Time-dependent increase in Nogo-A expression after focal cerebral ischemia in marmoset monkeys

Nogo-A is a myelin-associated protein that has been shown to inhibit axonal sprouting after lesions to the CNS. Several studies have demonstrated that blocking the activity or expression of this inhibitor can induce structural and functional recovery after CNS lesions. However, there are limited and contradictory data on the expression of Nogo-A after CNS lesions. In the present study, marmoset monkeys received permanent occlusion of the middle cerebral artery (MCAo). Two, 3, or 4 months after the onset of injury brain sections were stained for Nogo-A protein. Two sham operated marmosets were included as a control. Nogo-A protein expression was quantified in white matter and grey matter in the areas adjacent to the lesion (or the equivalent areas in the intact side). At 2 months after injury, but not at 3 or 4 months, there was a significant increase in the number of oligodendrocytes that were Nogo-A immunopositive. This increase was observed in white matter structures that were adjacent to the lesion (e.g. corona radiate (CR)); but not in: white matter structures distal to the lesion (e.g. corpus callosum (CC)); cortical regions adjacent to the lesion; contralateral regions or in sham operated marmosets. These data suggest that Nogo-A levels are significantly increased within oligodendrocytes in areas adjacent to the lesion up to 2 months following cerebral ischeamia. Future studies will determine whether this offers the opportunity to promote plasticity by targeting Nogo-A weeks or months following stroke.