No description available.

No description available.

The sciatic nerves of rats were crushed with fine forceps and allowed to survive for 3 or 7 days, at which time the 5th lumbar dorsal root ganglion was injected with [3H]glucosamine. Animals were killed 18 h later and the nerves proximal and distal to the crush site were cut into 3 mm segments. Gangliosides were purified from these segments, and radioactivity was separately measured in gangliosides, neutral glycolipids and glycoprotein. For all 3 fractions, radioactivity was distributed similarly between the crush site the point of maximum axonal elongation. A second smaller peak of ganglioside radioactivity was seen to span a few segments immeidately distal to the point of maximum axonal elongation. We propose two possible explanation for this: (1) it represents ganglioside synthesis by Schwann cells (from blood-borne [3H]glucosamine) as part of the mitogenic response of these cells to the reappearance of axons; or (2) recently synthesized, transported gangliosides are released from the growth cone and taken up by adjacent mitogenic Schwann cells.

No description available.

[Truncated abstract] Formation and consolidation of the retinotectal projection during optic nerve regeneration has been associated with two major interlinked processes. Initially, retinal ganglion cell (RGC) axons are guided by molecular guidance cues, such as the Eph receptor tyrosine kinases and their ligands, the ephrins, to their approximately correct location and form a coarse topographic map in the optic tecum. Such axon guidance occurs in the absence of neural activity and is considered to be activity-independent. The second process involves glutamatergic excitation, whereby correctly located connections are strengthened by correlated neural activity, whilst removing inappropriately located ones thereby sharpening the topography.The second process is considered to be activitydependent. Here, a number of experiments were undertaken to further examine the interrelationships of activity-dependent and independent processes with respect to functional outcomes. Two models of optic nerve regeneration were studied. In goldfish, following optic nerve crush, regeneration is successful. … In goldfish, guidance along the medio-lateral tectal axis may occur through preordering of axons prior to entering the tectum via the appropriate medial and lateral brachium, with EphA/ephrin-A then guiding axons over the rostral-caudal axis establishing gross topography. The increase in involvement of NMDA-mediated transmission during the period of activity-dependent refinement consolidated the role of this receptor in synapse plasticity. However what triggers NMDA-mediated activity to increase is still largely unresolved, although as the factors governing receptor trafficking during development and synaptic plasticity become better understood, these can be applied to the period of plasticity associated with regenerating axons. And finally, as GABAergic inhibition appears to suppress activity-dependent refinement, means of overcoming this inhibition through 4 such methods as visual training or pharmacological intervention may have significance for mammalian regeneration.

