Delayed plasma kallikrein inhibition fosters post-stroke recovery by reducing thrombo-inflammation

Haupeltshofer, S; Mencl, S; Szepanowski, RD; Hansmann, C; Casas, AI; Abberger, H; Hansen, W; Blusch, A; Deuschl, C; Forsting, M; Hermann, DM; Langhauser, F; Kleinschnitz, C

Author(s): Haupeltshofer, S; Mencl, S; Szepanowski, RD; Hansmann, C; Casas, AI; Abberger, H; Hansen, W; Blusch, A; Deuschl, C; Forsting, M; Hermann, DM; Langhauser, F; Kleinschnitz, C;
Details: Publication Year 2024-06-13,Volume 21,Issue #1,Page 155
Journal Title: Journal of Nueroinflammation
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.
Publisher: BMC
Keywords: Animals; *Recovery of Function/drug effects/physiology; Male; *Plasma Kallikrein/antagonists & inhibitors/metabolism; Mice; Mice, Inbred C57BL; Infarction, Middle Cerebral Artery; Blood-Brain Barrier/drug effects/metabolism; Stroke/drug therapy; Thrombosis; Ischemic Stroke/drug therapy; Inflammation; Blood-brain barrier; Extravasation; Ischemic stroke; Kallikrein-kinin system; Plasma kallikrein; Recovery; Subacute; Thrombo-inflammation
Research Division(s): Immunology
PubMed ID: 38872149
Publisher's Version: https://doi.org/10.1186/s12974-024-03149-w
Open Access at Publisher's Site: https://doi.org/10.1186/s12974-024-03149-w
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-06-24 11:29:53

Last Modified: 2024-06-24 11:34:39