Nas lesões onde há secção de nervos o cirurgião necessita restabelecer a continuidade entre dois cotos. Apesar de ser considerado como o método padrão, a sutura com fios de náilon pode ocasionar reação inflamatória prejudicando o processo de regeneração ou ser de difícil execução, nos casos de nervos de calibres reduzidos. O reparo com adesivo de fibrina é uma opção ao reparo com sutura convencional, mas a comparação entre esses dois métodos apresenta resultados conflitantes na literatura. O objetivo deste trabalho foi comparar os parâmetros usualmente empregados na avaliação da regeneração do nervo ciático do rato previamente seccionado com a utilização do reparo com a sutura convencional, com o adesivo de fibrina ou uma combinação das duas técnicas. Previamente à secção do nervo ciático do lado direito, cada animal foi submetido à mensuração do índice funcional ciático a partir de medidas obtidas da impressão das patas traseiras durante a marcha. Após a exposição cirúrgica procedeu-se à avaliação eletrofisiológica que consistia na mensuração da latência, amplitude e velocidade de condução do potencial de ação do nervo e do potencial de ação motor. Com técnica microcirúrgica, os nervos foram seccionados e reparados de forma imediata. Três grupos com 10 animais cada foram formados de acordo com o reparo utilizado. No grupo A, o reparo foi realizado com a sutura utilizando-se quatro pontos de fio de náilon 10-0; no grupo B a coaptação dos cotos do nervo foi realizada com a aplicação do adesivo de fibrina; no grupo C o reparo foi realizado com um ponto de náilon 10-0 associado com a aplicação do adesivo de fibrina. Após 12 semanas o índice funcional ciático foi avaliado nos três grupos e a avaliação funcional da regeneração foi obtida comparando-se os valores deste índice. Após 24 semanas os animais foram reoperados para avaliação eletrofisiológica com as medidas dos mesmos parâmetros que foram avaliados antes da secção do nervo. A avaliação eletrofisiológica da regeneração comparou os valores da amplitude, latência e velocidade de condução dos potencias de ação do nervo e motor, os valores da razão entre a velocidade de condução na reoperação e a velocidade de condução antes da secção do nervo para os dois potenciais e a razão entre a amplitude na reoperação e a amplitude antes da secção dos nervos dos dois potenciais. Após esta avaliação, os nervos foram fixados e retirados para a obtenção de segmentos proximais e distais à região do reparo com a finalidade de se proceder ao estudo histomorfométrico com contagem total dos axônios regenerados, mensuração dos diâmetros desses axônios nesses segmentos e quantificação do número de axônios regenerados em situação extrafascicular no segmento distal. A análise estatística foi realizada através de comparação dos parâmetros obtidos entre os grupos com a análise de variância ou com o teste de Kruskal-Wallis. Quando era identificada uma diferença significativa entre os grupos, para p < 0,05, foi utilizado um teste de comparações múltiplas através do método de Tukey ou Duncan. Após 12 semanas do reparo os resultados do índice funcional ciático no grupo B foram superiores aos do grupo A. Não houve diferença significativa na avaliação desse parâmetro entre os grupos B e C. Os animais do grupo B apresentaram melhores resultados na regeneração em comparação com o grupo A quando avaliados a latência, a velocidade de condução após o período de observação e a razão entre a velocidade de condução realizada na reoperação e o mesmo parâmetro obtido antes da secção do nervo durante a mensuração do potencial de ação motor. Os animais do grupo C apresentaram melhores resultados na regeneração em comparação com o grupo A quando avaliada a razão entre a velocidade de condução realizada na reoperação e o mesmo parâmetro obtido antes da secção do nervo na mensuração do potencial de ação motor. Não houve diferença na regeneração avaliada pelo estudo eletrofisiológico entre os grupos B e C. Não houve diferenças significativas na avaliação histomorfométrica entre os três grupos. Considerando os resultados conclui-se que o reparo com o adesivo de fibrina forneceu as melhores condições para a regeneração em comparação com a sutura / Injuries involving nerves section require the surgeon to reestablish the continuity between the two stumps. Although direct suturing of the nerve using Nylon is considered a standard procedure, it can cause inflammatory reaction impairing the regeneration, or the procedure can be difficult due to reduced nerve caliber. The repair with fibrin glue is an alternative to the conventional suture technique, but comparison between these two techniques have presented conflicting results in the literature. The objective of this study was to compare the parameters commonly applied in assesssing the regeneration of the sectioned rat sciatic nerve, using conventional suture, fibrin glue and a combination of both techniques. Before