INTRODUÇÃO: Embora a população diabética seja extremamente significativa e crescente nos últimos anos, os estudos envolvendo regeneração nervosa e diabetes mellitus (DM) não são muitos e, frequentemente, mostram resultados conflitantes e pouco conclusivos. O objetivo deste trabalho foi estudar a regeneração nervosa em ratos diabéticos. MÉTODOS: O trabalho foi realizado no Laboratório de Microcirurgia Experimental (LIM 4) do HC-FMUSP. Utilizaram-se 40 ratos machos, que foram separados em 2 grupos principais, cada um com 20 animais: grupo controle e grupo diabetes. Cada grupo foi subdividido em 2 subgrupos de 10 animais: controle com neurorrafia término-terminal (CN), controle com enxerto de nervo (CE), diabético com neurorrafia términoterminal (DN) e diabético com enxerto de nervo (DE). A indução do DM foi feita pela inoculação de estreptozotocina na dose de 60mg/Kg, por via intraperitoneal e após 8 semanas os animais foram submetidos à cirurgia. Diversas avaliações foram feitas: massa corporal, glicemias, testes da marcha e eletrofisiológico, índice de peso do músculo tríceps sural (pata operada/não operada) e análises histomorfométricas. RESULTADOS: Ocorreram 3 óbitos, 1 no CN, 1 no DN e 1 no DE. Nas avaliações pósoperatórias o peso dos animais do grupo controle foi maior que o do grupo diabetes (p<0,05). Todos os ratos do grupo diabetes mostraram níveis glicêmicos bem superiores aos do grupo controle (p<0,05), mantendo-se sempre maiores que 200mg/dL. No 20o PO o teste da marcha foi mais próximo do normal nos animais do grupo controle do que no grupo diabetes (p<0,05), sendo melhor nos subgrupos com neurorrafia do que com enxerto de nervo (p<0,05). No 40o PO o panorama se manteve, exceto pela comparação do DN com o DE (p>0,05). Já no 60o PO o teste foi semelhante entre os animais do grupo controle (CN e CE) e o DN (p>0,05), se mostrando pior no DE (p<0,05). No teste eletrofisiológico com 60 dias de evolução, as amplitudes do potencial evocado foram semelhantes entre os subgrupos controles e diabéticos (p>0,05). O índice de peso do músculo tríceps sural foi maior no CN em comparação com os outros 3 subgrupos (p<0,05), não se verificando o mesmo nas demais comparações (p>0,05). No 60o PO não se encontraram diferenças estatisticamente significativas na comparação dos subgrupos controles e diabéticos em relação à densidade axonal, medidas das áreas das secções transversas das fibras nervosas, dos axônios e das células de Schwann. CONCLUSÕES: O teste da marcha mostrou que a recuperação funcional foi mais rápida nos animais do grupo controle, porém, com 60 dias, o DN apresentava uma recuperação semelhante aos animais controles, ao passo que o DE ainda não. A resposta da musculatura tríceps sural ao estímulo do nervo ciático com 60 dias de evolução, verificada no teste eletrofisiológico, se mostrou parecida nos animais controles e diabéticos, não havendo diferença estatística. A atrofia muscular, vista pelo índice de peso do músculo tríceps sural, foi menor em CN, porém sem diferença estatística entre CE, DN e DE. A densidade de axônios, assim como os calibres das fibras nervosas e dos axônios não foram estatisticamente diferentes nos animais diabéticos no 60o PO / INTRODUCTION: Although the diabetic population is highly significant and has been growing during the past few years, studies involving nerve regeneration and diabetes mellitus (DM) are rather uncommon, frequently demonstrating divergent results and few conclusions. The objective of this study is to evaluate nerve regeneration in diabetic rats. METHODS: The study was accomplished in the Experimental Microsurgery Laboratory (LIM 4) of the HC-FMUSP. The study included 40 male rats, separated into two main groups: 20 controls and 20 diabetic animals. Each group was then further subdivided into two subgroups with 10 animals in each: control with end-toend neurorrhaphy (CN); control with nerve graft (CE); diabetic with end-toend neurorrhaphy (DN); and diabetic with nerve graft (DE). DM was accomplished by intraperitoneal innoculation of 60mg/Kg of streptozocin and the animals underwent surgery eight weeks later. Various evaluations were performed: body mass, glycemias, walking and electrophysiology tests, triceps surae muscle weight index (operated/non-operated paw) and histomorphometric analysis. RESULTS: Three deaths occurred; one in CN, one in DN, and one in DE. In the postoperative evaluations the weight of the control animals was greater than that of the diabetic group (p<0.05). All the rats in the diabetic group demonstrated glycemic levels very superior to those of the control group (p<0.05), always remaining over 200mg/dL. On the 20th PO day, the walking test was closer to normal in the control group than in the diabetic one (p<0.05), better in the neurorrhaphy subgroups than in the nerve graft ones (p<0.05). On the 40th PO day the range was maintained, except for comparison of DN with DE (p>0.05). Already on the 60th PO day, the test was similar among the animals of control group (CN and CE) and DN (p>0.05), seeming worse on DE (p<0.05). At 60 days the potential amplitudes of the electrophysiological test were similar among the control and diabetic subgroups (p>0.05). Triceps surae muscle weight index was greater in the CN compared with the other three subgroups (p<0.05), which was not seen in the other comparisons (p>0.05). On the 60th PO day no statistically significant differences were observed when comparing the control and the diabetic subgroups regarding the axonal density, measurent of the areas of the transverse sections of the nerve fibers, axons and Schwann cells. CONCLUSIONS: The walking test showed that the functional recovery was swifter in the control group animals. At 60 days, however, DN presented a recovery similar to that of the control animals, whereas DE still did not. Triceps surae muscle response upon stimulation of the sciatic nerve at 60 days, verified by the electrophysiological test, showed it to be similar in the control and diabetic animals, without a statistical difference. The muscular atrophy observed by the triceps surae muscle weight index was less in CN, however, without a statistical difference among CE, DN and DE. The axon densities as well as the calibers of the nerve fibers and axons were not statistically different in the diabetic animals at 60 days PO

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.

