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

Haupeltshofer, Steffen LU ; Mencl, Stine ; Szepanowski, Rebecca D. ; Hansmann, Christina ; Casas, Ana I. ; Abberger, Hanna ; Hansen, Wiebke ; Blusch, Alina LU ; Deuschl, Cornelius and Forsting, Michael , et al. (2024) In Journal of Neuroinflammation 21(1).
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
keywords
Blood-brain barrier, Extravasation, Inflammation, Ischemic stroke, Kallikrein-kinin system, Plasma kallikrein, Recovery, Subacute, Thrombo-inflammation, Thrombosis
in
Journal of Neuroinflammation
volume
21
issue
1
article number
155
publisher
BioMed Central (BMC)
external identifiers
  • pmid:38872149
  • scopus:85195899222
ISSN
1742-2094
DOI
10.1186/s12974-024-03149-w
language
English
LU publication?
no
additional info
Publisher Copyright: © The Author(s) 2024.
id
aca7bdd0-b79b-4294-aec5-edf2b65b22a3
date added to LUP
2026-02-04 15:42:03
date last changed
2026-02-04 15:42:37
@article{aca7bdd0-b79b-4294-aec5-edf2b65b22a3,
  abstract     = {{<p>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.</p>}},
  author       = {{Haupeltshofer, Steffen and Mencl, Stine and Szepanowski, Rebecca D. and Hansmann, Christina and Casas, Ana I. and Abberger, Hanna and Hansen, Wiebke and Blusch, Alina and Deuschl, Cornelius and Forsting, Michael and Hermann, Dirk M. and Langhauser, Friederike and Kleinschnitz, Christoph}},
  issn         = {{1742-2094}},
  keywords     = {{Blood-brain barrier; Extravasation; Inflammation; Ischemic stroke; Kallikrein-kinin system; Plasma kallikrein; Recovery; Subacute; Thrombo-inflammation; Thrombosis}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Journal of Neuroinflammation}},
  title        = {{Delayed plasma kallikrein inhibition fosters post-stroke recovery by reducing thrombo-inflammation}},
  url          = {{http://dx.doi.org/10.1186/s12974-024-03149-w}},
  doi          = {{10.1186/s12974-024-03149-w}},
  volume       = {{21}},
  year         = {{2024}},
}