Caspase-1 inhibition prevents neuronal death by targeting the canonical inflammasome pathway of pyroptosis in a murine model of cerebral ischemia.

ABSTRACT:

Aims

The involvement of pyroptosis in ischemic stroke remains to be established. Therefore, we used the specific pyroptosis inhibitor Vx765 as an experimental intervention target in a murine model of stroke.

Methods

A total of 564 C57BL/6 mice were subjected to photothrombotic procedures and treated via gavage with Vx765 at 1-hour post-ischemia. We subsequently assessed the expression of Gasdermin D (GSDMD), inflammasomes, caspase-1, and interleukin-1β (IL-1β) using immunofluorescence (IF) and Western blot (WB) analyses. We also examined ultrastructural changes of cortical neurons with transmission electron microscopy (TEM) and measured infarct volumes dynamically by magnetic resonance imaging (MRI). Moreover, we evaluated the neurologic deficits by modified neurological sev

SUBMITTER: Li J 

PROVIDER: S-EPMC7415206 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature