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

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 t...

Full description

Saved in:
Bibliographic Details
Published in:Journal of neuroinflammation 2024-06, Vol.21 (1), p.155-12, Article 155
Main Authors: Haupeltshofer, Steffen, Mencl, Stine, Szepanowski, Rebecca D, Hansmann, Christina, Casas, Ana I, Abberger, Hanna, Hansen, Wiebke, Blusch, Alina, Deuschl, Cornelius, Forsting, Michael, Hermann, Dirk M, Langhauser, Friederike, Kleinschnitz, Christoph
Format: Article
Language:English
Subjects:
Analysis
Animals
Blood clot
Blood-brain barrier
Blood-Brain Barrier - drug effects
Blood-Brain Barrier - metabolism
Brain damage
Care and treatment
Diagnosis
Health aspects
Identification and classification
Infarction, Middle Cerebral Artery
Inflammation
Ischemia
Ischemic stroke
Ischemic Stroke - drug therapy
Kallikrein
Male
Mice
Mice, Inbred C57BL
Patient outcomes
Plasma kallikrein
Plasma Kallikrein - antagonists & inhibitors
Plasma Kallikrein - metabolism
Proteases
Recovery
Recovery of Function - drug effects
Recovery of Function - physiology
Stroke (Disease)
Stroke - drug therapy
Subacute
Thrombo-inflammation
Thrombosis
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1742-2094
1742-2094
DOI:10.1186/s12974-024-03149-w