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1.
Spinal Cord ; 49(3): 472-9, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20838405

RESUMEN

STUDY DESIGN: Cell transplantation strategies are gaining increasing interest for spinal cord injury (SCI) with the objective of promoting spinal cord repair. To avoid allogenic graft rejection, an adequate immune suppression is required, and one of the most potent and commonly used immunosuppressives is cyclosporin A (CsA). In SCI, permanent sensory motor loss is combined with modifications of drug absorption, distribution and elimination. OBJECTIVES: The objectives of this study were to thoroughly explore histological and functional outcomes of CsA treatment in a rat model of spinal cord compression. SETTING: Experiments were carried out at the Institute for Neurosciences of Montpellier (France), the Integrative Biology of Neurodegeneration Laboratory (Spain) and in the Novartis Institutes for BioMedical Research (Switzerland) for CsA blood concentration determination. METHODS: We first evaluated histological outcomes of CsA treatment on kidneys and spinal cord after SCI. We then investigated whether SCI modified CsA blood concentration. Finally, using behavioral analysis, we assessed the potential CsA impact on functional recovery. RESULTS: When spinal-cord-injured rats were treated with a CsA dose of 10 mg kg(-1) per day, we observed deleterious effects on kidneys, associated with modifications of CsA blood concentration. Adding an antibiotic treatment reduced kidney alteration without modifying CsA blood concentration. Finally, we showed that CsA treatment per se modified neither functional recovery nor lesion extension. CONCLUSION: This study pinpoints the absolute requirement of careful CsA monitoring in the clinical setting for patients with SCI to minimize potential unexpected effects and avoid therapeutic failure.


Asunto(s)
Trasplante de Células/métodos , Ciclosporina/toxicidad , Rechazo de Injerto/tratamiento farmacológico , Enfermedades Renales/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Animales , Trasplante de Células/efectos adversos , Ciclosporina/sangre , Ciclosporina/uso terapéutico , Modelos Animales de Enfermedad , Quimioterapia Combinada/métodos , Rechazo de Injerto/fisiopatología , Rechazo de Injerto/prevención & control , Inmunosupresores/sangre , Inmunosupresores/uso terapéutico , Inmunosupresores/toxicidad , Enfermedades Renales/inducido químicamente , Masculino , Ratas , Ratas Wistar , Traumatismos de la Médula Espinal/cirugía , Resultado del Tratamiento
2.
J Cell Biol ; 133(4): 853-63, 1996 May.
Artículo en Inglés | MEDLINE | ID: mdl-8666670

RESUMEN

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein expressed predominantly in astrocytes. The study of its expression in the astrocyte lineage during development and in reactive astrocytes has revealed an intricate relationship with the expression of vimentin, another intermediate filament protein widely expressed in embryonic development. these findings suggested that vimentin could be implicated in the organization of the GFAP network. To address this question, we have examined GFAP expression and network formation in the recently generated vimentin knockout (Vim-) mice. We show that the GFAP network is disrupted in astrocytes that normally coexpress vimentin and GFAP, e.g., those of the corpus callosum or the Bergmann glia of cerebellum. Furthermore, Western blot analysis of GFAP protein content in the cerebellum suggests that posttranslational mechanisms are implicated in the disturbance of GFAP network formation. The role of vimentin in this process was further suggested by transfection of Vim-cultured astrocytes with a vimentin cDNA, which resulted in the normal assembly of the GFAP network. Finally, we examined GFAP expression after stab wound-induced astrogliosis. We demonstrate that in Vim- mice, reactive astrocytes that normally express both GFAP and vimentin do not exhibit GFAP immunoreactivity, whereas those that normally express GFAP only retain GFAP immunoreactivity. Taken together, these results show that in astrocytes, where vimentin is normally expressed with GFAP fails to assemble into a filamentous network in the absence of vimentin. In these cells, therefore, vimentin appears necessary to stabilize GFAP filaments and consequently the network formation.


