{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:03:07Z","timestamp":1791259387757,"version":"4.1.0"},"reference-count":151,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>The ageing global population is experiencing an increased prevalence of cerebrovascular diseases, such as stroke and dementia. This highlights a need for understanding the pathophysiological mechanisms of age\u2010related cerebrovascular alterations, alongside benefits of interventions such as physical activity. Therefore, our aims were to: (1) examine the impact of ageing and exercise training on cerebrovascular function and (2) to characterize age\u2010 and exercise training\u2010related changes in the hippocampus transcriptome. Young and old male rats were randomized to a sedentary condition or exercise training for 10\u00a0weeks. In the first protocol, cerebral arteries were isolated to test vasomotor reactivity, quantify gene\/protein expression and assess nitric oxide production. In the second protocol, anhedonia was assessed and hippocampal tissue collected for RNA\u2010sequencing. Bioinformatic analyses (i.e. protein\u2013protein interaction mapping) were performed. Ageing impaired endothelium\u2010dependent vasoreactivity in the posterior communicating artery (PCoA), with a shift from endothelial nitric oxide synthase (NOS)\u2010 to neuronal NOS\u2010mediated vasorelaxation, as well as alterations in oxidative stress production. In support, PCoA superoxide\u2010mediated vasoreactivity and neuronal NOS\u2010mediated production of NO decreased with age. Exercise enhanced vasodilatation in young rats, but the results suggested reduced cerebrovascular plasticity in older animals. In the second protocol, exercise training attenuated the age\u2010related increase in anhedonia behaviour. Hippocampal RNA\u2010sequencing revealed altered inflammatory and oxidative stress pathways with ageing that were mitigated by exercise training. Our findings underscore the complex interplay between vascular\/neuronal factors in the ageing brain. Furthermore, these findings highlight the therapeutic potential of exercise in mitigating the adverse effects of ageing on cerebral health.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70004-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Ageing is associated with increased risks of cerebrovascular disease and neurocognitive decline.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Little is known about the underlying mechanisms involved in this process, limiting our ability to design appropriate interventions.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Ageing is associated with alterations in cerebrovascular function, including possible changes in the mechanisms underlying vasomotor reactivity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Hippocampal RNA\u2010seq revealed age\u2010related alterations in neuronal, vascular, immune and oxidative\u2010stress related signalling pathways.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Exercise training may have mitigated many of these age\u2010related changes, suggesting that enhancing physical activity may be a feasible means to preserve cerebral health in older individuals.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp288866","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T11:57:06Z","timestamp":1754481426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of ageing and exercise training on cerebrovascular vasomotor reactivity, depressive behaviour and the hippocampal transcriptome"],"prefix":"10.1113","author":[{"given":"Britton","family":"Scheuermann","sequence":"first","affiliation":[{"name":"Department of Kinesiology Kansas State University  Manhattan KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Nichol","sequence":"additional","affiliation":[{"name":"Institute for Brain Aging and Dementia University of California at Irvine  Irvine CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy","family":"Levenson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Florida State University College of Medicine  Tallahassee FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiana","family":"Schulze","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Kansas State University  Manhattan KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Vied","sequence":"additional","affiliation":[{"name":"Translational Science Laboratory Florida State University, College of Medicine  Tallahassee FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Woodman","sequence":"additional","affiliation":[{"name":"Department of Health and Kinesiology Texas A&amp;M University  College Station TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda","family":"Prisby","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology West Virginia University School of Medicine  Morgantown WV USA"},{"name":"Division of Exercise Science West Virginia University School of Medicine  Morgantown WV USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology West Virginia University School of Medicine  Morgantown WV USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk","family":"Evanson","sequence":"additional","affiliation":[{"name":"Department of Health, Nutrition, and Food Sciences Florida State University  Tallahassee FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lih","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology Texas A&amp;M University Health Science Center  Bryan TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Ade","sequence":"additional","affiliation":[{"name":"Department of Kinesiology Kansas State University  Manhattan KS USA"},{"name":"Department of Physician's Assistant Studies Kansas State University  Manhattan KS USA"},{"name":"Johnson Cancer Research Center Kansas State University  Manhattan KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Muller\u2010Delp","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Florida State University College of Medicine  Tallahassee FL USA"},{"name":"Department of Physiology and Pharmacology West Virginia University School of Medicine  Morgantown WV USA"},{"name":"Department of Anatomy and Physiology Kansas State University  Manhattan KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.freeradbiomed.2013.08.190","article-title":"Sulforaphane preconditioning of the Nrf2\/HO\u20101 defense pathway protects the cerebral vasculature against blood\u2010brain barrier disruption and neurological deficits in stroke","volume":"65","author":"Alfieri A.","year":"2013","journal-title":"Free Radical Biology and Medicine"},{"issue":"7","key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1161\/STROKEAHA.109.547869","article-title":"Relative risks