Endogenous Neuronal Replacement in the Juvenile Brain Following Cerebral Ischemia

Krista M. Rodgers*, Jared T. Ahrendsen, Olivia P. Patsos, Frank A. Strnad, Joan C. Yonchek, Richard J. Traystman, Wendy B. Macklin, Paco S. Herson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Replacement of dead neurons following ischemia, either via enhanced endogenous neurogenesis or stem cell therapy, has long been sought. Unfortunately, while various therapies that enhance neurogenesis or stem cell therapies have proven beneficial in animal models, they have all uniformly failed to truly replace dead neurons in the ischemic core to facilitate long-term recovery. Remarkably, we observe robust repopulation of medium-spiny neurons within the ischemic core of juvenile mice following experimental stroke. Despite extensive neuronal cell death in the injured striatum of both juveniles and adults at acute time points after ischemia (24 h and 7 d), mature newborn neurons replaced lost striatal neurons at 30 d post-ischemia. This neuronal repopulation was found only in juveniles, not adults, and importantly, was accompanied by enhanced post-ischemic behavioral recovery at 30 d. Ablation of neurogenesis using irradiation prevented neuronal replacement and functional recovery in MCAo-injured juvenile mice. In contrast, findings in adults were consistent with previous reports, that newborn neurons failed to mature and died, offering little therapeutic potential. These data provide support for neuronal replacement and consequent functional recovery following ischemic stroke and new targets in the development of novel therapies to treat stroke.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalNeuroscience
Volume380
DOIs
StatePublished - Jun 1 2018

Keywords

  • cerebral ischemia
  • endogenous recovery
  • neural stem cells
  • neurogenesis
  • neuron replacement

ASJC Scopus subject areas

  • Neuroscience(all)

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