar大鼠随机分为海人酸(kainic acid or kainite，KA)组(KA对照组)与KA GluR2Q组，分别观察两组大鼠的癫痫行为。结果KA对照组大鼠癫痫发作程度较轻，主要以部分性发作为主且发作次数少，持续时间短，较少出现全面性发作。KA GluR2Q组大鼠癫痫发作程度剧烈，部分性癫痫发作较KA对照组更早、更频繁且由部分性发作转化为全面性发作的比率高于KA对照组。结论通过HVJ-脂质体基因转染技术将GluR2Q基因转染到下丘脑乳头体可以提高其兴奋性，并使该兴奋性冲动通过下丘脑与海马之间的联络纤维传导至海马齿状回及CA3、CA1区，使海马区原有的兴奋性加强，表现为癫痫行为的加重，从而促进了癫痫的发展及传播。     

GABA受体基因转染对癫痫大鼠皮层脑电的影响

目的探讨在下丘脑乳头体上核内转染γ-氨基丁酸(GABA)受体基因后对海人藻酸(KA)致痫大鼠皮层脑电产生的影响,从而为难治性癫痫的治疗开辟新的途径。方法在右侧杏仁核内注射KA制备癫痫动物模型作对照,GABA基因转染组则利用仙台病毒(HVJ)-脂质体转染法预先在下丘脑的乳头体上核内转染被脂质体包被的GABA受体基因,48h后在杏仁核内注射KA,两组大鼠分别进行皮层脑电测定。结果KA致痫组大鼠脑电在尖波的背景上出现持续性放电,GABA转基因组大鼠则以散发的尖波、棘波以及阵发性放电为主,出现持续性放电的时间明显缩短。结论下丘脑内转染GABA受体基因后可以抑制癫痫发作的程度。     

GABA受体基因转染对癫痫大鼠海马区病理变化的影响

目的探讨在下丘脑乳头体上核内转染γ-氨基丁酸(GABA)受体基因后对海人藻酸(KA)致痫大鼠海马病理变化的影响,从而为难治性癫痫的治疗开辟新的途径。方法在右侧杏仁核内注射KA制备癫痫动物模型作对照,GABA基因转染组则利用仙台病毒(HVJ)-脂质体转染法预先在下丘脑的乳头体上核内转染被脂质体包被的GABA受体基因,48h后在杏仁核内注射KA,两组大鼠分别进行HE染色观察。结果 GABA基因转染组大鼠海马区病理改变较KA对照组明显减轻。结论下丘脑内转染GABA受体基因后可以抑制癫痫发作的程度。     

大鼠海马干细胞移植治疗颞叶癫痫的初步研究

目的 通过神经干细胞移植至癫痫鼠后与宿主细胞的整合及其对损伤宿主的修复作用，为神经干细胞移植治疗癫痫提供理论依据。方法 分离、培养新生鼠海马干细胞，移植至海人酸(KA)所致癫痫模型鼠的右侧海马内，应用Timm、Nissl、HE染色及动态脑电记录仪记录脑电图。在光镜及电镜下比较正常对照组、移植组及KA未移植组大鼠，在移植后的1周、4周、8周及24周苔状纤维发芽(MSF)、海马CA3区锥体神经元损伤情况及海马、杏仁核的脑电变化。结果 海马干细胞的移植可以显著抑制KA引起的MFS，其抑制作用从移植后第4周开始，第8周时最强，持续至第24周；同时亦明显的减轻了KA所致的CA3区锥体细胞缺失，其作用在第8周最强；KA所致CA3区锥体神经元超微结构的损伤亦得到一定程度的修复；但是，干细胞的移植并未使宿主恢复到损伤前的水平，海马干细胞移植可减少癫痫动物脑电的痫性发放，并降低其癫痫波的波幅约50％。结论 神经干细胞移植对于KA诱发癫痫鼠具有显著的修复作用，其具体作用机制还有待于进一步的研究。     

