Neuronal replacement from endogenous precursors in the adult brain after stroke

Abstract

In the adult brain, new neurons are continuously generated in the subventricular zone and dentate gyrus, but it is unknown whether these neurons can replace those lost following damage or disease. Here we show that stroke, caused by transient middle cerebral artery occlusion in adult rats, leads to a marked increase of cell proliferation in the subventricular zone. Stroke-generated new neurons, as well as neuroblasts probably already formed before the insult, migrate into the severely damaged area of the striatum, where they express markers of developing and mature, striatal medium-sized spiny neurons. Thus, stroke induces differentiation of new neurons into the phenotype of most of the neurons destroyed by the ischemic lesion. Here we show that the adult brain has the capacity for self-repair after insults causing extensive neuronal death. If the new neurons are functional and their formation can be stimulated, a novel therapeutic strategy might be developed for stroke in humans.

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Figure 1: Stroke-induced neurogenesis in the adult striatum.
Figure 2: Ara-C treatment inhibits proliferation in SVZ and striatal neurogenesis after stroke.
Figure 3: Stroke-generated cells migrate from the subventricular zone into the ischemic lesion.
Figure 4: Stroke-generated cells express markers of developing striatal neurons.
Figure 5: Stroke-generated cells express markers of mature striatal medium-sized spiny neurons.

Change history

  • 23 August 2002

    Update panel b of Figure 1

Notes

  1. 1.

    NOTE: In the AOP version of this article, in Fig. 1b a line of text was missing on the x axis. Below the second bar it should have read "MCAO intact" and below the third bar it should have read "MCAO total". This has been corrected in the HTML and PDF versions, and will appear correctly in a forthcoming print issue.

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Acknowledgements

This work was supported by the Swedish Research Council, The Söderberg Foundation, Kock, Crafoord, and Elsa and Thorsten Segerfalk Foundations, the Swedish Stroke Foundation and the Swedish Association of Neurologically Disabled.

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Correspondence to Andreas Arvidsson.

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Arvidsson, A., Collin, T., Kirik, D. et al. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8, 963–970 (2002). https://doi.org/10.1038/nm747

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