Asunto(s)
Astrocitos/metabolismo , Proteína Ácida Fibrilar de la Glía/biosíntesis , Vimentina/fisiología , Animales , Astrocitos/citología , Astrocitos/ultraestructura , Secuencia de Bases , Lesiones Encefálicas/metabolismo , Células Cultivadas , Cartilla de ADN , Proteína Ácida Fibrilar de la Glía/ultraestructura , Humanos , Filamentos Intermedios/metabolismo , Filamentos Intermedios/ultraestructura , Ratones , Ratones Noqueados , Datos de Secuencia Molecular , Transfección , Vimentina/deficiencia , Vimentina/genética
3.
J Neurosci ; 21(16): 6147-58, 2001 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-11487638

RESUMEN

Intermediate filaments (IFs) are a major component of the cytoskeleton in astrocytes. Their role is far from being completely understood. Immature astrocytes play a major role in neuronal migration and neuritogenesis, and their IFs are mainly composed of vimentin. In mature differentiated astrocytes, vimentin is replaced by the IF protein glial fibrillary acidic protein (GFAP). In response to injury of the CNS in the adult, astrocytes become reactive, upregulate the expression of GFAP, and reexpress vimentin. These modifications contribute to the formation of a glial scar that is obstructive to axonal regeneration. Nevertheless, astrocytes in vitro are considered to be the ideal substratum for the growth of embryonic CNS axons. In the present study, we have examined the potential role of these two major IF proteins in both neuronal survival and neurite growth. For this purpose, we cocultured wild-type neurons on astrocytes from three types of knock-out (KO) mice for GFAP or/and vimentin in a neuron-astrocyte coculture model. We show that the double KO astrocytes present many features of immaturity and greatly improve survival and neurite growth of cocultured neurons by increasing cell-cell contact and secreting diffusible factors. Moreover, our data suggest that the absence of vimentin is not a key element in the permissivity of the mutant astrocytes. Finally, we show that only the absence of GFAP is associated with an increased expression of some extracellular matrix and adhesion molecules. To conclude, our results suggest that GFAP expression is able to modulate key biochemical properties of astrocytes that are implicated in their permissivity.


Asunto(s)
Proteína Ácida Fibrilar de la Glía/biosíntesis , Proteínas del Tejido Nervioso , Moléculas de Adhesión de Célula Nerviosa/biosíntesis , Neuritas/metabolismo , Neuronas/metabolismo , Vimentina/biosíntesis , Animales , Astrocitos/metabolismo , Astrocitos/ultraestructura , Cadherinas/metabolismo , Adhesión Celular/fisiología , Recuento de Células , Supervivencia Celular/genética , Células Cultivadas , Técnicas de Cocultivo , Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Marcación de Gen , Proteína Ácida Fibrilar de la Glía/deficiencia , Proteína Ácida Fibrilar de la Glía/genética , Proteínas de Filamentos Intermediarios/biosíntesis , Filamentos Intermedios/metabolismo , Filamentos Intermedios/ultraestructura , Ratones , Ratones Endogámicos , Ratones Noqueados , Modelos Biológicos , Nestina , Moléculas de Adhesión de Célula Nerviosa/metabolismo , Neuritas/ultraestructura , Neuronas/citología , Vimentina/deficiencia , Vimentina/genética
4.
Neuroscience ; 95(1): 173-82, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10619473

RESUMEN

Transection of the spinal cord yields a permanent deficit due to the interruption of descending and ascending tracts which subserve the supraspinal control of spinal cord functions. We have shown previously that transplantation below the level of the section of embryonic monoaminergic neurons can promote the recovery of some segmental functions via a local serotonergic and noradrenergic reinnervation. Moreover, the up-regulation of the corresponding receptors resulting from the section was corrected by the transplants. The aim of the present work was to determine whether such a graft could also influence non-monoaminergic local neurons, the GABAergic interneurons of the spinal cord. Following spinal cord transection, the number of cells which express glutamate decarboxylase (mol. wt 67,000) messenger RNA--a marker of GABA synthesis--increased significantly below the lesion compared with the intact animal. In contrast, in lesioned animals which had been grafted one week later with raphe neuroblasts, this number was close to control level. These post-grafting modifications were further associated with increased GABA immunoreactivity in the host tissue. These data suggest that the graft of embryonic raphe cells which compensates the deficit of serotonin in the distal segment also regulates the expression of the GABAergic phenotype in the host spinal cord. This regulation could be mediated by the re-establishment of a local functional innervation by both serotonin and GABAergic transplanted neurons and/or by trophic factors released from the embryonic cells. It appears then that grafted cells influence the host tissue in a complex manner, through the release and/or regulation of several neurotransmitter systems.


