Delayed plasma kallikrein inhibition fosters post-stroke recovery by reducing thrombo-inflammation.
Blood-brain barrier
Extravasation
Inflammation
Ischemic stroke
Kallikrein-kinin system
Plasma kallikrein
Recovery
Subacute
Thrombo-inflammation
Thrombosis
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
13 Jun 2024
13 Jun 2024
Historique:
received:
04
03
2024
accepted:
06
06
2024
medline:
14
6
2024
pubmed:
14
6
2024
entrez:
13
6
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38872149
doi: 10.1186/s12974-024-03149-w
pii: 10.1186/s12974-024-03149-w
doi:
Substances chimiques
Plasma Kallikrein
EC 3.4.21.34
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
155Informations de copyright
© 2024. The Author(s).
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