{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:56:41Z","timestamp":1792292201924,"version":"4.4.0"},"reference-count":92,"publisher":"SAGE Publications","issue":"s1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2024,4,22]]},"abstract":"<jats:p>The deterioration of the brain\u2019s microvasculature, particularly in the hippocampus, appears to be a very early event in the development of Alzheimer\u2019s disease (AD), preceding even the deposition of amyloid-\u03b2. A damaged microvasculature reduces the supply of oxygen and glucose to this region and limits the production of energy, ATP. The damage may be a function of the rise with age in the expression and activity of NADPH oxidase (NOX) in these microvessels. This rise renders these vessels vulnerable to the effects of oxidative stress and inflammation. The rise in NOX activity with age is even more marked in the AD brain where an inverse correlation has been demonstrated between NOX activity and cognitive ability. Apocynin, a putative NOX inhibitor, has been shown to block the damaging effects of NOX activation. Apocynin acts as a strong scavenger of H2O2, and as a weak scavenger of superoxide. Like apocynin, sodium oxybate (SO) has also been shown to block the toxic effects of NOX activation. The application of SO generates NADPH and ATP. SO inhibits oxidative stress and maintains normal cerebral ATP levels under hypoxic conditions. Moreover, it acts epigenetically to attenuate the expression of NOX. SO may delay the onset and slow the progress of AD by suppling energy and maintaining an antioxidative environment in the brain throughout the night. The slow wave activity produced by SO may also activate the glymphatic system and promote the clearance of amyloid-\u03b2 from the brain.<\/jats:p>","DOI":"10.3233\/jad-230415","type":"journal-article","created":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T11:39:58Z","timestamp":1692099598000},"page":"S109-S118","source":"Crossref","is-referenced-by-count":8,"title":["The Alzheimer\u2019s Disease Brain, Its Microvasculature, and NADPH Oxidase"],"prefix":"10.1177","volume":"99","author":[{"given":"Mortimer","family":"Mamelak","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Baycrest Hospital, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-230415_ref1","doi-asserted-by":"crossref","first-page":"e13061","DOI":"10.1111\/bpa.13061","article-title":"Pathological changes within the cerebral vasculature in Alzheimer\u2019s disease: New perspectives","volume":"32","author":"Fisher","year":"2022","journal-title":"Brain Pathol"},{"key":"10.3233\/JAD-230415_ref2","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1080\/01616412.1993.11740127","article-title":"Can disturbed brain microcirculation cause Alzheimer\u2019s disease?","volume":"15","author":"De la Torre","year":"1993","journal-title":"Neurol Res"},{"key":"10.3233\/JAD-230415_ref3","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3109\/07853898909149194","article-title":"Alzheimer\u2019s disease as a capillary dementia","volume":"21","author":"Scheibel","year":"1989","journal-title":"Ann Med"},{"key":"10.3233\/JAD-230415_ref4","doi-asserted-by":"crossref","first-page":"11934","DOI":"10.1038\/ncomms11934","article-title":"Early role of vascular dysregulation on late-onset Alzheimer\u2019s disease based on multifactorial data-driven analysis","volume":"7","author":"Iturria-Medina","year":"2016","journal-title":"Nat Commun"},{"key":"10.3233\/JAD-230415_ref5","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1365-2990.2010.01139.x","article-title":"Review: Cerebral microvascular pathology in ageing and neurodegeneration","volume":"37","author":"Brown","year":"2011","journal-title":"Neuropathol Appl Neurobiol"},{"key":"10.3233\/JAD-230415_ref6","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1007\/BF00294246","article-title":"Altered angioarchitecture in selected areas of brains with Alzheimer\u2019s disease","volume":"79","author":"Fischer","year":"1990","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-230415_ref7","doi-asserted-by":"crossref","first-page":"e36893","DOI":"10.1371\/journal.pone.0036893","article-title":"Morphological and pathological evolution of the brain microcirculation in aging and Alzheimer\u2019s disease","volume":"7","author":"Hunter","year":"2012","journal-title":"PLoS