Asunto(s)
Trasplante de Células , Trasplante de Tejido Fetal , Núcleos del Rafe/embriología , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/cirugía , Ácido gamma-Aminobutírico/metabolismo , Animales , Embrión de Mamíferos/citología , Femenino , Inmunohistoquímica , Hibridación in Situ , Interneuronas/fisiología , Fenotipo , Núcleos del Rafe/citología , Ratas , Ratas Sprague-Dawley , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/patología
5.
Histol Histopathol ; 16(3): 883-93, 2001 07.
Artículo en Inglés | MEDLINE | ID: mdl-11510980

RESUMEN

Treatment of neurodegenerative diseases by classical pharmacotherapy is restricted by blood-brain barrier which prevents access to the brain of potentially therapeutic molecules. Recent progress in the knowledge of pathophysiological molecular processes, and in the development of molecular biotechnology have opened the way to new therapeutic interventions for these disorders. This chapter reviews the most recent gene therapy strategies using experimental models for neurodegenerative diseases.


Asunto(s)
Terapia Genética/métodos , Enfermedades Neurodegenerativas/terapia , Enfermedad de Alzheimer/terapia , Esclerosis Amiotrófica Lateral/terapia , Animales , Sordera/terapia , Vectores Genéticos , Humanos , Enfermedad de Huntington/terapia , Neuronas , Enfermedad de Parkinson/terapia , Trastornos Parkinsonianos/terapia , Regiones Promotoras Genéticas , Retinitis Pigmentosa/terapia
6.
Histol Histopathol ; 19(1): 271-80, 2004 01.
Artículo en Inglés | MEDLINE | ID: mdl-14702195

RESUMEN

A great deal of interest has attracted the attention of researchers on the potential use of (neural) stem cells in cell replacement or restorative therapies for heretofore incurable CNS pathologies such as brain stroke, spinal cord injury, Parkinson's disease or multiple sclerosis. This short perspective illustrates our view of neural stem cell research with a focus on the stem cell concept, on the in situ identity of neural stem cells and on selected aspects of embryonic and adult neurogenesis. A brief survey of current stem cell-based experimental literature tries to provide a realistic picture of how far we have gone in the quest to establish a restorative neurology.


Asunto(s)
Neurología , Neuronas/citología , Células Madre/citología , Animales , Diferenciación Celular , Humanos , Esclerosis Múltiple/terapia , Enfermedad de Parkinson/terapia , Investigación , Traumatismos de la Médula Espinal/terapia , Accidente Cerebrovascular/terapia
7.
Ann N Y Acad Sci ; 860: 393-411, 1998 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-9928327

RESUMEN

Severe traumatic lesions of the spinal cord yield a permanent deficit of motricity in adult mammals and specifically a loss of locomotor activity of hindlimbs when the lesion is located at the lower thoracic level. To restore this function, we have developed a paradigm of transplantation in rats based on a transection model of the spinal cord and the subsequent injection at the sublesional level of a suspension of embryonic brainstem monoaminergic neurons which play a key role in the modulation of locomotion. A genuine locomotion was characterized in transplanted animals by electromyographic and electroneurographic recordings. This correlated with a specific reinnervation pattern of targets, where typical synapses were found, and with the normalization of biochemical parameters.


Asunto(s)
Locomoción/fisiología , Neuronas Motoras/trasplante , Paraplejía/cirugía , Traumatismos de la Médula Espinal/cirugía , Médula Espinal , Animales , Aminas Biogénicas/fisiología , Neuronas Motoras/química , Neuronas Motoras/fisiología , Paraplejía/fisiopatología , Paraplejía/rehabilitación , Ratas , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/rehabilitación
8.
Neuroreport ; 6(18): 2473-8, 1995 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-8741745

RESUMEN

Several growth factors are candidates for the therapy of motor neurone diseases. However, there is no efficient, safe, and practicable administration route which hampers the clinical use of these potentially therapeutic agents. We show that specific and high yield gene transfer into motor neurones can be obtained by peripheral intramuscular injections of recombinant adenoviruses. These vectors are retrogradely transported from muscular motor units to motor neurone cell bodies. Gene transfer can thus be specifically targeted to particular regions of the spinal cord by appropriate choice of the injected muscle. The efficiency of gene transfer is high, with 58-100% of the motor neurones afferent to the injected muscle expressing the transgene. This new therapeutic protocol allows specific targeting of motor neurones without lesioning the spinal cord, and should avoid undesirable side effects associated with systemic administration of therapeutic factors.


