RYK在小鼠皮质脊髓束神经通路发育过程中的表达变化

目的观察RYK在皮质脊髓束发育投射通路中的表达情况,为进一步研究RYK在其中的功能提供重要线索。方法通过原位杂交和免疫荧光组织化学法,分别检测了E14.5、E16、E18.5和出生后P3、P5、P7等不同时间点RYK在小鼠大脑运动皮层和皮质脊髓束神经通路中的表达情况。结果RYK的表达出现在胚胎E18.5 d运动皮层神经元中,到P0时逐渐增强并表达在脑内投射的皮质脊髓束神经通路,从P0~P5,RYK持续表达在皮质脊髓束在脑内和脊髓的整个神经通路上,而后逐渐减弱。结论RYK的表达与皮质脊髓束神经通路在脊髓中的发育投射有密切关系。     

Anatomical plasticity of the tectospinal tract after unilateral lesion of the superior colliculus in the neonatal rat

Summary After unilateral ablation of the superior colliculus (SC) in neonatal or adult rats, the reorganization of the tectospinal tract (TST) was examined using the technique of anterograde transport of horseradish peroxidase to which wheat germ agglutinin had been conjugated (WGA-HRP). In neonatally lesioned rats, aberrant labeled terminals of TST axons were found on the ipsilateral side of the spinal cord. Postnatal development of the TST was then studied by retrograde transport of HRP to determine whether the aberrant tectospinal projections resulted from normally transient ipsilateral projections that persisted in operated rats or were due to collateral sprouting of projections to the contralateral projection field. The results failed to show an ipsilateral projection from the SC to spinal cord in normal neonatal rats. However, in neonatally lesioned rats, aberrant labeled fibers were observed recrossing the midline of the cervical spinal cord. Therefore, the increase in labeled terminals on the ipsilateral side following unilateral SC ablation appeared to originate from collateral sprouting at the spinal cord level of TST fibers from the intact pathway.     

皮质脊髓束损伤后胶质细胞激活相关microRNA的筛选与验证

目的检测皮质脊髓束损伤头侧和尾侧microRNA及其靶基因mRNA的表达变化,探讨microRNA在皮质脊髓束损伤修复过程中的生物学作用。方法在左侧延髓锥体切断大鼠锥体束(30只),建立单侧大鼠皮质脊髓束损伤模型,采用BBB评分进行行为学评价;实验以左侧大鼠皮质脊髓束损伤模型作为研究对象,利用生物信息学方法筛选差异表达的microRNA预测靶基因与mRNA的差异筛选取交集,进行microRNA和mRNA共表达分析;Real-time PCR检测12只大鼠miR-342-5p、Irf8的表达水平;Western blotting检测6只大鼠Irf8、Iba1蛋白的表达变化。结果皮质脊髓束损伤后观察到右后肢运动不协调,BBB评分表明运动功能受限,但是6只大鼠没有完全瘫痪,损伤后2 h,1、3、5和7 d BBB评分与对照组相比差异有统计学意义(P<0.05),提示模型制备成功。头侧和尾侧5 d与2h相比,聚集于与修复再生相关的生物学过程。Real-time PCR结果显示,尾侧5 d与2h相比,miR-342-5p表达差异有显著性(P<0.01),并且与Irf8呈现反向调节关系,而在头侧miR-342-5p表达差异无统计学意义(P>0.05)。Real-time PCR数据分析显示,Irf8与芯片结果一致,与对照组相比差异有统计学意义(P<0.01)。Western blotting结果显示,5 d和2h相比尾侧Irf8的表达显著增加,Iba1的表达明显增高,差异有统计学意义(P<0.01)。结论皮质脊髓束损伤后损伤头侧和尾侧均有显著性上调或下调的差异表达基因,在损伤尾侧miR-342-5p和Irf8呈反向调节,提示miR-342-5p与胶质细胞激活从而促进脊髓损伤修复再生密切相关。     

