Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1

The capacity of the adult brain and spinal cord to repair lesions by axonal regeneration or compensatory fibre growth is extremely limited. A monoclonal antibody (IN-1) raised against NI-220/250, a myelin protein that is a potent inhibitor of neurite growth, promoted axonal regeneration and compensatory plasticity following lesions of the central nervous system (CNS) in adult rats. Here we report the cloning of nogo A, the rat complementary DNA encoding NI-220/250. The nogo gene encodes at least three major protein products (Nogo-A, -B and -C). Recombinant Nogo-A is recognized by monoclonal antibody IN-1, and it inhibits neurite outgrowth from dorsal root ganglia and spreading of 3T3 fibroblasts in an IN-1-sensitive manner. Antibodies against Nogo-A stain CNS myelin and oligodendrocytes and allow dorsal root ganglion neurites to grow on CNS myelin and into optic nerve explants. These data show that Nogo-A is a potent inhibitor of neurite growth and an IN-1 antigen produced by oligodendrocytes, and may allow the generation of new reagents to enhance CNS regeneration and plasticity.     

Recognition of myelin-associated glycoprotein by the monoclonal antibody HNK-1

Myelin-associated glycoprotein (MAG) is a quantitatively minor component in both peripheral and central myelin sheaths that is thought to have a role in cell-cell interactions within the nervous system. We show here that a mouse monoclonal antibody, HNK-1, which is directed against human natural killer cells also recognizes an antigenic determinant of human central and peripheral nervous system white matter by immunoperoxidase staining of tissue sections. Immunoblot analysis of myelin proteins and purified extracted MAG indicates that the antigen recognized is MAG.     

Functional regeneration of sensory axons into the adult spinal cord

The arrest of dorsal root axonal regeneration at the transitional zone between the peripheral and central nervous system has been repeatedly described since the early twentieth century. Here we show that, with trophic support to damaged sensory axons, this regenerative barrier is surmountable. In adult rats with injured dorsal roots, treatment with nerve growth factor (NGF), neurotrophin-3 (NT3) and glial-cell-line-derived neurotrophic factor (GDNF), but not brain-derived neurotrophic factor (BDNF), resulted in selective regrowth of damaged axons across the dorsal root entry zone and into the spinal cord. Dorsal horn neurons were found to be synaptically driven by peripheral nerve stimulation in rats treated with NGF, NT3 and GDNF, demonstrating functional reconnection. In behavioural studies, rats treated with NGF and GDNF recovered sensitivity to noxious heat and pressure. The observed effects of neurotrophic factors corresponded to their known actions on distinct subpopulations of sensory neurons. Neurotrophic factor treatment may thus serve as a viable treatment in promoting recovery from root avulsion injuries. I     

Effect of Jiaji electroacupuncture in transected rat spinal cord

We evaluated the effect of Jiaji electroacupuncture on cell proliferation and the expression of markers of endogenous neural stem cell activation after complete spinal cord transection. Female Wistar rats were assigned to 4 groups (n = 24 each): a sham-operated group, a control group, a Jiaji electroacupuncture group, and a Jiaji electroacupuncture preconditioning group. Motor function was significantly improved in the acupuncture groups compared to the control group at 7 and 14 d. Numbers of bromodeoxyuridine (BrdU)-, nestin-, and glial fibrillary acidic protein (GFAP)-positive cells were significantly greater in the acupuncture groups than in the controls at each time point. Expression of nestin and GFAP mRNA was significantly higher in the acupuncture groups than in the controls at each time point. Thus, Jiaji electroacupuncture and preconditioning may promote the proliferation of endogenous neural stem cells after spinal cord transection.     