Asunto(s)
Técnicas de Transferencia de Gen , Enfermedad de la Neurona Motora/terapia , Médula Espinal/enzimología , Animales , Recuento de Células , Masculino , Neuronas Motoras/enzimología , Ratas , Ratas Sprague-Dawley , beta-Galactosidasa/metabolismo
9.
Neuroreport ; 7(1): 373-8, 1995 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-8742491

RESUMEN

Several growth factors are candidates for the therapy of motor neurone diseases. However, there is no efficient, safe, and practicable administration route which hampers the clinical use of these potentially therapeutic agents. We show that specific and high yield gene transfer into motor neurones can be obtained by peripheral intramuscular injections of recombinant adenoviruses. These vectors are retrogradely transported from muscular motor units to motor neurone cell bodies. Gene transfer can thus be specifically targeted to particular regions of the spinal cord by appropriate choice of the injected muscle. The efficiency of gene transfer is high, with 58-100% of the motor neurones afferent to the injected muscle expressing the transgene. This new therapeutic protocol allows specific targeting of motor neurones without lesioning the spinal cord, and should avoid undesirable side effects associated with systemic administration of therapeutic factors.


Asunto(s)
Adenoviridae/genética , Técnicas de Transferencia de Gen , Terapia Genética , Vectores Genéticos , Enfermedad de la Neurona Motora/terapia , beta-Galactosidasa/genética , Animales , Código Genético , Inyecciones Intramusculares , Masculino , Factores de Crecimiento Nervioso/genética , Ratas , Ratas Sprague-Dawley
10.
Brain Res ; 707(2): 245-55, 1996 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-8919302

RESUMEN

The synaptic connections established by grafted noradrenergic (NA) neurons into the lesioned adult rat spinal cord were analysed using immunocytochemistry at the electron microscopic level. An embryonic cell suspension of the locus coeruleus region from E-13 rat embryos was transplanted into the spinal cord following either: (1) spinal cord transection or (2), partial selective denervation by 6-hydroxy dopamine (6-OH DA). One month after grafting, the NA-neurons established, in the two models, an innervation pattern similar to that found in the intact spinal cord. In both models, the transplanted NA-immunoreactive neurons formed extensive synaptic contacts with dendrites, spines and perikarya. The proportion of axodendritic and axospinous contacts was inverse in the two models. The first model thus reproduced more closely the normal synaptic pattern prefering dendritic targets, which could correspond to a better integration of the graft. In the second model, a partially NA-denervated spinal cord, there existed a competition between residual intrinsic and grafted neuron-derived fibres, which presumably affects synaptogenesis. In conclusion, the present study illustrate the complexity of cell interations conducting to the formation of a specific circuitry. Recognition phenomenon are likely modulated by space constraints, which ultimately shape-up the geometry of synaptic contacts.


Asunto(s)
Trasplante de Tejido Encefálico/fisiología , Trasplante de Células/fisiología , Trasplante de Tejido Fetal/fisiología , Neuronas/trasplante , Norepinefrina/fisiología , Traumatismos de la Médula Espinal/cirugía , Vías Aferentes/fisiología , Animales , Inmunohistoquímica , Locus Coeruleus/citología , Locus Coeruleus/trasplante , Masculino , Oxidopamina , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/patología , Simpatectomía Química , Sinapsis/fisiología , Sinapsis/ultraestructura
11.
Brain Res ; 677(1): 1-12, 1995 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-7606453

RESUMEN

This study examined, in the adult rat, whether the intraspinal transplantation of a cell suspension of embryonic day (ED)13 rat locus coeruleus primordia was able to normalize the lesion-induced increase of spinal alpha 1-adrenoceptors. Two experimental models of spinal denervation were studied. The first model consisted of a complete spinal cord transection (thoracic vertebrae level T8-T9) and 1 week later, the cell suspension was transplanted below the section; the second one was obtained by a selective chemical lesion of the noradrenergic (NA) system and one month later, the cell suspension was implanted at the same level as in transected rats. Five weeks after grafting, all animals were sacrificed and spinal cord tissue sections were processed for immunohistochemical detection of noradrenaline or for quantification of alpha 1-adrenoceptors binding sites densities using [3H]prazosin as a ligand. After 6-OHDA lesion, as well as caudally to the transection, a significant increase by 21% (P < 0.01) to 68% (P < 0.001) of alpha 1-adrenoceptors densities was detected. The implantation of embryonic NA neurons into the denervated spinal cord led to a reversal of the lesion-induced increase of spinal alpha 1-adrenoceptors, five weeks later. Moreover, this reversal seems to be more effective after mechanical than after chemical denervation.