for stroke by age, sex, and population based on follow\u2010up of 18 European populations in the MORGAM Project","volume":"40","author":"Asplund K.","year":"2009","journal-title":"Stroke; A Journal of Cerebral Circulation"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3389\/fnagi.2019.00301","article-title":"Aging impairs cerebrovascular reactivity at preserved resting cerebral arteriolar tone and vascular density in the laboratory rat","volume":"11","author":"B\u00e1lint A. R.","year":"2019","journal-title":"Frontiers in Aging Neuroscience"},{"issue":"1","key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3233\/BPL-180075","article-title":"Exercise improves vascular function, but does this translate to the brain?","volume":"4","author":"Barnes J. N.","year":"2018","journal-title":"Brain Plast"},{"issue":"1","key":"e_1_2_6_6_1","first-page":"D991","article-title":"NCBI GEO: Archive for functional genomics data sets\u2013update","volume":"41","author":"Barrett T.","year":"2013","journal-title":"Nucleic Acids Research"},{"issue":"4","key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1161\/01.HYP.30.4.817","article-title":"Anatomic heterogeneity of vascular aging: Role of nitric oxide and endothelin","volume":"30","author":"Barton M.","year":"1997","journal-title":"Hypertension"},{"issue":"5","key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/jcbfm.1994.90","article-title":"Widespread attenuation of the cerebrovascular reactivity to hypercapnia following inhibition of nitric oxide synthase in the conscious rat","volume":"14","author":"Bonvento G.","year":"1994","journal-title":"Journal of Cerebral Blood Flow and Metabolism"},{"issue":"1","key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/ana.25380","article-title":"Attributable risk of Alzheimer's dementia attributed to age\u2010related neuropathologies","volume":"85","author":"Boyle P. A.","year":"2019","journal-title":"Annals of Neurology"},{"issue":"11","key":"e_1_2_6_10_1","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1161\/STROKEAHA.111.623462","article-title":"Cerebrovascular disease pathology and parkinsonian signs in old age","volume":"42","author":"Buchman A. S.","year":"2011","journal-title":"Stroke; A Journal of Cerebral Circulation"},{"key":"e_1_2_6_11_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.4103\/bc.bc_6_18","article-title":"Cerebrovascular dysfunction with stress and depression","volume":"4","author":"Burrage E.","year":"2018","journal-title":"Brain circulation"},{"issue":"12","key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1177\/0271678X18793324","article-title":"Sex differences in stroke: Challenges and opportunities","volume":"38","author":"Bushnell C. D.","year":"2018","journal-title":"Journal of Cerebral Blood Flow and Metabolism"},{"issue":"1","key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"H1","DOI":"10.1152\/ajpheart.00885.2020","article-title":"Aerobic exercise training reduces cardiac function and coronary flow\u2010induced vasodilation in mice lacking adiponectin","volume":"321","author":"Caldwell J. T.","year":"2021","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"issue":"1","key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1096\/fasebj.2020.34.s1.06201","article-title":"Impact of Nrf2\u2010deficiency on vasoreactivity of posterior cerebral arteries is sex\u2010specific","volume":"34","author":"Caldwell J. T.","year":"2020","journal-title":"The Federation of American Societies for Experimental Biology Journal"},{"issue":"12","key":"e_1_2_6_15_1","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1016\/j.jocn.2015.04.020","article-title":"The role of age in intracerebral hemorrhages","volume":"22","author":"Camacho E.","year":"2015","journal-title":"Journal of Clinical Neuroscience"},{"key":"e_1_2_6_16_1","doi-asserted-by":"crossref","first-page":"806","DOI":"10.3389\/fphys.2018.00806","article-title":"Oxidative stress: A major player in cerebrovascular alterations associated to neurodegenerative events","volume":"9","author":"Carvalho C.","year":"2018","journal-title":"Frontiers in physiology"},{"issue":"2","key":"e_1_2_6_17_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0168-0102(96)01038-3","article-title":"Identification of nitric oxide synthases in isolated bovine brain vessels","volume":"25","author":"Catal\u00e1n R. E.","year":"1996","journal-title":"Neuroscience Research"},{"key":"e_1_2_6_18_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.niox.2013.10.009","article-title":"Long\u2010term aerobic exercise increases redox\u2010active iron through nitric oxide in rat hippocampus","volume":"36","author":"Chen Q.","year":"2014","journal-title":"Nitric Oxide"},{"issue":"5","key":"e_1_2_6_19_1","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nrneurol.2010.36","article-title":"Ischemic stroke in the elderly: An overview of evidence","volume":"6","author":"Chen R. L.","year":"2010","journal-title":"Nature reviews Neurology"},{"issue":"11","key":"e_1_2_6_20_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.molmed.2008.09.003","article-title":"The role of oxidative stress and NADPH oxidase in cerebrovascular disease","volume":"14","author":"Chrissobolis S.","year":"2008","journal-title":"Trends in Molecular Medicine"},{"key":"e_1_2_6_21_1","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The Genotype\u2010Tissue Expression (GTEx) project","volume":"45","author":"Consortium T. G.","year":"2013","journal-title":"Nature Genetics"},{"issue":"10","key":"e_1_2_6_22_1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1001\/jama.2012.271","article-title":"Preventing depression: A global priority","volume":"307","author":"Cuijpers P.","year":"2012","journal-title":"The Journal of the American Medical Association"},{"issue":"1","key":"e_1_2_6_23_1","doi-asserted-by":"crossref","first-page":"D1257","DOI":"10.1093\/nar\/gkac833","article-title":"Comparative toxicogenomics database (CTD): Update 2023","volume":"51","author":"Davis A. P.","year":"2023","journal-title":"Nucleic Acids Research"},{"issue":"8","key":"e_1_2_6_24_1","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1161\/01.STR.0000131749.81508.18","article-title":"Cerebral vascular dysfunction mediated by superoxide in hyperhomocysteinemic mice","volume":"35","author":"Dayal S.","year":"2004","journal-title":"Stroke; A Journal of Cerebral Circulation"},{"issue":"1","key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1146\/annurev-physiol-021119-034338","article-title":"Contributions of aging to cerebral small vessel disease","volume":"82","author":"De Silva T. M.","year":"2020","journal-title":"Annual Review of