sectioning the right sciatic nerve, the sciatic functional index of each rat was determined by measuring the printing of the posterior limbs during gait. After the surgical exposure, the electrophysiologic evaluation was performed. It consisted of measuring the latency, magnitude and conduction velocity of the nerve and muscular action potentials. Using the microsurgical techniques, the nerves were sectioned at middle and repaired immediately. Thirty rats were divided evenly into three groups accordingly to the nerve repair technique. In group A, the nerve was repaired with four-stitch suture using Nylon 10-0; in group B the stumps were united using fibrin glue; in group C, the nerve was repaired with a single-stitch suture using Nylon 10-0 and fibrin glue. After 12 weeks, the sciatic functional index of the three groups was evaluated. The functional evaluation of the nerve regeneration was obtained by comparing the sciatic functional index of the three groups. After 24 weeks, the rats underwent reoperation for electrophysiologic assessment based on the same parameters used before the nerve section. The electrophysiologic evaluation of the nerve regeneration consisted of comparing the results of the same parameters evaluated in the first surgery, the ratio between the conduction velocity of the action potential at the reoperation and the same velocity before the division of the nerve and the ratio between the magnitude of the action potential at the reoperation and before the nerve section. After electrophysiologic evaluation, the nerves were fixed and removed to obtain the proximal and the distal stumps for histomorphometric study. The histomorphometric study consisted of total count of regenerated axons, measurement of the regenerated axons diameter in both stumps, and the determination of the number of the regenerated axons in extrafascicular location in the distal stump. Statistical analysis was performed by comparing the parameters obtained from the three groups using ANOVA or the Kruskal-Wallis test. Whenever a significant difference between the groups was identified, with p<0.05, a multiple comparison test (Tukey or Duncan) was applied. With regards to the sciatic functional index 12 weeks after the repair, the rats of group B presented better outcome than those of group A. There was no significant difference between groups B and C. When latency and the nerve conduction velocity assessed at the reoperation, and the ratio between the conduction velocity at the reoperation and before the nerve division in the motor action potential evaluation were measured, the rats of group B presented better results in regeneration than those of group A. As for regeneration, with the motor action potential evaluation, rats of group C presented better results than those of group A when the ratio between the nerve conduction velocity at the reoperation and before the nerve division was considered. No difference between groups B and C was found in regeneration evaluated by means of electrophysiologic study. There were no significant differences in regard to the histomorphometric evaluation between the three groups. Based on the results, we conclude that nerve repair using fibrin glue provided the best conditions for regeneration than the suture

OBJETIVO: avaliar o efeito das neuregulinas 1-alfa e 1-beta na regeneração de nervos ciáticos de camundongos C57BL/6J, adultos, machos, através da técnica de tubulização. MÉTODOS: Utilizaram-se 18 animais, divididos em 3 grupos, implantando-se prótese de polietileno em falhas de 4,0 mm no nervo ciático esquerdo: grupo 1 contendo apenas colágeno purificado (Vitrogen®); grupo 2, colágeno associado a neuregulina 1-alfa; grupo 3 com colágeno e neuregulina 1-beta. O grupo controle foi formado por 6 segmentos de nervos ciáticos direitos. Após 4 semanas, os animais foram sacrificados; extraiu-se segmento do ponto médio do nervo regenerado no interior das próteses, padronizaram-se cortes histológicos e confecção das lâminas para análise histomorfométrica. Confrontaram-se os resultados estatisticamente. RESULTADOS: Os animais tratados com neuregulinas tiveram maior número de axônios mielinizados, com diferença estatisticamente significante quando comparados ao grupo colágeno. Não houve diferença estatística entre os grupos de neuregulinas 1-alfa e 1-beta. CONCLUSÃO: a adição de neuregulinas proporcionou aumento significativo do número de fibras mielinizadas. / PURPOSE: To evaluate the effect of neuregulins 1-alpha and 1-beta on the regeneration the sciatic nerves of male adult C57BL/6J mice, using the tubulization technique. METHODS: Eighteen animals were used, divided into three groups. A polyethylene prosthesis was implanted in a 4.0 mm defect of the left sciatic nerve, as follows: group 1 containing only purified collagen (Vitrogen®); group 2, collagen with neuregulin 1-alpha; group 3, collagen with neuregulin 1-beta. The control group was formed by