In adult mammals, CNS damage does not repair well spontaneously. The Nogo receptor (NgR) signaling pathway prevents axonal regrowth and promotes neuronal apoptosis. This pathway, and pathways like it, may be part of the reason why nerves do not regrow. A number of preclinical experiments inhibiting portions of the NgR pathway have yielded limited induction of nerve repair. Here, we developed a small hairpin RNA (shRNA) to knock down NgR expression. With the use of rat hippocampal slices in tissue culture, we induced neuronal damage similar to that of ischemia-reperfusion injury by exposing the cultured tissues to oxygen-glucose deprivation. We then assayed the effect of NgR knockdown in this model system. Adenovirally delivered NgR shRNA decreased NgR mRNA and protein expression. Thirty minutes of oxygen-glucose deprivation resulted in widespread tissue damage, including apoptosis and loss of neurite extension, 72 h after termination of oxygen-glucose deprivation. The NgR shRNA knockdown reduced, but did not eliminate, the effects of oxygen-glucose deprivation. Thus, NgR shRNA shows promise as a potential tool for the treatment of nerve damage.
© 2010 Japanese Society of Neuropathology.