Department of Neurology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Neurology, The Chaim Sheba Medical Center, Ramat Gan, Israel.
PLoS One. 2021 Mar 15;16(3):e0248431. doi: 10.1371/journal.pone.0248431. eCollection 2021.
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.
缺血性脑卒中是一种常见且使人虚弱的疾病，治疗选择有限。蛋白酶激活受体 1（PAR1）是中枢神经系统（CNS）中的基本细胞信号转导介质。它可以被许多蛋白酶激活，包括凝血酶和纤溶酶，在脑缺血后产生各种下游效应。
在 PAR1 KO 和 WT C57BL/6J 雄性小鼠中使用永久性大脑中动脉闭塞（PMCAo）模型。通过神经功能缺损评分（神经严重程度评分，NSS）、梗死体积（氯化四唑，TTC）以及脑切片中的纤溶酶和凝血酶活性来评估小鼠。
与 WT 相比，PAR1 KO 中纤溶酶和凝血酶的活性水平显著降低（1.6±0.4 与 3.2±0.6 ng/μl，p<0.05 和 17.2±1.0 与 21.2±1.0 mu/ml，p<0.01），同时梗死体积减小（178.9±14.3 与 134.4±13.3 mm3，p<0.05）。
PAR1 KO 小鼠的梗死体积较小，凝血酶和纤溶酶活性水平较低。这些发现可能表明 PAR1 的调节可能是缺血性脑卒中未来药物治疗的潜在靶点。
