{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:22:56Z","timestamp":1790126576019,"version":"4.0.1"},"reference-count":58,"publisher":"Frontiers Media SA","funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["11\/14395-1"],"award-info":[{"award-number":["11\/14395-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["11\/51410-9"],"award-info":[{"award-number":["11\/51410-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["15\/24935-4"],"award-info":[{"award-number":["15\/24935-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["304060\/2011-9"],"award-info":[{"award-number":["304060\/2011-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["305940\/2015-5"],"award-info":[{"award-number":["305940\/2015-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"DOI":"10.3389\/fphys.2017.01048","type":"journal-article","created":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T07:56:06Z","timestamp":1513065366000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":61,"title":["Maintenance of Blood-Brain Barrier Integrity in Hypertension: A Novel Benefit of Exercise Training for Autonomic Control"],"prefix":"10.3389","volume":"8","author":[{"given":"Leila","family":"Buttler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria T.","family":"Jord\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus G.","family":"Fragas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Ruggeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Ceroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisete C.","family":"Michelini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2017,12,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1007\/s00395-011-0231-7","article-title":"Chronic exercise modulates RAS components and improves balance between pro-and anti-inflammatory cytokines in the brain of SHR","volume":"106","author":"Agarwal","year":"2011","journal-title":"Basic Res. Cardiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1159\/000098260","article-title":"Time course of hyperosmolar opening of the blood-brain and blood-CSF barriers in spontaneously hypertensive rats","volume":"44","author":"Al-Sarraf","year":"2007","journal-title":"J. Vasc. Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1081\/CEH-120023545","article-title":"Arterial hypertension and brain damage\u2013evidence from animal models (review)","volume":"25","author":"Amenta","year":"2003","journal-title":"Clin. Exp. Hypertens."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1113\/JP271584","article-title":"Compromised blood-brain barrier permeability: novel mechanism by which circulating angiotensin II signals to sympathoexcitatory centres during hypertension","volume":"594","author":"Biancardi","year":"2016","journal-title":"J. Physiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1161\/HYPERTENSIONAHA.113.01743","article-title":"Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier","volume":"63","author":"Biancardi","year":"2014","journal-title":"Hypertension"},{"key":"B6","doi-asserted-by":"publisher","first-page":"H404","DOI":"10.1152\/ajpheart.00247.2015","article-title":"Cross talk between AT1 receptors and Toll-like receptor 4 in microglia contributes to angiotensin II-derived ROS production in the hypothalamic paraventricular nucleus","volume":"310","author":"Biancardi","year":"2016","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"H397","DOI":"10.1152\/ajpheart.00679.2010","article-title":"The cerebrovascular dysfunction induced by slow pressor doses of angiotensin II precedes the development of hypertension","volume":"300","author":"Capone","year":"2011","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"R958","DOI":"10.1152\/ajpregu.00104.2011","article-title":"Afferent signaling drives oxytocinergic preautonomic neurons and mediates training-induced plasticity","volume":"301","author":"Cavalleri","year":"2011","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1113\/expphysiol.2008.046128","article-title":"Chronic absence of baroreceptor inputs prevents training-induced cardiovascular adjustments in normotensive and spontaneously hypertensive rats","volume":"94","author":"Ceroni","year":"2009","journal-title":"Exp. Physiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e0137395","DOI":"10.1371\/journal.pone.0137395","article-title":"Early training-induced reduction of angiotensinogen in autonomic areas-the main effect of exercise on brain renin-angiotensin system in hypertensive rats","volume":"10","author":"Chaar","year":"2015","journal-title":"PLoS ONE"},{"key":"B11","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.brainres.2015.05.026","article-title":"Physical training improves non-spatial memory, locomotor skills and the blood brain barrier in diabetic rats","volume":"1618","author":"de Senna","year":"2015","journal-title":"Brain Res."