Reduced post-stroke glial scarring in the infant primate brain reflects age-related differences in the regulation of astrogliosis

Leon Teo, Anthony G. Boghdadi, Mitchell de Souza, James A. Bourne

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

Ischemic stroke remains a leading cause of disability worldwide. Surviving patients often suffer permanent neurological impairments, and spontaneous recovery rarely occurs. However, observations that early-life brain injuries, including strokes, elicit less severe long-term functional impairments, compared to adults, continue to intrigue. While much research has focussed on neuronal changes and plasticity, less is known regarding the regulation of astrogliosis and glial scar formation after a stroke at different stages of life. Therefore, we investigated the cellular, molecular and temporal differences in chronic scar development in the infant and adult nonhuman primate (NHP) post-stroke as it bears greater clinical relevance in the close temporal and pathophysiological homology with humans. This project utilized the endothelin-1 model of focal ischemic stroke in the infant and adult primary visual cortex and investigated differences in the subacute and chronic period. We report here that the post-stroke infant neocortex generates a smaller, more discrete chronic scar, correlating to greater neuronal sparing. Reactive astrocytes that comprise the chronic scar are generated earlier in infants compared to adults, and the expression of critical markers of astrocyte reactivity differs in the subacute period between post-stroke infants and adults. Most importantly, we report that unlike adults, infant astrocyte reactivity is not dependent on several crucial regulators: signal transducer and activator of transcription 3, lipocalin2 and collagen I. Our results demonstrate that infant reactive astrocytes are not regulated by the same intrinsic and extrinsic factors that control these processes in adults, resulting in a more discrete chronic glial scar that is more permissible to neuronal sparing.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalNeurobiology of Disease
Volume111
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • Astrocyte
  • Brain injury
  • Marmoset
  • Neocortex
  • Regeneration

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