Persistent infiltration and impaired response of peripherally-derived monocytes after traumatic brain injury in the aged brain

Austin Chou, Karen Krukowski, Josh M. Morganti, Lara Kirstie Riparip, Susanna Rosi

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Traumatic brain injury (TBI) is a leading cause for neurological disabilities world-wide. TBI occurs most frequently among the elderly population, and elderly TBI survivors suffer from reduced recovery and poorer quality of life. The effect of age on the pathophysiology of TBI is still poorly understood. We previously established that peripherally-derived monocytes (CCR2+) infiltrate the injured brain and contribute to chronic TBI-induced cognitive deficits in young animals. Furthermore, age was shown to amplify monocyte infiltration acutely after injury. In the current study, we investigated the impact of age on the subchronic response of peripherally-derived monocytes (CD45hi; CCR2+) and their role in the development of chronic cognitive deficits. In the aged brain, there was a significant increase in the number of peripherally-derived monocytes after injury compared to young, injured animals. The infiltration rate of peripherally-derived monocytes remained elevated subchronically and corresponded with enhanced expression of CCR2 chemotactic ligands. Interestingly, the myeloid cell populations observed in injured aged brains had impaired anti-inflammatory responses compared to those in young animals. Additionally, in the aged animals, there was an expansion of the blood CCR2+ monocyte population after injury that was not present in the young animals. Importantly, knocking out CCR2 to inhibit infiltration of peripherally-derived monocytes prevented chronic TBI-induced spatial memory deficits in the aged mice. Altogether, these results demonstrate the critical effects of age on the peripherally-derived monocyte response during the progression of TBI pathophysiology.

Original languageEnglish
Article number1616
JournalInternational Journal of Molecular Sciences
Volume19
Issue number6
DOIs
StatePublished - Jun 2018

Bibliographical note

Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Ageing
  • Cognition
  • Inflammation
  • Monocyte
  • Traumatic brain injury

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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