The pathophysiological role of astrocytic endothelin-1. (September 2016)

• Record Type: Journal Article
• Authors: Hostenbach, Stéphanie; D'haeseleer, Miguel; Kooijman, Ron; De Keyser, Jacques
• Is Part Of: Progress in neurobiology. Volume 144(2016:Sep.)
• Page Start: 88
• Page End: 102
• Publication Date: 2016-09
• Subjects: Aβ amyloid beta -- AD Alzheimer's disease -- Akt protein kinase B -- ALS amyotrophic lateral sclerosis -- AP-1 activator protein-1 -- BBB blood brain barrier -- BDNF brain-derived neurotropic factor -- CB cannabinoid -- CBF cerebral blood flow -- CSF cerebrospinal fluid -- ECE endothelin-converting enzyme -- ET endothelin -- EAE experimental autoimmune encephalomyelitis -- ERK extracellular signal-regulated kinase -- GDNF glial cell line-derived neurotropic factor -- HIV human immunodeficiency virus -- HIF-1 hypoxia inducible factor-1 -- IL interleukin; -- IP3 inositol triphosphate -- MAPK mitogen-activated protein kinase -- MCAO middle cerebral artery occlusion -- MMP matrix metalloproteinase -- MS multiple sclerosis -- OPCs oligodendrocyte progenitor cells -- PI 3-kinase phosphoinositide 3-kinase -- RCT randomized controlled trial -- SAH subarachnoid hemorrhage -- TBI traumatic brain injury -- TNFα tumor necrosis factor alfa -- VEGF vascular endothelial growth factor; Endothelin-1 -- Astrocytes -- Neurological disorders -- Cerebral blood flow -- Blood Brain barrier -- Astrogliosis -- Astrocytoma -- Pain; Neurobiology -- Periodicals; Neurology -- Periodicals; Neurology -- Periodicals; Neurobiologie -- Périodiques; 612.8
• DOI: 10.1016/j.pneurobio.2016.04.009
• Languages: English
• ISSNs: 0301-0082

Abstract

Highlights: Reactive astrocytes express high levels of endothelin-1. Endothelin-1 released from reactive astrocytes may cause secondary damage in a variety of neurological diseases. Counteracting the deleterious effects of astrocytic endothelin-1 may represent a promising target for neuroprotection. Abstract: In the normal central nervous system, endothelin-1 (ET-1) is found in some types of neurons, epithelial cells of the choroid plexus, and endothelial cells of microvessels, but it is usually not detectable in glial cells. However, in different pathological conditions, astrocytes adapting a reactive phenotype express high levels of ET-1 and its receptors, mainly the ETB receptor. ET-1 released by reactive astrocytes appears mainly to have neurodeleterious effects by mechanisms that include constriction of cerebral arterioles leading to impairment of the cerebral microcirculation, increase of blood brain barrier permeability, inflammation, excitotoxicity, impairment of fast axonal transport, and astrogliosis. A few studies in rodents found that ET-1 increased the astrocytic expression of brain-derived neurotrophic factor, glial cell-line derived neurotrophic factor and neurotropin-3, and the production of endocannabinoids. However, whether this occurs in physiological or pathological conditions is unclear. This review summarizes current knowledge about the role of the astrocytic ET-1 system in acute and chronic neurological conditions, including multiple sclerosis, ischemic stroke and hypoxic/ischemic brain injury, traumatic brain injury, subarachnoid hemorrhage, Alzheimer's disease, Binswanger's disease and post-stroke dementia, amyotrophic lateral sclerosis, and CNS infections. Counteracting the harmful effects of astrocytic ET-1 may represent a promising therapeutic target for mitigating secondary brain damage in a variety of neurological diseases. We also briefly address the role of astrocytic ET-1 in astrocytic tumors and pain.