Postnatal development of the corticospinal tract in the rat

Summary Horseradish-peroxidase was used to anterogradely label and thus to trace the growth of corticospinal axons in rats ranging in age from one day to six months. Three to eight HRP-gels were implanted in the left cerebral hemisphere of the cortex. In each spinal cord three levels were studied, the cervical intumescence (C5), the mid-thoracic region (T5) and the lumbar enlargement (L3). The methodology employed for the electron microscopic visualization of HRP has been described previously (Joosten et al. 1987a).The outgrowth of labelled unmyelinated corticospinal tract axons in the rat spinal cord primarily occurs during the first ten postnatal days. The outgrowth of the main weve of these fibres is preceded by a number of pathfinding axons, characterized by dilatations at their distal ends, the growth cones. By contrast, later appearing unmyelinated axons, which presumably grow along the pathfinding axons, do not exhibit such growth cones. The first labelled pioneer axons can be observed in the cervical intumescence at postnatal day one (P1), in the mid-thoracic region at day three (P3) and in the lumbar enlargement at day five (P5).Prior to the entrance of the axons, the prospective corticospinal area or the pre-arrival zone is composed of fascicles consisting of unlabelled, unmyelinated fibres surrounded by lucent amorphous structures. During the outgrowth phase of the corticospinal fibres some myelinated axons could be observed within the outgrowth area even before day 14. These axons, however, were never labelled. These findings strongly suggest that the outgrowth area, which is generally denoted as the pyramidal tract, contains other axons besides the corticospinal fibres (and glial cells). The process of myelination of the labelled corticospinal tract axons in the rat spinal cord starts rostrally (C5) at about day 14 and progresses caudally during the third and fourth postnatal weeks. Although myelination seems to be largely complete at day 28 at all three spinal cord levels, some labelled unmyelinated axons are still present in the adult stage.     

Growth and target finding by axons of the corticospinal tract in prenatal and postnatal rats

The growth of the corticospinal tract was studied in prenatal and neonatal rats using the anterograde transport of horseradish peroxidase injected into the cerebral cortex as a marker in lightmicroscopic preparations. The findings were compared with electron-microscopic observations on normal material at the same ages. Labelled corticofugal axons traverse the diencephalon by gestational day 17.5, reach the pontine nuclei by gestational day 19.5, and the caudal limit of the medulla oblongata by gestational day 20.5, just before birth. On the day after birth, labelled corticospinal axons have crossed in the pyramidal decussation and extended into the dorsal columns of the upper cervical spinal cord. Corticospinal axons reach the thoracic segments by postnatal day 3, the lumbar segments by day 6 and the sacral segments by day 9. The lower end of the spinal cord is reached only after postnatal day 14. Beside the principal corticospinal tract in the dorsal columns, two other smaller corticospinal tracts occupy an intermediate position in the base of the cervical dorsal horn and a lateral position in the lateral white column. The intermediate tract is not found below cervical levels. Growth cones are seen at the tips of axons in light- and electron-microscopic material. The first corticospinal axons, less than 0.5 microns in diameter and grouped in tight fascicles, grow through a dense fabric of astrocytic and other glial processes in which no obvious pre-existing channels could be identified. Growth of corticospinal axons into the dorsal horn adjacent to the main tract is delayed until 2–3 days after the initial arrival of the tract at a given segment. This begins in the cervical segments only after the thalamocortical fibers have invaded the sensory-motor cortex though the parent pyramidal cells of the tract are still highly immature. The rate of extension of corticospinal axons is not constant. Growth down the dorsal columns is characterized by accelerated growth spurts on postnatal days 4 and 9. Much slower growth characterizes initial outgrowth through the diencephalon and later ingrowth into the spinal gray matter. There is approximately a three-fold increase in the numbers of corticospinal axons in the cervical segments between postnatal days 5 and 10. Myelination commences between postnatal days 10 and 12.It is concluded that the development of the corticospinal tract in the rat displays features that are common to other developing pathways in the rat and other species. Initial outgrowth of corticospinal axons is independent of afferent innervation, occurring at a time when the parent cell bodies are very immature. The early growth of corticospinal axons to the vicinity of their targets is followed by a substantial waiting period, comparable to that seen in other systems, before final invasion of the target. The factors responsible for the initiation of the second growth spurt, carrying axons into the target gray matter are not known. However, the final invasion of gray matter takes place only after the cells of origin of corticospinal axons have received a substantial afferent input. The rate of initial growth of corticospinal axons down the dorsal columns is not constant, but varies from region to region. Electronmicroscopy has failed to detect any morphological evidence for factors that might guide or promote the growth of corticospinal axons. The majority of corticospinal axons exclusive of the first ‘pathfinders’ seem to grow as tight fascicles in which individual axons contact only one another.     

