Delayed Inhibition of Plasma Kallikrein Promotes Stroke Recovery: By Reducing Thromboinflammation

Academic Background

Stroke is a common neurovascular event affecting over 60 million patients worldwide annually. Current treatments for cerebral ischemia are limited to thrombolysis and mechanical thrombectomy, which are constrained by the feasibility within the acute phase time window of stroke. However, there are no effective treatments for the recovery phase after cerebral ischemia. Therefore, this paper aims to explore the role of plasma kallikrein (PK) during the recovery phase after stroke and to evaluate the impact of subacute PK inhibition on the recovery process.

Paper Source

This study, led by Steffen Haupeltshofer, involves researchers from several institutions including the Department of Neurology at the University Hospital of Essen, Maastricht University in the Netherlands, Darmstadt University of Technology in Germany, and the Walter and Eliza Hall Institute of Medical Research in Australia. The findings were published in the 2024 issue of the Journal of Neuroinflammation, where the article explores the role of thromboinflammation in ischemic stroke and how subacute PK inhibition can promote recovery after stroke by reducing thromboinflammation.

Research Details

Researchers established the Clinical Translational Neurobehavioral Sciences Center to implement multi-methodological research. The study examined the impact of subacute PK inhibition on the recovery process in C57BL/6J mice using the transient middle cerebral artery occlusion model (tMCAO). Initial steps involved extracellular and flow cytometry measurements, followed by magnetic resonance imaging analysis and histological analysis. Additionally, real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assays were used to evaluate inflammatory and angiogenic markers. The research team monitored cerebral blood flow dynamics and assessed the successful occlusion and reperfusion of the middle cerebral artery based on laser Doppler rheometry. Mice were randomly assigned αPK antibody or control treatment, and changes in post-ischemic infarct volume were evaluated by MRI scans.

Major Findings

The study demonstrated that subacute PK inhibition reduces infarct volume, improves functional recovery, decreases thrombosis in cerebral microvasculature, reduces immune cell infiltration, and enhances the integrity of the blood-brain barrier. These protective effects promote tight junction reintegration, reduce harmful matrix metalloproteinases, and upregulate regenerative angiogenic markers. Notably, mice treated with the αPK antibody exhibited more significant weight gain, indicating functional recovery.

Conclusion and Significance

The study concludes that delayed PK inhibition during the subacute phase after stroke can be a promising strategy to accelerate the recovery process. This research is not only scientifically valuable but also offers potential application value, demonstrating significant implications for stroke recovery treatment. Additionally, the study highlights the role of plasma kallikrein regulation in enhancing vascular repair and promoting angiogenesis signaling.

Research Highlights

The research emphasizes plasma kallikrein as a key regulator of neuroinflammation and thromboinflammatory morphology, establishing a connection between thromboinflammation and the recovery process after cerebral ischemia. By validating the delayed inhibition of PK strategy, the study provides new treatment options for post-stroke recovery and may support the development of new therapeutic approaches for stroke recovery with theoretical foundations and experimental data.

Paper Significance

This study offers new insights into treatment methodologies during the recovery phase after stroke and is anticipated to further promote the research and development of stroke treatment regimes. The paper also underscores the potential clinical value of delayed PK inhibition, which may usher in new opportunities for stroke recovery treatments.