{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T03:40:40Z","timestamp":1785901240480,"version":"3.56.0"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T00:00:00Z","timestamp":1702598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Current evidence suggests that microvessel disease is involved in Alzheimer\u2019s disease (AD). Cerebrovascular disease correlates with cardiovascular disease and is complicated in \u224840% of AD patients. The protein kinase C (PKC) \u03b5 activator DCPLA can stimulate human antigen (Hu) R that prevents degradation and promotes the translation of mitochondrial Mn-superoxide dismutase (MnSOD) and vascular endothelial growth factor-A (VEGF) mRNAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To induce brain microinfarcts, we injected triple transgenic (3\u00d7Tg) and wild-type (WT) control mice with microbeads (20\u2009\u03bcm caliber) into common carotid arteries, with or without the DCPLA-ME (methyl-ester) for 2\u2009weeks. After water maze training, mice at 16\u2009months old were examined for confocal immunohistochemistry at a single cell or microvessel level in the hippocampal CA1 area, important for spatial memory storage, and in the dorsal hippocampus by western blots.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 3\u00d7Tg mice without cerebral microinfarcts, an accelerating age-related increase in (mild) oxidative stress and hypoxia inducible factor (HIF)-1\u03b1, but a reduction in VEGF, mitochondrial transcription factor A (TFAM), and MnSOD were associated with capillary loss. The change was less pronounced in arterioles. However, in 3\u00d7Tg mice with cerebral microinfarcts, increasing arteriolar diameter and their wall cells were related with the strong oxidative DNA damage 8-hydroxy-2\u2032-deoxyguanosine (8-OHdG), apoptosis (cleaved caspase 3), and sustained hypoxia (increased HIF-1\u03b1 and VEGF\/PKC\u03b5\/extracellular signal regulated kinase or ERK pathway). Microocclusion enhanced the loss of the synaptic marker spinophilin, astrocytic number, and astrocyte-vascular coupling areas and demyelination of axons. DCPLA-ME prevented spatial memory defect; strong oxidative stress-related apoptosis; sustained hypoxia (by reducing HIF-1\u03b1 and VEGF); and exaggerated cell repair in arteriolar walls, pericapillary space dilation, neuro-glial-vascular disruption, and demyelination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, in 3\u00d7Tg mice with cerebral microinfarcts, sustained hypoxia (increased HIF-1\u03b1 and VEGF signals) is dominant with arteriolar wall thickening, and DCPLA has a protective effect on sustained hypoxia.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2023.1272361","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T10:34:26Z","timestamp":1702636466000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["PKC\u03b5 activator protects hippocampal microvascular disruption and memory defect in 3\u00d7Tg-Alzheimer\u2019s disease mice with cerebral microinfarcts"],"prefix":"10.3389","volume":"15","author":[{"given":"Huaixing","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongxiu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarin","family":"Hongpaisan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e12939","DOI":"10.1111\/bpa.12939","article-title":"Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change and microvascular pathologies in community-dwelling older persons","volume":"31","author":"Agrawal","year":"2021","journal-title":"Brain Pathol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2454","DOI":"10.1172\/jci60842","article-title":"Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease","volume":"122","author":"Argaw","year":"2012","journal-title":"J. Clin. Invest."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/bpa.12365","article-title":"The relationship of cerebral vessel pathology to brain microinfarcts","volume":"27","author":"Arvanitakis","year":"2017","journal-title":"Brain Pathol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1161\/strokeaha.110.595082","article-title":"Microinfarct pathology, dementia, and cognitive systems","volume":"42","author":"Arvanitakis","year":"2011","journal-title":"Stroke"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12916-014-0206-2","article-title":"The overlap between vascular disease and Alzheimer\u2019s disease\u2014lessons from pathology","volume":"12","author":"Attems","year":"2014","journal-title":"BMC Med."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e0124362","DOI":"10.1371\/journal.pone.0124362","article-title":"Pericytes contribute to the disruption of the cerebral endothelial barrier via increasing VEGF expression: implications for stroke","volume":"10","author":"Bai","year":"2015","journal-title":"PLoS One"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2530","DOI":"10.1101\/gad.1024602","article-title":"C-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression","volume":"16","author":"Baudino","year":"2002","journal-title":"Genes Dev."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00709-013-0515-x","article-title":"Do we age because we have mitochondria?","volume":"251","author":"Bereiter-Hahn","year":"2014","journal-title":"Protoplasma"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-020-02235-6","article-title":"Brain arteriolosclerosis","volume":"141","author":"Blevins","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref11","doi-asserted-by":"publisher","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":"ref12","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.mvr.2005.10.004","article-title":"Vascular endothelial growth factor-induced endothelial cell proliferation is regulated by interaction between VEGFR-2, SH-PTP1 and eNOS","volume":"71","author":"Cai","year":"2006","journal-title":"Microvasc. Res."