El trauma raquimedular

A medula espinhal dos mamíferos adultos não permite a regeneração de axônios. Por razões ainda desconhecidas, as fibras neurais falham em cruzar o sítio da lesão, como se não houvesse crescimento, desde a primeira tentativa. Quais mecanismos poderiam explicar a perda da capacidade de regeneração? As cicatrizes formadas pelas células da glia seriam uma consequência da falha na regeneração ou a causa? Diversas linhas de evidência sugerem que a regeneração da medula espinhal seria impedida no sistema nervoso central pela ação de fatores locais no sítio da lesão, e que o sistema nervoso central não-lesado é um meio permissivo para o crescimento axonal, na direção de alvos específicos. Uma vez que os axônios são induzidos adequadamente a cruzar a lesão com o auxílio de implantes, fármacos ou células indiferenciadas, as fibras em regeneração podem encontrar a via específica e estabelecer conexões corretas. O que ainda não se sabe é que combinação de moléculas induz/inibe o potencial de regeneração do tecido e que mecanismos permitem aos neurônios formarem conexões específicas com os alvos com os quais são programados a fazer.The adult mammal spinal cord does not allow axons regeneration. For unknown reasons, the neural fibers fail in coming across the site of the lesion, as if there were no growing from the first try. What mechanisms may explain the lost of regeneration capability? Are scars formed by glial cells a consequence of regeneration fail or the cause? Several evidence lines suggest that spinal cord regeneration would be blocked in the central nervous system by actions of local factors in the site of the wound, and no injured central nervous system is a permissive way for the axonal growing into specific targets. If axons are correctly induced to cross the injury, supported by implants, drugs and undifferentiated cells, the fibers in regeneration may find a specific way to establish the right connections. The combination of molecules which induce/inhibit the regeneration potential of the tissue remains unknown, as well as the mechanisms that enable the neuron to make specific connections with targets it is programmed to connect with.La medula espinal de los mamíferos adultos no permite la regeneración de los axones. Por razones aun no conocidas, las fibras neurales fallan en la tarea de cruzar por el sitio de la lesión, como si no hubiese crecimiento, desde el primer intento. ¿Cuáles mecanismos podrían explicar la pérdida de la capacidad de la regeneración? ¿Las cicatrices formadas por las células de la glía son una consecuencia del fallo en la regeneración o serían la causa? Diversas líneas de evidencia sugieren que la regeneración de la medula espinal sería impedida en el sistema nervioso central por la acción de factores locales en el sitio de la lesión, y que el sistema nervioso central no lesionado es un medio permisivo para el crecimiento axonal, en la dirección de dianas específicas. Una vez que los axones sean inducidos adecuadamente a cruzar la lesión, con auxilio de implantes, fármacos o células indiferenciadas, las fibras en regeneración podrían encontrar la vía específica y establecer conexiones correctas. Lo que aun es desconocido es que combinación de moléculas induce/inhibe el potencial de regeneración del tejido y cuáles mecanismos permiten a las neuronas formar conexiones específicas, con las dianas que son programadas a hacer.FAPESPCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)CNP

Nitric oxide system and basal ganglia physiopathology

Nitric oxide (NO) is a pleiotropic molecule that is needed for physiological functions, especially in the brain NO induces vasodilatation, inhibits apoptosis and plays an important role in memory processes. A population of interneurons has been distinguished in the striatum by nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining, an enzyme that is identical with NO synthase (NOS). These interneurons are aspiny cells with dendritic branches and axonal arborisation extending to form a wide field. Single action potentials in these cells produce large inhibitory postsynaptic currents in medium-sized spiny neurons. Release of NO from these neurons facilitates the concurrent release of dopamine and glutamate (GLU). Although the influence of NOS-positive interneurons on striatal neuronal activity remains to be thoroughly characterized, evidence has accumulated suggesting that NO signaling may mediate and/or regulate multiple aspects of striatal neurotransmission. Striatal NO signaling has a major impact on the responsiveness of dopaminergic (DA) neurons to electrical stimulation of the striatum and to some extent, the prefrontal cortex. Moreover, it is likely that NO signalling plays an important role in regulating the activity of striatal output neurons. Thus, striatal NOS interneurons may be critically involved in integrating corticostriatal sensorimotor information within striatal networks and synchronizing the activity of functionally related striatonigral sub-systems. Our studies showed that systemic injections of the inhibitors of NOS decrease either elevate plus maze exploration or rearing in an open field arena. These results may involve motor effects of these compounds, since inhibitors of NOS induced catalepsy in mice. This effect was also found in rats after systemic, intracebroventricular or intrastriatal administration. Chronic NO synthesis inhibition induces plastic changes in NO producing neurons in areas related to motor control. In the same way, the application of NOS inhibitor twice a day, during four days caused cross-tolerance to the cataleptic effect of haloperidol. This raises the possibility that such treatments could decrease motor side effects associated with antipsychotic medications. However, NO can be harmful mainly under oxidative stress conditions due to the oxidation and nitrotyrosilation of functional proteins. Considerable existing evidences indicate a role for NO–DA interactions in pathophysiological conditions such as Parkinson's disease (PD) and schizophrenia. However, the findings on the impact of nitrergic mechanisms in schizophrenia and PD are contradictory. In addition, the slow progression of these diseases, complicates experimental approaches to modeling their pathophysiological mechanism. Inducing experimental Parkinson in rats we found an interaction between NO system and neurodegenerative processes in the nigrostriatal pathway. Because NOS is an enzyme widely distributed and involved in a plethora of necessary physiological responses inside and outside the brain, the role of NO in human neurodegenerative disease is not as easily understood.peer-reviewe