大鼠颞叶癫痫模型的建立及评价

目的 探讨海马局部给药建立颞叶癫痫模型方法及其行为、形态学、脑电和影像学改变。方法 通过立体定向术向大鼠海马局部注射海人酸fKA）建立颞叶癫痫模型。观察其行为学、形态学、脑电和影像学改变情况。结果 KA注入海马后模型大鼠麻醉清醒后有典型癫痫发作表现：凝视、湿狗样抖动、口的咀嚼运动、点头、肢体阵挛等，随后表现为阵发性旋转，并身体立起、向上窜跳、跌倒、四肢抽搐，约8h后发作停止，逐渐恢复到正常大鼠状态。以后每周发作1-2次，主要为Ⅳ～Ⅴ级。同时有额叶皮层和海马的癫痫放电脑电图及病理、影像学表现。结论 大鼠脑内局部注入KA后癫痫发作明显，其行为表现、海马病理改变、脑电及影像改变类似人类颞叶癫痫．可作为较好的研究颞叶癫痫的工具。     

全脑照射治疗大鼠癫痫的实验研究

目的 观察20Gy外照射对大鼠癫痫模型癫痫发作的影响，并着重检测该剂量照射后大鼠脑皮层内兴奋性氨基酸类递质—谷氨酸含量的变化。方法 建立戊四氮慢性癫痫模型，继以用20Gy剂量对模型大鼠皮层进行垂直照射。照射后48h，观察大鼠对致癫刺激的反应，并在接受致癫刺激后30min，取大鼠皮层，利用高压液相检测其中谷氨酸含量。结果 癫痫模型大鼠接受20Gy照射后48h，其癫痫发作明显受抑制。谷氨酸的检测结果显示，未接受照射的模型大鼠，受到致癫刺激后，脑内谷氨酸含量明显升高；而照射后的模型大鼠，接受相同刺激，脑内谷氨酸含量却没有明显升高。结论20Gy外照射后48h即可抑制模型大鼠癫痫发作，其抑制作用可能与照射降低了脑内兴奋性氨基酸类递质—谷氨酸的作用有关。     

迷走神经刺激对癫痫大鼠行为及脑电图的影响

目的：观察颈部迷走神经干电刺激对癫痫大鼠行为及额叶、海马、杏仁核脑区放电的影响，为迷走神经刺激（Vagus Nerve Stimulation,VNS)抗痫机制研究提供理论依据。方法：利用脑立体定位手段，将电极埋入大鼠脑部双侧额叶皮质、海马和杏仁核，记录VNS前后由红藻氨酸（KA）诱发复杂部分性癫痫大鼠脑电变化并观察动物行为的改变。结果：VNS后大鼠癫痫强直－阵挛发作次数明显减少，首次发作潜伏期延长，癫痫发作平均持续时间缩短；VNS尤其对杏仁核放电有明显的抑制作用。结论：VNS能有效抑制KA诱发的复杂部分性癫痫发作，并且杏仁核可能是抑痫作用的关键核因。     

癫痫起因研究的新进展

人们已经认识到，幼儿期大脑的兴奋性相对增高，这种结构特点使脑在发育过程中容易受到外来刺激的损害，形成突触性和非突触性异常连接，导致神经元的过度同步化放电，引起癫痫。同样，在脑的发育过程中，兴奋性与抑制性受体的可塑性变化（包括向上调节和向下调节）可引起神经元兴奋环路的活性变化，导致脑内兴奋性与抑制性神经传导系统的失衡［１，２］。一、兴奋性神经传导的形成脑内兴奋性神经递质主要包括谷氨酸和天门冬氨酸。目前已发现多种谷氨酸的特异性结合受体。谷氨酸的两个核基端很易与不同的受体结合而发挥生物效应。其受体按其…     