基因重组碱性成纤维细胞生长因子对大鼠脊髓损伤神经保护作用

目的 :探索碱性成纤维细胞生长因子 (bFGF)对大鼠脊髓损伤的神经保护作用 方法 :将吸入bFGF的胶原蛋白海绵或空白海绵贴敷于大鼠脊髓损伤处 ,术后 1、2、3周 ,对大鼠机能进行评分 ,并对大脑运动皮质进行电镜观察分析 结果 :术后 1、2、3周 ,bFGF组大鼠运动评分均明显优于对照组 (Ρ <0 .0 5) ,运动皮质电镜结果显示bFGF组线粒体、内质网轻度肿胀 ,神经毡结构正常 ,无明显胶质细胞增生 程度较对照组明显减轻 结论 :bFGF对大鼠脊髓受损神经纤维起源脑区—运动皮质的神经细胞具有明显的保护作用 ,进而使大鼠运动功能受损明显减轻     

Changes in spinal cord reflexes after cross-anastomosis of cutaneous and muscle nerves in the adult rat

Evidence exists that the specification of afferent nerves and their central connections in the embryo may depend in part on influences from the peripheral target innervated. We have now investigated whether such peripheral determination persists in the adult rat using the unmyelinated afferent system of C fibres, which differ chemically in the adult depending on their target. We have previously shown that if the cutaneous sural nerve and the muscle gastrocnemius nerve are cross-anastomosed so that they grow to each other's target, the A fibres establish functional endings and the C fibres change their chemistry to that which is appropriate for the new target. Here we report that in normal adult rats, a short train of stimuli to the cutaneous sural nerve produced a brief facilitation of the flexion reflex, lasting on average only 5 min, whereas similar stimulation of the gastrocnemius-muscle nerve enhanced this reflex for an average of 54 min. In cross-anastomosed animals, stimulation of the gastrocnemius nerve (innervating skin) induced a brief potentiation of the flexion reflex, lasting on average only 3 min. By contrast, stimulation of sural nerve (innervating muscle) produced a potentiation of this reflex lasting 57 min. Thus the ability of adult afferent nerves to potentiate the flexion reflex depends on the target with which they make contact. We propose that tissue-specific factors influence some of the central actions of primary afferent neurons in the adult.     

Dynamic receptive field plasticity in rat spinal cord dorsal horn following C-primary afferent input

The central terminals of cutaneous primary afferent neurons are spatially ordered in the dorsal horn in a highly organized fashion such that a point-to-point map represents the body surface. This afferent terminal somatotopic map correlates with the map of the receptive fields of the cells on which they terminate. The location, size and modality of the cutaneous receptive fields of dorsal horn neurons necessarily depend upon the anatomical presence of afferent nerve fibres which deliver information from the periphery, directly or indirectly, to the cells. However the receptive field size and modality of a cell do not depend only on anatomical connections. Excitatory and inhibitory interneurons, descending influences and facilitations or depressions of synaptic contacts can alter receptive field properties. Here we show that prolonged and substantial cutaneous receptive field changes can be produced by brief inputs from peripheral unmyelinated afferent fibres.     

Morphological and electrophysiological evidence for regeneration of transected spinal cord fibers and restoration of motor functions in adult rats

The evoked potentials are regarded as an efficientindex to evaluate the functional status of a nervoussystem[1]. When stimulating the motor area of cerebralcortex with transcranial magnetic stimulation, elec-tronic signals can be obtained at the spinal co…     

Somatic/ visceral sensory neurons in the spinal cord and synaptic/junctional activity in the spinal ganglion

Somato-visceral interaction or acupoint-visceral interaction is an important subject that greatly concerns scholars of both Chinese traditional and Western modern medicine. The role of our newly discovered spinal projection neurons and type A or C spinal ganglion neurons in convergence and integration of somato-visceral sensation is introduced. The possible challenge brought about by these related results onto some traditional concepts in neuroscience is also discussed.     