six segments of right sciatic nerves. Four weeks later, the animals were sacrificed. A segment from the midpoint of the nerve regenerated inside the prostheses was extracted, histological sections were standardized and slides were made up for histomorphometric analysis. The results were statistically compared using the Tukey multiple comparisons test and Students t test. RESULTS: The animals treated with neuregulins had greater numbers of myelinized axons, with a statistically significant difference in relation to the collagen-only group. There was no statistical difference between the neuregulin 1-alpha and 1- beta groups. CONCLUSION: It was concluded that the addition of neuregulins provided a significant increase in the number of myelinized fibers.

Este trabalho teve como objetivo estudar as alterações microvasculares intraneurais agudas em nervo isquiático de rato submetido à esmagamento por diferentes cargas. Foram utilizados sessenta ratos machos da linhagem Wistar, distribuídos em dois grupos experimentais de acordo com o protocolo de injeção de vasos e subdivididos de acordo com a carga de esmagamento. Os nervos isquiáticos direitos de cada grupo experimental foram isolados e submetidos ao esmagamento com diferentes cargas (0,5 Kg, 1 Kg, 5 Kg, 10 kg e 15 kg) por 10 minutos e os nervos isquiáticos esquerdos foram utilizados como controle. Após o esmagamento, 30 animais foram submetidos ao Protocolo I, que constou de: cateterização da aorta abdominal, perfusão manual da solução composta de tinta da China e gelatina 5% em formol 10%, dissecação e retirada dos nervos direitos e esquerdos, desidratação e diafanização para análise longitudinal dos vasos intraneurais. Os outros trinta animais foram submetidos ao Protocolo II, que constou de: cateterização da aorta abdominal e perfundidos com solução composta de tinta da China e gelatina 5% em soro fisiológico e, após, mantidos em freezer -20°C por uma hora. Em seguida os nervos foram dissecados e retirados em toda a sua extensão, cortados em 3 fragmentos, congelados em isopentano em gelo seco e armazenados em freezer -70°C, seccionados em cortes transversais semi-seriados em criostato para análise e contagem dos vasos intraneurais. Os resultados mostraram regiões de hematoma endoneural e epineural nas diferentes cargas utilizadas indicando que as forças de esmagamento foram suficientes para lesar os vasos intraneurais do nervo isquiático, especialmente com cargas elevadas. A análise morfométrica mostrou um comportamento diferente nas três regiões estudadas, constatando menor número de vasos na região do esmagamento e não nas regiões acima e abaixo da mesma. Estes resultados sugerem lesão localizada dos vasos intraneurais que foi proporcional à carga de esmagamento, causando hematoma endoneural e epineural, o que criará um microambiente desfavorável para a regeneração das fibras nervosas que também foram lesadas nesse modelo. / The objective of this work was to study the acute intraneurial microvascular changes in the rat sciatic nerve submitted to a crush injury by different loads. Sixty Wistar male rats were used and distributed into two experimental groups according to vessel injection protocol and subdivided according to the crush load. The right sciatic nerves of each experimental group were isolated and submitted to crush by different loads (0,5 Kg, 1 Kg, 5 Kg, 10 kg and 15 kg) for ten minutes. The left sciatic nerves were used as controls. After the crush, thirty animals were submitted to Protocol I, which consisted of: abdominal aorta catheterization, manual perfusion withf a solution composed of China ink and gelatin 5% in formaldehyde 10%. After that the right and left nerves were collected, fixed in formaldehyde10%, dehydrated and diaphanized for longitudinal analysis of the intraneurial vessels. The other thirty animals were submitted to Protocol II, which consisted of: abdominal aorta catheterization, as described above and perfused with a solution of China ink and gelatin 5% in physiologic saline and then placed in a freezer at -20°C for one hour. After that the nerves were dissected and removed in their entire length, cut into three fragments, frozen in isopentane and dry ice and placed in a freezer at -70°C, cut in semi-serial histological transverse sections for analysis and intraneurial vessel quantification.The results showed endoneurial and epineurial haematoma areas in the different groups, indicating that the crush forces were enough to damage the intraneurial vessels, specially with high loads. The morphometrical analysis showed a different profile in the three fragments, with smaller number of vessels in the crush region then above and below, suggesting that the damage to intraneurial vessels was proportional to the crush load, causing endoneurial and epineurial haematoma, which creates an unfavorable microenvironment for the regeneration of the nerve fibers that were also damaged in that model.

