The Protective Effect of Safinamide in Ischemic Stroke Mice and a Brain Endothelial Cell Line
- PDF / 2,425,110 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 37 Downloads / 194 Views
ORIGINAL ARTICLE
The Protective Effect of Safinamide in Ischemic Stroke Mice and a Brain Endothelial Cell Line Tingting Xu 1
&
Rui Sun 1 & Guoshi Wei 1 & Shanshan Kong 1
Received: 26 April 2020 / Revised: 4 June 2020 / Accepted: 17 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Stroke is one of the leading causes of mortality in cardiovascular diseases. The disruption of the brain-blood barrier is the common feature of stroke-related complications. Safinamide is a newly approved add-on drug to treat Parkinson’s disease, and previously studies suggest safinamide could have a potential role on neuroprotection. In this study, we investigated its preventive effect in both acutely induced stroke animals and brain endothelial cells. By the induction of middle cerebral artery occlusion (MCAO) in mice, we established a transit stroke model. Mice were administered 90 mg/kg/day safinamide prior to MCAO and during ischemia and reperfusion. Results indicate that the administration of safinamide significantly ameliorated MCAO-caused cerebral infarction volume, neurological deficit, disruption of the brain-blood barrier (BBB), and impaired expression of tight junction protein occludin and ZO-1. In cultured brain endothelial cell line bEND.3, pre-treatment with safinamide alleviated oxygen and glucose deprivation/reperfusion (OGD/R) caused cytotoxicity and favored cell survival. Transwell assay showed safinamide prevented OGD/R-induced hyperpermeability and the reduction of occludin and ZO-1. Moreover, safinamide treatment suppressed OGD/R-caused induction of metalloproteinase 2 (MMP-2) and 9 (MMP-9). Collectively, our data conclude safinamide has a preventive neuroprotection in acute stroke animals. The protective effect of safinamide on brain endothelial cells suggests the drug may ameliorate BBB disruption and improve vascular integrity in ischemia stroke. Keywords Safinamide . Stroke . Glucose deprivation/reperfusion (OGD/R) . Brain-blood barrier (BBB)
Introduction Stroke is one of the common causes of death and a major cause of disability worldwide (Donnan et al. 2008). According to data from World Health Organization (WHO), 15 million people suffer a stroke annually, and the death toll caused from stroke is about 5 million every year (http). In clinical practice, stroke is defined as a neurological deficit associated with an acute focal injury of the brain due to cerebral infarction, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). A majority of strokes manifested as an ischemic condition due to arterial occlusion. Pathological
* Tingting Xu [email protected] 1
Department of Clinical Pharmacy, Luoyang Central Hospital Affiliated to Zhengzhou University, #288 Zhongzhou Middle Road, Xigong District, Luoyang 471009, Henan Province, China
investigation has shown the occlusion in major cerebral arteries and other small branches results from chronic atherosclerosis and thrombosis (Deb et al. 2010). Ischemia stroke– induced hypoxia exposes a high risk of oxygen
Data Loading...
