Yin Junxiang, Wu Michael, White Jennifer, StClair Ellie, Mocco J, Waters Michael F
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Barrow-ASU Center for Preclinical Imaging, Barrow Neurological Institute, Phoenix, Arizona, USA.
CNS Neurosci Ther. 2025 Jun;31(6):e70461. doi: 10.1111/cns.70461.
Futile recanalization affects more than half of acute ischemic stroke (AIS) patients. Neutrophil extracellular traps (NETs) are a major factor of microvascular hypoperfusion after stroke. Deoxyribonuclease I (DNase) targeting NETs exhibited a neuroprotective effect in young mice with AIS. This study explored a novel direct intra-arterial administration of DNase therapy and its effect in aged mice with AIS.
AIS was induced in aged C57BL/6 mice followed by reperfusion and immediate, intra-arterial DNase administration via the internal carotid artery. Cerebral blood flow (CBF), neurological function, cerebral infarct volume, and NET markers were examined.
Direct intra-arterial DNase therapy significantly increased CBF, reduced neurological deficit scores, increased the latency to fall in the wire hang test, reduced cerebral infarct volume, and decreased neutrophil and NET count in both the parenchyma and micro vessels in aged mice with AIS compared with age-matched vehicle controls.
Our data is the first to demonstrate that successful, direct intra-arterial DNase therapy provides more efficient cerebral reperfusion and better outcomes after recanalization during the treatment of large vessel occlusion in aged mice. This study provides evidence for the potential clinical application of catheter-delivered intra-arterial DNase therapy post-recanalization.
无效再灌注影响超过半数的急性缺血性卒中（AIS）患者。中性粒细胞胞外陷阱（NETs）是卒中后微血管灌注不足的主要因素。靶向NETs的脱氧核糖核酸酶I（DNase）在患有AIS的年轻小鼠中显示出神经保护作用。本研究探索了一种新型的直接动脉内注射DNase疗法及其在患有AIS的老年小鼠中的效果。
在老年C57BL/6小鼠中诱导AIS，随后进行再灌注，并通过颈内动脉立即进行动脉内DNase给药。检测脑血流量（CBF）、神经功能、脑梗死体积和NET标志物。
与年龄匹配的载体对照组相比，直接动脉内DNase疗法显著增加了患有AIS的老年小鼠的CBF，降低了神经功能缺损评分，增加了悬线试验中的坠落潜伏期，减小了脑梗死体积，并减少了实质和微血管中的中性粒细胞和NET计数。
我们的数据首次证明，成功的直接动脉内DNase疗法在老年小鼠大血管闭塞治疗期间的再灌注后提供了更有效的脑再灌注和更好的结果。本研究为导管输送动脉内DNase疗法再灌注后的潜在临床应用提供了证据。