Le syndrome du muscle piriforme (SMP) est une entité clinique probablement méconnue et sous-estimée en pratique courante. L'objectif de ce travail est d'apporter des arguments permettant d'aider à concrétiser la réalité de la responsabilité du muscle piriforme dans la souffrance provoquée sur le nerf ischiatique lors de son passage dans le foramen infra-piriforme.A partir de ("évaluation des rapports anatomiques locaux certaines manœuvres susceptibles de provoquer les contraintes du muscle piriforme sur le nerf ischiatique semblent plus sensibles et spécifiques. C'est ce qui est mis en évidence dans ce travail pour les manœuvres de Freiberg, PAIR et de Beatty. Il valide également la manœuvre « TG-CL » que nous mettons en avant.Pour optimiser le diagnostic de SMP, nous avons élaboré un score clinique à partir de 12 items. Ce score a été évalué sur une série personnelle de 250 patients comparés à 30 témoins avec conflit disco-radiculaire et 30 témoins sains. La sensibilité et la spécificité du score étaient respectivement de 96,4% et 100%, alors que la valeur prédictive était de 100% et la valeur prédictive négative de 86,9%. Pour les patients avec SMP nous avons proposé une prise en charge thérapeutique standardisée centrée sur le muscle piriforme. Le protocole médicamenteux et rééducatif permet d'obtenir 51,2% de guérison. Cent vingt deux patients en échec ont bénéficié d'injections de toxine botulinique. Les résultats évalués par l'EVA étaient très bons et bons dans 94 cas (77%), moyens dans 8 cas (7,4%) et mauvais dans 19 cas (15,6%). Quinze des 19 patients en échec ont été pris en charge chirurgicalement avec de très bons et bons résultats dans 12 cas / The piriformis muscle syndrome ( PMS ) has remained an ill-defined entity. It is a form of entrapment neuropathy involving compression of the sciatic nerve in the infrapiriformis canal. Our objective is, on the basis of anatomical descriptions of the piriformis muscle, to provide support for pathophysiological hypotheses. The manoeuvres that we have been reviewed are aimed at putting the piriformis muscle under stress in a variety of situation. We favour the PAIR and Freiberg stretching manoeuvres and Beatty's resisted contraction manoeuvre. When hip flexion surpasses 90°, the piriformis muscle is stretched in lateral rotation, and we have consequently laid emphasis on the manoeuvre we have termed Heel Contra-Lateral Knee (HCLK).To optimize the diagnosis of SMP , we developed a clinical score from 12 items. This score was evaluated on a personal series of 250 patients compared to 30 controls with disco-radicular conflict and 30 healthy controls. Sensitivity and specificity of the score were 96.4 % and 100 %, respectively, while the positive predictive value was 100 % and the negative predictive value of 86.9 %.Therapeutic management consists primarily of rehabilitation, making the patient aware of the benefits of daily self rehabilitation exercises. Combined medication and rehabilitation treatments had a cure rate of 51,2%.Hundred and twenty-two patients (48,8%) were unresponsive to treatment and received OnabotulinumtoxinA. Visual Analogue Scale (VAS) results were Very good/ Good' in 77%, 'Average' in 7,4% and 'Poor' in 15,6%. Fifteen of 19 patients unresponsive to treatment underwent surgery with Very good/ Good' results in 12 cases

Orientador: Alexandre Leite Rodrigues de Oliveira / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-22T08:32:53Z (GMT). No. of bitstreams: 1 Perez_Matheus_M.pdf: 2859331 bytes, checksum: 541101c0093208622bf70dc9b70cf007 (MD5) Previous issue date: 2013 / Resumo: O sistema nervoso é muito sensível à lesões e sua capacidade regenerativa é limitada. Assim, na maioria dos casos, o reparo tecidual não ocorre ou ocorre de forma incompleta, causando danos irreversíveis. Embora o sistema nervoso do neonato apresente maior capacidade regenerativa do que o adulto, a regeneração também é um processo