Influencia del estrechamiento del canal vertebral y del tiempo para la descompresión en la recuperación locomotora de ratas

OBJETIVO: o objetivo deste trabalho foi estudar as consequências da lesão por contusão da medula espinhal, associada ao estreitamento do canal vertebral, no comportamento motor de ratos, avaliando-se o efeito do tempo para descompressão na recuperação neurológica dos animais. MÉTODOS: foram utilizados ratos Wistar machos (n=6 por grupo), subdivididos nos seguintes grupos experimentais: laminectomia (T9-T10, Grupo Controle), contusão por queda de peso (10 g de peso, 15 cm de altura), estreitamento do canal vertebral em 35% (hastes de policarbonato; espessura de 0,78 mm) e contusão associada ao estreitamento do canal vertebral. O grupo de lesão associada foi ainda subdividido em sem ou com descompressão 24 ou 72 horas após a cirurgia. Os animais foram sacrificados sete dias após os procedimentos cirúrgicos. A função locomotora dos animais foi avaliada por meio do teste do campo aberto, do teste do plano inclinado e pela aplicação da escala BBB, antes da cirurgia, 24 e 72 horas depois da cirurgia e após 7 dias do procedimento cirúrgico. RESULTADOS: a lesão por queda de peso e compressão da medula espinhal, bem como a lesão mista, prejudicaram o comportamento motor dos animais, sendo que a descompressão cirúrgica após 24 e 72 horas da cirurgia não melhorou a recuperação motora dos animais, como mostram os resultados da avaliação de campo aberto, no plano inclinado e pela escala BBB. Por outro lado, os animais que sofreram lesão medular por queda de peso apresentaram melhores escores na escala BBB e ângulos maiores no plano inclinado do que aqueles que sofreram lesão por estreitamento do canal vertebral ou lesão mista. CONCLUSÕES: a lesão por queda de peso ou estreitamento do canal vertebral provocou alterações no comportamento motor dos animais, sendo que a descompressão não trouxe melhora funcional significativa.OBJECTIVE: the aim of this study was to investigate the consequences of contusion injury of spinal cord associated with narrowing of vertebral canal on motor behavior of rats, as assessing the effect of decompression time on the neurologic recovery of the animals. METHODS: male Wistar rats (n=6 per group) were divided into three experimental groups: submitted to laminectomy (T9-T10, Control Group), contusion due to weight drop (10 g from a height of 15 cm), 35% narrowing of the vertebral canal obtained with 0.78 mm thick polycarbonate rods and contusion injury associated with narrowing of the vertebral canal. In this last group, decompression was not performed or it was made after 24 or 72 hours of the surgery, as the animals were divided into subgroups. Rats were sacrificed seven days after surgical procedures. The motor behavior of the animals was assessed in open arena, inclined plane and by means of Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, before and after 24, 48 hours and 7 days of surgical procedures. RESULTS: contusion injury, narrowing of the spinal canal and mixed injury impaired the motor behavior of the animals. Surgical decompression (24 and 72 hours) did not improve motor recovery as assessed in open arena, BBB scale and inclined plane test. On the other hand, animals injured with weight drop showed better scores on BBB scale and higher angles in the inclined plane when compared to the ones that were injured with narrowing of the vertebral canal and mixed lesion. CONCLUSIONS: spinal cord injury by weight drop and narrowing of the vertebral canal induced alterations on the motor behavior, which did not significantly improve with decompression.OBJETIVO: estudiar las consecuencias de la lesión por contusión de la médula espinal, asociada al estrechamiento del canal vertebral en el comportamiento de ratas, evaluando el efecto del tiempo para la descompresión en la recuperación neurológica de los animales. MÉTODOS: fueron utilizadas ratas Wistar machos (n=6, por grupo), subdivididos en los siguientes grupos experimentales: laminectomía (T9-T10, Grupo Control), contusión por caída de peso (10 g de peso, 15 cm de altura), estrechamiento del canal vertebral de 35% (astas de policarbonato; espesura de 0.78 mm) y contusión asociada al estrechamiento del canal vertebral. El grupo de lesión asociada fue subdividido en sin o con descompresión, 24 o 72 horas después de la cirugía. Los animales fueron sacrificados siete días después de los procedimientos quirúrgicos. La función locomotora de los animales fue evaluada por medio del teste de campo abierto, del plano inclinado y por la aplicación de la escala BBB, antes de la cirugía, 24, 72 horas y 7 días después del procedimiento quirúrgico. RESULTADOS: la lesión por caída de peso y compresión de la médula espinal, así como la lesión mixta perjudicaron el comportamiento motor de los animales, siendo que la descompresión quirúrgica 24 y 72 horas después de la cirugía no mejoró la recuperación motora de los animales, cuando los mismos fueron evaluados en el campo abierto, en el plano inclinado y por la escala BBB. Por otro lado, los animales que sufrieron lesión medular por caída de peso presentaron mejores índices en la escala BBB y ángulos mayores en el plano inclinado, cuando comparados con aquellos que sufrieron lesión por estrechamiento del canal vertebral o la lesión mixta. CONCLUSIONES: la lesión por caída de peso o estrechamiento del canal vertebral provocó alteraciones en el comportamiento motor de los animales, siendo que la descompresión no trajo mejoría funcional significativa

