Necrostatin-1 Attenuates Inflammatory Response and Improves Cognitive Function in Chronic Ischemic Stroke Mice.

Shehong Zhang,Wen Si,Yuyang Wang,Yi Wu,Junfa Wu,Dake Li

doi:10.3390/medicines3030016

Shehong Zhang, Wen Si + Show 4 more

Open Access

https://doi.org/10.3390/medicines3030016

Copy DOI

Journal: Medicines	Publication Date: Jul 1, 2016
Citations: 65	License type: CC BY 4.0

Affiliation: Huashan Hospital, Fudan University

Abstract

Multiple cell death is involved in ischemic brain injury. Necroptosis, a recently reported cell death, may be the most suitable cell death mechanism in a subpopulation of neurons under ischemic injury. It reported that a small molecule, necrostatin-1 (Nec-1), has a potent inhibitory effect on necroptotic cell death in vivo and in vitro. The aim of the current study was to investigate the role of Nec-1 on cognitive function in chronic ischemic stroke mice induced by bilateral common carotid artery stenosis (BCAS). Here, 12-week-old C57BL/6 mice received intragastric administration with Nec-1 or vehicle for two weeks after stroke, and then, the effect and possible mechanism were determined. We demonstrated that inhibition of necroptosis prevented cognitive impairment and reduced inflammatory response in the ischemic brain injury mouse model. These data suggested that inhibition of necroptosis provided a potential therapeutic option for cognitive rehabilitation in chronic ischemic stroke.

Highlights

Ischemic stroke accounts for about 80% of all cases of stroke [1] and frequently leads to cognitive dysfunction [2]
Experimental studies demonstrated that white matter lesions (MWLs) from ischemia are the main factor mediating the pathological process of VCI [5,6,7]
WM alternations are regulated by many factors and multiple processes, such as vascular dysfunction and inflammation, blood-brain barrier (BBB) disruption, glial activation, damaged oligodendrocytes, and demyelination [5]

Summary

Introduction

Ischemic stroke accounts for about 80% of all cases of stroke [1] and frequently leads to cognitive dysfunction [2]. Experimental studies demonstrated that white matter lesions (MWLs) from ischemia are the main factor mediating the pathological process of VCI [5,6,7]. White matter ischemic injury is a critical pathological hallmark of small vessel diseases, a subset of cerebrovascular diseases resulting in stroke and cognitive decline [8]. Experimental and clinical studies demonstrated that a persistent and chronic reduction in cerebral blood flow leading to hypoperfusion resulted in white matter ischemic damage [5,9,10]. WM alternations are regulated by many factors and multiple processes, such as vascular dysfunction and inflammation, blood-brain barrier (BBB) disruption, glial activation, damaged oligodendrocytes, and demyelination [5]

Objectives

Results

Conclusion