Stroke is the leading cause of permanent disability and death in the world. The therapy for acute stroke is still limited due to the complex mechanisms underlying stroke-induced neuronal death. The generation of a 17-kDa neurotoxic tau fragment was reported in Alzheimer’s disease but it has not been well studied in stroke. In this study, we observed the accumulation of 17-kDa tau fragment in cultured primary neurons and media after oxygen-glucose deprivation/reperfusion (OGD/R) treatment that could be diminished by the presence of a calpain inhibitor. This calpain-mediated proteolytic tau fragment was also detected in brain tissues from middle cerebral artery occlusion–injured rats and acute ischemic stroke patients receiving strokectomy, and human plasma samples collected within 48 h after the onset of stroke. The mass spectrometry analysis of this 17-kDa fragment identified 2 peptide sequences containing 195–224 amino acids of tau, which agrees with the previously reported tau_45-230 or tau_125-230 as the calpain-cleaved tau fragment. Ectopic expression of tau_45-230-GFP but not tau_125-230-GFP in cultured neurons induced the formation of tortuous processes without evident cell death. In summary, the 17-kDa tau fragment is a novel stroke biomarker and may play a pathophysiological role to affect post-stroke neuronal health.

中风是世界上导致永久性残疾和死亡的主要原因。由于中风引起的神经元死亡的复杂机制，急性中风的治疗仍然受到限制。据报道在阿尔茨海默病中产生了 17 kDa 神经毒性 tau 片段，但在中风中尚未得到很好的研究。在这项研究中，我们观察到氧-葡萄糖剥夺/再灌注 (OGD/R) 治疗后培养的原代神经元和培养基中 17 kDa tau 片段的积累，钙蛋白酶抑制剂的存在可能会减少这种积累。这种钙蛋白酶介导的蛋白水解 tau 片段也在大脑中动脉闭塞损伤的大鼠和接受中风切除术的急性缺血性中风患者的脑组织中检测到，以及在中风发作后 48 小时内收集的人血浆样本中检测到。_45-230或 tau _125-230作为钙蛋白酶切割的 tau 片段。_{tau 45-230} -GFP 而不是 tau _125-230 -GFP 在培养的神经元中的异位表达诱导了曲折过程的形成，而没有明显的细胞死亡。总之，17-kDa tau 片段是一种新的中风生物标志物，可能在影响中风后神经元健康方面发挥病理生理作用。