TY - JOUR
T1 - PEG hydrogel containing dexamethasone-conjugated hyaluronic acid reduces secondary injury and improves motor function in a rat moderate TBI model
AU - Jones, Claire
AU - Elliott, Bradley
AU - Liao, Zhen
AU - Johnson, Zack
AU - Ma, Fuying
AU - Bailey, Zachary S.
AU - Gilsdorf, Janice
AU - Scultetus, Anke
AU - Shear, Deborah
AU - Webb, Ken
AU - Lee, Jeoung Soo
N1 - Funding Information:
The authors would like to thank Krista Henrie for her assistance with preparations for animal surgery. We also would like to thank Godley-Snell Research Center for the assistance with animal care and Dr. Patrick Gerard, Mathematical and Statistical Sciences, Clemson University for his assistance with statistical analysis. This study was funded by US Department of Army and Combat Casualty Care Research Program under award number W81XWH-20-C-0114. This study was partly supported by Bioengineering Center for Regeneration and Formation of Tissues (SC BioCRAFT) Voucher Program at Clemson University funded by NIH/NIGMS P30GM131959 .
Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/11
Y1 - 2023/11
N2 - Traumatic brain injury (TBI) leads to long-term impairments in motor and cognitive function. TBI initiates a secondary injury cascade including a neuro-inflammatory response that is detrimental to tissue repair and limits recovery. Anti-inflammatory corticosteroids such as dexamethasone can reduce the deleterious effects of secondary injury; but challenges associated with dosing, administration route, and side effects have hindered their clinical application. Previously, we developed a hydrolytically degradable hydrogel (PEG-bis-AA/HA-DXM) composed of poly (ethylene) glycol-bis-(acryloyloxy acetate) (PEG-bis-AA) and dexamethasone-conjugated hyaluronic acid (HA-DXM) for local and sustained dexamethasone delivery. In this study, we evaluated the effect of locally applied PEG-bis-AA/HA-DXM hydrogel on secondary injury and motor function recovery after moderate controlled cortical impact (CCI) TBI. Hydrogel treatment significantly improved motor function evaluated by beam walk and rotarod tests compared to untreated rats over 7 days post-injury (DPI). We also observed that the hydrogel treatment reduced lesion volume, inflammatory response, astrogliosis, apoptosis, and increased neuronal survival compared to untreated rats at 7 DPI. These results suggest that PEG-bis-AA/HA-DXM hydrogels can mitigate secondary injury and promote motor functional recovery following moderate TBI.
AB - Traumatic brain injury (TBI) leads to long-term impairments in motor and cognitive function. TBI initiates a secondary injury cascade including a neuro-inflammatory response that is detrimental to tissue repair and limits recovery. Anti-inflammatory corticosteroids such as dexamethasone can reduce the deleterious effects of secondary injury; but challenges associated with dosing, administration route, and side effects have hindered their clinical application. Previously, we developed a hydrolytically degradable hydrogel (PEG-bis-AA/HA-DXM) composed of poly (ethylene) glycol-bis-(acryloyloxy acetate) (PEG-bis-AA) and dexamethasone-conjugated hyaluronic acid (HA-DXM) for local and sustained dexamethasone delivery. In this study, we evaluated the effect of locally applied PEG-bis-AA/HA-DXM hydrogel on secondary injury and motor function recovery after moderate controlled cortical impact (CCI) TBI. Hydrogel treatment significantly improved motor function evaluated by beam walk and rotarod tests compared to untreated rats over 7 days post-injury (DPI). We also observed that the hydrogel treatment reduced lesion volume, inflammatory response, astrogliosis, apoptosis, and increased neuronal survival compared to untreated rats at 7 DPI. These results suggest that PEG-bis-AA/HA-DXM hydrogels can mitigate secondary injury and promote motor functional recovery following moderate TBI.
KW - Dexamethasone
KW - PEG-bis-AA/HA-DXM hydrogel
KW - Secondary injury, neuroinflammation, motor function
KW - Traumatic brain injury (TBI)
UR - http://www.scopus.com/inward/record.url?scp=85170656026&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2023.114533
DO - 10.1016/j.expneurol.2023.114533
M3 - Article
C2 - 37666386
AN - SCOPUS:85170656026
SN - 0014-4886
VL - 369
JO - Experimental Neurology
JF - Experimental Neurology
M1 - 114533
ER -