complexo e limitado. Para melhor compreensão dos mecanismos e limitações da regeneração do SNC, tanto na fase neonatal como na fase adulta, diversos modelos de lesão têm sido propostos por vários autores, inclusive transecção de nervo periférico. Através desses estudos experimentais, diferentes modalidades terapêuticas foram sugeridas, com intuito de evitar as alterações que levam à morte neuronal, seja na fase neonatal ou adulta. Para isso, muitas substâncias, com propriedades neuroprotetoras, têm sido testadas no processo de regeneração, plasticidade sináptica e para evitar a morte neuronal após lesão do sistema nervoso. Dentre a grande variedade de substâncias com potencial neuroprotetor, estão alguns derivados da planta Cannabis sativa. Um deles, o canabidiol (CBD), é o principal componente não-psicotrópico produzido nas glândulas encontradas na superfície das folhas da planta. O presente trabalho teve como objetivo investigar o potencial neuroprotetor do canabidiol e, para isso, foram utilizados ratos neonatos da linhagem Wistar, divididos nos seguintes grupos experimentais: grupo submetido à axotomia do nervo isquiático e tratamento com o canabidiol (grupo CBD), grupo submetido à axotomia e tratamento veículo (grupo PB) e grupo controle, com axotomia sem tratamento (grupo sem tratamento). Assim, cortes histológicos utilizando coloração de Nissl mostraram que os grupos tratados com canabidiol (15 e 30mg/kg) mostraram maior sobrevivência (21%; p<0.0001) de motoneurônios medulares, quando comparados aos grupos que não foram tratados com canabidiol ou tratados com canabidiol (5mg/kg). A análise imunohitoquímica, empregando o anticorpo anti-sinaptofisina revelou, no grupo tratado com canabidiol, preservação de imunoreatividade, refletindo preservação de circuitos sinápticos medulares. Tal manutenção de terminais foi 30% superior nos grupos tratados com canabidiol, comparativamente aos grupos controle (p=0,0003). A imunoistoquímica para os anticorpos anti-GFAP (astrócito) e anti-IBA 1(migroglia) revelou uma menor imunomarcação para o grupo tratado com canabidiol, quando comparado aos grupos não tratados. Tal fato demonstra que o canabidiol reduz astrogliose (anti-GFAP) em 30% (p=0,0149) e reação microglial em 27% (p=0,0086). A análise para detecção de células apoptóticas, através reação de TUNEL (teminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling), mostrou que o tratamento com canabidiol foi neuroprotetor, quando comparado ao grupo axotomia sem tratamento (p=0,0063). Em conjunto, os presentes resultados mostram que o canabidiol apresenta promissora propriedade neuroprotetora, devendo ser melhor investigado, com vistas ao seu emprego clínico futuro / Abstract: The CNS is very sensitive to injury and their regenerative capacity is limited, so in most cases the tissue repair does not occur or occurs incompletely, leading to irreversible damage. Although the nervous system of neonatal rats presents a greater regenerative capacity than adults, the regenerative process is still complex and limited. To better understand the mechanisms and limitations of CNS regeneration, both in the neonatal and adulthood, various injury models have been proposed by several authors, including peripheral nerve transaction. Through these experimental studies several therapeutic modalities have been proposed, in order to prevent the neuronal death caused by injuries and pathological processes. For this reason, many substances with neuroprotective properties have been tested in the regeneration process, synaptic plasticity and to prevent neuronal death after nervous system injury. Among the wide variety of substances with potential neuroprotective action, some are derived from the Cannabis sativa. One, cannabidiol (CBD) is the major non-psychotropic component produced by the glands found on the surface of plant leaves. The present study aimed to investigate the neuroprotective potential of