Nogo is well established for its inhibitory action on axon regeneration in the adult central nervous system. It binds to the Nogo receptor (NgR) through an extracellular active site on the protein-Nogo-66. Although it is reported that Nogo is widely expressed in the developing brain, its exact function during development of the nervous system is unclear. / The contribution of Nogo on patterning the axon routing at the optic chiasm of mouse embryo was investigated in this thesis. Using immunocytochemical staining, Nogo protein was localized on the Miller glial cells in the retina and at the optic disk. A few migrating retinal neurons also expressed Nogo. In the chiasm, Nogo was localized exclusively on the radial glia, which generate a midline domain where turning of uncrossed axons occurs. In vitro study showed expression of NgR on retinal neurites and growth cones, and neurite outgrowth from both dorsal nasal (contralaterally projecting) and ventral temporal (ipsilaterally projecting) retina was inhibited by Nogo. In the pathway, NgR expression was regionally regulated. NgR was obvious in the optic stalk and the optic tract, but not in the chiasm. Blocking Nogo function with NEP1-40, a peptide antagonist of NgR, in brain slice culture of the pathway produced significant reduction in the uncrossed projection, but had no effect on axon crossing at the midline. Furthermore, the age related fiber arrangement in the optic tract was abolished after disturbing of Nogo function. Similar abnormalities were observed in slices treated with Nogo blocking antibody. In vitro studies showed that NEP1-40 rescued the inhibition of Nogo to the retinal neurites. The downregulation of NgR at the chiasm was supported by in vitro assays showing significant reduction of receptor expression on dorsal nasal but not ventral temporal growth cones when they encountered the chiasm, thus generating a differential inhibition to ventral temporal neurites. / These results provide evidences that Nogo is a guidance molecule during the development of CNS. Interaction of Nogo and its receptor plays important role for patterning the axon divergence in the mouse optic pathway and the age related fiber order in the optic tract. / Wang Jun. / "September 2006." / Adviser: Sun-On Chan. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1474. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 130-142). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Ling Eva. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 175-202). / Abstracts in English and Chinese. / Abstract --- p.i / 論文摘要 --- p.iv / Acknowledgement --- p.vi / Abbreviations Frequently Used --- p.vii / Table of Contents --- p.viii / Chapter Chapter One --- Introduction --- p.1 / Chapter Chapter Two --- Materials and Methods --- p.35 / Chapter Chapter Three --- Results --- p.64 / Chapter Chapter Four --- Discussion --- p.148 / References --- p.175 / Tables --- p.203

