Neurosteroids and their receptors in ischemic stroke: From molecular mechanisms to therapeutic opportunities. (October 2020)

• Record Type: Journal Article
• Authors: Vahidinia, Zeinab; Karimian, Mohammad; Joghataei, Mohammad Taghi
• Is Part Of: Pharmacological research. Volume 160(2020)
• Publication Date: 2020-10
• Subjects: 5a-DHPROG 5a-dihydroprogesterone -- AP1 activator protein 1 -- ATP adenosine triphosphate -- BBB blood–brain barrier -- BCAO bilateral carotid artery occlusion -- BDNF brain-derived neurotrophic factor -- BZA bazedoxifene -- cAMP cyclic adenosine monophosphate -- CNS central nervous system -- COX-2 cyclooxygenase 2 -- DG dentate gyrus -- DHEA dehydroepiandrosterone -- DHEAs dehydroepiandrosterone sulfate -- DNMTs DNA methyltransferases -- DPN diarylpropiolnitrile -- E1 estrone -- E2 estradiol -- E3 estriol -- ER estrogen receptors -- ERE estrogen responsive elements -- ERK extracellular-signal-regulated kinase -- ERα estrogen receptor alpha -- ERβ estrogen receptor beta -- FDA Food and Drug Administration -- GABA gamma-aminobutyric acid -- Gal-3 galectin-3 -- GCI global cerebral ischemia -- GDNF glial cell-derived neurotrophic factor -- GPCR G protein-coupled receptor -- GPER-1 G protein-coupled estrogen receptor 1 -- GPR30 G protein-coupled receptor 30 -- GSH glutathione -- GSK3 glycogen synthase kinase 3 -- HIF-1α hypoxia-inducible factor 1-alpha -- IL-1β interleukin 1 beta -- IL-6 interleukin 6 -- IP3R inositol triphosphate receptors -- LPS lipopolysaccharides -- MAPKs mitogen-activated protein kinases -- MCAO middle cerebral artery occlusion -- MDA malondialdehyde -- miRNAs microRNAs -- MMP matrix metallopeptidase -- NF-κB nuclear factor kappa B -- NIH National Institutes of Health -- NMDA N-methyl-d-aspartate -- NOX2 NADPH oxidase 2 -- NR3A NMDA receptor subunit GluN3A -- OGD oxygen glucose deprivation -- OGD/R oxygen-glucose deprivation/reperfusion -- p-CREB phospho-cAMP-responsive element binding -- PI3K phosphoinositide 3-kinases -- PKB protein kinase B -- PKC protein kinase C -- PLC phospholipase C -- PPT propyl pyrazole triol -- PR progestogen receptor -- PXR pregnane X receptor -- ROS reactive oxygen species -- RXR retinoic acid receptor -- SERM selective estrogen receptor modulator -- SGZ subgranular zone -- SK2 small conductance calcium-activated potassium channel protein 2 -- SP1 specificity protein 1 -- SVZ subventricular zone -- TBI traumatic brain injury -- tMCAO transient middle cerebral artery occlusion -- TNFα tumor necrosis factor alpha -- TPA tissue plasminogen activator -- VDR vitamin D receptor -- VDRE vitamin d-responsive element -- VEGF vascular endothelial growth factor -- WHI Women's Health Initiative -- σ1R sigma-1 receptor; Ischemic stroke -- Neurosteroids -- Neuroprotection -- Molecular mechanisms; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.105163
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Extensive progress has been made to understand the pathophysiology of stroke but it is still a major cause of mortality and disability worldwide. There are few strategies for the treatment of this disease and the use of thrombolytic tissue plasminogen activator is limited due to the narrow time window. However, the administration of neuroactive steroids could be considered as a potential treatment approach to decrease ischemia-induced lesions. Neurosteroids receptors play important roles in neuroprotection mediated by these hormones. Membrane and intracellular receptors are both involved in the protective effects of estrogen and progesterone on ischemic brain injury. The intracellular receptors often regulate the gene transcription while the membrane receptors act through modulation of signal transduction pathways. Besides, allopregnanolone acts as a potent positive modulator of the GABA receptor. Moreover, the neuroprotective effects of vitamin D and dehydroepiandrosterone (DHEA) are mediated through the binding to vitamin D receptor (VDR) and several intracellular and membrane receptors, respectively. Activation of VDR could affect various processes including apoptosis, calcium metabolism, oxidative stress, immune modulation, inflammation and detoxification, and DHEA can modulate neurogenesis, neuronal function, and mitochondrial oxidative capacity. The present study aimed to describe the neuroprotective roles of the aforementioned neurosteroids with a focus on their receptors against ischemic stroke.