One"},{"key":"10.3233\/JAD-230415_ref8","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1111\/bpa.12895","article-title":"Distinct changes in all major components of the neurovascular unit across different neuropathological stages of Alzheimer\u2019s disease","volume":"30","author":"Kirabali","year":"2020","journal-title":"Brain Pathol"},{"key":"10.3233\/JAD-230415_ref9","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jns.2012.07.010","article-title":"The vascular factor in Alzheimer\u2019s disease: A study in Golgi technique and electron microscopy","volume":"322","author":"Baloyannis","year":"2012","journal-title":"J Neurol Sci"},{"key":"10.3233\/JAD-230415_ref10","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/BF00294173","article-title":"Pathological alterations of the cerebral microvasculature in Alzheimer\u2019s disease and related dementing disorders","volume":"87","author":"Bu\u00e9e","year":"1994","journal-title":"Acta Neuropathol"},{"key":"10.3233\/JAD-230415_ref11","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nrn.2017.74","article-title":"Prefrontal-hippocampal interactions in episodic memory","volume":"18","author":"Eichenbaum","year":"2017","journal-title":"Nat Rev Neurosci"},{"key":"10.3233\/JAD-230415_ref12","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1126\/science.6474172","article-title":"Alzheimer\u2019s disease: cell-specific pathology isolates the hippocampal formation","volume":"225","author":"Hymen","year":"1984","journal-title":"Science"},{"key":"10.3233\/JAD-230415_ref13","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.neuron.2014.12.032","article-title":"Blood-Brain barrier breakdown in the aging human hippocampus","volume":"85","author":"Montagne","year":"2015","journal-title":"Neuron"},{"key":"10.3233\/JAD-230415_ref14","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","article-title":"Blood\u2013brain barrier breakdown is an early biomarker of human cognitive dysfunction","volume":"25","author":"Nation","year":"2019","journal-title":"Nat Med"},{"key":"10.3233\/JAD-230415_ref15","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.neulet.2015.09.025","article-title":"Shedding of soluble platelet-derived growth factor receptor-\u03b2 from human brain pericytes","volume":"607","author":"Sagare","year":"2015","journal-title":"Neurosci Lett"},{"key":"10.3233\/JAD-230415_ref16","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13024-021-00512-w","article-title":"Dynamic changes of CSF sPDGFR\u03b2 during ageing and AD progression and associations with CSF ATN biomarkers","volume":"17","author":"Wang","year":"2022","journal-title":"Mol Neurodegener"},{"key":"10.3233\/JAD-230415_ref17","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nature09522","article-title":"Pericytes regulate the blood-brain barrier","volume":"468","author":"Armulik","year":"2010","journal-title":"Nature"},{"key":"10.3233\/JAD-230415_ref18","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1111\/bpa.12897","article-title":"Denser brain capillary network with preserved pericytes in Alzheimer\u2019s disease","volume":"30","author":"Fernandez-Klett","year":"2020","journal-title":"Brain Pathol"},{"key":"10.3233\/JAD-230415_ref19","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/bpa.12004","article-title":"Deficiency in mural vascular cells coincides with blood-brain barrier disruption in Alzheimer\u2019s disease","volume":"23","author":"Sengillo","year":"2013","journal-title":"Brain Pathol"},{"key":"10.3233\/JAD-230415_ref20","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/bpa.12152","article-title":"The pericyte: A forgotten cell type with important implications for alzheimer\u2019s disease?","volume":"24","author":"Winkler","year":"2014","journal-title":"Brain Pathol"},{"key":"10.3233\/JAD-230415_ref21","doi-asserted-by":"crossref","first-page":"3190","DOI":"10.1038\/s41467-021-23508-y","article-title":"Neurovascular coupling and oxygenation are decreased in hippocampus compared to neocortex because of microvascular differences","volume":"12","author":"Shaw","year":"2021","journal-title":"Nat Commun"},{"key":"10.3233\/JAD-230415_ref22","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1016\/j.ajpath.2021.07.003","article-title":"Interplay between brain