TY - JOUR
T1 - Platelet-like particles reduce coagulopathy-related and neuroinflammatory pathologies post-experimental traumatic brain injury
AU - Todd, Jordan
AU - Bharadwaj, Vimala N.
AU - Nellenbach, Kimberly
AU - Nandi, Seema
AU - Mihalko, Emily
AU - Copeland, Connor
AU - Brown, Ashley C.
AU - Stabenfeldt, Sarah E.
N1 - Publisher Copyright:
© 2021 Wiley Periodicals LLC
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - blood–brain barrier
KW - coagulopathy
KW - neuroinflammation
KW - permeability
KW - platelet-like particles
KW - traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=85107732006&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85107732006&partnerID=8YFLogxK
U2 - 10.1002/jbm.b.34888
DO - 10.1002/jbm.b.34888
M3 - Article
C2 - 34117693
AN - SCOPUS:85107732006
SN - 1552-4973
VL - 109
SP - 2268
EP - 2278
JO - Journal of Biomedical Materials Research - Part B Applied Biomaterials
JF - Journal of Biomedical Materials Research - Part B Applied Biomaterials
IS - 12
ER -