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1136\/jnnp.2003.019273","article-title":"White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer\u2019s disease","volume":"75","author":"Capizzano","year":"2004","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"102146","DOI":"10.1016\/j.nicl.2019.102146","article-title":"Arterial spin labeling versus 18F-FDG-PET to identify mild cognitive impairment","volume":"25","author":"Dolui","year":"2020","journal-title":"NeuroImage Clin."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1212\/WNL.0b013e3182a43e45","article-title":"Neuropathologic basis of white matter hyperintensity accumulation with advanced age","volume":"81","author":"Erten-Lyons","year":"2013","journal-title":"Neurology"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1007\/s11481-007-9073-3","article-title":"Therapeutic angiogenesis for brain ischemia: a brief review","volume":"2","author":"Fan","year":"2007","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"H2012","DOI":"10.1152\/ajpheart.00495.2005","article-title":"Activation of PKC modulates blood-brain barrier endothelial cell permeability changes induced by hypoxia and posthypoxic reoxygenation","volume":"289","author":"Fleegal","year":"2005","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e73146","DOI":"10.1371\/journal.pone.0073146","article-title":"C-Myc is essential to prevent endothelial pro-inflammatory senescent phenotype","volume":"8","author":"Florea","year":"2013","journal-title":"PLoS One"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"104515","DOI":"10.1016\/j.mvr.2023.104515","article-title":"Perivascular clearance of blood proteins after blood-brain barrier disruption in a rat model of microinfarcts","volume":"148","author":"Georgakopoulou","year":"2023","journal-title":"Microvasc. Res."},{"key":"ref20","first-page":"616","article-title":"Brain microvasculature and hypoxia-related proteins in Alzheimer\u2019s disease","volume":"4","author":"Grammas","year":"2011","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1038\/sj.jcbfm.9600408","article-title":"Vascular response to hypoxic preconditioning in the immature brain","volume":"27","author":"Gustavsson","year":"2007","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/s0169-328x(02)00175-4","article-title":"VEGF mRNA expressed in microvessels of neonatal and adult rat cerebral cortex","volume":"101","author":"Hoehn","year":"2002","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"19571","DOI":"10.1073\/pnas.0709311104","article-title":"A structural basis for enhancement of long-term associative memory in single dendritic spines regulated by PKC","volume":"104","author":"Hongpaisan","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref24","doi-asserted-by":"publisher","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":"ref25","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1007\/s00401-009-0635-8","article-title":"Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer\u2019s disease, and dementia with Lewy bodies","volume":"119","author":"Ihara","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1152\/japplphysiol.00772.2020","article-title":"Hypoxic preconditioning attenuates ischemia-reperfusion injury in young healthy adults","volume":"130","author":"Jarrard","year":"2021","journal-title":"J. Appl. Physiol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1111\/bjd.12592","article-title":"Upregulated autocrine vascular endothelial growth factor (VEGF)\/VEGF receptor-2 loop prevents apoptosis in haemangioma-derived endothelial cells","volume":"170","author":"Ji","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1016\/j.bbadis.2018.08.008","article-title":"Endothelial cell senescence in aging-related vascular dysfunction","volume":"1865","author":"Jia","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.freeradbiomed.2023.05.011","article-title":"Chronic hypoxia of endothelial cells boosts HIF-1\u03b1-NLRP1 circuit in Alzheimer\u2019s disease","volume":"204","author":"Jung","year":"2023","journal-title":"Free Radic. Biol. Med."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.1161\/strokeaha.112.655803","article-title":"Cerebrovascular disease and mechanisms of cognitive impairment: evidence from clinicopathological studies in humans","volume":"43","author":"Kalaria","year":"2012","journal-title":"Stroke"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1007\/s00401-016-1571-z","article-title":"Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer\u2019s disease","volume":"131","author":"Kalaria","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"S115","DOI":"10.1097\/00002093-199912003-00017","article-title":"Overlap between pathology of Alzheimer disease and vascular dementia","volume":"13","author":"Kalaria","year":"1999","journal-title":"Alzheimer Dis. Assoc. Disord."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/s1383-5742(97)00035-5","article-title":"Analysis of a form of oxidative DNA damage, 8-hydroxy-2\u2032-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis","volume":"387","author":"Kasai","year":"1997","journal-title":"Mutat. Res."