Physiology"},{"issue":"12","key":"e_1_2_6_26_1","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1161\/01.CIR.102.12.1351","article-title":"Regular aerobic exercise prevents and restores age\u2010related declines in endothelium\u2010dependent vasodilation in healthy men","volume":"102","author":"DeSouza C. A.","year":"2000","journal-title":"Circulation"},{"issue":"2","key":"e_1_2_6_27_1","doi-asserted-by":"crossref","first-page":"H688","DOI":"10.1152\/ajpheart.00576.2001","article-title":"Effects of NADH and NADPH on superoxide levels and cerebral vascular tone","volume":"282","author":"Didion S. P.","year":"2002","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"key":"e_1_2_6_28_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.lfs.2017.03.016","article-title":"Mechanisms underlying sodium nitroprusside\u2010induced tolerance in the mouse aorta: Role of ROS and cyclooxygenase\u2010derived prostanoids","volume":"176","author":"Diniz M. C.","year":"2017","journal-title":"Life Sciences"},{"key":"e_1_2_6_29_1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.freeradbiomed.2016.04.024","article-title":"Exercise\u2010induced Nrf2\u2010signaling is impaired in aging","volume":"96","author":"Done A. J.","year":"2016","journal-title":"Free Radical Biology and Medicine"},{"issue":"6","key":"e_1_2_6_30_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1080\/10715762.2017.1353689","article-title":"Effect of exercise intensity on Nrf2 signalling in young men","volume":"51","author":"Done A. J.","year":"2017","journal-title":"Free Radical Research"},{"issue":"1","key":"e_1_2_6_31_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1017\/S1461145712000016","article-title":"Altered expression of synapse and glutamate related genes in post\u2010mortem hippocampus of depressed subjects","volume":"16","author":"Duric V.","year":"2013","journal-title":"The International Journal of Neuropsychopharmacology"},{"issue":"2","key":"e_1_2_6_32_1","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1152\/japplphysiol.01044.2005","article-title":"Reactive oxygen species: Influence on cerebral vascular tone","volume":"100","author":"Faraci F. M.","year":"2006","journal-title":"Journal of Applied Physiology (1985)"},{"issue":"1","key":"e_1_2_6_33_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1161\/01.RES.66.1.8","article-title":"Regulation of large cerebral arteries and cerebral microvascular pressure","volume":"66","author":"Faraci F. M.","year":"1990","journal-title":"Circulation Research"},{"issue":"6","key":"e_1_2_6_34_1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S0301-0082(00)00068-X","article-title":"Cerebral microvascular pathology in aging and Alzheimer's disease","volume":"64","author":"Farkas E.","year":"2001","journal-title":"Progress in Neurobiology"},{"issue":"1","key":"e_1_2_6_35_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0306-4522(96)00607-0","article-title":"Regional distribution of iron, transferrin, ferritin, and oxidatively\u2010modified proteins in young and aged Fischer 344 rat brains","volume":"79","author":"Focht S. J.","year":"1997","journal-title":"Neuroscience"},{"issue":"5","key":"e_1_2_6_36_1","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s11357-018-0047-6","article-title":"Nrf2 deficiency in aged mice exacerbates cellular senescence promoting cerebrovascular inflammation","volume":"40","author":"Fulop G. A.","year":"2018","journal-title":"Geroscience"},{"issue":"8","key":"e_1_2_6_37_1","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"ShinyGO: A graphical gene\u2010set enrichment tool for animals and plants","volume":"36","author":"Ge S. X.","year":"2020","journal-title":"Bioinformatics"},{"issue":"4","key":"e_1_2_6_38_1","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1152\/japplphysiol.00275.2003","article-title":"Selected contribution: Effects of aging on cerebrovascular tone and [Ca2+]i","volume":"95","author":"Geary G. G.","year":"2003","journal-title":"Journal of Applied Physiology (1985)"},{"key":"e_1_2_6_39_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.niox.2019.04.007","article-title":"Site and mechanism of uncoupling of nitric\u2010oxide synthase: Uncoupling by monomerization and other misconceptions","volume":"89","author":"Gebhart V.","year":"2019","journal-title":"Nitric Oxide"},{"issue":"7","key":"e_1_2_6_40_1","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.2337\/diabetes.47.7.1114","article-title":"Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation, and oxidant\u2010induced apoptosis","volume":"47","author":"Giardino I.","year":"1998","journal-title":"Diabetes"},{"key":"e_1_2_6_41_1","first-page":"173","article-title":"Comparative anatomy of the arterial vascularization of the hippocampus in man and in experimental animals (cat, rabbit and sheep)","volume":"30","author":"Goetzen B.","year":"1992","journal-title":"Neuropatologia Polska"},{"issue":"11","key":"e_1_2_6_42_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1212\/WNL.0b013e3182a43e33","article-title":"Physical activity is related to the structural integrity of cerebral white matter","volume":"81","author":"Gons R. A.","year":"2013","journal-title":"Neurology"},{"issue":"3","key":"e_1_2_6_43_1","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.bbagen.2006.08.019","article-title":"Nitric\u2010oxide synthase: A cytochrome P450 family foster child","volume":"1770","author":"Gorren A. C.","year":"2007","journal-title":"Biochimica Et Biophysica Acta"},{"issue":"6","key":"e_1_2_6_44_1","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1152\/japplphysiol.01252.2003","article-title":"Exercise training improves aortic endothelium\u2010dependent vasorelaxation and determinants of nitric oxide bioavailability in spontaneously hypertensive rats","volume":"96","author":"Graham D. A.","year":"2004","journal-title":"Journal of Applied Physiology (1985)"},{"issue":"9","key":"e_1_2_6_45_1","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.exger.2009.06.006","article-title":"Age\u2010dependent and gender\u2010specific changes in mouse tissue iron by strain","volume":"44","author":"Hahn P.","year":"2009","journal-title":"Experimental Gerontology"},{"issue":"1","key":"e_1_2_6_46_1","first-page":"118","article-title":"The role of oxygen radicals in human disease, with particular reference to the vascular system","volume":"23","author":"Halliwell B.","year":"1993","journal-title":"Haemostasis"},{"issue":"6","key":"e_1_2_6_47_1","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1152\/japplphysiol.01296.2013","article-title":"Structural remodeling of coronary resistance arteries: Effects of age and exercise training","volume":"117","author":"Hanna M. A.","year":"2014","journal-title":"Journal