癫痫大鼠不同脑区神经内钙离子浓度变化与细胞凋亡的相互关系

目的 探讨海人酸（KA）注射后至癫大鼠不同脑区细胞内钙离子浓度变化和细胞凋亡的关系及意义。方法 通过建立KA杏仁核注射至癫痫模型，采用Fluo-3和PI方法分别检测了致痫鼠胞内钙离子浓度(IECa^2 )和细胞凋亡发率。结果 实验组各脑区IECa^2 增高，细胞凋亡百分率也相应增高，与手术对照组相比，有明显差异。在KA注射1周内，随时间延长，IECa^2 和细胞凋亡百分率均呈逐渐上升趋势。结论 KA致癫痫鼠不同脑区IECa^2 增高与神经细胞凋亡呈正相关。     

Connections of the ventral telencephalon (subpallium) in the zebrafish (Danio rerio)

Connections of the medial precommissural subpallial ventral telencephalon, i.e., dorsal (Vd, interpreted as part of striatum) and ventral (Vv, interpreted as part of septum) nuclei of area ventralis telencephali, were studied in the zebrafish (Danio rerio) using two tracer substances (DiI or biocytin). The following major afferent nuclei to Vd/Vv were identified: medial and posterior pallial zones of dorsal telencephalic area, and the subpallial supracommissural and postcommissural nuclei of the ventral telencephalic area, the olfactory bulb, dorsal entopeduncular, anterior and posterior parvocellular preoptic and suprachiasmatic nuclei, anterior, dorsal and central posterior dorsal thalamic, as well as rostrolateral nuclei, periventricular nucleus of the posterior tuberculum, posterior tuberal nucleus, various tuberal hypothalamic nuclei, dorsal tegmental nucleus, superior reticular nucleus, locus coeruleus, and superior raphe nucleus. Efferent projections of the ventral telencephalon terminate in the supracommissural nucleus of area ventralis telencephali, the posterior zone of area dorsalis telencephali, habenula, periventricular pretectum, paracommissural nucleus, posterior dorsal thalamus, preoptic region, midline posterior tuberculum (especially the area dorsal to the posterior tuberal nucleus), tuberal (midline) hypothalamus and interpeduncular nucleus. Strong reciprocal interconnections likely exist between septum and preoptic region/midline hypothalamus and between striatum and dorsal thalamus (dopaminergic) posterior tuberculum. Regarding ascending activating/modulatory systems, the pallium shares with the subpallium inputs from the (noradrenergic) locus coeruleus, and the (serotoninergic) superior raphe, while the subpallium additionally receives such inputs from the (dopaminergic) posterior tuberculum, the (putative cholinergic) superior reticular nucleus, and the (putative histaminergic) caudal hypothamalic zone.     

Propranolol (Inderal) and clonidine (Catapressan) in the prophylactic treatment of migraine

Twenty-one patients continued a double-blind crossover study to compare the prophylactic effect on migraine of propranolol and clonidine. The daily dosage of propranolol and clonidine was 160 mg and 100 μg, respectively.
Statistical analysis did not show any significant difference between the two drugs in respect to headache or nausea. The number of sickleave days and the use of symptomatic drugs were both less on propranolol treatment than on clonidine, but there was no statistically conclusive difference.     

Hydroxyindole-O-methyltransferase (HIOMT), catechol-O-methyltransferase (COMT) and histamine-N-methyl-transferase (HNMT) in the pineal gland of the vizcacha

Summary The activities of three methylating enzymes HIOMT, COMT, and HNMT were determined in pineal glands from 2 groups of adult vizcachas of both sexes, one (I) maintained under permanent lighting (15 days) and the other (II) kept in darkness. The control determinations (III) were carried out in pineal glands from animals hunted and killed during the night.In (I) the HIOMT activity decreased and the COMT activity increased; no changes were exhibited by HNMT. In (II) showed a diminished HIOMT activity.In captivity illumination affected HIOMT and COMT activities in a similar form to that observed in other species of rodents. The decrease in HIOMT activity in (II) suggests that captivity may affect pineal function, possibly as a consequence of a decrease in locomotor activity.     