c-fos, Um gene de ativação imediata como marcador neural de nocicepção

A dor é uma experiência complexa, que inclui componentes sensoriais e afetivos, sendo composta por sensações de desprazer, essenciais para o ser humano. A manifestação clínica da dor pode ser interpretada como expressão da capacidade de resposta plástica do sistema nervoso. Existem evidências de que os estímulos nocivos poderiam, também, produzir variações de longa duração nos processos celulares, no SNC, através da modulação da expressão dos genes de ativação imediata como o c-fos e o c-jun. Assim, a distribuição da proteína Fos, em áreas do SNC, após estimulação nociva, térmica, inclui: 1)estruturas envolvidas com respostas emocionais que parecem participar do componente afetivo da dor (núcleos do complexo amigdalóide, hipotálamo e componentes límbicos corticais); 2) estruturas classicamente relacionadas à nocicepção, porém também com atuação sobre o componente afetivo da dor (substância cinzenta, periaquedutal e núcleos da rafe); e 3) áreas com evidências de forte participação na modulação de impulsos nociceptivos (substância cinzenta, periaquedutal e núcleo pré-tectal, anterior). A expressão da proteína Fos, induzida por estímulo nocivo, pode também ter relação com neuroplasticidade à dor patológica e hiperalgesia, bem como com o efeito profilático da “preemptive” analgesia na dor pós-cirúrgica. Enfim, atuando como “terceiros mensageiros” nucleares, o c-fos poderia estimular a síntese de peptídeos opióides, que desempenhariam um papel na modulação da dor. Paralelamente, esse gene pode ser usado como um marcador transináptico de atividade neuronal, após estímulos nocivos, permitindo o estudo de grandes populações de neurônios através da marcação de estruturas centrais, ativadas por estímulo periférico.Pain is a complex experience that involves sensorial and affective components, and is composed by displeasure sensation, which are important for human being. Clinical manifestation of pain may be understood as the expression of nervous system ability for plastic response. There is evidence showing that nocive stimulation could also induce long-term variation in CNS cellular processes by modulating the expression of immediate early genes such as c-fos and c-jun. Fos protein distribution in CNS areas following heat nocive stimulation includes: 1)structures involved in emotional responses that seem to play a role in the affective component of pain (amygdaloid complex, hypothalamus, and cortical limbic structures); 2) structures usually responsible for descending pain control systems, that also play a role in the affective component of pain (periaqueductal gray and raphe nuclei); and 3) regions with evidence of taking part on the modulation of nociceptive impulse (periaqueductal gray and anterior pretectal nucleus). Expression of Fos protein in CNS following nocive stimuli may also be related to neuroplasticity in pathological pain and hiperalgesia, as well as to the prolific effect of the “pre-emptive” analgesia in pain following surgeries. In addition, as a nuclear “third messenger”, c-fos could stimulate synthesis of opioid peptide, which would play a role in pain modulation. Finally, this gene could be used as a transinaptic marker for neuronal activity, which allow the study of large neuronal population of structures that are activated by periferic stimulation