of Applied Physiology (1985)"},{"key":"e_1_2_6_48_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.niox.2017.12.008","article-title":"Neuronal nitric oxide synthase regulation of skeletal muscle functional hyperemia: Exercise training and moderate compensated heart failure","volume":"74","author":"Hirai D. M.","year":"2018","journal-title":"Nitric Oxide"},{"issue":"6","key":"e_1_2_6_49_1","doi-asserted-by":"crossref","first-page":"H1559","DOI":"10.1152\/ajpheart.00129.2020","article-title":"Exercise training ameliorates cerebrovascular dysfunction in a murine model of Alzheimer's disease: Role of the P2Y2 receptor and endoplasmic reticulum stress","volume":"318","author":"Hong J.","year":"2020","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"issue":"7","key":"e_1_2_6_50_1","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/0092-8674(93)90615-W","article-title":"Targeted disruption of the neuronal nitric oxide synthase gene","volume":"75","author":"Huang P. L.","year":"1993","journal-title":"Cell"},{"issue":"5180","key":"e_1_2_6_51_1","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1126\/science.7522345","article-title":"Effects of cerebral ischemia in mice deficient in neuronal nitric oxide synthase","volume":"265","author":"Huang Z.","year":"1994","journal-title":"Science"},{"issue":"1","key":"e_1_2_6_52_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neuron.2017.07.030","article-title":"The neurovascular unit coming of age: A journey through neurovascular coupling in health and disease","volume":"96","author":"Iadecola C.","year":"2017","journal-title":"Neuron"},{"issue":"4","key":"e_1_2_6_53_1","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1152\/jappl.1999.87.4.1476","article-title":"Hindlimb unweighting decreases ecNOS gene expression and endothelium\u2010dependent dilation in rat soleus feed arteries","volume":"87","author":"Jasperse J. L.","year":"1999","journal-title":"Journal of Applied Physiology (1985)"},{"issue":"7","key":"e_1_2_6_54_1","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1016\/j.neuron.2021.02.006","article-title":"Brain microvasculature has a common topology with local differences in geometry that match metabolic load","volume":"109","author":"Ji X.","year":"2021","journal-title":"Neuron"},{"issue":"5","key":"e_1_2_6_55_1","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1161\/01.STR.10.5.572","article-title":"Cerebral vasomotor reactivity in normotensive and spontaneously hypertensive rats","volume":"10","author":"Johansson B. B.","year":"1979","journal-title":"Stroke; A Journal of Cerebral Circulation"},{"issue":"3","key":"e_1_2_6_56_1","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1161\/STROKEAHA.122.038263","article-title":"Hippocampal vascular supply and its role in vascular cognitive impairment","volume":"54","author":"Johnson A. C.","year":"2023","journal-title":"Stroke; A Journal of Cerebral Circulation"},{"issue":"4","key":"e_1_2_6_57_1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1177\/0271678X19848510","article-title":"Memory impairment in spontaneously hypertensive rats is associated with hippocampal hypoperfusion and hippocampal vascular dysfunction","volume":"40","author":"Johnson A. C.","year":"2020","journal-title":"Journal of Cerebral Blood Flow and Metabolism"},{"issue":"9","key":"e_1_2_6_58_1","doi-asserted-by":"crossref","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 R. N.","year":"2012","journal-title":"Stroke; A Journal of Cerebral Circulation"},{"issue":"6","key":"e_1_2_6_59_1","doi-asserted-by":"crossref","first-page":"H2105","DOI":"10.1152\/ajpheart.00349.2010","article-title":"Aging and estrogen alter endothelial reactivity to reactive oxygen species in coronary arterioles","volume":"300","author":"Kang L. S.","year":"2011","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"issue":"3","key":"e_1_2_6_60_1","doi-asserted-by":"crossref","first-page":"H1087","DOI":"10.1152\/ajpheart.00356.2009","article-title":"Aging impairs flow\u2010induced dilation in coronary arterioles: Role of NO and H(2)O(2)","volume":"297","author":"Kang L. S.","year":"2009","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"issue":"2","key":"e_1_2_6_61_1","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/fcp.12103","article-title":"Enhancement on reactive oxygen species and COX\u20101 mRNA levels modulate the vascular relaxation induced by sodium nitroprusside in denuded mice aorta","volume":"29","author":"Kangussu L. M.","year":"2015","journal-title":"Fundamental and Clinical Pharmacology"},{"key":"e_1_2_6_62_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2019.104601","article-title":"The pivotal role of nuclear factor erythroid 2\u2010related factor 2 in diabetes\u2010induced endothelial dysfunction","volume":"153","author":"Karan A.","year":"2020","journal-title":"Pharmacological Research"},{"issue":"7","key":"e_1_2_6_63_1","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1161\/01.STR.29.7.1311","article-title":"Changes of cerebrovascular CO2 reactivity during normal aging","volume":"29","author":"Kastrup A.","year":"1998","journal-title":"Stroke; A Journal of Cerebral Circulation"},{"issue":"4","key":"e_1_2_6_64_1","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1161\/01.RES.57.4.508","article-title":"George E. Brown memorial lecture. Oxygen radicals in cerebral vascular injury","volume":"57","author":"Kontos H. A.","year":"1985","journal-title":"Circulation Research"},{"issue":"1","key":"e_1_2_6_65_1","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: A comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov M. V.","year":"2016","journal-title":"Nucleic Acids Research"},{"issue":"8","key":"e_1_2_6_66_1","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1177\/1747493020984090","article-title":"Relation between physical activity and cerebral small vessel disease: A nine\u2010year prospective cohort study","volume":"16","author":"Landman T. R.","year":"2021","journal-title":"International Journal of Stroke"},{"issue":"1","key":"e_1_2_6_67_1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1152\/japplphysiol.00246.2002","article-title":"Short\u2010term training enhances endothelium\u2010dependent dilation of coronary arteries, not arterioles","volume":"94","author":"Laughlin M. H.","year":"2003","journal-title":"Journal of Applied Physiology (1985)"},{"issue":"6","key":"e_1_2_6_68_1","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1152\/jappl.1990.68.6.2337","article-title":"Skeletal muscle oxidative capacity, antioxidant enzymes, and exercise training","volume":"68","author":"Laughlin M. H.","year":"1990","journal-title":"Journal of Applied Physiology (1985)"},{"issue":"1","key":"e_1_2_6_69_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1748-1716.2011.02256.x","article-title":"The neurovascular unit in brain function and disease","volume":"203","author":"Lecrux C.","year":"2011","journal-title":"Acta Physiologica (Oxford)"},{"issue":"18","key":"e_1_2_6_70_1","doi-asserted-by":"crossref","first-page":"6973","DOI":"10.3390\/ijms21186973","article-title":"The role of the Nrf2 signaling in obesity and insulin resistance","volume":"21","author":"Li S.","year":"2020","journal-title":"International Journal of Molecular Sciences"},{"issue":"10","key":"e_1_2_6_71_1","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1038\/s41419-020-03137-x","article-title":"Age\u2010related cerebral small vessel disease and inflammaging","volume":"11","author":"Li T.","year":"2020","journal-title":"Cell Death, & Disease"},{"issue":"3","key":"e_1_2_6_72_1","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1161\/01.STR.28.3.526","article-title":"The canadian study of health and aging: Risk factors for vascular dementia","volume":"28","author":"Lindsay J.","year":"1997","journal-title":"Stroke; A Journal of Cerebral Circulation"},{"issue":"7","key":"e_1_2_6_73_1","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1002\/hipo.10138","article-title":"Nitric oxide synthase and arginase in the rat hippocampus and the entorhinal, perirhinal, postrhinal, and temporal cortices: Regional variations and age\u2010related changes","volume":"13","author":"Liu P.","year":"2003","journal-title":"Hippocampus"},{"issue":"3","key":"e_1_2_6_74_1","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/S0306-4522(03)00210-0","article-title":"Regional variations and age\u2010related changes in nitric oxide synthase and arginase in the sub\u2010regions of the hippocampus","volume":"119","author":"Liu P.","year":"2003","journal-title":"Neuroscience"},{"key":"e_1_2_6_75_1","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.freeradbiomed.2017.04.026","article-title":"Neurovascular\u2010neuroenergetic coupling axis in the brain: Master regulation by nitric oxide and consequences in aging and neurodegeneration","volume":"108","author":"Louren\u00e7o C. F.","year":"2017","journal-title":"Free Radical Biology and Medicine"},{"key":"e_1_2_6_76_1","doi-asserted-by":"crossref","first-page":"913","DOI":"10.3389\/fphys.2018.00913","article-title":"Age\u2010dependent impairment of neurovascular and neurometabolic coupling in the hippocampus","volume":"9","author":"Louren\u00e7o C. F.","year":"2018","journal-title":"Frontiers in Physiology"},{"issue":"12","key":"e_1_2_6_77_1","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA\u2010seq data with DESeq2","volume":"15","author":"Love M. I.","year":"2014","journal-title":"Genome Biology"},{"issue":"5","key":"e_1_2_6_78_1","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1111\/bpa.12401","article-title":"Cerebral hypoperfusion and the energy deficit in Alzheimer's disease","volume":"26","author":"Love S.","year":"2016","journal-title":"Brain Pathology"},{"key":"e_1_2_6_79_1","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.freeradbiomed.2020.08.024","article-title":"Nuclear factor (erythroid\u2010derived 2)\u2010like 2 (Nrf2) and exercise","volume":"160","author":"Mallard A. R.","year":"2020","journal-title":"Free Radical Biology and Medicine"},{"issue":"10","key":"e_1_2_6_80_1","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1001\/archneur.1992.00530340029014","article-title":"Regional cerebral oxygen consumption, blood flow, and blood volume in healthy human aging","volume":"49","author":"Marchal G.","year":"1992","journal-title":"Archives of Neurology"},{"issue":"3","key":"e_1_2_6_81_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1093\/brain\/124.3.457","article-title":"Severely impaired cerebrovascular reactivity predicts stroke and TIA risk in patients with carotid artery stenosis and occlusion","volume":"124","author":"Markus H.","year":"2001","journal-title":"Brain"},{"issue":"9","key":"e_1_2_6_82_1","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1161\/01.STR.25.9.1760","article-title":"Differential effect of three cyclooxygenase inhibitors on human cerebral blood flow velocity and carbon dioxide reactivity","volume":"25","author":"Markus H. S.","year":"1994","journal-title":"Stroke; A Journal of Cerebral Circulation"},{"key":"e_1_2_6_83_1","first-page":"e41","article-title":"2025 Heart Disease and Stroke statistics: A report of US and global data from the American Heart Association","volume":"151","author":"Martin S. S.","year":"2025","journal-title":"Circulation"},{"issue":"8","key":"e_1_2_6_84_1","doi-asserted-by":"crossref","first-page":"e347","DOI":"10.1161\/CIR.0000000000001209","article-title":"2024 Heart Disease and stroke statistics: A report of US and global data from the American Heart Association","volume":"149","author":"Martin S. S.","year":"2024","journal-title":"Circulation"},{"issue":"11","key":"e_1_2_6_85_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.0030442","article-title":"Projections of global mortality and burden of disease from 2002 to 2030","volume":"3","author":"Mathers C. D.","year":"2006","journal-title":"PLoS Medicine"},{"issue":"3","key":"e_1_2_6_86_1","doi-asserted-by":"crossref","first-page":"H1013","DOI":"10.1152\/ajpheart.00873.2010","article-title":"Exercise training normalizes impaired NOS\u2010dependent responses of cerebral arterioles in type 1 diabetic rats","volume":"300","author":"Mayhan W. G.","year":"2011","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"issue":"3","key":"e_1_2_6_87_1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1080\/10739680701641421","article-title":"Age\u2010related alterations in reactivity of cerebral arterioles: Role of oxidative stress","volume":"15","author":"Mayhan W. G.","year":"2008","journal-title":"Microcirculation"},{"key":"e_1_2_6_88_1","first-page":"H1138","article-title":"Effects of aging on responses of cerebral arterioles","volume":"258","author":"Mayhan W. G.","year":"1990","journal-title":"American Journal of Physiology"},{"key":"e_1_2_6_89_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.neuroimage.2018.07.007","article-title":"The aging brain and cerebrovascular reactivity","volume":"181","author":"McKetton L.","year":"2018","journal-title":"Neuroimage"},{"issue":"5","key":"e_1_2_6_90_1","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1152\/japplphysiol.00272.2011","article-title":"Age\u2010induced endothelial dysfunction: Is it time to redefine the \u201creactivity\u201d of reactive oxygen species?","volume":"110","author":"Muller\u2010Delp J. M.","year":"2011","journal-title":"Journal of