Abstract
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. 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. 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). 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.
Highlights
Stroke is a common disease, caused by acute deprivation of oxygen and nutrients to tissue due to ischemia or hemorrhage
Low levels of plasmin and thrombin activities were found in Protease activated receptor 1 (PAR1) KO compared to WT (1.6±0.4 vs. 3.2±0.6 ng/μl, p
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
Summary
Stroke is a common disease, caused by acute deprivation of oxygen and nutrients to tissue due to ischemia or hemorrhage. Thrombolysis is achieved with the use of recombinant tissue-type plasminogen activator (rtPA) aimed to generate plasmin as part of an induced fibrinolysis process. The relatively limited treatment options call for further evaluation of the molecular mechanisms involved in neural damage processes following ischemia. 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
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