Department of Anesthesiology, University Medical Center of Johannes Gutenberg University, Langenbeckstrasse 1, 55131, Mainz, Germany.
Faculty of Health, University Witten/Herdecke, Witten, Germany.
Sci Rep. 2023 Mar 16;13(1):4348. doi: 10.1038/s41598-023-30421-5.
Traumatic brain injury (TBI) causes the release of danger-associated molecular patterns (DAMP) from damaged or dead cells, which contribute to secondary brain damage after TBI. Cell-free DNA (cfDNA) is a DAMP known to cause disruption of the blood-brain barrier (BBB), promote procoagulant processes, brain edema, and neuroinflammation. This study tested the hypothesis that administration of deoxyribonuclease-I (DNase-I) has a beneficial effect after TBI. Mice (n = 84) were subjected to controlled cortical impact (CCI) and posttraumatic intraperitoneal injections of low dose (LD) or high dose (HD) of DNase-I or vehicle solution at 30 min and 12 h after CCI. LD was most effective to reduce lesion volume (p = 0.003), brain water content (p < 0.0001) and to stabilize BBB integrity (p = 0.019) 1 day post-injury (dpi). At 6 h post injury LD-treated animals showed less cleavage of fibrin (p = 0.0014), and enhanced perfusion as assessed by micro-computer-tomography (p = 0.027). At 5 dpi the number of Iba1-positive cells (p = 0.037) were reduced, but the number of CD45-positive cells, motoric function and brain lesion volume was not different. Posttraumatic-treatment with DNase-I therefore stabilizes the BBB, reduces the formation of brain edema, immune response, and delays secondary brain damage. DNase-I might be a new approach to extend the treatment window after TBI.
创伤性脑损伤（TBI）会导致受损或死亡细胞释放危险相关分子模式（DAMP），从而导致 TBI 后的继发性脑损伤。无细胞 DNA（cfDNA）是一种已知会破坏血脑屏障（BBB）、促进促凝过程、脑水肿和神经炎症的 DAMP。本研究检验了以下假设：在 TBI 后给予脱氧核糖核酸酶-I（DNase-I）具有有益作用。将小鼠（n = 84）进行皮质控制冲击（CCI），并在 CCI 后 30 分钟和 12 小时，通过腹膜内注射低剂量（LD）或高剂量（HD）DNase-I 或载体溶液。LD 最有效地减少损伤体积（p = 0.003）、脑含水量（p < 0.0001）和稳定 BBB 完整性（p = 0.019）在损伤后 1 天（dpi）。在损伤后 6 小时，LD 治疗的动物显示出纤维蛋白裂解减少（p = 0.0014），并且通过微计算机断层扫描（p = 0.027）评估的灌注增强。在 5 dpi 时，Iba1 阳性细胞的数量减少（p = 0.037），但 CD45 阳性细胞的数量、运动功能和脑损伤体积没有差异。因此，TBI 后用 DNase-I 治疗可稳定 BBB、减少脑水肿形成、免疫反应并延迟继发性脑损伤。DNase-I 可能是延长 TBI 后治疗窗口的新方法。
