RESUMO
Following spinal cord injury (SCI), the pathological sequelae which ensue through the secondary mechanisms of degeneration produce myelin deposits which are potent inhibitors of endogenous neuroregeneration. We have enhanced the immune-mediated response following a hemisection lesion by immunizing adult C57Bl/6 female mice against the inhibitor of neurite outgrowth Nogo-A(623-640) peptide. Moderate anti-Nogo-A(623-640) antibody titre levels were obtained by using Montanide as the adjuvant. However, this antibody response was not obtained using incomplete Freund's adjuvant (IFA). Significant benefit in locomotor performance was demonstrated only in animals which were vaccinated with IFA and not with Montanide. No further benefit could be demonstrated with the Nogo-A(623-640) peptide beyond that seen for adjuvant alone. These data imply that generating antibodies against Nogo-A(623-640) in vivo alone is not sufficient to enhance locomotor recovery and that subcutaneous injection of IFA prior to SCI can enhance locomotor performance.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Adjuvante de Freund/uso terapêutico , Lipídeos/uso terapêutico , Atividade Motora/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas da Mielina/imunologia , Proteínas Nogo , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
Adult neural precursor cells (NPCs) in the mammalian central nervous system (CNS) have been demonstrated to be responsive to conditions of injury and disease. Here we investigated the response of NPCs in mouse models of spinal cord disease [motor neuron disease (MND)] with and without sciatic nerve axotomy, and spinal cord injury (SCI). We found that neither axotomy, nor MND alone brought about a response by Nestin-positive NPCs. However, the combination of the two resulted in mobilization of NPCs in the spinal cord. We also found that there was an increase in the number of NPCs following SCI which was further enhanced by systemic administration of the neuregulatory cytokine, leukaemia inhibitory factor (LIF). NPCs were demonstrated to differentiate into astrocytes in axotomized MND mice. However, significant differentiation into the various neural cell phenotypes was not demonstrated at 1 or 2 weeks following SCI. These data suggest that factors inherent to injury mechanisms are required for induction of an NPC response in the mammalian spinal cord.
Assuntos
Modelos Animais de Doenças , Neurônios/fisiologia , Doenças da Medula Espinal/patologia , Células-Tronco/fisiologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Axotomia/métodos , Contagem de Células/métodos , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica/métodos , Marcação In Situ das Extremidades Cortadas/métodos , Interleucina-6/farmacologia , Proteínas de Filamentos Intermediários/metabolismo , Fator Inibidor de Leucemia , Subunidade alfa de Receptor de Fator Inibidor de Leucemia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/metabolismo , Nestina , Neurônios/classificação , Neurônios/efeitos dos fármacos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores de Citocinas/metabolismo , Receptores de OSM-LIF , Neuropatia Ciática/metabolismo , Neuropatia Ciática/fisiopatologia , Doenças da Medula Espinal/metabolismo , Doenças da Medula Espinal/fisiopatologia , Células-Tronco/efeitos dos fármacos , Superóxido Dismutase/genéticaRESUMO
In the superoxide dismutase 1 (SOD1)(G93A G1H) transgenic mouse, the primary pathology and disease signs are associated with the degeneration of motor neurons in the lumbar spinal cord. It is unclear if the descending motor pathways from the cortex and brainstem are also compromised. The retrograde tracer Fluorogold was inserted into the T(12) segment of the spinal cord and the number of labelled neurons counted in the sensorimotor cortex and brainstem of 60, 90 and 110 day-old mice. A small loss of corticospinal and bulbospinal projections was detected at 60 days. By 110 days, 53% of corticospinal, 41% of bulbospinal and 43% of rubrospinal neurons were lost. The progressive loss of corticospinal axons was confirmed using the stereological fractionator method. These findings suggest that the expression of the SOD1(G93A G1H) mutant protein results in a disease that resembles the late stages of human motor neuron disease. This involves not only the destruction of lower motor neurons in the spinal cord, but also additional loss of descending cortical and bulbar neurons.
Assuntos
Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Córtex Cerebral/patologia , Degeneração Neural/patologia , Medula Espinal/patologia , Superóxido Dismutase/genética , Animais , Axônios/fisiologia , Tronco Encefálico/patologia , Tronco Encefálico/fisiologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Vias Neurais/patologiaRESUMO
A fusion protein containing the alternately spliced Extra Domain B [ED-B(+)] sequence of canine fibronectin was expressed in E. coli and the purified protein was used to produce an antibody specific for the ED-B(+) segment. This antibody recognized canine cartilage fibronectin but not canine plasma or synovial fluid fibronectin. Using this antibody, it was determined that ED-B(+) fibronectin increased proportionally with the total fibronectin in osteoarthritic cartilage. From this result, it was concluded that the chondrocyte is the source of much of the elevated fibronectin that appears in osteoarthritic cartilage.
