A Role of the Podoplanin-CLEC-2 Axis in Promoting Inflammatory Response After Ischemic Stroke in Mice.
Danyang MengXiaohua MaHui LiXuechun WuYongjun CaoZhigang MiaoXia ZhangPublished in: Neurotoxicity research (2020)
C-type lectin-like receptor 2 (CLEC-2) is a platelet surface-activating receptor with the prominent involvement in platelet activation, which was found to be associated with the progression and prognosis of acute ischemic stroke patients. Although podoplanin is the only known endogenous ligand for CLEC-2, the role of podoplanin/CLEC-2 in cerebral ischemia injury was unclear. In this study, we examined their role by using a mouse middle cerebral artery occlusion (MCAO) model. The expression of CLEC-2 and podoplanin increased after ischemia/reperfusion (I/R) injury, peaked at 24 h, and then decreased gradually. Podoplanin and CLEC-2 co-localized mainly in the ischemia/reperfusion cortex and expressed on neurons and microglia. Anti-podoplanin antibody pretreatment reduced cerebral infarct volume from 52.67 ± 4.67 to 34.08 ± 6.04% (P < 0.05) and attenuated the neurological deficits during acute stage and recovery stage. Moreover, a significant decrease of IL-18 and IL-1β was observed in the mice pretreated with the anti-podoplanin antibody. Our results demonstrate that the podoplanin-CLEC-2 axis might play an important role in cerebral ischemia/reperfusion injury in mice by promoting inflammatory reactions.
Keyphrases
- cerebral ischemia
- subarachnoid hemorrhage
- inflammatory response
- middle cerebral artery
- liver failure
- high fat diet induced
- blood brain barrier
- brain injury
- poor prognosis
- traumatic brain injury
- type diabetes
- signaling pathway
- acute myocardial infarction
- coronary artery disease
- oxidative stress
- binding protein
- intensive care unit
- aortic dissection
- acute coronary syndrome
- insulin resistance
- adipose tissue
- long non coding rna
- wild type
- mechanical ventilation
- cerebral blood flow