透到髓状细胞衍生型的properdin显著促进在缺血性中风后微质介导的神经炎症
Pin-Yi Liu1, Hui-Qin Li1, Meng-Qi Dong1
1Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People's Republic of China.
Journal of neuroinflammation
|November 11, 2023
概括
普罗珀丁通过通过Mincle激活微质来加剧缺血性中风. 阻止这种properdin-Mincle相互作用可能会改善中风的结果.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 脑卒中研究 脑卒中研究
背景情况:
- 髓状细胞通过微质相互作用影响缺血性中风的进展.
- 普罗珀丁是一种与补充通路无关的蛋白质,具有与损伤相关的分子模式 (DAMP) 特性.
- 素在中风后的神经炎症中由微质细胞介导的作用尚不清楚.
研究的目的:
- 为了调查properdin在缺血性中风后微质介导的神经炎症中的作用.
- 为了阐明properdin调节微质激活并加剧脑损伤的机制.
主要方法:
- 使用全球性和骨髓细胞特异性properdin-knockout小鼠接受过渡性中脑动脉封闭 (tMCAO).
- 采用单细胞RNA测序,免疫光和转录组测序来分析properdin表达及其对微质细胞的影响.
- 研究了微质中properdin和巨诱导性C型乳清素 (Mincle) 之间的相互作用.
主要成果:
- 在缺血性大脑中,properdin水平增加,中性粒细胞和巨细胞是主要来源.
- 在tMCAO小鼠中,properdin淘汰赛减弱了微质过度活化和炎症.
- 普罗珀丁直接与微质Mincle结合,激活下游的炎症途径并增强神经毒性.
结论:
- 在缺血性中风中,properdin 作为外周髓状细胞和微质细胞之间的新型调解者.
- 普罗珀丁通过Mincle受体激活微质细胞,从而加剧脑损伤.
- 针对properdin-Mincle相互作用为缺血性中风提供了一个潜在的治疗策略.
相关概念视频
01:16Vascular Spasm
The vascular phase, also known as vasospasm, is the initial stage of hemostasis, crucial for preventing excessive bleeding when a blood vessel is injured. After a vessel is cut, nerves in the damaged area trigger pain and other sensory impulses. Simultaneously, the smooth muscles in the vessel wall contract, resulting in a vascular spasm. This contraction reduces the vessel's diameter at the injury site, slowing or stopping blood loss through the vessel wall. Vascular spasms typically last for...
01:22Formation of the Platelet Plug
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
01:20Extrinsic and Intrinsic Pathways of Hemostasis
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...
01:28Inflammatory Response
An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
01:25Acute Inflammation III: Local and Systemic Effects
Acute inflammation produces a coordinated set of local and systemic changes that limit injury, eliminate pathogens, and initiate repair. These responses arise within minutes of infection, trauma, or chemical insult and are driven by vascular alterations and leukocyte-derived mediators. When the stimulus resolves, the reaction typically abates within days.Local EffectsAt the site of injury, arteriolar vasodilation increases blood flow, resulting in redness and warmth. Simultaneously, increased...
01:25Secondary Spinal Cord Injury llI: Pathophysiology
Early Ischemia and Ionic ImbalanceWithin minutes of spinal cord injury, a secondary cascade begins, progressing over hours to weeks. Vascular damage reduces blood flow, causing ischemia and mitochondrial dysfunction. ATP depletion leads to ion pump failure, membrane depolarization, sodium influx, potassium efflux, and water accumulation, resulting in cellular swelling. Increased intracellular calcium further disrupts mitochondria and accelerates cellular injury.Excitotoxicity and Neuronal...