Asunto(s)
Trasplante de Tejido Encefálico/fisiología , Trasplante de Células/fisiología , Trasplante de Tejido Fetal/fisiología , Locus Coeruleus/trasplante , Norepinefrina/fisiología , Receptores Adrenérgicos alfa 1/metabolismo , Médula Espinal/fisiología , Animales , Autorradiografía , Inmunohistoquímica , Masculino , Norepinefrina/metabolismo , Oxidopamina , Prazosina , Ratas , Ratas Sprague-Dawley , Médula Espinal/metabolismo , Simpatectomía Química
12.
Brain Res Dev Brain Res ; 111(2): 147-57, 1998 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-9838085

RESUMEN

We have investigated in this study the influence of a moderate hypergravity (1.8 G) on the development of monoaminergic projections to the spinal cord in the rat. Pregnant dams and their offspring were submitted to hypergravity from day 11 of gestation to postnatal day 15. Some animals were sacrificed at birth, other at postnatal day 15 and other after 8 months of normal gravity. In newborn animals, a substantial delay of the development of monoaminergic projections to the spinal cord was evidenced. In 15 days and 8 months animals, the pattern of innervation appeared anarchic, with numerous dystrophic profiles, mainly of serotonergic system. Ultrastructural examination of serotonergic projections revealed a paucity of synapses, and the frequent enveloping of serotonergic boutons by thin astrocytic profiles. We conclude that rats submitted to hypergravity during the critical period of onset of monoaminergic projections to the spinal cord are affected durably in the organization and the ultrastructure of these projections. Future studies are directed to the functional analysis of hypergravity animals, and to the influence of microgravity on the same system.


Asunto(s)
Gravedad Alterada , Serotonina/análisis , Médula Espinal/química , Médula Espinal/embriología , Animales , Centrifugación , Femenino , Microscopía Electrónica , Neuronas/química , Neuronas/ultraestructura , Embarazo , Ratas , Ratas Sprague-Dawley , Médula Espinal/citología
13.
Rev Neurol (Paris) ; 153(8-9): 515-20, 1997 Sep.
Artículo en Francés | MEDLINE | ID: mdl-9684001

RESUMEN

The dogma of abortive axonal regrowth set by Cajal (1914) is now broken since the demonstration by Aguayo (1982) that severed axons can regrow in an appropriate environment. Over the last decade, the impediments to such a regrowth in the central nervous system of higher vertebrates have been identified, or, at least, some of them. On the one hand, the inhibitory molecules synthesized and secreted by oligodendrocytes have been counteracted by appropriate antibodies (Schnell & Schwab, 1990), which have permitted some regrowth of severed cortico-spinal axons in the rat spinal cord. On the other hand, the reduction by a pharmacological treatment of hypertrophy and hyperplasia of astrocytes has permitted some regrowth of monoaminergic axons in an hemisected cord (Gimenez y Ribotta et al. 1995). Finally, the identification of a subcategory of astrocytes, the tanycytes of the basal hypothalamus, as a permissive substrate for axonal regeneration opens a new avenue for future research.


Asunto(s)
Axones/fisiología , Regeneración Nerviosa , Neuroglía/fisiología , Animales , Astrocitos/fisiología , Humanos , Oligodendroglía/fisiología , Ratas
17.
J Neurosci Res ; 57(1): 117-23, 1999 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-10397641

RESUMEN

To investigate the characteristics of neurotropic signaling involved in specific target recognition by grafted embryonic serotonergic cells, we have developed an in vitro grafting model. Specific raphe nuclei (B1/B2 and B3) were respectively dissected from 14-day-old rat embryos, and partially dissociated cells were cocultured on spinal cord slices from 20-day-old fetuses. After serotonin immunodetection, neurite growth patterns were analyzed by standard photonic or confocal scanning microscopy. Computer reconstruction (maximal signal projection) was used to track individual neurites in spite of their changing depth levels. Whereas the direction and branching of the initial neurite segments did not seem to be significantly influenced by any specific environment, specific growth patterns were developed at some distance from the cell bodies, indicating that neurites are able to recognize their specific targets.


