含地塞米松水凝胶的损伤处治疗可改善创伤性脑损伤后的认知功能并减轻继发性损伤反应。
Point-of-Injury Treatment with Hydrogel Containing Dexamethasone Improves Cognitive Function and Reduces Secondary Injury Response After TBI.
作者信息
Jones Claire E, Elliott Bradley, Ma Fuying, Bailey Zachary, Gilsdorf Janice, Scultetus Anke H, Shear Deborah, Webb Ken, Lee Jeoung Soo
机构信息
Drug Design, Development and Delivery Laboratory, Department of Bioengineering, Clemson University, Clemson, SC 29634, USA.
Brain Trauma Neuroprotection Branch, Walter Reed Army Institute of Research (WRAIR), Silver Spring, MD 20910, USA.
出版信息
Gels. 2025 Aug 1;11(8):600. doi: 10.3390/gels11080600.
Functional recovery after traumatic brain injury (TBI) is hindered by progressive neurodegeneration resulting from neuroinflammation and other secondary injury processes. Dexamethasone (DX), a synthetic glucocorticoid, has been shown to reduce inflammation, but its systemic administration can cause a myriad of other medical issues. We aim to provide a local, sustained treatment of DX for TBI. Previously, we demonstrated that PEG-bis-AA/HA-DXM hydrogels composed of polyethyleneglycol-bis-(acryloyloxy acetate) (PEG-bis-AA) and dexamethasone-conjugated hyaluronic acid (HA-DXM) reduced secondary injury and improved motor functional recovery at 7 days post-injury (DPI) in a rat moderate controlled cortical impact (CCI) TBI model. In this study, we evaluated the effect of PEG-bis-AA/HA-DXM hydrogel on cognitive function and secondary injury at 14 DPI. Immediately after injury, hydrogel disks were placed on the surface of the injured cortex. Cognitive function was evaluated using the Morris Water Maze test, and secondary injury was evaluated by histological analysis. The hydrogel treatment group demonstrated significantly shorter latency to target, decreased distance to find the hidden target, increased number of target crossings, increased number of entries to the platform zone, and decreased latency to first entry of target zone compared to untreated TBI rats for probe test. We also observed reduced lesion volume, inflammatory response, and apoptosis in the hydrogel treatment group compared to the untreated TBI group.
创伤性脑损伤(TBI)后的功能恢复受到神经炎症和其他继发性损伤过程导致的进行性神经变性的阻碍。地塞米松(DX)是一种合成糖皮质激素,已被证明可减轻炎症,但其全身给药会引发众多其他医学问题。我们旨在为TBI提供局部、持续的DX治疗。此前,我们证明了由聚乙二醇-双-(丙烯酰氧基乙酸酯)(PEG-bis-AA)和地塞米松共轭透明质酸(HA-DXM)组成的PEG-bis-AA/HA-DXM水凝胶在大鼠中度控制性皮质撞击(CCI)TBI模型中,可在损伤后7天(DPI)减少继发性损伤并改善运动功能恢复。在本研究中,我们评估了PEG-bis-AA/HA-DXM水凝胶在14 DPI时对认知功能和继发性损伤的影响。损伤后立即将水凝胶圆盘置于受伤皮质表面。使用莫里斯水迷宫试验评估认知功能,并通过组织学分析评估继发性损伤。与未治疗的TBI大鼠相比,水凝胶治疗组在探针试验中表现出明显更短的到达目标潜伏期、找到隐藏目标的距离缩短、目标穿越次数增加、进入平台区的次数增加以及首次进入目标区的潜伏期缩短。我们还观察到,与未治疗的TBI组相比,水凝胶治疗组的损伤体积、炎症反应和细胞凋亡减少。