Jing Shi1, Guofeng Wu2, Xiaohua Zou3, Ke Jiang3. 1. The Second Affiliated Hospital of Suzhou University, Suzhou, China; The Affiliated Hospital of Guizhou Medical University, Guiyang China. 2. The Second Affiliated Hospital of Suzhou University, Suzhou, China; The Affiliated Hospital of Guizhou Medical University, Guiyang China. Electronic address: wuguofeng2013@sina.com. 3. The Affiliated Hospital of Guizhou Medical University, Guiyang China.
Abstract
BACKGROUND: Intracerebral haemorrhage (ICH) as a devastating form of stroke has remained a public health threat due to lack of FDA-approved therapy. Oxidative stress originated from blood cell degradation products plays a crucial role in the ICH pathogenesis. In this study we evaluated oleuropein, a potent natural antioxidant from olive, in a well-established rat ICH model from overall symptoms to detailed molecular mechanism. METHODS: ICH model was established by collagenase injection to the brain of rats, which were randomly divided into groups with vehicle mock treatment, followed by treatment with different doses of oleuropein via daily intraperitoneal injection post-ICH for 3days. The overall neurological deficit, brain edema level and blood-brain barrier (BBB) integrity were then measured in different treatment groups. To understand the protection mechanism of oleuropein in ICH, BBB structural components ZO-1 and occludin, oxidative stress and MAPK signalling pathways were also examined. RESULTS: Oleuropein treatment showed overall alleviation of ICH-associated neurological deficit and brain edema in a dose dependent manner. Consistently, it could preserve the BBB structure and attenuate oxidative stress as well as ICH-induced MAPK activation in brain tissue. CONCLUSION: Our study suggests oleuropein could be used as a promising therapeutic agent for ICH.
BACKGROUND: Intracerebral haemorrhage (ICH) as a devastating form of stroke has remained a public health threat due to lack of FDA-approved therapy. Oxidative stress originated from blood cell degradation products plays a crucial role in the ICH pathogenesis. In this study we evaluated oleuropein, a potent natural antioxidant from olive, in a well-established ratICH model from overall symptoms to detailed molecular mechanism. METHODS:ICH model was established by collagenase injection to the brain of rats, which were randomly divided into groups with vehicle mock treatment, followed by treatment with different doses of oleuropein via daily intraperitoneal injection post-ICH for 3days. The overall neurological deficit, brain edema level and blood-brain barrier (BBB) integrity were then measured in different treatment groups. To understand the protection mechanism of oleuropein in ICH, BBB structural components ZO-1 and occludin, oxidative stress and MAPK signalling pathways were also examined. RESULTS: Oleuropein treatment showed overall alleviation of ICH-associated neurological deficit and brain edema in a dose dependent manner. Consistently, it could preserve the BBB structure and attenuate oxidative stress as well as ICH-induced MAPK activation in brain tissue. CONCLUSION: Our study suggests oleuropein could be used as a promising therapeutic agent for ICH.
Authors: Jennifer K Lee; Polan T Santos; May W Chen; Caitlin E O'Brien; Ewa Kulikowicz; Shawn Adams; Henry Hardart; Raymond C Koehler; Lee J Martin Journal: J Neuropathol Exp Neurol Date: 2021-01-20 Impact factor: 3.685