},{"key":"B12","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0031-6997(24)01320-6","article-title":"The blood-brain barrier in neuroinflammatory diseases","volume":"49","author":"de Vries","year":"1997","journal-title":"Pharmacol. Rev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e50326","DOI":"10.3791\/50326","article-title":"Direct intraventricular delivery of drugs to the rodent central nervous system","volume":"12","author":"DeVos","year":"2013","journal-title":"J. Vis. Exp."},{"key":"B14","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1179\/016164106X98053","article-title":"Exercise pre-conditioning strengthens brain microvascular integrity in a rat stroke model","volume":"28","author":"Ding","year":"2006","journal-title":"Neurol. Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"3224","DOI":"10.1161\/01.CIR.96.9.3224","article-title":"Sympathovagal balance: a critical appraisal","volume":"96","author":"Eckberg","year":"1997","journal-title":"Circulation"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1038\/jcbfm.2013.135","article-title":"Blood-brain barrier dysfunction as a cause and consequence of Alzheimer's disease","volume":"33","author":"Erickson","year":"2013","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B17","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1161\/HYPERTENSIONAHA.113.01063","article-title":"Hypertension: a harbinger of stroke and dementia","volume":"62","author":"Faraco","year":"2013","journal-title":"Hypertension"},{"key":"B18","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1161\/HYPERTENSIONAHA.107.094474","article-title":"Training-induced pressure fall in spontaneously hypertensive rats is associated with reduced angiotensinogen mRNA expression within the nucleus tractus solitarii","volume":"50","author":"Felix","year":"2007","journal-title":"Hypertension"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3095","DOI":"10.1161\/CIRCULATIONAHA.106.677989","article-title":"Exercise training normalizes sympathetic outflow by central antioxidant mechanisms in rabbits with pacing-induced chronic heart failure","volume":"115","author":"Gao","year":"2007","journal-title":"Circulation"},{"key":"B20","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.semcdb.2014.12.006","article-title":"The molecular, cellular, and morphological components of blood-brain barrier development during embryogenesis","volume":"38","author":"Hagan","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"R1717","DOI":"10.1152\/ajpregu.00613.2006","article-title":"Exercise training-induced remodeling of paraventricular nucleus (nor)adrenergic innervation in normotensive and hypertensive rats","volume":"292","author":"Higa-Taniguchi","year":"2007","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/j.neuron.2014.12.056","article-title":"Dangerous leaks: blood-brain barrier woes in the aging hippocampus","volume":"85","author":"Iadecola","year":"2015","journal-title":"Neuron"},{"key":"B23","doi-asserted-by":"publisher","first-page":"6241","DOI":"10.1113\/JP272730","article-title":"Exercise training preserves vagal preganglionic neurones and restores parasympathetic tonus in heart failure","volume":"594","author":"Ichige","year":"2016","journal-title":"J. Physiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1001\/jama.2013.284427","article-title":"2014 Evidence-Based guideline for the management of high blood pressure in adults: report from the panel members appointed to the eighth joint national committee (JNC 8)","volume":"311","author":"James","year":"2014","journal-title":"JAMA"},{"key":"B25","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/0165-1838(90)90132-3","article-title":"Spectral analysis of blood pressure and heart rate in conscious rats: effects of autonomic blockers","volume":"30","author":"Japundzic","year":"1990","journal-title":"J. Auton. Nerv. Syst."