pericytes and endothelial cells in dementia","volume":"191","author":"Procter T","year":"2021","journal-title":"Am J Pathol"},{"key":"10.3233\/JAD-230415_ref23","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/s41586-021-04369-3","article-title":"A human brain vascular atlas reveals diverse mediators of Alzheimer\u2019s risk","volume":"603","author":"Yang","year":"2022","journal-title":"Nature"},{"key":"10.3233\/JAD-230415_ref24","doi-asserted-by":"crossref","first-page":"e0144062","DOI":"10.1371\/journal.pone.0144062","article-title":"Regional heterogeneity of cerebral microvessels and brain susceptibility to oxidative stress","volume":"10","author":"Austin","year":"2015","journal-title":"PLoS One"},{"key":"10.3233\/JAD-230415_ref25","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/brain\/awx194","article-title":"The cerebellum in Alzheimer\u2019s disease: Evaluating its role in cognitive decline","volume":"141","author":"Jacobs","year":"2018","journal-title":"Brain"},{"key":"10.3233\/JAD-230415_ref26","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1007\/s00424-010-0867-4","article-title":"Endothelial nitric oxide synthase transgenic models of endothelial dysfunction","volume":"460","author":"Atochin","year":"2010","journal-title":"Pflugers Arch Eur J Physiol"},{"key":"10.3233\/JAD-230415_ref27","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1253\/circj.CJ-16-0423","article-title":"Neurovascular protective function of endothelial nitric oxide \u2013 recent advances \u2013","volume":"80","author":"Katusic","year":"2016","journal-title":"Circ J"},{"key":"10.3233\/JAD-230415_ref28","doi-asserted-by":"crossref","first-page":"9220","DOI":"10.1073\/pnas.95.16.9220","article-title":"Superoxide generation by endothelial nitric oxide synthase: The influence of cofactors","volume":"95","author":"V\u00e1squez-Vivar","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-230415_ref29","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1006\/bbrc.1999.1422","article-title":"Oxidation of tetrahydrobiopterin by peroxynitrite: Implications for vascular endothelial function","volume":"263","author":"Milstien","year":"1999","journal-title":"Biochem Biophys Res Commun"},{"key":"10.3233\/JAD-230415_ref30","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.tips.2008.10.003","article-title":"Vascular protection by tetrahydrobiopterin: progress and therapeutic prospects","volume":"30","author":"Katusic","year":"2009","journal-title":"Trends Pharmacol Sci"},{"key":"10.3233\/JAD-230415_ref31","doi-asserted-by":"crossref","first-page":"3374","DOI":"10.1172\/JCI125173","article-title":"Nox2 contributes to age-related oxidative damage to neurons and the cerebral vasculature","volume":"129","author":"Fan","year":"2019","journal-title":"J Clin Invest"},{"key":"10.3233\/JAD-230415_ref32","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s10522-012-9392-5","article-title":"Dietary supplementation with N-acetyl cysteine, a-tocopherol and a-lipoic acid reduces the extent of oxidative stress and proinflammatory state in aged rat brain","volume":"13","author":"Thakurta","year":"2012","journal-title":"Biogerontology"},{"key":"10.3233\/JAD-230415_ref33","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1089\/ars.2009.2823","article-title":"NOX Activity is increased in mild cognitive impairment","volume":"12","author":"Bruce-Keller","year":"2010","journal-title":"Antioxidants Redox Signal"},{"key":"10.3233\/JAD-230415_ref34","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.freeradbiomed.2011.03.025","article-title":"NADPH-oxidase activation and cognition in Alzheimer disease progression","volume":"51","author":"Ansari","year":"2011","journal-title":"Free Radic Biol Med"},{"key":"10.3233\/JAD-230415_ref35","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1093\/gerona\/glac083","article-title":"Dysregulation of ACE-1 in normal aging and the early stages of Alzheimer\u2019s disease","volume":"77","author":"MacLachlan","year":"2022","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.3233\/JAD-230415_ref36","doi-asserted-by":"crossref","first-page":"12094","DOI":"10.1074\/jbc.M209793200","article-title":"Mechanism of endothelial cell NADPH oxidase activation by angiotensin II: Role of the p47phox