Applied Physiology (1985)"},{"issue":"1","key":"e_1_2_6_91_1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1152\/japplphysiol.00459.2017","article-title":"Effects of age and exercise training on coronary microvascular smooth muscle phenotype and function","volume":"124","author":"Muller\u2010Delp J. M.","year":"2018","journal-title":"Journal of Applied Physiology (1985)"},{"issue":"4","key":"e_1_2_6_92_1","doi-asserted-by":"crossref","first-page":"H1662","DOI":"10.1152\/ajpheart.00004.2002","article-title":"Aging impairs endothelium\u2010dependent vasodilation in rat skeletal muscle arterioles","volume":"283","author":"Muller\u2010Delp J. M.","year":"2002","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"issue":"4749","key":"e_1_2_6_93_1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/188497a0","article-title":"Relative vascularity of certain anatomical areas of the brain and other organs of the rat","volume":"188","author":"Nair V.","year":"1960","journal-title":"Nature"},{"issue":"21","key":"e_1_2_6_94_1","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.123.029619","article-title":"Arterial stiffness and cardiorespiratory fitness impairment in the community","volume":"12","author":"Nayor M.","year":"2023","journal-title":"Journal of the American Heart Association"},{"issue":"6","key":"e_1_2_6_95_1","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1161\/01.RES.88.6.600","article-title":"Cyclooxygenase\u20101 participates in selected vasodilator responses of the cerebral circulation","volume":"88","author":"Niwa K.","year":"2001","journal-title":"Circulation Research"},{"issue":"7","key":"e_1_2_6_96_1","doi-asserted-by":"crossref","DOI":"10.1093\/gerona\/glae083","article-title":"Exercise to mitigate cerebrovascular aging: A geroscience perspective","volume":"79","author":"Norling A. M.","year":"2024","journal-title":"Journals of Gerontology. Series A, Biological Sciences and Medical Sciences"},{"issue":"3","key":"e_1_2_6_97_1","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s00401-011-0925-9","article-title":"Cerebral hypoperfusion accelerates cerebral amyloid angiopathy and promotes cortical microinfarcts","volume":"123","author":"Okamoto Y.","year":"2012","journal-title":"Acta Neuropathologica"},{"issue":"4","key":"e_1_2_6_98_1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1161\/01.STR.15.4.635","article-title":"Regional cerebral blood flow and oxygen consumption in human aging","volume":"15","author":"Pantano P.","year":"1984","journal-title":"Stroke; A Journal of Cerebral Circulation"},{"key":"e_1_2_6_99_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuroimage.2018.03.033","article-title":"Age\u2010related changes in cerebrovascular reactivity and their relationship to cognition: A four\u2010year longitudinal study","volume":"174","author":"Peng S. L.","year":"2018","journal-title":"Neuroimage"},{"issue":"7","key":"e_1_2_6_100_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3000410","article-title":"The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research","volume":"18","author":"Percie du Sert N.","year":"2020","journal-title":"Plos Biology"},{"key":"e_1_2_6_101_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/601515","article-title":"Cerebral endothelial function determined by cerebrovascular reactivity to L\u2010arginine","volume":"2014","author":"Pretnar\u2010Oblak J.","year":"2014","journal-title":"BioMed research international"},{"issue":"4","key":"e_1_2_6_102_1","doi-asserted-by":"crossref","first-page":"H478","DOI":"10.1152\/ajpheart.00586.2015","article-title":"The NRF2 knockout rat: A new animal model to study endothelial dysfunction, oxidant stress, and microvascular rarefaction","volume":"310","author":"Priestley J. R.","year":"2016","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"key":"e_1_2_6_103_1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.euroneuro.2023.08.496","article-title":"Sucrose preference test: A systematic review of protocols for the assessment of anhedonia in rodents","volume":"77","author":"Primo M. J.","year":"2023","journal-title":"European Neuropsychopharmacology"},{"issue":"3","key":"e_1_2_6_104_1","doi-asserted-by":"crossref","first-page":"H689","DOI":"10.1152\/ajpheart.00592.2023","article-title":"Impact of arterial stiffness on cerebrovascular function: A review of evidence from humans and preclincal models","volume":"326","author":"Reeve E. H.","year":"2024","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"issue":"3","key":"e_1_2_6_105_1","doi-asserted-by":"crossref","first-page":"H1516","DOI":"10.1152\/ajpheart.01045.2006","article-title":"Exercise\u2010induced brachial artery vasodilation: Role of free radicals","volume":"292","author":"Richardson R. S.","year":"2007","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"issue":"23","key":"e_1_2_6_106_1","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.123.032616","article-title":"Associations of cerebrovascular regulation and arterial stiffness with cerebral small vessel disease: A systematic review and meta\u2010analysis","volume":"12","author":"Scheuermann B. C.","year":"2023","journal-title":"Journal of the American Heart Association"},{"issue":"4","key":"e_1_2_6_107_1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1159\/000347061","article-title":"Train the vessel, gain the brain: Physical activity and vessel function and the impact on stroke prevention and outcome in cerebrovascular disease","volume":"35","author":"Schmidt W.","year":"2013","journal-title":"Cerebrovascular Diseases"},{"key":"e_1_2_6_108_1","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.brainres.2005.12.024","article-title":"New variability in cerebrovascular anatomy determines severity of hippocampal injury following forebrain ischemia in the Mongolian gerbil","volume":"1073","author":"Seal J. B.","year":"2006","journal-title":"Brain Research"},{"issue":"2","key":"e_1_2_6_109_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0304-3940(97)00912-9","article-title":"Differential expression of neuronal and endothelial nitric oxide synthase in blood vessels of the rat brain","volume":"239","author":"Seidel B.","year":"1997","journal-title":"Neuroscience Letters"},{"issue":"11","key":"e_1_2_6_110_1","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1007\/s00702-022-02546-w","article-title":"The impact of cerebral vasomotor reactivity on cerebrovascular diseases and cognitive impairment","volume":"129","author":"Sforza M.","year":"2022","journal-title":"Journal of neural transmission (Vienna, Austria: 1996)"},{"issue":"1","key":"e_1_2_6_111_1","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 K.","year":"2021","journal-title":"Nature