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.

中文翻译：

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血小板样颗粒减少实验性创伤性脑损伤后与凝血病相关和神经炎症的病理

创伤性脑损伤 (TBI) 后可能会发生凝血障碍，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 (PLP)、聚（N-异丙基丙烯酰胺-co）的使用-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。本研究的目的是通过 PLP 治疗减少小鼠 TBI 模型（受控皮质影响）中的凝血病，并随后降低血脑屏障 (BBB) 通透性和神经炎症。在 TBI 后急性静脉注射 PLP 后，我们分析了 TBI 后 24 小时和 7 天的 BBB 渗透性、离体凝血参数和神经炎症。PLP 处理和对照粒子处理均显着降低了 BBB 通透性并改善了损伤后 24 小时的凝块结构。此外，与未治疗的队列相比，PLP 治疗的队列在 24 小时至 7 天之间没有观察到组织保留的显着变化。只有 PLP 处理导致星形胶质细胞表达在 7 天和从 24 小时到 7 天的百分比差异显着减少。最后，与未处理的对照相比，PLP 处理显着降低了小胶质细胞/巨噬细胞密度从 24 小时到 7 天的百分比差异。这些结果表明，PLP 治疗解决了急性低凝和降低 BBB 通透性，随后在受伤后 7 天减少了神经炎症和折叠变化组织损失。这些有希望的结果表明 PLP 可能是 TBI 的潜在治疗方式。这些结果表明，PLP 治疗解决了急性低凝和降低 BBB 通透性，随后在受伤后 7 天减少了神经炎症和折叠变化组织损失。这些有希望的结果表明 PLP 可能是 TBI 的潜在治疗方式。这些结果表明，PLP 治疗解决了急性低凝和降低 BBB 通透性，随后在受伤后 7 天减少了神经炎症和折叠变化组织损失。这些有希望的结果表明 PLP 可能是 TBI 的潜在治疗方式。