Asunto(s)
Neuronas/fisiología , Núcleos del Rafe/fisiología , Médula Espinal/fisiología , Animales , Técnicas de Cocultivo , Inmunohistoquímica , Microscopía Confocal , Neuritas/metabolismo , Neuritas/fisiología , Neuronas/trasplante , Núcleos del Rafe/citología , Núcleos del Rafe/embriología , Ratas , Ratas Sprague-Dawley , Serotonina/metabolismo , Médula Espinal/embriología
18.
Curr Opin Neurol ; 11(6): 647-54, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9870132

RESUMEN

Spinal cord injury is frequently followed by the loss of supraspinal control of sensory, autonomus and motor functions at sublesional level. To enhance recovery in patients with spinal cord injuries, three fundamental strategies have been developed in experimental models. These strategies involve three different time points for postlesional intervention in the spinal cord. Neuroprotection soon after injury uses pharmacological tools to reduce the progressive secondary injury processes that follow during the first week after the initial lesion occurs, in order to limit tissue damage. A second strategy, which is initiated shortly after the lesion occurs, aims at promoting axonal regeneration by acting pharmacologically on inhibitors or barriers of regeneration, or by the application of cell or gene therapy as a source of neurotrophic factors or as a bridge or support to enhance the regeneration of lesioned axons. Finally, a mid-term substitutive strategy is the management of the sublesional spinal cord by sensorimotor stimulation or the supply of missing key afferents, such as monoaminergic systems. These three strategies are reviewed. Only a combination of these different approaches can provide an optimal basis for potential therapeutic interventions aimed at functional recovery after spinal cord injury.


Asunto(s)
Traumatismos de la Médula Espinal/rehabilitación , Animales , Tratamiento Basado en Trasplante de Células y Tejidos , Terapia Genética , Humanos , Factores de Crecimiento Nervioso , Regeneración Nerviosa/efectos de los fármacos , Regeneración Nerviosa/fisiología , Proteínas del Tejido Nervioso/administración & dosificación , Fármacos Neuroprotectores/administración & dosificación , Médula Espinal/efectos de los fármacos , Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Resultado del Tratamiento
19.
Proc Natl Acad Sci U S A ; 100(15): 8999-9004, 2003 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-12861073

RESUMEN

The lack of axonal regeneration in the injured adult mammalian spinal cord leads to permanent functional disabilities. The inability of neurons to regenerate their axon is appreciably due to an inhospitable environment made of an astrocytic scar. We generated mice knock-out for glial fibrillary acidic protein and vimentin, the major proteins of the astrocyte cytoskeleton, which are upregulated in reactive astrocytes. These animals, after a hemisection of the spinal cord, presented reduced astroglial reactivity associated with increased plastic sprouting of supraspinal axons, including the reconstruction of circuits leading to functional restoration. Therefore, improved anatomical and functional recovery in the absence of both proteins highlights the pivotal role of reactive astrocytes in axonal regenerative failure in adult CNS and could lead to new therapies of spinal cord lesions.


Asunto(s)
Proteína Ácida Fibrilar de la Glía/deficiencia , Traumatismos de la Médula Espinal/fisiopatología , Vimentina/deficiencia , Animales , Astrocitos/fisiología , Axones/fisiología , Femenino , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ratones Noqueados , Actividad Motora , Regeneración Nerviosa , Plasticidad Neuronal , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/terapia , Vimentina/genética , Vimentina/fisiología
20.
Exp Brain Res ; 113(3): 443-54, 1997 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-9108211

RESUMEN

Locomotor movements are programmed in a specialised neuronal network that is localised in the central nervous system and referred to as the central pattern generator (CPG) for locomotion. This CPG can be activated by pharmacological agents such as monoamines. The aim of the present study was to try to activate the CPGs by using cells that are supposed to release serotonin locally. Adult chronic spinal rats were injected with embryonic brainstem neurons within the spinal cord under a thoracic transection. This procedure resulted in a monoaminergic reinnervation of the lumbar enlargement. With the help of a specific neurotoxin for noradrenergic neurons (6-hydroxydopamine), it was possible to isolate the serotonergic system. After such transplantation of monoaminergic neurons and even with serotonergic neurons alone, a bilateral, alternating, rhythmic locomotor-like activity recovered in hindlimbs. Furthermore, this locomotor-like activity was clearly facilitated when the re-uptake of serotonin was blocked by zimelidine. Therefore, we conclude that transplanted embryonic serotonergic neurons are able to activate the CPG for locomotion.


Asunto(s)
Locomoción/fisiología , Fenómenos Fisiológicos del Sistema Nervioso , Neuronas/trasplante , Serotonina/metabolismo , Médula Espinal/trasplante , Animales , Femenino , Ratas , Ratas Sprague-Dawley
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