Communications"},{"issue":"11","key":"e_1_2_6_112_1","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1161\/01.STR.0000143725.19053.60","article-title":"White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion","volume":"35","author":"Shibata M.","year":"2004","journal-title":"Stroke; A Journal of Cerebral Circulation"},{"issue":"2","key":"e_1_2_6_113_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0006-8993(02)03575-8","article-title":"Age\u2010related changes of the nitric oxide system in the rat brain","volume":"956","author":"Siles E.","year":"2002","journal-title":"Brain Research"},{"issue":"5","key":"e_1_2_6_114_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1001\/archpsyc.62.5.565","article-title":"Variability of familial risk of Alzheimer disease across the late life span","volume":"62","author":"Silverman J. M.","year":"2005","journal-title":"Archives of General Psychiatry"},{"issue":"15","key":"e_1_2_6_115_1","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.1113\/jphysiol.2009.172221","article-title":"Effects of ageing and exercise training on eNOS uncoupling in skeletal muscle resistance arterioles","volume":"587","author":"Sindler A. L.","year":"2009","journal-title":"The Journal of Physiology"},{"issue":"5","key":"e_1_2_6_116_1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1152\/japplphysiol.00341.2012","article-title":"Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles","volume":"114","author":"Sindler A. L.","year":"2013","journal-title":"Journal of applied physiology (Bethesda, Md.: 1985)"},{"issue":"8","key":"e_1_2_6_117_1","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1089\/ars.2017.7290","article-title":"The role of sirtuins in antioxidant and redox signaling","volume":"28","author":"Singh C. K.","year":"2018","journal-title":"Antioxid Redox Signaling"},{"issue":"1","key":"e_1_2_6_118_1","doi-asserted-by":"crossref","first-page":"D977","DOI":"10.1093\/nar\/gkac1010","article-title":"The NHGRI\u2010EBI GWAS Catalog: Knowledgebase and deposition resource","volume":"51","author":"Sollis E.","year":"2023","journal-title":"Nucleic Acids Research"},{"issue":"5","key":"e_1_2_6_119_1","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1093\/gerona\/glp021","article-title":"Exercise training modulates the nitric oxide synthase profile in skeletal muscle from old rats","volume":"64","author":"Song W.","year":"2009","journal-title":"Journals of Gerontology. Series A, Biological Sciences and Medical Sciences"},{"issue":"3","key":"e_1_2_6_120_1","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1113\/jphysiol.2003.060301","article-title":"Effects of ageing and exercise training on endothelium\u2010dependent vasodilatation and structure of rat skeletal muscle arterioles","volume":"556","author":"Spier S. A.","year":"2004","journal-title":"The Journal of Physiology"},{"key":"e_1_2_6_121_1","volume-title":"Methods in Enzymology","author":"Srere P.","year":"1969"},{"issue":"7","key":"e_1_2_6_122_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0102550","article-title":"Gene expression in peripheral immune cells following cardioembolic stroke is sexually dimorphic","volume":"9","author":"Stamova B.","year":"2014","journal-title":"PLoS ONE"},{"issue":"2","key":"e_1_2_6_123_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1034\/j.1600-0447.2003.02056.x","article-title":"The association between age and depression in the general population: A multivariate examination","volume":"107","author":"Stordal E.","year":"2003","journal-title":"Acta Psychiatrica Scandinavica"},{"issue":"3","key":"e_1_2_6_124_1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1161\/01.STR.15.3.413","article-title":"Cerebral autoregulation","volume":"15","author":"Strandgaard S.","year":"1984","journal-title":"Stroke; A Journal of Cerebral Circulation"},{"issue":"4","key":"e_1_2_6_125_1","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1002\/jmri.20686","article-title":"Significance of the perfusion\u2010diffusion mismatch in chronic cerebral ischemia","volume":"24","author":"Surikova I.","year":"2006","journal-title":"Journal of Magnetic Resonance Imaging"},{"issue":"25","key":"e_1_2_6_126_1","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.1161\/01.CIR.101.25.2896","article-title":"Physical activity prevents age\u2010related impairment in nitric oxide availability in elderly athletes","volume":"101","author":"Taddei S.","year":"2000","journal-title":"Circulation"},{"issue":"1","key":"e_1_2_6_127_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1046\/j.1365-201X.2003.01100.x","article-title":"Exercise training improves ageing\u2010induced decrease in eNOS expression of the aorta","volume":"178","author":"Tanabe T.","year":"2003","journal-title":"Acta Physiologica Scandinavica"},{"issue":"9","key":"e_1_2_6_128_1","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1093\/brain\/awt188","article-title":"Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer's Coordinating Centre","volume":"136","author":"Toledo J. B.","year":"2013","journal-title":"Brain"},{"issue":"4","key":"e_1_2_6_129_1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.bbrc.2016.06.010","article-title":"Effects of environmental enrichment in aged mice on anxiety\u2010like behaviors and neuronal nitric oxide synthase expression in the brain","volume":"476","author":"Tomiga Y.","year":"2016","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"e_1_2_6_130_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.neulet.2020.135083","article-title":"Effects of inosine monophosphate and exercise training on neuronal nitric oxide synthase in the mouse brain","volume":"734","author":"Tomiga Y.","year":"2020","journal-title":"Neuroscience Letters"},{"key":"e_1_2_6_131_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.niox.2017.03.002","article-title":"Exercise training rescues high fat diet\u2010induced neuronal nitric oxide synthase expression in the hippocampus and cerebral cortex of mice","volume":"66","author":"Tomiga Y.","year":"2017","journal-title":"Nitric Oxide"},{"issue":"6","key":"e_1_2_6_132_1","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/jcbfm.1994.124","article-title":"Distribution of nitric oxide synthase in the human cerebral blood vessels and brain tissues","volume":"14","author":"Tomimoto H.","year":"1994","journal-title":"Journal of Cerebral Blood Flow and Metabolism"},{"issue":"1","key":"e_1_2_6_133_1","doi-asserted-by":"crossref","first-page":"H1","DOI":"10.1152\/ajpheart.00581.2016","article-title":"Functional vascular contributions to cognitive impairment and dementia: Mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging","volume":"312","author":"Toth