Concussion is a widely recognized environmental risk factor for neurodegenerative diseases, including Parkinson’s disease (PD). Small-vessel disease of the brain has been reported to contribute to neurodegenerative diseases. In this study, we observed BBB disruption in wild-type (WT) mice, but not in matrix metalloproteinase 9 (MMP-9) knockout mice, subjected to single severe traumatic brain injury (ssTBI). Furthermore, treating ssTBI mice with the MMP-9 inhibitor GM6001 effectively maintained BBB integrity, promoted the elimination of damaged mitochondria via mitophagy, and then prevented neuronal death and progressive neurodegeneration. However, we did not observe this neuroprotective effect of MMP-9 inhibition in beclin-1^−/+ mice. Collectively, these findings revealed that concussion led to BBB disruption via MMP-9, and that GM6001 prevented the development of PD via the autophagy pathway.

脑震荡是公认的神经退行性疾病的环境风险因素，包括帕金森病 (PD)。据报道，大脑的小血管疾病会导致神经退行性疾病。在这项研究中，我们观察到野生型 (WT) 小鼠的 BBB 破坏，但在遭受单一严重创伤性脑损伤 (ssTBI) 的基质金属蛋白酶 9 (MMP-9) 敲除小鼠中没有观察到。此外，用 MMP-9 抑制剂 GM6001 治疗 ssTBI 小鼠可有效维持 BBB 完整性，通过线粒体自噬促进受损线粒体的消除，然后防止神经元死亡和进行性神经退行性变。然而，我们没有观察到 MMP-9 抑制在 beclin-1 ^{-/+中的这种神经保护作用}老鼠。总的来说，这些研究结果表明，脑震荡通过 MMP-9 导致 BBB 破坏，而 GM6001 通过自噬途径阻止了 PD 的发展。