Proliferation of the rat myocardium after early postnatal injury

A small quantity of 96% ethanol was injected into the left ventricle of noninbred albino rats aged 7, 14, and 30 days, causing focal necrosis of the myocardium. The animals were killed 2–30 days after the operation. The mitotic index (MI) of the muscle nuclei was determined in different parts of the heart: in the left and right atria and their auricles, the trabecular and compact myocardium and the subepicardial zones of both ventricles, and also in the zone around the focus. Proliferation of myocytes in the compact myocardium was found to be inhibited and was not resumed after injury to the left ventricle. In all other zones, in which mitoses were present in the control animals, MI of the myocytes increased after trauma to the heart. The later the injury was inflicted, the less marked the rise in MI. In animals aged 7 days, MI on the 4th day after the operation reached 320–500% of the control, and on the 7th day it reached 120–380%. MI in the group of animals undergoing the operation at the ages of 14 and 30 days was increased only in some high-mitosis rats and not in all parts of the heart. The ability of connective tissue to replace the defect increases with growth of the heart.Laboratory of Growth and Development, Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 2, pp. 234–236, February, 1980.     

Anatomical location of the corticospinal tract according to somatotopies in the centrum semiovale

Little is known about the somatotopic location of the corticospinal tract (CST) in the centrum semiovale (CS). We investigated the somatotopic location of the CST in the CS in the human brain using diffusion tensor tractography (DTT). Fifty-two healthy volunteers were recruited for this study. Diffusion tensor images (DTIs) were obtained at 1.5 T, and CSTs for the hand and leg were obtained using FMRIB software. Normalized DTT images were reconstructed using the Montreal Neurological Institute echo-planar imaging template supplied with the SPM. Individual DTI data were calculated as number of pixels in the CS. In the mediolateral direction, average distances of the highest probabilistic locations for hand and leg somatotopies were 25.57 mm and 21.72 mm from the midline between the right and left hemispheres, respectively. For the anteroposterior direction, the average distance of the highest probabilistic locations for hand and leg somatotopies were 0.4 mm and 5.2 mm behind the horizontal line between the medial end of the central sulcus and midline, respectively. In conclusion, hand somatotopy of the CST was found to be located at about 26 mm lateral to the midline almost along the horizon line between the medial end of central sulcus and midline, and leg somatotopy of the CST was found to be located medioposteriorly to the hand somatotopy of the CST.     

Molecular mechanisms of axon guidance in the developing corticospinal tract

The great repertoire of movements in higher order mammals comes courtesy of the corticospinal tract (CST) which is able to initiate precise movement of the entire musculature of the axial and limb muscle groups. It forms the longest axonal trajectory in the mammalian central nervous system and its axons must navigate the entire length of the central nervous system--from its origins in the deeper layers of the cerebral cortex down through the cerebral peduncles and brainstem and along the entire length of the spinal cord. This period of navigation is incredibly complex, and relies upon the coordinated regulation of a collection of molecular guidance cues - coming from all of the known major families of guidance cues - the ephrins, slits, Netrins and Semaphorins - that work together to steer the growing axonal tips through the brain and spinal cord. As such a long tract, the CST forms an excellent experimental model to investigate the nature of molecular cues that sequentially guide axons through the central nervous system. Using the rodent as a model system, this review discusses each step of axonal guidance through the major brain regions--starting from the decision to grow ventrally out of the cortical plate to the eventual activity-dependent refinement of circuitry in the spinal grey matter. In recent years, the identification of these guidance cues and their proposed mode of action is beginning to give us a picture at a molecular level of how the CST is guided so accurately over such a long distance.     

Nature of factors inactivating postural asymmetry factor on intial stages of compensatory adjustments in animals with unilateral destruction of the motor neocortex

I. P. Pavlov Department of Physiology, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR. Department of Normal Physiology, I. P. Pavlov First Leningrad Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. N. Klimov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 108, No. 10, pp. 402–404, October, 1989.     

Postnatal histogenesis and proliferation of cells of the parietal neocortex in normal mice and after brain trauma

The postnatal histogenesis of the parietal region of the neocortex and the ability of the principal cell types in it to proliferate were studied in normal mice and after a stab wound of the brain by analysis of cells labeled with [³H]thymidine in semithin sections. In the postnatal period no microneurons were formed in the parietal cortex of the mice either by migration of undifferentiated cells or by proliferation. Trauma to the right hemisphere caused no change in the direction of the histogenetic transformations of cells migrating into the parietal cortex toward their differentiation into microneurons.Laboratories of Brain Ultrastructure, Brain Cytoarchitectonics, and Functional Synaptology, Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Central Research Laboratory, Patrice Lumumba Peoples' Friendship University, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 2, pp. 234–237, February, 1978.     

