Jiang Yinghua, Liu Ning, Han Jinrui, Li Yadan, Spencer Pierce, Vodovoz Samuel J, Ning Ming-Ming, Bix Gregory, Katakam Prasad V G, Dumont Aaron S, Wang Xiaoying
Clinical Neuroscience Research Center, Departments of Neurosurgery and Neurology, Tulane University School of Medicine, New Orleans, LA, 70122, USA.
Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02129, USA.
Transl Stroke Res. 2021 Jun;12(3):416-427. doi: 10.1007/s12975-020-00872-3. Epub 2020 Nov 2.
Intravenous administration of tissue-type plasminogen activator (IV tPA) therapy has long been considered a mainstay in ischemic stroke management. However, patients respond to IV tPA therapy unequally with some subsets of patients having worsened outcomes after treatment. In particular, diabetes mellitus (DM) is recognized as a clinically important vascular comorbidity that leads to lower recanalization rates and increased risks of hemorrhagic transformation (HT). In this short-review, we summarize the recent advances in understanding of the underlying mechanisms involved in post-IV tPA worsening of outcome in diabetic stroke. Potential pathologic factors that are related to the suboptimal tPA recanalization in diabetic stroke include higher plasma plasminogen activator inhibitor (PAI)-1 level, diabetic atherogenic vascular damage, glycation of the tPA receptor annexin A2, and alterations in fibrin clot density. While factors contributing to the exacerbation of HT in diabetic stroke include hyperglycemia, vascular oxidative stress, and inflammation, tPA neurovascular toxicity and imbalance in extracellular proteolysis are discussed. Besides, impaired collaterals in DM also compromise the efficacy of IV tPA therapy. Additionally, several tPA combination approaches developed from experimental studies that may help to optimize IV tPA therapy are also briefly summarized. In summary, more research efforts are needed to improve the safety and efficacy of IV tPA therapy in ischemic stroke patients with DM/poststroke hyperglycemia.
静脉注射组织型纤溶酶原激活剂（IV tPA）疗法长期以来一直被视为缺血性中风治疗的主要手段。然而，患者对IV tPA疗法的反应并不相同，部分患者亚组在治疗后预后恶化。特别是，糖尿病（DM）被认为是一种临床上重要的血管合并症，会导致再通率降低和出血性转化（HT）风险增加。在这篇简短综述中，我们总结了近期在理解糖尿病性中风患者IV tPA治疗后预后恶化所涉及的潜在机制方面的进展。与糖尿病性中风中tPA再通不理想相关的潜在病理因素包括血浆纤溶酶原激活剂抑制剂（PAI）-1水平升高、糖尿病致动脉粥样硬化性血管损伤、tPA受体膜联蛋白A2的糖基化以及纤维蛋白凝块密度的改变。而导致糖尿病性中风中HT加重的因素包括高血糖、血管氧化应激和炎症，同时还讨论了tPA神经血管毒性和细胞外蛋白水解失衡。此外，DM中侧支循环受损也会影响IV tPA疗法的疗效。此外，还简要总结了一些基于实验研究开发的可能有助于优化IV tPA疗法的tPA联合治疗方法。总之，需要更多的研究努力来提高IV tPA疗法在糖尿病性中风/中风后高血糖缺血性中风患者中的安全性和疗效。
