Abstract
Ischemic stroke is a leading cause of human death in present times. Two phases of pathological impact occur during an ischemic stroke, namely, ischemia and reperfusion. Both periods include individual characteristic effects on cell injury and apoptosis. Moreover, these conditions can cause severe cell defects and harm the blood-brain barrier (BBB). Also, the BBB components are the major targets in ischemia-reperfusion injury. The BBB owes its enhanced protective roles to capillary endothelial cells, which maintain BBB permeability. One of the nerve growth factor (NGF) receptors initiating cell signaling, once activated, is the p75 neurotrophin receptor (p75NTR). This receptor is involved in both the survival and apoptosis of neurons. Although many studies have attempted to explain the role of p75NTR in neurons, the mechanisms in endothelial cells remain unclear. Endothelial cells are the first cells to encounter p75NTR stimuli. In this study, we found the upregulated p75NTR expression and reductive expression of tight junction proteins after in vivo and in vitro ischemia-reperfusion injury. Moreover, astaxanthin (AXT), an antioxidant drug, was utilized and was found to reduce p75NTR expression and the number of apoptotic cells. This study verified that p75NTR plays a prominent role in endothelial cell death and provides a novel downstream target for AXT.
Highlights
About 795,000 people suffer from strokes annually in the United States, making it the leading cause of disability [1]
We investigated the role of p75 neurotrophin receptor (p75NTR) in cerebral microvascular endothelial cells under stress induced by ischemia-reperfusion injury and focused on the blood-brain barrier (BBB) hyperpermeability resulting from the dysregulation of tight junction proteins
We have demonstrated that p75NTR in endothelial cells under ischemia-reperfusion injury lead to apoptosis, and the protective effect of AXT is accomplished via the downregulation of p75NTR
Summary
About 795,000 people suffer from strokes annually in the United States, making it the leading cause of disability [1]. Oxidative stress and neuroinflammation are significant contributors to blood-brain barrier (BBB) damage because they can disrupt endothelial tight junction proteins, resulting in increased paracellular permeability [11,12]. Neurovascular unit dysfunction can result from BBB hyperpermeability, in association with oxidative stress and neuroinflammation in selected neurological disorders, such as strokes, epilepsy, Alzheimer’s disease, traumatic brain injury, and multiple sclerosis [15]. Tight junction proteins are the most crucial factors for modulating barrier integrity, including the claudin family, occludin, and zonula occludens-1 (ZO-1), which are present in cerebral vascular endothelial cells [16]. It has been suggested that neurovascular unit dysfunction after an ischemia-reperfusion injury is regarded as the dysregulation of tight junction proteins [16,17,18]
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