Distribution of thyrotropin-releasing hormone (TRH) immunoreactivity in the brain of the zebrafish (Danio rerio)

The distribution of thyrotropin-releasing hormone (TRH) in the brain of the adult zebrafish was studied with immunohistochemical techniques. In the telencephalon, abundant TRH-immunoreactive (TRHir) neurons were observed in the central, ventral, and supra- and postcommissural regions of the ventral telencephalic area. In the diencephalon, TRHir neurons were observed in the anterior parvocellular preoptic nucleus, the suprachiasmatic nucleus, the lateral hypothalamic nucleus, the rostral parts of the anterior tuberal nucleus and torus lateralis, and the posterior tuberal nucleus. Some TRHir neurons were also observed in the central posterior thalamic nucleus and in the habenula. The mesencephalon contained TRHir cells in the rostrodorsal tegmentum, the Edinger-Westphal nucleus, the torus semicircularis, and the nucleus of the lateral lemniscus. Further TRHir neurons were observed in the interpeduncular nucleus. In the rhombencephalon, TRHir cells were observed in the nucleus isthmi and the locus coeruleus, rostrally, and in the vagal lobe and vagal motor nucleus, caudally. In the forebrain, TRHir fibers were abundant in several regions, including the medial and caudodorsal parts of the dorsal telencephalic area, the ventral and commissural parts of the ventral telencephalic area, the preoptic area, the posterior tubercle, the anterior tuberal nucleus, and the posterior hypothalamic lobe. The dorsal thalamus exhibited moderate TRHir innervation. In the mesencephalon, the optic tectum received a rich TRHir innervation between the periventricular gray zone and the stratum griseum centrale. A conspicuous TRHir longitudinal tract traversed the tegmentum and extended to the rhombencephalon. The medial and lateral mesencephalic reticular areas and the interpeduncular nucleus were richly innervated by TRHir fibers. In the rhombencephalon, the secondary gustatory nucleus received abundant TRHir fibers. TRHir fibers moderately innervated the ventrolateral and ventromedial reticular area and richly innervated the vagal lobe and Cajal's commissural nucleus. Some TRHir fibers coursed in the lateral funiculus of the spinal cord. Some TRHir amacrine cells were observed in the retina. The wide distribution of TRHir neurons and fibers observed in the zebrafish brain suggests that TRH plays different roles. These results in the adult zebrafish reveal a number of differences with respect to the TRHir systems reported in other adult teleosts but were similar to those found during late developmental stages of trout (Díaz et al., 2001).     

Ontogenesis of peptide-histidine-isoleucine (PHI)-containing neurons in the suprachiasmatic nucleus (SCN) of the rat

The morphologic and ontogenetic changes in PHI (peptide-histidine-isoleucine)-containing neurons in the suprachiasmatic nucleus (SCN) of the rat were studied using immunohistochemistry. PHI immunoreactivity first appeared in neural perikarya and processes as early as day 18 of gestation, long before they became evident (day 10 postnatally) in other brain structures. PHI neurons in the SCN were initially small and exhibited faint staining. They gradually increased in number during fetal life, and were found throughout this nucleus by day 21. After birth, they rapidly increased in number and staining intensity. In the 20-day-old rat, PHI-containing perikarya were concentrated in the ventral and medial aspects of the SCN while fibers were located primarily within the dorsal and caudal portions, as in the adult rat. These findings suggest that PHI exerts a physiological role in the developing SCN.     