Serotonin receptors are involved in the spinal mediation of descending facilitation of surgical incision-induced increase of Fos-like immunoreactivity in rats

<p>Abstract</p> <p>Background</p> <p>Descending pronociceptive pathways may be implicated in states of persistent pain. Paw skin incision is a well-established postoperative pain model that causes behavioral nociceptive responses and enhanced excitability of spinal dorsal horn neurons. The number of spinal c-Fos positive neurons of rats treated intrathecally with serotonin, noradrenaline or acetylcholine antagonists where evaluated to study the descending pathways activated by a surgical paw incision.</p> <p>Results</p> <p>The number of c-Fos positive neurons in laminae I/II ipsilateral, lamina V bilateral to the incised paw, and in lamina X significantly increased after the incision. These changes: remained unchanged in phenoxybenzamine-treated rats; were increased in the contralateral lamina V of atropine-treated rats; were inhibited in the ipsilateral lamina I/II by 5-HT_1/2B/2C(methysergide), 5-HT_2A(ketanserin) or 5-HT_{1/2A/2C/5/6/7}(methiothepin) receptors antagonists, in the ipsilateral lamina V by methysergide or methiothepin, in the contralateral lamina V by all the serotonergic antagonists and in the lamina X by LY 278,584, ketanserin or methiothepin.</p> <p>Conclusions</p> <p>We conclude: (1) muscarinic cholinergic mechanisms reduce incision-induced response of spinal neurons inputs from the contralateral paw; (2) 5-HT_1/2A/2C/3receptors-mediate mechanisms increase the activity of descending pathways that facilitates the response of spinal neurons to noxious inputs from the contralateral paw; (3) 5-HT_1/2A/2Cand 5-HT_1/2Creceptors increases the descending facilitation mechanisms induced by incision in the ipsilateral paw; (4) 5-HT_2A/3receptors contribute to descending pronociceptive pathways conveyed by lamina X spinal neurons; (5) α-adrenergic receptors are unlikely to participate in the incision-induced facilitation of the spinal neurons.</p

Inhibition of the NMDA receptor/Nitric Oxide pathway in the dorsolateral periaqueductal gray causes anxiolytic-like effects in rats submitted to the Vogel conflict test

<p>Abstract</p> <p>Background</p> <p>Several studies had demonstrated the involvement of the dorsolateral portion of periaqueductal grey matter (dlPAG) in defensive responses. This region contains a significant number of neurons containing the enzyme nitric oxide synthase (NOS) and previous studies showed that non-selective NOS inhibition or glutamate NMDA-receptor antagonism in the dlPAG caused anxiolytic-like effects in the elevated plus maze.</p> <p>Methods</p> <p>In the present study we verified if the NMDA/NO pathway in the dlPAG would also involve in the behavioral suppression observed in rats submitted to the Vogel conflict test. In addition, the involvement of this pathway was investigated by using a selective nNOS inhibitor, Nω-propyl-L-arginine (N-Propyl, 0.08 nmol/200 nL), a NO scavenger, carboxy-PTIO (c-PTIO, 2 nmol/200 nL) and a specific NMDA receptor antagonist, LY235959 (4 nmol/200 nL).</p> <p>Results</p> <p>Intra-dlPAG microinjection of these drugs increased the number of punished licks without changing the number of unpunished licks or nociceptive threshold, as measure by the tail flick test.</p> <p>Conclusion</p> <p>The results indicate that activation of NMDA receptors and increased production of NO in the dlPAG are involved in the anxiety behavior displayed by rats in the VCT.</p

Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice

Background: Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeated treatment with glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as an animal model of schizophrenia-like signs. In the present study, we evaluated if repeated treatment with CBD would attenuate the behavioral and molecular modifications induced by chronic administration of one of these antagonists, MK-801. Methods: Male C57BL/6J mice received daily i.p. injections of MK-801 (0.1, 0.5, or 1mg/kg) for 14, 21, or 28 days. Twenty-four hours after the last injection, animals were submitted to the prepulse inhibition (PPI) test. After that, we investigated if repeated treatment with CBD (15, 30, and 60mg/kg) would attenuate the PPI impairment induced by chronic treatment with MK-801 (1mg/kg; 28 days). CBD treatment began on the 6th day after the start of MK-801 administration and continued until the end of the treatment. Immediately after the PPI, the mice brains were removed and processed to evaluate the molecular changes. We measured changes in FosB/ΔFosB and parvalbumin (PV) expression, a marker of neuronal activity and a calciumbinding protein expressed in a subclass of GABAergic interneurons, respectively. Changes in mRNA expression of the NMDAR GluN1 subunit gene (GRN1) were also evaluated. CBD effects were compared to those induced by the atypical antipsychotic clozapine. Results: MK-801 administration at the dose of 1mg/kg for 28 days impaired PPI responses. Chronic treatment with CBD (30 and 60mg/kg) attenuated PPI impairment. MK-801 treatment increased FosB/ΔFosB expression and decreased PV expression in the medial prefrontal cortex. A decreased mRNA level of GRN1 in the hippocampus was also observed. All the molecular changes were attenuated by CBD. CBD by itself did not induce any effect. Moreover, CBD effects were similar to those induced by repeated clozapine treatment

Perfil antipsicótico do canabidiol

O canabidiol, fitocanabinóide presente na planta Cannabis sativa é desprovido dos efeitos psicotomiméticos característicos do principal composto da Cannabis, o ∆9-tetraidrocanabinol, mais conhecido como delta 9-THC. Um conjunto crescente de evidências sugere que o canabidiol apresente potencial terapêutico para o tratamento dos sintomas de distúrbios psiquiátricos, como a depressão, a ansiedade e as psicoses. A observação em humanos, mas também em modelos animais experimentais da capacidade do canabidiol de antagonizar os efeitos psicotomiméticos do delta 9-THC constitui uma importante evidência de seu potencial para utilização clínica. Embora os efeitos farmacológicos do canabidiol tenham sido investigados em diferentes sistemas biológicos in vitro e in vivo, seu mecanismo de ação ainda não é claro. O delta 9-THC ativa os receptores canabinóides do tipo CB1 e CB2 contudo o canabidiol apresenta uma baixa afinidade por esses receptores. Adicionalmente, o canabidiol tem apresentado boa tolerabilidade em testes com humanos, tornando-o alvo de grande interesse da comunidade científica. O objetivo dessa revisão é apresentar, de forma breve, algumas das principais evidências experimentais e clínicas do provável perfil antipsicótico do canabidiol.Cannabidiol an important phytocannabinoid present in the Cannabis sativa opposing to the major plant compound D9-tetrahydrocannabinol, known as delta-9-THC, is devoid of the psychotomimetic effects. Growing set of evidence suggest that cannabidiol may be used for the treatment of the symptoms of psychiatric disorders such as depression, anxiety and psychosis. The first evidence of the cannabidiol therapeutic potential was the observation of its ability to antagonize delta-9-THC effects either on human and experimental animal models. Pharmacological effects of CBD has been investigated in different biological systems, in vitro and in vivo, however, the mechanisms responsible for their therapeutic potential are still unclear. delta-9-THC effects results from activation of the cannabinoid receptors CB1 and CB2, however, the cannabidiol has low affinity for these receptors. The good tolerability of canabidiol in human trials makes this compound an interesting target of the scientific community. The aim of this paper is to present concisely some experimental and clinical evidence about the cannabidiol antipsychotic profile

Modelo de degeneración del disco intervertebral por punción de la cola de ratas Wistar: evaluación histológica y radiográfica