CBD. We used Wistar neonatal rats that were divided into the following experimental groups: sciatic nerve axotomy and CBD treatment (CBD group), axotomy and veículo treatment (PB group) and a control group, without treatment (no-treatment group). Thus, Nissl stainning in spinal cord cross sections showed that the CBD groups (15 e 30mg/kg) had a higher neuronal survival (21%, p <0,0001) when compared to the CBD 5mg/kg group, PLB and no treatment groups. Immunohistochemical analysis, done by ipsi/contralateral ratio of integrated density of pixels quantification, of anti-synaptophysin labeling showed that CBD groups had a greater immunostaining pattern when compared to the other experimental groups (30%, p<0,0003) reflecting a higher preservation of synapses after CBD treatment. Imunolabeling Anti-GFAP and anti-Iba 1 revealed a lower immunostaining in CBD group, showing that CBD treatment decreases the astrocytosis process in 30% (p = 0,0149) and reduce reactive microgliosis in 27% (p=0,0086), when compared to the others experimental groups. Aimed to detect apoptotic cells, we used TUNEL reaction. Quantitative analysis showed that the CBD treatment reduced the apoptotic nuclei detectable, when compared to other experimental groups. These results show that CBD presents promising neuroprotective property and should be better investigated aiming its future clinical use / Mestrado / Anatomia / Mestre em Biologia Celular e Estrutural

Hip arthroscopy is a minimally invasive alternative to open hip surgery. Despite its minimally invasive nature, there can still be significant reported pain following these procedures. The impact of combined sciatic and lumbar plexus nerve blocks on postoperative pain scores and opioid consumption in patients undergoing hip arthroscopy was investigated. A retrospective analysis of 176 patients revealed that compared with patients with no preoperative peripheral nerve block, significant reductions in pain scores to 24 hours were reported and decreased opioid consumption during the post anesthesia care unit (PACU) stay was recorded; no significant differences in opioid consumption out to 24 hours were discovered. A subgroup analysis comparing two approaches to the sciatic nerve block in patients receiving the additional lumbar plexus nerve block failed to reveal a significant difference for this patient population. We conclude that peripheral nerve blockade can be a useful analgesic modality for patients undergoing hip arthroscopy.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Understanding the mechanical properties of peripheral nerves is essential for chronically implanted device design. The work in this thesis aimed to understand the relationship between local deformation responses to global strain changes in peripheral nerves. A custom-built mechanical testing rig and sample holder enabled an improved cyclical uniaxial tensile testing environment on rabbit sciatic nerves (N=5). A speckle was placed on the surface of the nerve and recorded with a microscope camera to track local deformations. The development of a semi-automated digital image processing algorithm systematically measured local speckle dimension and nerve diameter changes. Combined with the measured force response, local and global strain values constructed a stress-strain relationship and corresponding elastic modulus. Preliminary exploration of models such as Fung and 2-Term Mooney-Rivlin confirmed the hyperelastic nature of the nerve. The results of strain analysis show that, on average, local strain levels were approximately five times smaller than globally measured strains; however, the relationship was dependent on global strain magnitude. Elastic modulus values corresponding to ~9% global strains were 2.070 ± 1.020 MPa globally and 10.15 ± 4 MPa locally. Elastic modulus values corresponding to ~6% global strains were 0.173 ± 0.091 MPa globally and 1.030 ± 0.532 MPa locally.

