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Updated: Jul 20, 2026
Induction of Acute Ischemic Stroke in Mice Using the Distal Middle Artery Occlusion Technique
Published on: December 15, 2023
Time-dependent increase in Nogo-A expression after focal cerebral ischemia in marmoset monkeys
Andisheh Eslamboli1, Robert I Grundy, Elaine A Irving
1Neurology and GI CEDD, GlaxoSmithKline, New Frontiers Science Park North, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom.
Abstract:
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 ischaemia. Future studies will determine whether this offers the opportunity to promote plasticity by targeting Nogo-A weeks or months following stroke.
Insights
Nogo-A protein, an inhibitor of axonal regrowth, significantly increases in oligodendrocytes near stroke lesions in marmosets up to two months post-injury. This finding may reveal therapeutic targets for stroke recovery.
Area of Science:
- Neuroscience
- Neurobiology
- Regenerative Medicine
Background:
- Nogo-A is a myelin-associated protein inhibiting axonal sprouting after central nervous system (CNS) lesions.
- Blocking Nogo-A activity shows potential for structural and functional recovery post-CNS injury.
- Data on Nogo-A expression following CNS lesions are limited and contradictory.
Purpose of the Study:
- To investigate the temporal and spatial expression of Nogo-A protein in the brain following a stroke-like injury.
- To determine if Nogo-A expression changes in specific brain regions and cell types after cerebral ischemia.
Main Methods:
- Marmoset monkeys underwent permanent middle cerebral artery occlusion (MCAo) to model ischemic stroke.
- Brain sections were analyzed for Nogo-A protein expression at 2, 3, and 4 months post-MCAo.
- Nogo-A immunopositivity was quantified in oligodendrocytes within white and grey matter regions adjacent to the lesion.
Main Results:
- A significant increase in Nogo-A immunopositive oligodendrocytes was observed in white matter adjacent to the lesion at 2 months post-MCAo.
- This increase was not detected at 3 or 4 months post-injury.
- Nogo-A levels did not increase in distal white matter, adjacent cortical regions, or contralateral hemispheres.
Conclusions:
- Nogo-A levels are significantly elevated in oligodendrocytes near the lesion site up to 2 months after cerebral ischemia in marmosets.
- This temporal upregulation suggests a potential window for therapeutic intervention targeting Nogo-A to promote plasticity and recovery after stroke.
