oleuropein and Brain-Edema

This study was designed to evaluate the underlying protective mechanisms of oleuropein involved in alleviating brain damage in a rat model of ischemic stroke. Male Wistar rats were divided into four groups; Control, stroke (MCAO), MCAO + clopidogrel (Clop) and MCAO + oleuropein (Ole). Results showed that the MCAO group evidenced significant brain edema (+ 9%) as well as increases of plasma cardiac markers such as lactate deshydrogenase (LDH), creatine kinase (CK-MB), fibrinogen and Trop-T by 11 %, 43%, 168 and 590%, respectively, as compared to the control group. Moreover, infarcted rats exhibited remarkable elevated levels of angiotensin converting enzyme (ACE), both in plasma and brain tissue, with astrocyte swelling and necrotic neurons in the infarct zone, hyponatremia, and increased rate of thiobarbituric acid-reactive substances (TBARS) by 89% associated with decreases in the activity of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (Cat) by 51%, 44 and 42%, respectively, compared to normal control rats. However, MCAO rats treated with oleuropein underwent mitigation of cerebral edema, correction of hyponatremia, remarkable decrease of plasma fibrinogen and cardiac dysfunctional enzymes, inhibition of ACE activity and improvement of oxidative stress status in brain tissue. Furthermore, in silico analysis showed considerable inhibitions of ACE, protein disulfide isomerase (PDI) and TGF-β1, an indicative of potent anti-embolic properties. Overall, oleuropein offers a neuroprotective effect against ischemic stroke through its antioxidative and antithrombotic activities.

Topics: Acetylcholinesterase; Animals; Brain; Brain Edema; Clopidogrel; Free Radical Scavengers; Humans; Hyponatremia; Infarction, Middle Cerebral Artery; Iridoid Glucosides; Male; Molecular Docking Simulation; Neuroprotective Agents; Oxidative Stress; Peptidyl-Dipeptidase A; Protein Binding; Protein Disulfide-Isomerases; Rats, Wistar; Thiobarbituric Acid Reactive Substances

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.. 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.. 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.. Our study suggests oleuropein could be used as a promising therapeutic agent for ICH.

Topics: Animals; Antioxidants; Blood-Brain Barrier; Brain Edema; Cerebral Hemorrhage; Disease Models, Animal; Dose-Response Relationship, Drug; Injections, Intraperitoneal; Iridoid Glucosides; Iridoids; Male; MAP Kinase Signaling System; Oxidative Stress; Rats; Rats, Sprague-Dawley; Stroke