Inhibition of plasma kallikrein mitigates experimental hypertension-enhanced cerebral hematoma expansion
| Autor: | Weixiang Chen, Xiaoqin Tang, Xin Liu, Mingxi Li, Tunan Chen, Min Xia, Hua Feng, Zhengcai Jia, Chengcheng Li, Yi Yin, Jiantao Shi, Chao Guo, Jie Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Agonist medicine.drug_class Blood Pressure Pharmacology Mice 03 medical and health sciences 0302 clinical medicine Hematoma Crotalid Venoms medicine Animals Lectins C-Type cardiovascular diseases Plasma Kallikrein Cerebral Hemorrhage Intracerebral hemorrhage business.industry Angiotensin II General Neuroscience Convulxin Kallikrein medicine.disease Disease Models Animal Treatment Outcome 030104 developmental biology Hypertension Hemoglobin GPVI business 030217 neurology & neurosurgery |
| Zdroj: | Brain Research Bulletin. 170:49-57 |
| ISSN: | 0361-9230 |
| DOI: | 10.1016/j.brainresbull.2021.02.004 |
| Popis: | Rationale 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. Methods 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. Results 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. Conclusions These findings suggest that PK inhibition and GPVI agonist treatment might serve as potential methods to intervene in HE after ICH. |
| Databáze: | OpenAIRE |
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