Noch immer ist die Behandlung von Neuropathien mit den gängigen therapeutischen Mitteln für viele Patienten sehr unbefriedigend. Als erfolgsversprechender therapeutischer Ansatz werden zur Zeit Wege erforscht, welche direkt in die molekularen Entstehungsmechanismen pathologischer Veränderungen und regenerationsfördernder Mechanismen eingreifen, um dadurch eine Heilung von Nervenschäden zu ermöglichen. Bisher sind die Erkenntnisse über diese Mechanismen nicht vollständig genug, um daraus eine sichere Behandlungsmöglichkeit abzuleiten. Wegweisende Erkenntnisse deuten sich allerdings durch Studien von unterschiedlichen Vertretern des Zytokinnetzwerkes an - darunter auch TNF-alpha - welche als molekulare Ursache neuropathischer Veränderungen diskutiert werden. In dieser Studie wurde an Knockoutmäusen der Einfluss des jeweiligen TNF-alpha-Rezeptors auf morphologische Veränderungen nach CCI (Chronic constriction injury) und Crush-Verletzung des N. ischiadicus untersucht. Nach 3,7,15 und 36 Tagen (CCI) bzw. 3,7 und 28 Tagen (Crush) wurden in Methylenblau gefärbten Semidünnschnitten intakte und degenerierte Nervenfasern, Makrophagen, Angioproliferation, Ödembildung udn Veränderung des Anteils nicht neuronaler Zellen lichtmikroskopisch beurteilt. Zusätzlich wurden Mac-1+ Makrophagen immunzytochemisch erfasst. Die Ergebnisse zeigten in beiden Modellen und bei beiden Knockouttypen eine starke axonale Schädigung, die von einer großen endoneuroalen Makrophagenansammlung begleitet war. Bei TNF-R1-/- Mäusen war eine stärkere und verlängerte Degeneration mit entsprechend höheren Makrophagenzahlen sichtbar. In den Immunzytochemischen Färbungen wiesen die TNF-R1-/- Mäuse hingegen den geringsten Makropahgenanteil auf.Trotz der starken Schädigung war die anschließende Regeneration im Gegensatz zu WT und TNF-R2-/- Mäusen besser. Die Ödembildung war bei den TNF-R2-/- nach CCI besonders stark ausgeprägt und von einer schlechten Regeneration gefolgt. Während die gefundenen Daten auf eine Beteiligung beider Rezeptoren während degenerativer Prozesse hindeuten, scheint insbesondere TNF-R2 regenerationsfördernde Effekte zu vermitteln. / Current Treatment of neuropathic disorders is still dissatisfactory for many patients. A promising approach is the investigation of agents that directly interfere with molecular development of pathologic changes and regeneration. Up to now, consolidated findings of the underlying mechanisms are not yet sufficent to allow therapeutic intervention. Pathbreaking findings come from studies investigating different agents of the cytokine network - as e.g. TNF-alpha - that are discussed as molecular cause of neuropathic changes. This study investigated the influence of both TNF-alpha-receptors on morphologic changes after CCI (chronic constriction injury) and crush-injury of the sciatic nerve of TNF-R-knockoutmice. After 3,7,15 and 36 days (CCI), and 3,7 and 28 respectively (Crush),intact and degenerating nerve fibers, macrophages, angioproliferation, development of edema and changes in the amount of non-neuronal cells were acquired by light microscopy of toluidin-stained semithin sections. Additionally Mac-1+ macrophages were acquired via immuncytochemically stained sections. The results showed strong axonal damage in both knockout-types accompanied by large amounts of endoneurial macrophages. TNF-R1-/-mice showed a longer degeneration phase including respectively higher amounts of macrophages. In contrast the TNF-R1-/-mice revealed the fewest amount of macrophages in immunocytochemical sections. Despite the strong damage better nerve regeneration was observed compared to WT and TNF-R2-/-mice. Formation of edema was pronounced in TNF-R2-/- after CCI and followed by poorly regeneration. Whereas these findings point to a participation of both receptors in degeneration, TNF-R2 seems to support regeneration.

