Guo Zhihui, Jia Jia, Tu Yanling, Jin Chang, Guo Cen, Song Feifei, Wu Xuqing, Bao Haifeng, Fan Wei
Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Neurology, Shanghai Xuhui District Central Hospital, Shanghai, China.
Front Physiol. 2021 Jul 8;12:687947. doi: 10.3389/fphys.2021.687947. eCollection 2021.
Diabetes exacerbates brain damage in cerebral ischemic stroke. Our previous study has demonstrated that after cerebral ischemia, type 2 diabetes rats displayed worse neurological outcomes, larger cerebral infarction and severer blood-brain barrier disruption. However, our knowledge of the mechanisms of how diabetes impacts the cerebrovascular repair process is limited. This study was aimed to characterize structural alterations and potential mechanisms in brain microvessels before and after ischemic stroke in type 2 diabetic rats treated with high-fat diet and streptozotocin (HFD/STZ). Furtherly, we tested our hypothesis that dysregulated intercellular Jagged1-Notch1 signaling was involved in the dysfunctional cerebral neovascularization both before and after ischemic stroke in HFD/STZ rats. In our study, we found increased yet dysfunctional neovascularization with activated Jagged1-Notch1 signaling in the cerebrovasculature before cerebral ischemia in HFD/STZ rats compared with non-diabetic rats. Furthermore, we observed delayed angiogenesis as well as suppressed Jagged1-Notch1 signaling after ischemic stroke. Our results elucidate the potential mechanisms underlying diabetes-related cerebral microvasculature dysfunction after ischemic stroke.
糖尿病会加剧脑缺血性中风中的脑损伤。我们之前的研究表明，脑缺血后，2型糖尿病大鼠的神经功能结局更差，脑梗死面积更大，血脑屏障破坏更严重。然而，我们对糖尿病影响脑血管修复过程的机制了解有限。本研究旨在表征高脂饮食联合链脲佐菌素（HFD/STZ）处理的2型糖尿病大鼠缺血性中风前后脑微血管的结构改变和潜在机制。此外，我们检验了我们的假设，即细胞间Jagged1-Notch1信号失调参与了HFD/STZ大鼠缺血性中风前后功能失调的脑新生血管形成。在我们的研究中，我们发现与非糖尿病大鼠相比，HFD/STZ大鼠在脑缺血前脑血管中存在新生血管形成增加但功能失调且伴有Jagged1-Notch1信号激活的情况。此外，我们观察到缺血性中风后血管生成延迟以及Jagged1-Notch1信号受到抑制。我们的结果阐明了缺血性中风后糖尿病相关脑微血管功能障碍的潜在机制。