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s004010051083","article-title":"Microinfarction as a result of hypertension in a primate model of cerebrovascular disease","volume":"98","author":"Kemper","year":"1999","journal-title":"Acta Neuropathol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"45","DOI":"10.4062\/biomolther.2019.119","article-title":"The role of a neurovascular signaling pathway involving hypoxia-inducible factor and notch in the function of the central nervous system","volume":"28","author":"Kim","year":"2020","journal-title":"Biomol. Ther."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1126\/science.aam6808","article-title":"Engrams and circuits crucial for systems consolidation of a memory","volume":"356","author":"Kitamura","year":"2017","journal-title":"Science"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1111\/nan.12003","article-title":"The relationship between cerebral amyloid angiopathy and cortical microinfarcts in brain ageing and Alzheimer\u2019s disease","volume":"39","author":"K\u00f6vari","year":"2013","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"813536","DOI":"10.3389\/fimmu.2021.813536","article-title":"Multifocal cerebral microinfarcts modulate early Alzheimer\u2019s disease pathology in a sex-dependent manner","volume":"12","author":"Lecordier","year":"2021","journal-title":"Front. Immunol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1089\/ars.2009.2940","article-title":"PGC-1 alpha regulates expression of myocardial mitochondrial antioxidants and myocardial oxidative stress after chronic systolic overload","volume":"13","author":"Lu","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.mvr.2011.11.004","article-title":"Hypoxia induces angiogenic factors in brain microvascular endothelial cells","volume":"83","author":"Luo","year":"2012","journal-title":"Microvasc. Res."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"a020388","DOI":"10.1101\/cshperspect.a020388","article-title":"Astrocyte regulation of blood flow in the brain","volume":"7","author":"MacVicar","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"969","DOI":"10.21037\/qims-20-920","article-title":"VasoMetrics: unbiased spatiotemporal analysis of microvascular diameter in multi-photon imaging applications","volume":"11","author":"McDowell","year":"2021","journal-title":"Quant. Imaging Med. Surg."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"836634","DOI":"10.3389\/fnagi.2022.836634","article-title":"PKC\u03b5 activation restores loss of PKC\u03b5, manganese superoxide dismutase, vascular endothelial growth factor, and microvessels in aged and Alzheimer\u2019s disease hippocampus","volume":"14","author":"Millien","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.neurobiolaging.2019.10.021","article-title":"APOE \u03b54-specific associations of VEGF gene family expression with cognitive aging and Alzheimer\u2019s disease","volume":"87","author":"Moore","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref45","first-page":"1990","article-title":"SiRNA silencing of VEGF, IGFs, and their receptors in human retinal microvascular endothelial cells","volume":"10","author":"Nicolau","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"e12428","DOI":"10.1002\/rmb2.12428","article-title":"Hypoxia: role of SIRT1 and the protective effect of resveratrol in ovarian function","volume":"21","author":"Nishigaki","year":"2022","journal-title":"Reprod. Med. Biol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/s0896-6273(03)00434-3","article-title":"Triple-transgenic model of Alzheimer\u2019s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction","volume":"39","author":"Oddo","year":"2003","journal-title":"Neuron"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.ydbio.2019.11.016","article-title":"Neuron-derived VEGF contributes to cortical and hippocampal development independently of VEGFR1\/2-mediated neurotrophism","volume":"459","author":"Okabe","year":"2020","journal-title":"Dev. Biol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"202","DOI":"10.2174\/1567202611666140520122316","article-title":"Reduction in vascular endothelial growth factor expression in the superior temporal, hippocampal, and brainstem regions in Alzheimer\u2019s disease","volume":"11","author":"Provias","year":"2014","journal-title":"Curr. Neurovasc. Res."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.neurobiolaging.2021.04.019","article-title":"Microvascular degeneration occurs before plaque onset and progresses with age in 3\u00d7Tg AD mice","volume":"105","author":"Quintana","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1161\/atvbaha.108.162842","article-title":"Differential regulation of VEGF signaling by PKC-alpha and PKC-epsilon in endothelial cells","volume":"28","author":"Rask-Madsen","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1452696","DOI":"10.1155\/2020\/1452696","article-title":"PGC-1\u03b1, inflammation, and oxidative stress: an integrative view in metabolism","volume":"2020","author":"Rius-P\u00e9rez","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"107","DOI":"10.4161\/org.6.2.11687","article-title":"VEGF in the nervous system","volume":"6","author":"Rosenstein","year":"2010","journal-title":"Organogenesis"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"2146","DOI":"10.1111\/j.1532-5415.2009.02521.x","article-title":"High blood pressure and microinfarcts: a link between vascular risk factors, dementia, and clinical Alzheimer\u2019s