Corticosterone-Mediated Body Weight Loss Is an Important Catabolic Process for Poststroke Immunity and Survival Academic Article uri icon

Overview

MeSH Major

  • Brain Injuries
  • Cytokines
  • Diabetes Mellitus, Experimental
  • Gene Expression Regulation

abstract

  • Background and Purpose- Stroke-induced acute severe body weight (BW) loss is associated with a high rate of mortality during a critical poststroke period. Several interventions to reduce weight loss, however, have not been successful. Currently, the biological significance of this extraordinary catabolic process is not well understood. Spleen-derived monocytes/macrophages (MMs) are the major immune cells recruited to the injured brain. The trafficking of MMs has been shown to be important for tissue repair and recovery. The purpose of the study is to investigate whether the BW reduction is essential for MM-mediated immune response for mice to survive and whether a corticosterone-mediated catabolic event underlies the processes. Methods- C57BL/6 male mice (12-week-old) were subjected to transient middle cerebral artery occlusion. BW, total MMs, and their Ly-6Chigh and Ly-6Clow subsets were determined in the spleen, blood, and the brain in poststroke mice. Poststroke survival rate and MM subsets were determined in mice with adrenalectomy, sham-adrenalectomy, and adrenalectomy mice supplemented with corticosterone. Results- Stroke reduced BW with a maximum reduction at day 3 poststroke (17.2±5.2%). The reduction at day 3 was positively linked to injury severity and selective depletion of MMs, but no other types of immune cells, in the spleen. Notably, the splenic MM depletion was significantly greater in mice with severe BW reduction (≥18% at day 3). In the blood, stroke depleted circulating MMs to a similar degree in animals with moderate and severe BW loss. Ly-6C+ monocyte infiltration in the poststroke brain was greater in mice with severe BW loss. Blocking the catabolic process by adrenalectomy significantly increased poststroke mortality, but the mortality was partially rescued by corticosterone supplement in adrenalectomy mice. Conclusions- Stroke-induced BW loss facilitates MM-mediated immune response, and the adrenal corticosterone-mediated catabolic process is necessary for poststroke survival. Visual Overview- An online visual overview is available for this article.

publication date

  • September 2019

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC6710102

Digital Object Identifier (DOI)

  • 10.1161/STROKEAHA.119.026053

PubMed ID

  • 31345131

Additional Document Info

start page

  • 2539

end page

  • 2546

volume

  • 50

number

  • 9