Inhibition of plasma kallikrein mitigates experimental hypertension-enhanced cerebral hematoma expansion

• Published in: Brain research bulletin 2021-05, Vol.170, p.49-57
• Main Authors: Wang, Jie, Xia, Min, Tang, Xiaoqin, Jia, Zhengcai, Li, Chengcheng, Li, Mingxi, Yin, Yi, Guo, Chao, Shi, Jiantao, Liu, Xin, Chen, Weixiang, Chen, Tunan, Feng, Hua
• Format: Article
• Language: English
• Subjects: Angiotensin II; Animals; Blood Pressure - physiology; Cerebral Hemorrhage - complications; Cerebral Hemorrhage - drug therapy; Cerebral Hemorrhage - pathology; Crotalid Venoms - pharmacology; Crotalid Venoms - therapeutic use; Disease Models, Animal; Hematoma expansion; Hypertension; Hypertension - chemically induced; Hypertension - complications; Hypertension - drug therapy; Hypertension - pathology; Intracerebral hemorrhage; Lectins, C-Type - therapeutic use; Male; Mice; Plasma kallikrein; Plasma Kallikrein - antagonists & inhibitors; Treatment Outcome
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2021.02.004

[Display omitted] •PK is also involved in cerebral haematoma expansion in Ang II-induced experimental hypertensive mice.•Platelet GPVI activation decreased haematoma expansion and improved neurologic deficits after ICH. Clinical significance.•PK inhibition and platelet GPVI agonist treatment might serve as potential methods for HE intervention. Hematoma expansion (HE) aggravates brain injury after intracerebral hemorrhage (ICH) and hypertension is a key contributor to HE. Plasma kallikrein (PK) is involved in hemorrhagic transformation in ischemic stroke mice. This study was conducted to explore the role of PK in HE in hypertensive ICH. Hypertension was achieved by continuous infusion of angiotensin II (Ang II) with an osmotic pump in C57BL/6 mice. ICH was achieved by stereotactic intrastriatal injection of blood. PK-specific antibody and platelet glycoprotein VI (GPVI) agonists were administered to intervene in hematoma expansion. The hematoma volume was indicated by the erythrocyte components hemoglobin and carbonic anhydrase-1 in the ipsilateral brain hemisphere. Ang II-induced hypertensive mice showed enhanced hematoma expansion and worsened neurologic deficits after ICH modeling. Moreover, intrastriatal injection of blood from Ang II-treated mice into normal mice increased the area of secondary hemorrhage more than blood from untreated mice. Mechanistically, elevated PK was found in Ang II-infused mice whereas, inhibition of PK and administration of the GPVI agonist convulxin decreased hematoma expansion and improved neurologic deficits after ICH. These findings suggest that PK inhibition and GPVI agonist treatment might serve as potential methods to intervene in HE after ICH.