Developmental switch in the expression of GABA(A) receptor subunits alpha(1) and alpha(2) in the hypothalamus and limbic system of the rat

The GABA(A) receptor is a pentameric ligand gated ion channel complex assembled from a family of at least 17 different subunits encoded by distinct genes. Two subunits, alpha(1) and alpha(2), exhibit age dependent expression throughout several areas of the brain. In general, the density of immunoreactive product for alpha(1) is greatest in the adult brain, while alpha(2) is highest in younger tissue. Since the developmental switch in alpha(1) and alpha(2) coincides with the end of the sensitive period for steroid-mediated sexual differentiation of the brain, we hypothesized that GABA(A) receptor subunit expression may be involved in this process. We have examined the age-dependent expression of alpha(1) and alpha(2) in discrete regions of the hypothalamus and limbic system of males and females. While we did not detect any dramatic sex differences in alpha(1) or alpha(2) immunoreactive density, each region exhibited a unique developmental profile. In the ventromedial nucleus of neonatal animals immunoreactivity is highest for alpha(1), while in the adult the signal for alpha(2) is greater; the opposite of that observed in the ventrolateral thalamus. There is no age dependent change for alpha(1) in the preoptic area, while alpha(2) shows a small, but significant increase. Immunoreactive densities for both subunits increase in the arcuate nucleus and the hippocampus, but decrease in the lateral amygdala. We conclude that these regional differences in subunit expression across development determine individual characteristics of brain areas and may play a role in establishing unique physiological responses to GABA.     

Callosal axon arbors in the limb representations of the somatosensory cortex (SI) in the agouti (Dasyprocta primnolopha)

The present report compares the morphology of callosal axon arbors projecting from and to the hind- or forelimb representations in the primary somatosensory cortex (SI) of the agouti (Dasyprocta primnolopha), a large, lisencephlic Brazilian rodent that uses forelimb coordination for feeding. Callosal axons were labeled after single pressure (n = 6) or iontophoretic injections (n = 2) of the neuronal tracer biotinylated dextran amine (BDA, 10 kD), either into the hind- (n = 4) or forelimb (n = 4) representations of SI, as identified by electrophysiological recording. Sixty-nine labeled axon fragments located across all layers of contralateral SI representations of the hindlimb (n = 35) and forelimb (n = 34) were analyzed. Quantitative morphometric features such as densities of branching points and boutons, segments length, branching angles, and terminal field areas were measured. Cluster analysis of these values revealed the existence of two types of axon terminals: Type I (46.4%), less branched and more widespread, and Type II (53.6%), more branched and compact. Both axon types were asymmetrically distributed; Type I axonal fragments being more frequent in hindlimb (71.9%) vs. forelimb (28.13%) representation, while most of Type II axonal arbors were found in the forelimb representation (67.56%). We concluded that the sets of callosal axon connecting fore- and hindlimb regions in SI are morphometrically distinct from each other. As callosal projections in somatosensory and motor cortices seem to be essential for bimanual interaction, we suggest that the morphological specialization of callosal axons in SI of the agouti may be correlated with this particular function.     

Development of the cerebellum in the platypus (Ornithorhynchus anatinus) and short-beaked echidna (Tachyglossus aculeatus)

The monotremes are a unique group of mammals whose young are incubated in a leathery-shelled egg and fed with milk from teatless areolae after hatching. As soon as they hatch, monotreme young must be able to maneuver around the nest or maternal pouch to locate the areolae and stimulate milk ejection. In the present study, the embryological collections at the Museum für Naturkunde, Berlin, have been used to follow the development of the monotreme cerebellum through incubation and lactational phases, to determine whether cerebellar circuitry is able to contribute to the coordination of locomotion in the monotreme hatchling, and to correlate cerebellar development with behavioral maturation. The structure of the developing monotreme cerebellum and the arrangement of transitory neuronal populations are similar to those reported for fetal and neonatal eutherians, but the time course of the key events of later cerebellar development is spread over a much longer period. Expansion of the rostral rhombic lip and formation of the nuclear and cortical transitory zones occurs by the time of hatching, but it is not until after the end of the first post-hatching week that deep cerebellar neurons begin to settle in their definitive positions and the Purkinje cell layer can be distinguished. Granule cell formation is also prolonged over many post-hatching months and the external granular layer persists for more than 20 weeks after hatching. The findings indicate that cerebellar circuitry is unlikely to contribute to the coordination of movements in the monotreme peri-hatching period. Those activities are most likely controlled by the spinal cord and medullary reticular formation circuitry.