RESUMO
This study was undertaken as part of the NIH "Facilities of Research Excellence-Spinal Cord Injury", which supports independent replication of published studies. Here, we repeat an experiment reporting that intracortical delivery of inosine promoted trans-midline growth of corticospinal tract (CST) axons in the spinal cord after unilateral injury to the medullary pyramid. Rats received unilateral transections of the medullary pyramid and 1 day later, a cannula assembly was implanted into the sensorimotor cortex contralateral to the pyramidotomy to deliver either inosine or vehicle. The cannula assembly was attached to an osmotic minipump that was implanted sub-cutaneously. Seventeen or 18 days post-injury, the CST was traced by making multiple injections of miniruby-BDA into the sensorimotor cortex. Rats were killed for tract tracing 14 days after the BDA injections. Sections through the cervical spinal cord were stained for BDA and immunostained for GAP43 and GFAP. Our results revealed no evidence for enhanced growth of CST axons across the midline of the dorsal column in rats that received intracortical infusion of inosine. Possible reasons for the failure to replicate are discussed.
Assuntos
Axônios/fisiologia , Córtex Cerebral/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Inosina/administração & dosagem , Bulbo/lesões , Tratos Piramidais/crescimento & desenvolvimento , Animais , Axônios/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Masculino , Bulbo/efeitos dos fármacos , Bulbo/patologia , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/fisiologia , Tratos Piramidais/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
This study evaluates a major metabolite of misonidazole, desmethylmisonidazole, for its potential to induce peripheral nerve damage using the lysosomal enzyme correlates of neuropathological change, namely beta-glucuronidase and beta-galactosidase. The results showed that desmethylmisonidazole like misonidazole had a similar potential for inducing peripheral nerve damage as measured biochemically, but the dosing regimen had to be maintained for 10 consecutive days as opposed to the 7 days required for misonidazole.