subunit","volume":"278","author":"Li","year":"2003","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-230415_ref37","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.freeradbiomed.2017.05.008","article-title":"Aging-associated metabolic disorder induces Nox2 activation and oxidative damage of endothelial function","volume":"108","author":"Fan","year":"2017","journal-title":"Free Radic Biol Med"},{"key":"10.3233\/JAD-230415_ref38","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1089\/ars.2008.2220","article-title":"NADPH oxidase-dependent signaling in endothelial cells: Role in physiology and pathophysiology","volume":"11","author":"Frey","year":"2009","journal-title":"Antioxidants Redox Signal"},{"key":"10.3233\/JAD-230415_ref39","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.2337\/db12-1294","article-title":"Nox2 NADPH oxidase has a critical role in insulin resistance-related endothelial cell dysfunction","volume":"62","author":"Sukumar","year":"2013","journal-title":"Diabetes"},{"key":"10.3233\/JAD-230415_ref40","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.freeradbiomed.2004.09.036","article-title":"The expression of the NADPH oxidase subunit p22phox is regulated by a redox-sensitive pathway in endothelial cells","volume":"38","author":"Djordjevic","year":"2005","journal-title":"Free Radic Biol Med"},{"key":"10.3233\/JAD-230415_ref41","doi-asserted-by":"crossref","first-page":"562","DOI":"10.3390\/biom11040562","article-title":"Role of thrombin in central nervous system injury and disease","volume":"11","author":"Shlobin","year":"2021","journal-title":"Biomolecules"},{"key":"10.3233\/JAD-230415_ref42","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1038\/nn.2946","article-title":"Central nervous system pericytes in health and disease","volume":"14","author":"Winkler","year":"2011","journal-title":"Nat Neurosci"},{"key":"10.3233\/JAD-230415_ref43","doi-asserted-by":"crossref","first-page":"10990","DOI":"10.1073\/pnas.1707517114","article-title":"Systems biology analysis of longitudinal functional response of endothelial cells to shear stress","volume":"114","author":"Ajami","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JAD-230415_ref44","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/apha.12725","article-title":"Effects of shear stress on endothelial cells: go with the flow","volume":"219","author":"Chistiakov","year":"2017","journal-title":"Acta Physiol"},{"key":"10.3233\/JAD-230415_ref45","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1423-0127-21-3","article-title":"Shear-induced endothelial mechanotransduction: The interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications","volume":"21","author":"Hsieh","year":"2014","journal-title":"J Biomed Sci"},{"key":"10.3233\/JAD-230415_ref46","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1152\/ajpheart.00025.2004","article-title":"Membrane depolarization and NADPH oxidase activation in aortic endothelium during ischemia reflect altered mechanotransduction","volume":"288","author":"Matsuzaki","year":"2005","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.3233\/JAD-230415_ref47","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1080\/03602532.2021.1895203","article-title":"Pharmacology of apocynin: a natural acetophenone","volume":"53","author":"Savla","year":"2021","journal-title":"Drug Metab Rev"},{"key":"10.3233\/JAD-230415_ref48","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1089\/ars.2019.7915","article-title":"The NADPH oxidase family and its inhibitors","volume":"33","author":"Chocry","year":"2020","journal-title":"Antioxid Redox Signal"},{"key":"10.3233\/JAD-230415_ref49","doi-asserted-by":"crossref","first-page":"111342","DOI":"10.1016\/j.cbpa.2022.111342","article-title":"Apocynin reduces dihydroethidium fluorescence in naked mole-rat cortex independently of NADPH oxidase","volume":"276","author":"Eaton","year":"2023","journal-title":"Comp Biochem Physiol A Mol Integr Physiol"},{"key":"10.3233\/JAD-230415_ref50","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1161\/HYPERTENSIONAHA.107.100214","article-title":"Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant","volume":"51","author":"Heum\u00fcller","year":"2008","journal-title":"Hypertension"},{"key":"10.3233\/JAD-230415_ref51","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.3390\/molecules18032821","article-title":"Apocynin: Chemical and biophysical properties of a NADPH oxidase inhibitor","volume":"18","author":"Petr\u00f4nio","year":"2013","journal-title":"Molecules"},{"key":"10.3233\/JAD-230415_ref52","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.brainres.2006.03.060","article-title":"Apocynin protects against global cerebral ischemia-reperfusion-induced oxidative stress and injury in the gerbil hippocampus","volume":"1090","author":"Wang","year":"2006","journal-title":"Brain Res"},{"key":"10.3233\/JAD-230415_ref53","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.biopha.2017.10.123","article-title":"Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion hippocampus injury in rat brain","volume":"97","author":"Kapoor","year":"2018","journal-title":"Biomed Pharmacother"},{"key":"10.3233\/JAD-230415_ref54","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.abb.2018.03.027","article-title":"(-)-Epicatechin and its metabolites prevent palmitate-induced NADPH oxidase upregulation, oxidative stress and insulin resistance in HepG2 cells","volume":"646","author":"Cremonini","year":"2018","journal-title":"Arch Biochem Biophys"},{"key":"10.3233\/JAD-230415_ref55","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1007\/s00125-013-2858-4","article-title":"NADPH oxidase inhibition prevents beta cell dysfunction induced by prolonged elevation of oleate in rodents","volume":"56","author":"Koulajian","year":"2013","journal-title":"Diabetologia"},{"key":"10.3233\/JAD-230415_ref56","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.bbrc.2014.04.157","article-title":"Apocynin attenuates isoproterenol-induced myocardial injury and fibrogenesis","volume":"449","author":"Liu","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"key":"10.3233\/JAD-230415_ref57","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1080\/10715762.2017.1375486","article-title":"Inhibition of NADPH oxidase by apocynin promotes myocardial antioxidant response and prevents isoproterenol-induced myocardial oxidative stress in rats","volume":"51","author":"Tanriverdi","year":"2017","journal-title":"Free Radic Res"},{"key":"10.3233\/JAD-230415_ref58","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jss.2022.12.020","article-title":"Combination therapy of niacin and apocynin attenuates lung injury during sepsis in rats","volume":"285","author":"Park","year":"2023","journal-title":"J Surg Res"},{"key":"10.3233\/JAD-230415_ref59","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1152\/japplphysiol.00969.2013","article-title":"Vascular endothelial function and oxidative stress are related to dietary niacin intake among healthy middle-aged and older adults","volume":"116","author":"Kaplon","year":"2014","journal-title":"J Appl Physiol"},{"key":"10.3233\/JAD-230415_ref60","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1161\/STROKEAHA.115.009687","article-title":"Reduced nicotinamide adenine dinucleotide phosphate, a pentose phosphate pathway product, might be a novel drug candidate for ischemic stroke","volume":"47","author":"Li","year":"2016","journal-title":"Stroke"},{"key":"10.3233\/JAD-230415_ref61","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.freeradbiomed.2017.01.034","article-title":"Combined NADPH and the NOX inhibitor apocynin provides greater anti-inflammatory and neuroprotective effects in a mouse model of stroke","volume":"104","author":"Qin","year":"2017","journal-title":"Free Radic Biol Med"},{"key":"10.3233\/JAD-230415_ref62","volume-title":"Gamma-Hydroxybutyrate: Molecular, Functional and Clinical Aspects,","author":"Mamelak","year":"2002"},{"key":"10.3233\/JAD-230415_ref63","volume-title":"Gamma-Hydroxybutyrate: Molecular, Functional and Clinical Aspects,","author":"Kaufman","year":"2002"},{"key":"10.3233\/JAD-230415_ref64","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.freeradbiomed.2013.05.049","article-title":"A spontaneous mutation in the nicotinamide nucleotide transhydrogenase gene of C57BL\/6J mice results in mitochondrial redox abnormalities","volume":"63","author":"Ronchi","year":"2013","journal-title":"Free Radic Biol Med"},{"key":"10.3233\/JAD-230415_ref65","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/1357-2725(95)00080-9","article-title":"Different regulatory properties of the cytosolic