P.","year":"2017","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"},{"issue":"1","key":"e_1_2_6_134_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/1742-2094-7-63","article-title":"Cerebrovascular expression of proteins related to inflammation, oxidative stress and neurotoxicity is altered with aging","volume":"7","author":"Tripathy D.","year":"2010","journal-title":"Journal of neuroinflammation"},{"key":"e_1_2_6_135_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.lfs.2018.08.004","article-title":"Induction of brain Nrf2\u2010HO\u20101 pathway and antinociception after different physical training paradigms in mice","volume":"209","author":"Tutakhail A.","year":"2018","journal-title":"Life Sciences"},{"key":"e_1_2_6_136_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/230791","article-title":"Exercise training could improve age\u2010related changes in cerebral blood flow and capillary vascularity through the upregulation of VEGF and eNOS","volume":"2014","author":"Viboolvorakul S.","year":"2014","journal-title":"BioMed Research International"},{"issue":"10","key":"e_1_2_6_137_1","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.jnutbio.2012.03.005","article-title":"The Nrf2\u2010antioxidant response element pathway: a target for regulating energy metabolism","volume":"23","author":"Vomhof\u2010Dekrey E. E.","year":"2012","journal-title":"Journal of Nutritional Biochemistry"},{"issue":"9","key":"e_1_2_6_138_1","doi-asserted-by":"crossref","first-page":"e607","DOI":"10.1016\/S2666-7568(22)00167-2","article-title":"Life course, genetic, and neuropathological associations with brain age in the 1946 British Birth Cohort: a population\u2010based study","volume":"3","author":"Wagen A. Z.","year":"2022","journal-title":"The lancet\u2010Healthy longevity"},{"issue":"2","key":"e_1_2_6_139_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1161\/01.HYP.16.2.162","article-title":"H2O2 and endothelium\u2010dependent cerebral arteriolar dilation. Implications for the identity of endothelium\u2010derived relaxing factor generated by acetylcholine","volume":"16","author":"Wei E. P.","year":"1990","journal-title":"Hypertension"},{"key":"e_1_2_6_140_1","first-page":"H1262","article-title":"Mechanisms of cerebral vasodilation by superoxide, hydrogen peroxide, and peroxynitrite","volume":"271","author":"Wei E. P.","year":"1996","journal-title":"American Journal of Physiology"},{"key":"e_1_2_6_141_1","volume-title":"Global Status Report on the Public Health Response to Dementia","author":"WHO","year":"2021"},{"issue":"5","key":"e_1_2_6_142_1","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1113\/jphysiol.2013.268953","article-title":"Integrative regulation of human brain blood flow","volume":"592","author":"Willie C. K.","year":"2014","journal-title":"The Journal of Physiology"},{"issue":"4","key":"e_1_2_6_143_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s002130050456","article-title":"Validity, reliability and utility of the chronic mild stress model of depression: A 10\u2010year review and evaluation","volume":"134","author":"Willner P.","year":"1997","journal-title":"Psychopharmacology"},{"issue":"12","key":"e_1_2_6_144_1","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1212\/WNL.0b013e3181f39adc","article-title":"Neurodegenerative basis of age\u2010related cognitive decline","volume":"75","author":"Wilson R. S.","year":"2010","journal-title":"Neurology"},{"issue":"1","key":"e_1_2_6_145_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.14219\/jada.archive.1985.0292","article-title":"An oral disease prevention program for patients receiving radiation and chemotherapy","volume":"110","author":"Wright W. E.","year":"1985","journal-title":"Journal of the American Dental Association"},{"issue":"4","key":"e_1_2_6_146_1","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1161\/01.STR.8.4.456","article-title":"Developmental course of hypertension and regional cerebral blood flow in stroke\u2010prone spontaneously hypertensive rats","volume":"8","author":"Yamori Y.","year":"1977","journal-title":"Stroke; A Journal of Cerebral Circulation"},{"issue":"2","key":"e_1_2_6_147_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/BF02256026","article-title":"Chronic exercise increases both inducible and endothelial nitric oxide synthase gene expression in endothelial cells of rat aorta","volume":"9","author":"Yang A. L.","year":"2002","journal-title":"Journal of Biomedical Science"},{"issue":"12","key":"e_1_2_6_148_1","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1161\/01.STR.0000189997.84161.95","article-title":"The effect of superoxide anion on autoregulation of cerebral blood flow","volume":"36","author":"Zagorac D.","year":"2005","journal-title":"Stroke; A Journal of Cerebral Circulation"},{"issue":"1","key":"e_1_2_6_149_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1159\/000107376","article-title":"Oxidative stress, endothelial dysfunction and cerebrovascular disease","volume":"24","author":"Zalba G.","year":"2007","journal-title":"Cerebrovascular Diseases"},{"issue":"6","key":"e_1_2_6_150_1","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/s41440-018-0033-5","article-title":"Inhibition of endothelial nitric oxide synthase reverses the effect of exercise on improving cognitive function in hypertensive rats","volume":"41","author":"Zhang L.","year":"2018","journal-title":"Hypertension Research"},{"issue":"6","key":"e_1_2_6_151_1","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1093\/nsr\/nwz124","article-title":"High\u2010resolution mapping of brain vasculature and its impairment in the hippocampus of Alzheimer's disease mice","volume":"6","author":"Zhang X.","year":"2019","journal-title":"National Science Review"},{"issue":"5","key":"e_1_2_6_152_1","doi-asserted-by":"crossref","first-page":"H2332","DOI":"10.1152\/ajpheart.00473.2004","article-title":"Exercise training improves endogenous nitric oxide mechanisms within the paraventricular nucleus in rats with heart failure","volume":"288","author":"Zheng H.","year":"2005","journal-title":"American Journal of Physiology\u2010Heart and Circulatory Physiology"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP288866","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T11:57:27Z","timestamp":1754481447000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP288866"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,6]]},"references-count":151,"alternative-id":["10.1113\/JP288866"],"URL":"https:\/\/doi.org\/10.1113\/jp288866","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,6]]},"assertion":[{"value":"2025-03-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"JP288866"}}