INTRODUÇÃO: Embora a população diabética seja extremamente significativa e crescente nos últimos anos, os estudos envolvendo regeneração nervosa e diabetes mellitus (DM) não são muitos e, frequentemente, mostram resultados conflitantes e pouco conclusivos. O objetivo deste trabalho foi estudar a regeneração nervosa em ratos diabéticos. MÉTODOS: O trabalho foi realizado no Laboratório de Microcirurgia Experimental (LIM 4) do HC-FMUSP. Utilizaram-se 40 ratos machos, que foram separados em 2 grupos principais, cada um com 20 animais: grupo controle e grupo diabetes. Cada grupo foi subdividido em 2 subgrupos de 10 animais: controle com neurorrafia término-terminal (CN), controle com enxerto de nervo (CE), diabético com neurorrafia términoterminal (DN) e diabético com enxerto de nervo (DE). A indução do DM foi feita pela inoculação de estreptozotocina na dose de 60mg/Kg, por via intraperitoneal e após 8 semanas os animais foram submetidos à cirurgia. Diversas avaliações foram feitas: massa corporal, glicemias, testes da marcha e eletrofisiológico, índice de peso do músculo tríceps sural (pata operada/não operada) e análises histomorfométricas. RESULTADOS: Ocorreram 3 óbitos, 1 no CN, 1 no DN e 1 no DE. Nas avaliações pósoperatórias o peso dos animais do grupo controle foi maior que o do grupo diabetes (p<0,05). Todos os ratos do grupo diabetes mostraram níveis glicêmicos bem superiores aos do grupo controle (p<0,05), mantendo-se sempre maiores que 200mg/dL. No 20o PO o teste da marcha foi mais próximo do normal nos animais do grupo controle do que no grupo diabetes (p<0,05), sendo melhor nos subgrupos com neurorrafia do que com enxerto de nervo (p<0,05). No 40o PO o panorama se manteve, exceto pela comparação do DN com o DE (p>0,05). Já no 60o PO o teste foi semelhante entre os animais do grupo controle (CN e CE) e o DN (p>0,05), se mostrando pior no DE (p<0,05). No teste eletrofisiológico com 60 dias de evolução, as amplitudes do potencial evocado foram semelhantes entre os subgrupos controles e diabéticos (p>0,05). O índice de peso do músculo tríceps sural foi maior no CN em comparação com os outros 3 subgrupos (p<0,05), não se verificando o mesmo nas demais comparações (p>0,05). No 60o PO não se encontraram diferenças estatisticamente significativas na comparação dos subgrupos controles e diabéticos em relação à densidade axonal, medidas das áreas das secções transversas das fibras nervosas, dos axônios e das células de Schwann. CONCLUSÕES: O teste da marcha mostrou que a recuperação funcional foi mais rápida nos animais do grupo controle, porém, com 60 dias, o DN apresentava uma recuperação semelhante aos animais controles, ao passo que o DE ainda não. A resposta da musculatura tríceps sural ao estímulo do nervo ciático com 60 dias de evolução, verificada no teste eletrofisiológico, se mostrou parecida nos animais controles e diabéticos, não havendo diferença estatística. A atrofia muscular, vista pelo índice de peso do músculo tríceps sural, foi menor em CN, porém sem diferença estatística entre CE, DN e DE. A densidade de axônios, assim como os calibres das fibras nervosas e dos axônios não foram estatisticamente diferentes nos animais diabéticos no 60o PO / INTRODUCTION: Although the diabetic population is highly significant and has been growing during the past few years, studies involving nerve regeneration and diabetes mellitus (DM) are rather uncommon, frequently demonstrating divergent results and few conclusions. The objective of this study is to evaluate nerve regeneration in diabetic rats. METHODS: The study was accomplished in the Experimental Microsurgery Laboratory (LIM 4) of the HC-FMUSP. The study included 40 male rats, separated into two main groups: 20 controls and 20 diabetic animals. Each group was then further subdivided into two subgroups with 10 animals in each: control with end-toend neurorrhaphy (CN); control with nerve graft (CE); diabetic with end-toend neurorrhaphy (DN); and diabetic with nerve graft (DE). DM was accomplished by intraperitoneal innoculation of 60mg/Kg of streptozocin and the animals underwent surgery eight weeks later. Various evaluations were performed: body mass, glycemias, walking and electrophysiology tests, triceps surae muscle weight index (operated/non-operated paw) and histomorphometric analysis. RESULTS: Three deaths occurred; one in CN, one in DN, and one in DE. In the postoperative evaluations the weight of the control animals was greater than that of the diabetic group (p<0.05). All the rats in the diabetic group demonstrated glycemic levels very superior to those of the control group (p<0.05), always remaining over 200mg/dL. On the 20th PO day, the walking test was closer to normal in the control group than in the diabetic one (p<0.05), better in the neurorrhaphy subgroups than in the nerve graft ones (p<0.05). On the 40th PO day the range was maintained, except for comparison of DN with DE (p>0.05). Already on the 60th PO day, the test was similar among the animals of control group (CN and CE) and DN (p>0.05), seeming worse on DE (p<0.05). At 60 days the potential amplitudes of the electrophysiological test were similar among the control and diabetic subgroups (p>0.05). Triceps surae muscle weight index was greater in the CN compared with the other three subgroups (p<0.05), which was not seen in the other comparisons (p>0.05). On the 60th PO day no statistically significant differences were observed when comparing the control and the diabetic subgroups regarding the axonal density, measurent of the areas of the transverse sections of the nerve fibers, axons and Schwann cells. CONCLUSIONS: The walking test showed that the functional recovery was swifter in the control group animals. At 60 days, however, DN presented a recovery similar to that of the control animals, whereas DE still did not. Triceps surae muscle response upon stimulation of the sciatic nerve at 60 days, verified by the electrophysiological test, showed it to be similar in the control and diabetic animals, without a statistical difference. The muscular atrophy observed by the triceps surae muscle weight index was less in CN, however, without a statistical difference among CE, DN and DE. The axon densities as well as the calibers of the nerve fibers and axons were not statistically different in the diabetic animals at 60 days PO