Time‐dependent dual effect of NLRP3 inflammasome in brain ischaemia
Cerebral ischaemia
DOI:
10.1111/bph.15732
Publication Date:
2021-11-13T16:04:14Z
AUTHORS (11)
ABSTRACT
Background Inflammasomes are cytosolic multiprotein complexes which, upon assembly, activate the maturation and secretion of inflammatory cytokines IL‐1β IL‐18. However, participation NLRP3 inflammasome in ischaemic stroke remains controversial. Our aims were to determine role brain ischaemia, explore mechanism involved potential protective effect neurovascular unit. Methods WT knock‐out mice subjected ischaemia by middle cerebral artery occlusion (60 min) with or without treatment MCC950 at different time points post‐stroke. Brain injury was measured histologically 2,3,5‐triphenyltetrazolium chloride (TTC) staining. Results We identified a time‐dependent dual NLRP3. While neither pre‐treatment nor genetic approach (NLRP3 KO) proved be neuroprotective, post‐reperfusion significantly reduced infarct volume dose‐dependent manner. Importantly, improved neuro‐motor function expression pro‐inflammatory (IL‐1β TNF‐α), components pro‐caspase‐1), protease (MMP9), endothelial adhesion molecules (ICAM VCAM). observed marked protection blood–brain barrier (BBB), which also reflected recovery tight junction proteins (ZO‐1 Claudin‐5). Additionally, produced reduction CCL2 chemokine blood serum tissue, lead immune cell infiltration. Conclusions These findings suggest that inhibition may an effective acute therapy for protecting clinical translation.
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