},{"key":"B26","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1093\/cvr\/cvp073","article-title":"Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin II-induced hypertension","volume":"82","author":"Kang","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e56419","DOI":"10.1371\/journal.pone.0056419","article-title":"Blood-brain barrier breakdown after embolic stroke in rats occurs without ultrastructural evidence for disrupting tight junctions","volume":"8","author":"Krueger","year":"2013","journal-title":"PLoS ONE"},{"key":"B28","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/S0024-3205(02)01772-1","article-title":"Effects of losartan on the blood-brain barrier permeability in long-term nitric oxide blockade-induced hypertensive rats","volume":"71","author":"Kucuk","year":"2002","journal-title":"Life Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"R226","DOI":"10.1152\/ajpregu.00709.2002","article-title":"Comparison of various techniques used to estimate spontaneous baroreflex sensitivity (the EuroBaVar study)","volume":"286","author":"Laude","year":"2004","journal-title":"Am. J. Physiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/S0006-8993(00)02228-9","article-title":"Quantitative assessment of the normal cerebral microvasculature by endothelial barrier antigen (EBA) immunohistochemistry: application to focal cerebral ischemia","volume":"865","author":"Lin","year":"2000","journal-title":"Brain Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1038\/ijo.2017.57","article-title":"Antihypertensive agents do not prevent blood-brain barrier dysfunction and cognitive deficits in dietary-induced obese mice","volume":"41","author":"Mamo","year":"2017","journal-title":"Int. J. Obes."},{"key":"B32","doi-asserted-by":"publisher","first-page":"H1005","DOI":"10.1152\/ajpheart.00361.2014","article-title":"The low frequency power of heart rate variability is neither a measure of cardiac sympathetic tone nor of baroreflex sensitivity","volume":"307","author":"Martelli","year":"2014","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e94927","DOI":"10.1371\/journal.pone.0094927","article-title":"Time-dependent effects of training on cardiovascular control in spontaneously hypertensive rats: role for brain oxidative stress and inflammation and baroreflex sensitivity","volume":"9","author":"Masson","year":"2014","journal-title":"PLoS ONE"},{"key":"B34","doi-asserted-by":"publisher","first-page":"H1115","DOI":"10.1152\/ajpheart.00349.2015","article-title":"Aerobic training normalizes autonomic dysfunction, HMGB1 content, microglia activation and inflammation in hypothalamic paraventricular nucleus of SHR","volume":"309","author":"Masson","year":"2015","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1016\/j.prp.2014.05.007","article-title":"Acute hypertension induces brain injury and blood\u2013brain barrier disruption through reduction of claudins mRNA expression in rat","volume":"210","author":"Mohammadi","year":"2014","journal-title":"Pathol. Res. Pract."},{"key":"B36","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1161\/01.HYP.2.6.809","article-title":"Effect of chronic hypertension on the blood-brain barrier","volume":"2","author":"Mueller","year":"1980","journal-title":"Hypertension"},{"key":"B37","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.jchemneu.2008.06.002","article-title":"Protein components of the blood-brain barrier (BBB) in the mediobasal hypothalamus","volume":"36","author":"Norsted","year":"2008","journal-title":"J. Chem. Neuroanat."},{"key":"B38","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1161\/01.HYP.0000256955.74461.93","article-title":"Exercise training prevents arterial baroreflex dysfunction in rats treated with central angiotensin II","volume":"49","author":"Pan","year":"2007","journal-title":"Hypertension"},{"key":"B39","volume-title":"The Rat Brain in Stereotaxic Coordinates, 6th Edn","author":"Paxinos","year":"2007"},{"key":"B40","doi-asserted-by":"publisher","first-page":"93","DOI":"10.2174\/15734021113099990003","article-title":"RAS inhibition attenuates cognitive impairment by reducing blood- brain barrier permeability in hypertensive subjects","volume":"9","author":"Pelisch","year":"2013","journal-title":"Curr. Hypertens. Rev."},{"key":"B41","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1038\/ajh.2010.241","article-title":"Blockade of AT1 receptors protects the blood-brain barrier and improves cognition in Dahl salt-sensitive hypertensive rats","volume":"24","author":"Pelisch","year":"2011","journal-title":"Am. J. Hypertens."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1038\/jcbfm.2011.197","article-title":"Neurological diseases in relation to the blood\u2013brain barrier","volume":"32","author":"Rosenberg","year":"2012","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B43","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1161\/01.HYP.0000112030.79692.21","article-title":"Endogenous angiotensin and pressure modulate brain angiotensinogen and AT1A mRNA expression","volume":"43","author":"Sangaleti","year":"2004","journal-title":"Hypertension"},{"key":"B44","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.semcdb.2014.10.004","article-title":"The blood-brain barrier-gatekeeper to neuronal homeostasis: clinical implications in the setting of stroke","volume":"38","author":"Schoknecht","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1161\/HYPERTENSIONAHA.110.150409","article-title":"Brain microglial cytokines in neurogenic hypertension","volume":"56","author":"Shi","year":"2010","journal-title":"Hypertension"},{"key":"B46","doi-asserted-by":"publisher","first-page":"4723","DOI":"10.1007\/s12035-016-0014-0","article-title":"Physical exercise attenuates experimental autoimmune encephalomyelitis by inhibiting peripheral immune response and blood-brain barrier disruption","volume":"54","author":"Souza","year":"2016","journal-title":"Mol. Neurobiol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s12868-015-0165-3","article-title":"Hydrogen improves neurological function through attenuation of blood-brain barrier disruption in spontaneously hypertensive stroke-prone rats","volume":"16","author":"Takeuchi","year":"2015","journal-title":"BMC Neurosci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1161\/01.HYP.6.5.633","article-title":"Increased susceptibility to osmotic disruption of the blood-brain barrier in chronic hypertension","volume":"6","author":"Tamaki","year":"1984","journal-title":"Hypertension"},{"key":"B49","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1093\/oxfordjournals.eurheartj.a014868","article-title":"Heart rate variability standards of measurements, physiological interpretation and clinical use","volume":"17","year":"1996","journal-title":"Eur. Heart J."},{"key":"B50","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1111\/j.1365-2990.2008.00966.x","article-title":"The expression of P-glycoprotein is increased in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model","volume":"35","author":"Ueno","year":"2009","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1007\/s00401-004-0845-z","article-title":"Blood-brain barrier is impaired in the hippocampus of young adult spontaneously hypertensive rats","volume":"107","author":"Ueno","year":"2004","journal-title":"Acta Neuropathol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.resp.2011.05.004","article-title":"Contributions of vascular inflammation in the brainstem for neurogenic hypertension","volume":"178","author":"Waki","year":"2011","journal-title":"Respir. Physiol. Neurobiol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.neuroscience.2014.04.030","article-title":"Physical exercise training and neurovascular unit in ischemic stroke","volume":"271","author":"Wang","year":"2014","journal-title":"Neuroscience"},{"key":"B54","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.neuroscience.2013.04.023","article-title":"Intra-carotid angiotensin II activates tyrosine hydroxylase-expressing rostral ventrolateral medulla neurons following blood-brain barrier disruption in rats","volume":"245","author":"Yao","year":"2013","journal-title":"Neuroscience"},{"key":"B55","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1016\/j.neuroscience.2010.09.029","article-title":"Angiotensin II induced cerebral microvascular inflammation and increased blood-brain barrier permeability via oxidative stress","volume":"171","author":"Zhang","year":"2010","journal-title":"Neuroscience"},{"key":"B56","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.intimp.2015.05.024","article-title":"Apigenin protects blood-brain barrier and ameliorates early brain injury by inhibiting TLR4-mediated inflammatory pathway in subarachnoid hemorrhage rats","volume":"28","author":"Zhang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"11096","DOI":"10.3390\/ijms140611096","article-title":"Early exercise protects the blood-brain barrier from ischemic brain injury via the regulation of MMP-9 and Occludin in Rats","volume":"14","author":"Zhang","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1161\/HYPERTENSIONAHA.111.169748","article-title":"Autonomic-immune-vascular interaction: an emerging concept for neurogenic hypertension","volume":"57","author":"Zubcevic","year":"2011","journal-title":"Hypertension"}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fphys.2017.01048\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T10:31:36Z","timestamp":1751106696000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fphys.2017.01048\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,12]]},"references-count":58,"alternative-id":["10.3389\/fphys.2017.01048"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2017.01048","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,12]]},"article-number":"1048"}}