Ischemic stroke in PAR1 KO mice: Decreased brain plasmin and thrombin activity along with decreased infarct volume.

Abstract

BACKGROUND:

Ischemic stroke is a common and debilitating disease with limited treatment options. Protease activated receptor 1 (PAR1) is a fundamental cell signaling mediator in the central nervous system (CNS). It can be activated by many proteases including thrombin and plasmin, with various down-stream effects, following brain ischemia.

METHODS:

A permanent middle cerebral artery occlusion (PMCAo) model was used in PAR1 KO and WT C57BL/6J male mice. Mice were evaluated for neurological deficits (neurological severity score, NSS), infarct volume (Tetrazolium Chloride, TTC), and for plasmin and thrombin activity in brain slices.

RESULTS:

Significantly low levels of plasmin and thrombin activities were found in PAR1 KO compared to WT (1.6±0.4 vs. 3.2±0.6 ng/μl, p<0.05 and 17.2±1.0 vs. 21.2±1.0 mu/ml, p<0.01, respectively) along with a decreased infarct volume (178.9±14.3, 134.4±13.3 mm3, p<0.05).

CONCLUSIONS:

PAR1 KO mice have smaller infarcts, with lower thrombin and plasmin activity levels. These findings may suggest that modulation of PAR1 is a potential target for future pharmacological treatment of ischemic stroke.

• Authors: Efrat Shavit-Stein, Ekaterina Mindel, Shany Guly Gofrit, Joab Chapman, Nicola Maggio
• Journal: PloS one (PLoS One) Vol. 16 Issue 3 Pg. e0248431 ( 2021) ISSN: 1932-6203 [Electronic] United States
• PMID: 33720950 (Publication Type: Journal Article)

Chemical References

• Receptor, PAR-1
• Thrombin
• Fibrinolysin

Topics

• Animals
• Brain (metabolism, pathology)
• Fibrinolysin (genetics, metabolism)
• Ischemic Stroke (genetics, metabolism, pathology)
• Male
• Mice
• Mice, Knockout
• Receptor, PAR-1 (deficiency, metabolism)
• Thrombin (genetics, metabolism)