Quantitative inter-segmental and inter-laminar comparison of corticospinal projections from the forelimb area of the primary motor cortex of macaque monkeys

Corticospinal projections from the forelimb area of the primary motor cortex to the C2-Th2 spinal cord segments were quantitatively analyzed using the high resolution anterograde tracer, biotinylated dextran amine (BDA), in rhesus monkeys (n=5). The majority of descending axons were located in the contralateral dorsolateral funiculus (DLF) (85-98%), but a minor portion was observed in the ipsilateral DLF (1-12%) and ventromedial funiculus (VMF) (1-7%). In the gray matter, axon collaterals and terminal buttons were found mainly in the contralateral laminae VI-VII and IX and ipsilateral lamina VIII. The majority of projections to the contralateral gray matter originated from the contralateral DLF, but a minority originated from the ipsilateral DLF. Axons from the ipsilateral DLF were not found to project collaterals on the ipsilateral side, but directly entered the contralateral side after crossing the midline. On the other hand, projections to the ipsilateral lamina VIII were from the ipsilateral VMF, and commissural axons were from the contralateral DLF. Terminal buttons in the motoneuron pool in the contralateral lamina IX were found mainly at the C7-Th1 spinal cord segments, whereas the projections to the contralateral laminae VI-VII, ipsilateral lamina VIII, and commissural axons were also found in more rostral segments, abundantly at the C4-C8 segments, 1-3 segments rostral to the motoneuronal projections. These results suggest that cortical control of contralateral forelimb motoneurons accompanies regulation of interneuronal systems in the contralateral laminae VI-VII and the ipsilateral lamina VIII located a few segments rostral to the motoneurons.     

Reorganization of laryngeal motoneurons after crush injury in the recurrent laryngeal nerve of the rat

Motoneurons innervating laryngeal muscles are located in the nucleus ambiguus (Amb), but there is no general agreement on the somatotopic representation and even less is known on how an injury in the recurrent laryngeal nerve (RLN) affects this pattern. This study analyzes the normal somatotopy of those motoneurons and describes its changes over time after a crush injury to the RLN. In the control group (control group 1, n = 9 rats), the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were injected with cholera toxin‐B. In the experimental groups the left RLN of each animal was crushed with a fine tip forceps and, after several survival periods (1, 2, 4, 8, 12 weeks; minimum six rats per time), the PCA and TA muscles were injected as described above. After each surgery, the motility of the vocal folds was evaluated. Additional control experiments were performed; the second control experiment (control group 2, n = 6 rats) was performed labeling the TA and PCA immediately prior to the section of the superior laryngeal nerve (SLN), in order to eliminate the possibility of accidental labeling of the cricothyroid (CT) muscle by spread from the injection site. The third control group (control group 3, n = 5 rats) was included to determine if there is some sprouting from the SLN into the territories of the RLN after a crush of this last nerve. One week after the crush injury of the RLN, the PCA and TA muscles were injected immediately before the section of the SLN. The results show that a single population of neurons represents each muscle with the PCA in the most rostral position followed caudalwards by the TA. One week post‐RLN injury, both the somatotopy and the number of labeled motoneurons changed, where the labeled neurons were distributed randomly; in addition, an area of topographical overlap of the two populations was observed and vocal fold mobility was lost. In the rest of the survival periods, the overlapping area is larger, but the movement of the vocal folds tends to recover. After 12 weeks of survival, the disorganization within the Amb is the largest, but the number of motoneurons is similar to control, and all animals recovered the movement of the left vocal fold. Our additional controls indicate that no tracer spread to the CT muscle occurred, and that many of the labeled motoneurons from the PCA after 1 week post‐RLN injury correspond to motoneurons whose axons travel in the SLN. Therefore, it seems that after RLN injury there is a collateral sprouting and collateral innervation. Although the somatotopic organization of the Amb is lost after a crush injury of the RLN and does not recover in the times studied here, the movement of the vocal folds as well as the number of neurons that supply the TA and the PCA muscles recovered within 8 weeks, indicating that the central nervous system of the rat has a great capacity of plasticity.     

Effect of Transplantation of Embryonic Nervous Tissue on Reorganization of Interneuronal Relationships after Mechanical Damage to Sensorimotor Cortex

The effect of implanted embryonic nervous tissue on restoration of axonal connections in the cerebral cortex after mechanical injury was studied on albino rats using fluorescent lipophilic probe DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate) and confocal laser scanning microscope. Implantation of embryonic tissue to damaged area promotes the growth of axons through the transplant to adjacent tissue. The damaged area is impenetrable for axons growing without implantation.     

