Delayed plasma kallikrein inhibition fosters post-stroke recovery by reducing thrombo-inflammation
- PMID: 38872149
- PMCID: PMC11177352
- DOI: 10.1186/s12974-024-03149-w
Delayed plasma kallikrein inhibition fosters post-stroke recovery by reducing thrombo-inflammation
Abstract
Activation of the kallikrein-kinin system promotes vascular leakage, inflammation, and neurodegeneration in ischemic stroke. Inhibition of plasma kallikrein (PK) - a key component of the KKS - in the acute phase of ischemic stroke has been reported to reduce thrombosis, inflammation, and damage to the blood-brain barrier. However, the role of PK during the recovery phase after cerebral ischemia is unknown. To this end, we evaluated the effect of subacute PK inhibition starting from day 3 on the recovery process after transient middle artery occlusion (tMCAO). Our study demonstrated a protective effect of PK inhibition by reducing infarct volume and improving functional outcome at day 7 after tMCAO. In addition, we observed reduced thrombus formation in cerebral microvessels, fewer infiltrated immune cells, and an improvement in blood-brain barrier integrity. This protective effect was facilitated by promoting tight junction reintegration, reducing detrimental matrix metalloproteinases, and upregulating regenerative angiogenic markers. Our findings suggest that PK inhibition in the subacute phase might be a promising approach to accelerate the post-stroke recovery process.
Keywords: Blood-brain barrier; Extravasation; Inflammation; Ischemic stroke; Kallikrein-kinin system; Plasma kallikrein; Recovery; Subacute; Thrombo-inflammation; Thrombosis.
© 2024. The Author(s).
Conflict of interest statement
The authors declare no competing interests.
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