Platelet-like particles reduce coagulopathy-related and neuroinflammatory pathologies post-experimental traumatic brain injury

Jordan Todd, Vimala N. Bharadwaj, Kimberly Nellenbach, Seema Nandi, Emily Mihalko, Connor Copeland, Ashley C. Brown, Sarah E. Stabenfeldt

Research output: Contribution to journalArticlepeer-review

Abstract

Coagulopathy may occur following traumatic brain injury (TBI), thereby negatively affecting patient outcomes. Here, we investigate the use of platelet-like particles (PLPs), poly(N-isopropylacrylamide-co-acrylic-acid) microgels conjugated with a fibrin-specific antibody, to improve hemostasis post-TBI. The objective of this study was to diminish coagulopathy in a mouse TBI model (controlled cortical impact) via PLP treatment, and subsequently decrease blood–brain barrier (BBB) permeability and neuroinflammation. Following an acute intravenous injection of PLPs post-TBI, we analyzed BBB permeability, ex vivo coagulation parameters, and neuroinflammation at 24 hr and 7 days post-TBI. Both PLP-treatment and control particle-treatment had significantly decreased BBB permeability and improved clot structure 24 hr post-injury. Additionally, no significant change in tissue sparing was observed between 24 hr and 7 days for PLP-treated cohorts compared to that observed in untreated cohorts. Only PLP-treatment resulted in significant reduction of astrocyte expression at 7 days and percent difference from 24 hr to 7 days. Finally, PLP-treatment significantly reduced the percent difference from 24 hr to 7 days in microglia/macrophage density compared to the untreated control. These results suggest that PLP-treatment addressed acute hypocoagulation and decreased BBB permeability followed by decreased neuroinflammation and fold-change tissue loss by 7 days post-injury. These promising results indicate that PLPs could be a potential therapeutic modality for TBI.

Original languageEnglish (US)
JournalJournal of Biomedical Materials Research - Part B Applied Biomaterials
DOIs
StateAccepted/In press - 2021
Externally publishedYes

Keywords

  • blood–brain barrier
  • coagulopathy
  • neuroinflammation
  • permeability
  • platelet-like particles
  • traumatic brain injury

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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