O objetivo deste trabalho foi avaliar os efeitos da metilprednisolona empregada previamente ao traumatismo medular, tanto em relação aos possíveis efeitos benéficos quanto às possíveis complicações associadas. Foram utilizados 32 ratos Wistar, divididos em 4 grupos. Dois grupos receberam as drogas A (placebo) e B (metilprednisolona) imediatamente após a lesão. Outros 2 grupos receberam as mesmas drogas 4 horas antes da lesão. Todos foram avaliados por um período de 28 dias quanto à função locomotora e complicações associadas. Quanto aos índices motores, não houve diferença entre os grupos. Os ratos tratados com metilprednisolona quatro horas antes do trauma apresentaram um número de óbitos significativamente maior quando comparados aos ratos tratados com a mesma droga após o trauma / The objective of this work was to evaluate the effect of methylprednisolone previously used to spinal cord injury, in relation to the possible beneficial, and the possible associated complications. Thirty two Wistar rats had been used, divided in 4 groups. Two groups had received the drugs A (placebo) and B (methylprednisolone) immediately after the injury.The others 2 groups received the same drugs 4 hours before the injury. All had been evaluated to the locomotive function and complications associates by a period of 28 days. Concerning the motor indices, it did not show any difference between the groups. The rats treated with methylprednisolone four hours before the trauma presented a significantly higher number of deaths when compared with the rats treated with the same drug after the trauma

Spinal cord injury (SCI) results in a well-orchestrated inflammatory response which causes secondary tissue damage. Activated macrophages contribute to this cytotoxic response, which includes damage to neurons, glia and myelin, and tissue loss that worsens functional outcomes after SCI. However, activated macrophages in the spinal cord under other conditions are not cytotoxic, such as after intraspinal injection of lysophosphatidylcholine (LPC), a potent demyelinating agent. Recovery from SCI may be optimized by reducing the detrimental effects of macrophages while promoting their beneficial ones. Therefore, I compared spinal cord tissue, as well as purified macrophages, from mice after SCI (cytotoxic response) and intraspinal LPC injection (non-cytotoxic response). As a first step to carry out this work, I characterized the injury parameters for SCI contusion injury (i.e. injury force and spinal cord displacement) in mice using the Infinite Horizons impactor (Chapter 2). This lesioning model was used in other work for the thesis. The role T cells may play in mediating macrophage activation after LPC microinjection and SCI was also assessed using Nude mice (Chapter 3). Next, Affymetrix GeneChip analysis was carried out on spinal cord tissue obtained at the peak of the macrophage response after SCI and intraspinal LPC injection to identify potential candidate genes that may control the divergent inflammatory responses (Chapter 4). Several potential genes were identified. I next characterized the expression and role of one of these genes, MAPK activated protein kinase 2 (MK2), and showed that it mediates secondary tissue damage after SCI via several mechanisms (Chapter 5). The differences in gene expression profiles of macrophages purified from the spinal cord after SCI and LPC-injection were also assessed (Chapter 6). This microarray analysis of macrophages led to the identification of 10 novel candidate genes, two of which were validated at the protein level. Finally, I also examined the expression and role of secretory leukocyte protease inhibitor (SLPI) in SCI (Chapter 7). Using a combination of knockout/overexpressing transgenic mice and recombinant SLPI, I found that SLPI mediates protective anti-inflammatory effects after SCI. In conclusion, work done for this thesis has led to the identification of several novel molecules that influence the inflammatory response after injury and thus have led to the identification of potentially novel targets for the development of pharmacological approaches to treat acute SCI.

O objetivo deste trabalho foi avaliar os efeitos da metilprednisolona empregada previamente ao traumatismo medular, tanto em relação aos possíveis efeitos benéficos quanto às possíveis complicações associadas. Foram utilizados 32 ratos Wistar, divididos em 4 grupos. Dois grupos receberam as drogas A (placebo) e B (metilprednisolona) imediatamente após a lesão. Outros 2 grupos receberam as mesmas drogas 4 horas antes da lesão. Todos foram avaliados por um período de 28 dias quanto à função locomotora e complicações associadas. Quanto aos índices motores, não houve diferença entre os grupos. Os ratos tratados com metilprednisolona quatro horas antes do trauma apresentaram um número de óbitos significativamente maior quando comparados aos ratos tratados com a mesma droga após o trauma / The objective of this work was to evaluate the effect of methylprednisolone previously used to spinal cord injury, in relation to the possible beneficial, and the possible associated complications. Thirty two Wistar rats had been used, divided in 4 groups. Two groups had received the drugs A (placebo) and B (methylprednisolone) immediately after the injury.The others 2 groups received the same drugs 4 hours before the injury. All had been evaluated to the locomotive function and complications associates by a period of 28 days. Concerning the motor indices, it did not show any difference between the groups. The rats treated with methylprednisolone four hours before the trauma presented a significantly higher number of deaths when compared with the rats treated with the same drug after the trauma

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