Dataset Information

Podoplanin neutralization reduces thrombo-inflammation in experimental ischemic stroke by inhibiting interferon/caspase-1/GSDMD in microglia.

ABSTRACT:

Background

Cerebral ischemia/reperfusion (I/R) injury involves the interaction between thrombosis and inflammatory pathways. The aim of this study was to explore the therapeutic effect of podoplanin neutralizing antibody (α-PDPN, clone 8.1.1) on I/R-induced thrombo-inflammation in a mouse model of ischemic stroke.

Methods

Male C57BL/6 mice (weight: 22-25 g, aged 6-8 weeks, n=114) were subjected to transient middle cerebral artery occlusion (MCAO) and administered intracerebroventricular injection of α-PDPN (29 µg). Stroke outcomes and microvascular thromboses were examined by immunohistochemistry (IHC) and western blot analysis. In vitro, microglia BV2 cells were pre-treated with α-PDPN and then subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) insult. The microglia culture medium (MCM) was co-cultured with vascular endothelial b.End3 cells. The MCM-induced bEnd.3 cells dysfunction were examined by western blot assays and IHC.

Results

Blocking PDPN decreased the infarct size and ameliorated neurological deficit after MCAO without enhancing the risk of intracerebral hemorrhage. In addition, α-PDPN treatment significantly alleviated thrombus formation in the cerebral microvasculature. Furthermore, treatment with α-PDPN attenuated I/R-induced caspase-1 and gasdermin D expression in vivo and in vitro. The MCM containing α-PDPN reduced the expressions of von Willebrand factor and intercellular cell adhesion molecule-1 in bEnd.3 cells. Moreover, RNA sequencing analysis showed that α-PDPN decreased interferon signaling pathways in BV2 cells.

Conclusions

Blocking PDPN can alleviate thrombo-inflammation in acute ischemic stroke by inhibiting caspase-1 expression in microglia, and indirectly reduce endothelial cell dysfunction. These data indicated the beneficial effects of blocking podoplanin during stroke in mice.

SUBMITTER: Qian S

PROVIDER: S-EPMC9577791 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Podoplanin neutralization reduces thrombo-inflammation in experimental ischemic stroke by inhibiting interferon/caspase-1/GSDMD in microglia.

Qian Shuang S Qian Lei L Yang Ye Y Cui Jie J Zhao Yiming Y

Annals of translational medicine 20220901 18

<h4>Background</h4>Cerebral ischemia/reperfusion (I/R) injury involves the interaction between thrombosis and inflammatory pathways. The aim of this study was to explore the therapeutic effect of podoplanin neutralizing antibody (α-PDPN, clone 8.1.1) on I/R-induced thrombo-inflammation in a mouse model of ischemic stroke.<h4>Methods</h4>Male C57BL/6 mice (weight: 22-25 g, aged 6-8 weeks, n=114) were subjected to transient middle cerebral artery occlusion (MCAO) and administered intracerebroventr ...[more]

PMID: 36267799

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Dataset Information

Podoplanin neutralization reduces thrombo-inflammation in experimental ischemic stroke by inhibiting interferon/caspase-1/GSDMD in microglia.

Background

Methods

Results

Conclusions

Publications

Podoplanin neutralization reduces thrombo-inflammation in experimental ischemic stroke by inhibiting interferon/caspase-1/GSDMD in microglia.

Similar Datasets

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