OBJETIVO: descrever a caracterização histológica e radiográfica do método de indução da degeneração do disco intervertebral da cauda de ratos Wistar induzida por meio de punção. MÉTODOS: ratos Wistar machos adultos foram anestesiados, radiografados e submetidos à punção dos discos intervertebrais localizados entre a sexta e a sétima e a oitava e nona vértebras coccígeas. Para a punção foi utilizada agulha de 20G, que foi introduzida até o ânulo fibroso, e foi realizada dupla rotação de 360º, mantendo-se a mesma posição durante 30 segundos antes da retirada. O disco intermediário aos segmentos lesados (7-8) não foi puncionado e foi utilizado como controle. Foi selecionado o período pós-lesão de 30 dias (n=9) para sacrifício e análise dos discos intervertebrais. Os animais foram radiografados 30 dias após a lesão para análise da altura do disco intervertebral. Os segmentos da cauda foram removidos, fixados e desmineralizados, processados e corados com Hematoxilina-Eosina para avaliação histológica. RESULTADOS: a análise radiográfica revelou a redução significativa da altura dos discos lesados em relação ao controle. A avaliação histológica revelou alterações no núcleo pulposo e ânulo fibroso dos discos lesados em relação ao controle. Não foram observadas diferenças na intensidade de lesão entre os discos proximal e distal. CONCLUSÃO: a degeneração do disco intervertebral da cauda de ratos Wistar induzida por meio de punção mostrou ser método reprodutível para estudo da degeneração do disco intervertebral. Esse modelo mostrou validade para avaliação experimental de novas intervenções terapêuticas nos processos de degeneração do disco intervertebral.OBJECTIVE: to report the induction of intervertebral disc degeneration of the rat caudal spine by needle puncture and its radiographic and histologic characterization. METHODS: adult male Wistar rats were anesthetized, submitted to the X-Ray and then to the needle puncture (20G) of intervertebral disc between the sixth and seventh (proximal segment) and the eighth and ninth (distal segment) coccygeal vertebrae. Radiographies were taken 30 days after lesion for analysis of intervertebral disc height. The intermediate disc (7-8) to injured segments was not punctured and was considered as control. All segments were removed, fixed and demineralized, processed and stained with Hematoxylin-Eosin for histological evaluation. RESULTS: radiographic analysis revealed significant reduction in disc height of lesioned discs compared to control. Similarly, histological analysis revealed significant changes in the nucleus pulposus and annulus fibrosus of the lesioned discs (proximal and distal) relative to the control. There was no difference in the intensity of injury between the proximal and distal discs. CONCLUSION: the experimental model of tail intervertebral disc degeneration by needle puncture reproduced the steps of the intervertebral disc degeneration, assessed by different instruments, and it can be used for experimental evaluation of new therapeutic interventions for intervertebral disc degeneration process.OBJETIVO: describir la caracterización histológica y radiográfica del método de inducción de la degeneración del disco intervertebral de la cola de ratas Wistar, inducida por medio de la punción. MÉTODOS: ratas Wistar machos adultos fueron anestesiados, radiografiados y sometidos a la punción de los discos intervertebrales localizados, entre la sexta y la séptima; y la octava y novena vértebras coccígeas. Para la punción, fue utilizada una aguja de 20G, que fue introducida hasta el ánulo fibroso, y fue realizada una dupla rotación de 360º, manteniendo esta posición durante 30 segundos, previamente a la retirada. El disco intermediario a los segmentos lesionados (7-8) no fue puncionado y fue considerado como control. Fue seleccionado el periodo post-lesión de 30 días (n=9) para sacrificio y análisis de los discos intervertebrales. Los animales fueron radiografiados 30 días después de la lesión para análisis de la altura del disco intervertebral. Los segmentos de la cola fueron removidos, fijados y desmineralizados, procesados y coloreados con hematoxilina-eosina para evaluación histológica. RESULTADOS: el análisis radiográfico mostró una reducción significativa de la altura de los discos lesionados en relación al control. La evaluación histológica mostró alteraciones en el núcleo pulposo y el ánulo fibroso de los discos lesionados en relación al control. No fueron observadas diferencias en la intensidad de la lesión entre los discos proximal y distal. CONCLUSIÓNES: la degeneración del disco intervertebral de la cola de ratas Wistar inducida por medio de punción mostró ser un método reproducible para el estudio de la degeneración del disco intervertebral. Ese modelo mostró validez para la evaluación experimental de nuevas intervenciones terapéuticas en los procesos de la degeneración del disco intervertebral.Capes - PNPDFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Enzymatic inactivation of bradykinin by rat brain neuronal perikarya

1. Bradykinin (Bk; Arg 1 -Pro 2 -Pro 3 -Gly 4 -Phe 5 -Ser 6 -Pro 7 -Phe 8 -Arg 8 ) inactivation by bulk isolated neurons from rat brain is described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44287/1/10571_2004_Article_BF00711417.pd