We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Single-cell RNA sequencing unveils Lrg1's role in cerebral ischemia‒reperfusion injury by modulating various cells.
- Authors
Ruan, Zhaohui; Cao, Guosheng; Qian, Yisong; Fu, Longsheng; Hu, Jinfang; Xu, Tiantian; Wu, Yaoqi; Lv, Yanni
- Abstract
Background and purpose: Cerebral ischemia‒reperfusion injury causes significant harm to human health and is a major contributor to stroke-related deaths worldwide. Current treatments are limited, and new, more effective prevention and treatment strategies that target multiple cell components are urgently needed. Leucine-rich alpha-2 glycoprotein 1 (Lrg1) appears to be associated with the progression of cerebral ischemia‒reperfusion injury, but the exact mechanism of it is unknown. Methods: Wild-type (WT) and Lrg1 knockout (Lrg1−/−) mice were used to investigate the role of Lrg1 after cerebral ischemia‒reperfusion injury. The effects of Lrg1 knockout on brain infarct volume, blood‒brain barrier permeability, and neurological score (based on 2,3,5-triphenyl tetrazolium chloride, evans blue dye, hematoxylin, and eosin staining) were assessed. Single-cell RNA sequencing (scRNA-seq), immunofluorescence, and microvascular albumin leakage tests were utilized to investigate alterations in various cell components in brain tissue after Lrg1 knockout. Results: Lrg1 expression was increased in various cell types of brain tissue after cerebral ischemia‒reperfusion injury. Lrg1 knockout reduced cerebral edema and infarct size and improved neurological function after cerebral ischemia‒reperfusion injury. Single-cell RNA sequencing analysis of WT and Lrg1−/− mouse brain tissues after cerebral ischemia‒reperfusion injury revealed that Lrg1 knockout enhances blood‒brain barrier (BBB) by upregulating claudin 11, integrin β5, protocadherin 9, and annexin A2. Lrg1 knockout also promoted an anti-inflammatory and tissue-repairing phenotype in microglia and macrophages while reducing neuron and oligodendrocyte cell death. Conclusions: Our results has shown that Lrg1 mediates numerous pathological processes involved in cerebral ischemia‒reperfusion injury by altering the functional states of various cell types, thereby rendering it a promising therapeutic target for cerebral ischemia‒reperfusion injury. Highlights: Upregulated Lrg1 expression is observed in various cells in brain after cerebral ischemia‒reperfusion injury. Lrg1 knockout can attenuate brain damage and blood‒brain barrier dysfunction following cerebral ischemia‒reperfusion injury. Lrg1 knockout can alter the functional state of microglial cells towards the anti-inflammatory M2 phenotype. Lrg1 knockout can modulate the metabolic status of multiple cell types.
- Subjects
REPERFUSION injury; RNA sequencing; TETRAZOLIUM chloride; CEREBRAL infarction; BLOOD-brain barrier
- Publication
Journal of Neuroinflammation, 2023, Vol 20, Issue 1, p1
- ISSN
1742-2094
- Publication type
Article
- DOI
10.1186/s12974-023-02941-4