Neural stem cell transplantation in the repair of spinal cord injury

Neural stem cells are a pronising candidate for neural transplantation aimed at neural cell replacement and repair of the damaged host central nervous system (CNS). Recent studies using neural stem cells have shown that implanted neural stem cells can effectively incorporate into the damaged CNS and differentiate into neurons, astrocytes, and oligodendrocytes. The recent explosion in the field of neural stem cell research has provided insight into the inductive factors influencing neural stem cell differentiation and may yield potential therapies for several neurological disorders, including spinal cord injury. In this review, we summarize recent studies involving neural stem cell biology in both rodents and humans. We also discuss unique advantages and possible mechanisms of using neural stem cell trans plantation in the repair of spinal cord injury.     

A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord

Itching, or pruritus, is defined as an unpleasant cutaneous sensation that serves as a physiological self-protective mechanism to prevent the body from being hurt by harmful external agents. Chronic itch represents a significant clinical problem resulting from renal diseases and liver diseases, as well as several serious skin diseases such as atopic dermatitis. The identity of the itch-specific mediator in the central nervous system, however, remains elusive. Here we describe that the gastrin-releasing peptide receptor (GRPR) plays an important part in mediating itch sensation in the dorsal spinal cord. We found that gastrin-releasing peptide is specifically expressed in a small subset of peptidergic dorsal root ganglion neurons, whereas expression of its receptor GRPR is restricted to lamina I of the dorsal spinal cord. GRPR mutant mice showed comparable thermal, mechanical, inflammatory and neuropathic pain responses relative to wild-type mice. In contrast, induction of scratching behaviour was significantly reduced in GRPR mutant mice in response to pruritogenic stimuli, whereas normal responses were evoked by painful stimuli. Moreover, direct spinal cerebrospinal fluid injection of a GRPR antagonist significantly inhibited scratching behaviour in three independent itch models. These data demonstrate that GRPR is required for mediating the itch sensation rather than pain, at the spinal level. Our results thus indicate that GRPR may represent the first molecule that is dedicated to mediating the itch sensation in the dorsal horn of the spinal cord, and thus may provide a central therapeutic target for antipruritic drug development.     

A VIP-containing system concentrated in the lumbosacral region of human spinal cord

Neuropeptides were first localized in the human spinal cord by immunocytochemistry and substance P has been shown, by the same method, to be reduced ipsilaterally in the dorsal horn after limb amputation and bilaterally in the Riley-Day syndrome. Several neuropeptides increasingly fulfil the criteria to establish them as neurotransmitters or neuromodulators, and they may also have trophic actions in the spinal cord. Using radioimmunoassay and immunocytochemistry, we present here for the first time a quantitative regional distribution and localization of vasoactive intestinal polypeptide (VIP), substance P, somatostatin, bombesin and cholecystokinin (CCK-8) in normal postmortem human spinal cord. A comparison of the distribution of these peptides reveals an exceptional pattern for VIP, with relatively much higher levels in the lumbosacral region. Immunocytochemical analysis shows a distinctive distribution of VIP-containing fibres and terminals at the lumbosacral segments. This VIP-containing system may have an important role in the spinal control of urogenital function in man.     

Rho激酶抑制剂诱导PC12和PC12Adh细胞突起生长的差异比较

 PC12细胞是研究神经分化最常用的细胞之一.在rho激酶(ROCK)抑制剂的作用下,PC12细胞能够长出神经样突起.最近,美国菌种保存中心(ATCC)同时提供PC12细胞和PC12 Adh细胞.研究的主要目的是观察ROCK抑制剂诱导这2种细胞长突起是否存在差异.PC12细胞和PC12Adh细胞按照ATCC方法进行培养,用神经生长因子(NGF,1000ng/mL)或ROCK抑制剂(33μmol/L Y27632,33μmol/L法舒地尔)处理细胞1~4d.结果发现NGF能够诱导这2种细胞生长突起,而ROCK抑制剂只诱导PC12Adh细胞长突起,对PC12细胞不明显.因此,ROCK抑制剂诱导这2种细胞突起生长存在明显差异,PC12Adh细胞更适合用于ROCK抑制剂的神经诱导分化实验.