School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, USA.
Joint Department of Biomedical Engineering, North Carolina State University and The University of North Carolina at Chapel Hill, Raleigh, North Carolina, USA.
J Biomed Mater Res B Appl Biomater. 2021 Dec;109(12):2268-2278. doi: 10.1002/jbm.b.34888. Epub 2021 Jun 11.
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.
颅脑损伤（TBI）后可能会发生凝血功能障碍，从而对患者的预后产生负面影响。在这里，我们研究了血小板样颗粒（PLPs）的用途，即聚（N-异丙基丙烯酰胺-co-丙烯酸）微凝胶与纤维蛋白特异性抗体结合，以改善 TBI 后的止血效果。本研究的目的是通过 PLP 治疗减少小鼠 TBI 模型（皮质控制冲击）中的凝血功能障碍，进而降低血脑屏障（BBB）通透性和神经炎症。TBI 后急性静脉注射 PLP 后，我们在 24 小时和 7 天 TBI 后分析 BBB 通透性、体外凝血参数和神经炎症。PLP 治疗组和对照颗粒治疗组均显著降低了 BBB 通透性，并改善了损伤后 24 小时的血栓结构。此外，与未治疗组相比，PLP 治疗组在 24 小时和 7 天之间的组织保留率没有明显变化。只有 PLP 治疗组在 7 天时显著降低了星形胶质细胞的表达，与 24 小时相比差异显著。最后，PLP 治疗组与未治疗对照组相比，小胶质细胞/巨噬细胞密度的 24 小时至 7 天的差异百分比显著降低。这些结果表明，PLP 治疗可改善急性低凝状态，降低 BBB 通透性，进而降低神经炎症和 7 天内的组织损失。这些有希望的结果表明，PLP 可能是 TBI 的一种潜在治疗方法。