andmitochondrial forms of malic enzyme isolated from human brain","volume":"27","author":"Bukato","year":"1995","journal-title":"Int J Biochem Cell Biol"},{"key":"10.3233\/JAD-230415_ref66","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0304-3940(99)00748-X","article-title":"The regeneration of reduced glutathione in rat forebrain mitochondria identifies metabolic pathways providing the NADPH required","volume":"275","author":"Vogel","year":"1999","journal-title":"Neurosci Lett"},{"key":"10.3233\/JAD-230415_ref67","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/0028-3908(64)90074-7","article-title":"Sodium-4-hydroxybutyrate","volume":"3","author":"Laborit","year":"1964","journal-title":"Int J Neuropharmacol"},{"key":"10.3233\/JAD-230415_ref68","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1471-4159.1972.tb01334.x","article-title":"The action of gamma-hydroxybutyric acid on cerebral glucose metabolism","volume":"19","author":"Taberner","year":"1972","journal-title":"J Neurochem"},{"key":"10.3233\/JAD-230415_ref69","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.freeradbiomed.2016.08.003","article-title":"Inhibition of histone deacetylase reduces transcription of NADPH oxidases and ROS production and ameliorates pulmonary arterial hypertension","volume":"99","author":"Chen","year":"2016","journal-title":"Free Radic Biol Med"},{"key":"10.3233\/JAD-230415_ref70","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1124\/jpet.107.120188","article-title":"Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: Multiple mechanisms of action","volume":"321","author":"Hyeon","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"10.3233\/JAD-230415_ref71","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.cbpa.2016.06.019","article-title":"Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-\u03baB-mediated inflammation","volume":"33","author":"Leus","year":"2016","journal-title":"Curr Opin Chem Biol"},{"key":"10.3233\/JAD-230415_ref72","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.neuropharm.2009.04.013","article-title":"Pharmacological doses of gamma-hydroxybutyrate (GHB) potentiate histone acetylation in the rat brain by histone deacetylase inhibition","volume":"57","author":"Klein","year":"2009","journal-title":"Neuropharmacology"},{"key":"10.3233\/JAD-230415_ref73","doi-asserted-by":"crossref","first-page":"6237351","DOI":"10.1155\/2017\/6237351","article-title":"Proteomic analysis of HDAC3 selective inhibitor in the regulation of inflammatory response of primary microglia","volume":"2017","author":"Xia","year":"2017","journal-title":"Neural Plast"},{"key":"10.3233\/JAD-230415_ref74","doi-asserted-by":"crossref","first-page":"545","DOI":"10.3390\/cells11030545","article-title":"Prevention of lipotoxicity in pancreatic islets with gammahydroxybutyrate","volume":"11","author":"Yung","year":"2022","journal-title":"Cells"},{"key":"10.3233\/JAD-230415_ref75","doi-asserted-by":"crossref","first-page":"e0232413","DOI":"10.1371\/journal.pone.0232413","article-title":"Beneficial effects of benfotiamine, a NADPH oxidase inhibitor, in isoproterenol-induced myocardial infarction in rats","volume":"15","author":"Ahmed","year":"2020","journal-title":"PLoS One"},{"key":"10.3233\/JAD-230415_ref76","first-page":"275","article-title":"Cardioprotective action of sodium gamma-hydroxybutyrate against isoproterenol induced myocardial damage","volume":"74","author":"Kolin","year":"1993","journal-title":"Int J Exp Pathol"},{"key":"10.3233\/JAD-230415_ref77","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.brainres.2006.06.082","article-title":"NADPH-oxidase activity is elevated in penumbral and non-ischemic cerebral arteries following stroke","volume":"1111","author":"Miller","year":"2006","journal-title":"Brain Res"},{"key":"10.3233\/JAD-230415_ref78","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1196\/annals.1369.054","article-title":"Gamma-hydroxybutyrate (GHB), gamma-butyrolactone (GBL), and 1,4-butanediol (1,4-BD) reduce the volume of cerebral infarction in rhodent transient middle cerebral artery occlusion","volume":"1074","author":"Sadasivan","year":"2006","journal-title":"Ann NY Acad Sci"},{"key":"10.3233\/JAD-230415_ref79","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0006-8993(03)03252-9","article-title":"Effect of