The neuroprotective mechanism of lithium after ischaemic stroke.
Beina ChenManman ZhangMing JiDianjun ZhangBinjie ChenWenliang GongXinyu LiYuefei ZhouChengyi DongGehua WenXiaoni ZhanXiafang WuHuiya YuanEnyu XuMaosheng XiaAlexei VerkhratskyBaoman LiPublished in: Communications biology (2022)
Stroke causes degeneration and death of neurones leading to the loss of motor function and frequent occurrence of cognitive impairment and depression. Lithium (Li + ), the archetypal mood stabiliser, is neuroprotective in animal models of stroke, albeit underlying mechanisms remain unknown. We discover that Li + inhibits activation of nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes in the middle cerebral artery occlusion (MCAO) stroke model in mice. This action of Li + is mediated by two signalling pathways of AKT/GSK3β/β-catenin and AKT/FoxO3a/β-catenin which converge in suppressing the production of reactive oxygen species (ROS). Using immunocytochemstry, MRI imaging, and cell sorting with subsequent mRNA and protein quantification, we demonstrate that Li + decreases the infarct volume, improves motor function, and alleviates associated cognitive and depressive impairments. In conclusion, this study reveals molecular mechanisms of Li + neuroprotection during brain ischaemia, thus providing the theoretical background to extend clinical applications of Li + for treatment of ischemic stroke.
Keyphrases
- ion batteries
- solid state
- cerebral ischemia
- signaling pathway
- atrial fibrillation
- middle cerebral artery
- reactive oxygen species
- cell proliferation
- cognitive impairment
- epithelial mesenchymal transition
- binding protein
- bipolar disorder
- pi k akt
- magnetic resonance imaging
- high resolution
- blood brain barrier
- subarachnoid hemorrhage
- type diabetes
- sleep quality
- acute myocardial infarction
- acute coronary syndrome
- magnetic resonance
- single cell
- internal carotid artery
- metabolic syndrome
- small molecule
- insulin resistance
- left ventricular
- stress induced
- protein protein
- mass spectrometry
- functional connectivity