Department of Biomedical Sciences, University of Illinois at Chicago, College of Medicine Rockford, Rockford, IL, USA.
J Mol Med (Berl). 2024 Jun;102(6):709-717. doi: 10.1007/s00109-024-02441-9. Epub 2024 Mar 28.
Ischemic stroke is the major contributor to morbidity and mortality in people with diabetes mellitus. In ischemic stroke patients, neuroinflammation is now understood to be one of the main underlying mechanisms for cerebral damage and recovery delay. It has been well-established that toll-like receptor 4 (TLR4) signaling pathway plays a key role in neuroinflammation. Emerging research over the last decade has revealed that, compared to ischemic stroke without diabetes mellitus, ischemic stroke with diabetes mellitus significantly upregulates TLR4-mediated neuroinflammation, increasing the risk of cerebral and neuronal damage as well as neurofunctional recovery delay. This review aims to discuss how ischemic stroke with diabetes mellitus amplifies TLR4-mediated neuroinflammation and its consequences. Additionally covered in this review is the potential application of TLR4 antagonists in the management of diabetic ischemic stroke.
缺血性脑卒中是糖尿病患者发病率和死亡率的主要原因。在缺血性脑卒中患者中,神经炎症现在被认为是脑损伤和恢复延迟的主要潜在机制之一。现已证实,Toll 样受体 4(TLR4)信号通路在神经炎症中起着关键作用。过去十年的新研究表明,与无糖尿病的缺血性脑卒中相比,糖尿病性缺血性脑卒中显著上调 TLR4 介导的神经炎症,增加脑和神经元损伤以及神经功能恢复延迟的风险。本综述旨在讨论糖尿病性缺血性脑卒中如何放大 TLR4 介导的神经炎症及其后果。本综述还涵盖了 TLR4 拮抗剂在糖尿病性缺血性脑卒中治疗中的潜在应用。