gamma-hydroxybutyrate in two rat models of focal cerebral damage","volume":"986","author":"Ottani","year":"2003","journal-title":"Brain Res"},{"key":"10.3233\/JAD-230415_ref80","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/0006-8993(94)90815-X","article-title":"Delayed treatment with 1,3-butanediol reduces loss of CA1 neurons in the hippocampus of rats following brief forebrain ischemia","volume":"662","author":"Sims","year":"1994","journal-title":"Brain Res"},{"key":"10.3233\/JAD-230415_ref81","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0006-8993(78)90229-9","article-title":"The effects of gammahydroxybutyrate and gammabutyrolactone upon the energy metabolism of normoxic and hypoxic rat brain","volume":"146","author":"MacMillan","year":"1978","journal-title":"Brain Res"},{"key":"10.3233\/JAD-230415_ref82","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1124\/dmd.111.041749","article-title":"Brain uptake of the drug of abuse \u03b3-hydroxybutyric acid in rats","volume":"40","author":"Roiko","year":"2012","journal-title":"Drug Metab Dispos"},{"key":"10.3233\/JAD-230415_ref83","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/jcbfm.1990.91","article-title":"Effect of gamma-hydroxybutyrate on local and global glucose metabolism in the anesthetized cat brain","volume":"10","author":"Haller","year":"1990","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.3233\/JAD-230415_ref84","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s12964-020-00681-z","article-title":"Histone deacetylase 3 inhibition alleviates type 2 diabetes mellitus-induced endothelial dysfunction via Nrf2","volume":"19","author":"Huang","year":"2021","journal-title":"Cell Commun Signal"},{"key":"10.3233\/JAD-230415_ref85","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s00395-012-0283-3","article-title":"Transcriptional regulation of Nox4 by histone deacetylases in human endothelial cells","volume":"107","author":"Siuda","year":"2012","journal-title":"Basic Res Cardiol"},{"key":"10.3233\/JAD-230415_ref86","volume-title":"Biochemistry","author":"Stryer","year":"1988"},{"key":"10.3233\/JAD-230415_ref87","first-page":"245","article-title":"Gammahydroxybutyrate protects the liver from warm ischemia perfusion injury in the rat","volume":"3","author":"Wei","year":"2004","journal-title":"Hepatobiliary Pancreat Dis Int"},{"key":"10.3233\/JAD-230415_ref88","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.neurobiolaging.2014.10.003","article-title":"\u03b3-Hydroxybutyrate (Xyrem) ameliorates clinical symptoms and neuropathology in a mouse model of Alzheimer\u2019s disease","volume":"36","author":"Klein","year":"2015","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-230415_ref89","doi-asserted-by":"crossref","first-page":"eabe7099","DOI":"10.1126\/scitranslmed.abe7099","article-title":"Slow-wave sleep affects synucleinopathy and regulates proteostatic processes in mouse models of Parkinson\u2019s disease","volume":"13","author":"Morawska","year":"2021","journal-title":"Sci Transl Med"},{"key":"10.3233\/JAD-230415_ref90","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1001\/jamaneurol.2016.4370","article-title":"Association of perivascular localization of aquaporin-4 with cognition and Alzheimer disease in aging brains","volume":"74","author":"Zeppenfeld","year":"2017","journal-title":"JAMA Neurol"},{"key":"10.3233\/JAD-230415_ref91","doi-asserted-by":"crossref","first-page":"272","DOI":"10.2174\/1570159X19666210407151227","article-title":"Sleep, narcolepsy, and sodium oxybate","volume":"20","author":"Mamelak","year":"2021","journal-title":"Curr Neuropharmacol"},{"key":"10.3233\/JAD-230415_ref92","first-page":"564","article-title":"The treatment of Parkinson\u2019s disease with sodium oxybate","volume":"16","author":"Mamelak","year":"2022","journal-title":"Curr Mol Pharmacol"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-230415","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:08:54Z","timestamp":1777370934000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-230415"}},"subtitle":[],"editor":[{"given":"Pravat K.","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,4,22]]},"references-count":92,"journal-issue":{"issue":"s1"},"URL":"https:\/\/doi.org\/10.3233\/jad-230415","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,22]]}}}