disease","volume":"57","author":"Schneider","year":"2009","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.freeradbiomed.2018.03.034","article-title":"Hippocampal microvasculature changes in association with oxidative stress in Alzheimer\u2019s disease","volume":"120","author":"Sen","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"16462","DOI":"10.1074\/jbc.M116.730440","article-title":"Protein kinase C\u03f5 (PKC\u03f5) promotes synaptogenesis through membrane accumulation of the postsynaptic density protein PSD-95","volume":"291","author":"Sen","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"4966","DOI":"10.1007\/s12035-022-02890-8","article-title":"HIV promotes neurocognitive impairment by damaging the hippocampal microvessels","volume":"59","author":"Sharma","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1161\/strokeaha.117.016995","article-title":"Rodent models of cerebral microinfarct and microhemorrhage","volume":"49","author":"Shih","year":"2018","journal-title":"Stroke"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1038\/jcbfm.2015.8","article-title":"A mouse model of small-vessel disease that produces brain-wide-identified microocclusions and regionally selective neuronal injury","volume":"35","author":"Silasi","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/s1474-4422(11)70307-6","article-title":"Cerebral microinfarcts: the invisible lesions","volume":"11","author":"Smith","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"31834","DOI":"10.1074\/jbc.M109.025940","article-title":"Interleukin-25 expressed by brain capillary endothelial cells maintains blood-brain barrier function in a protein kinase Cepsilon-dependent manner","volume":"284","author":"Sonobe","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"32288","DOI":"10.1074\/jbc.M704001200","article-title":"A protein kinase Cepsilon-anti-apoptotic kinase signaling complex protects human vascular endothelial cells against apoptosis through induction of Bcl-2","volume":"282","author":"Steinberg","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/978-3-211-09469-3_36","article-title":"Development of a cerebral microvascular dysplasia model in rodents","volume":"105","author":"Su","year":"2008","journal-title":"Acta Neurochir. Suppl."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"108995","DOI":"10.1016\/j.jneumeth.2020.108995","article-title":"Unlocking the brain: a new method for western blot protein detection from fixed brain tissue","volume":"348","author":"Thacker","year":"2021","journal-title":"J. Neurosci. Methods"},{"key":"ref68","first-page":"220","article-title":"Neuronal damage of the dorsal hippocampus induced by long-term right common carotid artery occlusion in rats","volume":"17","author":"Thong-Asa","year":"2014","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1111\/jon.12264","article-title":"Cerebral hypoperfusion and hypometabolism detected by arterial spin labeling MRI and FDG-PET in early-onset Alzheimer\u2019s disease","volume":"26","author":"Verclytte","year":"2016","journal-title":"J. Neuroimaging"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"2870","DOI":"10.1523\/jneurosci.2112-16.2017","article-title":"Focal solute trapping and global glymphatic pathway impairment in a murine model of multiple microinfarcts","volume":"37","author":"Wang","year":"2017","journal-title":"J. Neurosci."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.mito.2023.01.007","article-title":"Mitochondrial oxidative stress in brain microvascular endothelial cells: triggering blood-brain barrier disruption","volume":"69","author":"Wang","year":"2023","journal-title":"Mitochondrion"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.neuroscience.2023.06.019","article-title":"ApoE4-related microvascular disease in the Alzheimer\u2019s disease hippocampal CA1 stratum radiatum","volume":"526","author":"Wang","year":"2023","journal-title":"Neuroscience"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.1523\/jneurosci.22-05-01858.2002","article-title":"The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer\u2019s disease","volume":"22","author":"Westerman","year":"2002","journal-title":"J. Neurosci."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"169","DOI":"10.3389\/fcell.2018.00169","article-title":"Possible role of PHD inhibitors as hypoxia-mimicking agents in the maintenance of neural stem cells\u2019 self-renewal properties","volume":"6","author":"Wu","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-019-0233-3","article-title":"Hypoxia and aging","volume":"51","author":"Yeo","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1212\/01.wnl.0000168863.49053.4d","article-title":"APOE, vascular pathology, and the AD brain","volume":"65","author":"Yip","year":"2005","journal-title":"Neurology"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"e01268","DOI":"10.1002\/brb3.1268","article-title":"Quantitative study of the capillaries within the white matter of the Tg2576 mouse model of Alzheimer\u2019s disease","volume":"9","author":"Zhang","year":"2019","journal-title":"Brain Behav."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2023.1272361\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T10:34:30Z","timestamp":1702636470000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2023.1272361\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,15]]},"references-count":73,"alternative-id":["10.3389\/fnagi.2023.1272361"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2023.1272361","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,15]]},"article-number":"1272361"}}