O uso concomitante da enzima hialuronidase (H) ao anestésico local (AL) é muito utilizado para melhorar a eficácia anestésica em oftalmologia; em odontologia, no entanto, não mostrou vantagens. Um novo protocolo foi testado com o objetivo de prolongar a anestesia local sem a realização de complementação anestésica. Esta possibilidade seria especialmente interessante para pacientes que apresentam restrição de dose máxima recomendada de AL ou vasoconstritor (ex. cardiopatas). Utilizou-se cloridrato de lidocaína 2% com epinefrina para bloqueio sensitivo, motor e proprioceptivo no nervo ciático em ratos (Truant,1958). Hialuronidase 75 UTR (unidade de turbidade reduzida) foi injetada no mesmo local 30 minutos após o início da analgesia (antes do término do efeito anestésico), utilizando-se a pata contralateral como controle (injeção de solução anestésica e veículo da hialuronidase solvente). A duração do bloqueio sensitivo foi avaliada através da ausência do reflexo de retirada da pata, utilizando-se um analgesímetro. O bloqueio motor foi avaliado pela duração da claudicação e da ausência do reflexo de estiramento da pata, enquanto o bloqueio proprioceptivo foi avaliado pela perda dos reflexos de salto e do reposicionamento da pata (Thalhammer et al., 1995). Foi também estudada a alteração tecidual induzida pela hialuronidase nos períodos de 1 h, 24 h, 48 h e 72 h pós-injeção. Foram avaliados os grupos: (1) falso operado (Sham); (2) AL +H; (3) AL+ solvente (Solv) e (4) Solv+Solv. Concluiu-se que a hialuronidase prolonga a duração de ação anestésica local quando injetada isoladamente antes da regressão do bloqueio de condução do nervo ciático de rato. Em todos os grupos analisados, exceto o grupo falso-operado, observou-se reação inflamatória após as injeções. Esta inflamação foi mais acentuada no grupo hialuronidase, que mostrava sinais de regressão após 72 horas. É possível que o mecanismo de ação da hialuronidase envolva a desorganização do tecido conjuntivo na região da injeção, facilitando a difusão da solução anestésica residual até o nervo. / The concomitant use of the enzyme hyaluronidase (H) and local anesthetics (LA) is widely employed in ophthalmology in order to improve the effectiveness of anesthesia; in dentistry, however, this association did not seem advantageous. A new protocol was tested with the aim of drawing out local anesthesia without supplementary anesthesia. This possibility is especially interesting for patients with restriction of maximum recommended dose of LA or vasoconstrictor due to pathological conditions (e.g. heart disease). We used 2% lidocaine hydrochloride with epinephrine for sensitive, motor and proprioceptive blockade of the sciatic nerve in rats (Truant, 1958). Hyaluronidase 75 UTR was injected 30 minutes after the beginning of the anesthesia (before the recovery of the sensory function), using the contralateral limb as control (injection of LA plus the H vehicle solvent). The duration of the sensitive blockade was evaluated through the absence of the paw withdrawal reflex, using an analgesymeter. The motor blockade was evaluated by the duration of claudication (complete absence of extensor postural thrust) and by the absence of the paw stretching reflex, while the proprioceptive blockade was evaluated by the absence of hopping and tactile placing response (Thalhammer et al., 1995). Histological changes induced by H were analyzed 1h, 24h, 48h, and 72 h after the injection in the following groups: (1) Sham; (2) LA + H; (3) LA + H solvent (solv) and (4) Solv + Solv. We concluded that H draws out local anesthesia when injected before the recovery of the sciatic nerve blockade in the rat. In all groups studied, with the exception of the Sham, there was an inflammatory reaction after the injections. Inflammation was more intense after H injection, showing signs of regression after 72 hours. It is possible that the mechanism of action of H involves disorganization of the connective tissue, thus facilitating the diffusion of the residual anesthetic solution to the nerve.