Monoamine content in the motor cortex after injury to the opposite motor cortex

In chronic experiments on eight cats a spectrofluorometric study was made of the serotonin, dopamine, and noradrenalin content in the sigmoid cortex of the left cerebral hemisphere 2, 3, 4, and 5–8 days after removal of the symmetrical cortex of the right hemisphere. A decrease in the dopamine content and a tendency for a decrease in the noradrenalin and serotonin content were observed on the 2nd day, at the time of maximal disturbances of locomotor function. On the 3rd–4th and 5th–8th days, during the period of recovery of motor activity, the serotonin level increased, the dopamine content remained low, whereas the noradrenalin level rose considerably. The role of biochemical changes in the motor cortex in the mechanisms of recovery of locomotor function after injury to the symmetrical cortical region is discussed.Laboratory of Pathophysiology of Neurohumoral Regulation, Institute of General Pathology and Pathophysiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 9, pp. 270–271, September, 1978.     

Iron-induced mucosal injury to the upper gastrointestinal tract

AIMS: To define the causes and associations of mucosal iron deposition in upper gastrointestinal biopsy specimens and to describe the morphological features of iron-related injury. METHODS: The histological pattern, intensity and distribution of iron in biopsies obtained from 1991 to 2005 were recorded and correlated with endoscopic and clinical findings. RESULTS: Twenty-five biopsies (16 gastric, four duodenal, five oesophageal) were accrued. Iron deposition was seen in two groups: 10 cases showed erosive injury, with brown-black crystalline material overlying eroded epithelium. These patients were taking oral iron tablets. The remaining 15 cases showed variable iron deposition in the surface epithelium, lamina propria and glands. In nine patients, there was a history of oral iron intake and at least eight had had blood transfusions. The most intense iron deposition was noted in patients with end-stage liver disease. The mean age of patients with erosive injury was 43% higher than in the iron overload group (76 versus 53 years). Iron stains were also performed on 15 normal gastric biopsies and five biopsies with chronic, non-specific gastritis; all were negative for haemosiderin deposition. CONCLUSIONS: Iron-related erosive injury is related to oral iron pill ingestion and occurs in older patients. Mucosal iron deposition is also associated with iron overload disorders.     

Erratum to: SDF1 in the dorsal corticospinal tract promotes CXCR4+ cell migration after spinal cord injury

Background  

Stromal cell-derived factor-1 (SDF1) and its major signaling receptor, CXCR4, were initially described in the immune system; however, they are also expressed in the nervous system, including the spinal cord. After spinal cord injury, the blood brain barrier is compromised, opening the way for chemokine signaling between these two systems. These experiments clarified prior contradictory findings on normal expression of SDF1 and CXCR4 as well as examined the resulting spinal cord responses resulting from this signaling.     

Somatotopic arrangement and location of the corticospinal tract in the brainstem of the human brain

The corticospinal tract (CST) is the most important motor pathway in the human brain. Detailed knowledge of CST somatotopy is important in terms of rehabilitative management and invasive procedures for patients with brain injuries. In this study, I conducted a review of nine previous studies of the somatotopical location and arrangement at the brainstem in the human brain. The results of this review indicated that the hand and leg somatotopies of the CST are arranged medio-laterally in the mid to lateral portion of the cerebral peduncle, ventromedial-dorsolaterally in the pontine basis, and medio-laterally in the medullary pyramid. However, few diffusion tensor imaging (DTI) studies have been conducted on this topic, and only nine have been reported: midbrain (2 studies), pons (4 studies), and medulla (1 study). Therefore, further DTI studies should be conducted in order to expand the literature on this topic. In particular, research on midbrain and medulla should be encouraged.     

单侧胸部撞击致对侧肺损伤动物模型的建立

目的建立单侧胸部撞击致对侧肺损伤动物模型,为胸部撞击肺损伤的实验研究提供参考依据。方法随机选取新西兰大白兔50只,采用BIM-Ⅱ型生物撞击机,以600 kPa驱动压力行右侧胸部准静态正面撞击,形成对侧肺损伤。结果右肺损伤与胸壁伤情、双肺损伤程度之间存在较好的相关关系。随着肋骨骨折数目的增加,右肺损伤明显加重,两者为正相关,P﹤0.01。随着右肺伤情的加重,左肺损伤也明显加重,两者呈较好的相关关系,P﹤0.05,而左肺损伤与胸壁伤情间无明显的相关,P﹥0.05。结论所建立的家兔单侧胸部撞击致对侧肺损伤动物模型操作简便,致伤撞击参数可控,且具有重复性,可引起不同程度的对侧肺损伤,病变典型,可作为研究胸部创伤较理想的实验动物模型。