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Vasodilatory lowering of blood pressure\u00a0has been shown to result in an increase of intracranial pressure, which, in normal circumstances should return to equilibrium by increased fluid efflux. In this study, we investigated the effect of blood pressure lowering on fluorescent cerebrospinal fluid tracer absorption into the systemic blood circulation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Blood pressure lowering\u00a0was performed by an i.v. administration of nitric oxide donor (sodium nitroprusside, 5\u00a0\u00b5g\u00a0kg<jats:sup>\u22121<\/jats:sup>\u00a0min<jats:sup>\u22121<\/jats:sup>) or the Ca<jats:sup>2+<\/jats:sup>-channel blocker (nicardipine hydrochloride,\u00a00.5\u00a0\u00b5g\u00a0kg<jats:sup>\u22121<\/jats:sup>\u00a0min<jats:sup>\u22121<\/jats:sup>) for 10, and 15 to 40\u00a0min, respectively. The effect of \ufeffblood pressure lowering on cerebrospinal fluid clearance was investigated by measuring the efflux of fluorescent tracers (40\u00a0kDa FITC-dextran, 45\u00a0kDa Texas Red-conjugated ovalbumin) into blood and deep cervical lymph nodes. The effect of nicardipine on cerebral hemodynamics was investigated by near-infrared spectroscopy. The distribution of cerebrospinal fluid tracers (40\u00a0kDa horse radish peroxidase,160\u00a0kDa nanogold-conjugated IgG) in exit pathways was also analyzed at an ultrastructural level using electron microscopy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Nicardipine and sodium nitroprusside reduced blood pressure by 32.0\u2009\u00b1\u200919.6% and 24.0\u2009\u00b1\u200913.3%, while temporarily elevating intracranial pressure by 14.0\u2009\u00b1\u20097.0% and 18.2\u2009\u00b1\u200915.0%, respectively. Blood pressure lowering\u00a0significantly increased tracer accumulation into dorsal dura, deep cervical lymph nodes and systemic circulation, but reduced perivascular inflow along penetrating arteries in the brain. The enhanced tracer efflux by blood pressure lowering into the systemic circulation was markedly reduced (\u2212\u00a066.7%) by ligation of lymphatic vessels draining into\u00a0deep cervical lymph nodes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This is the first study showing that\u00a0cerebrospinal fluid clearance can be improved with acute hypotensive treatment and that the effect of the treatment is reduced by ligation of a lymphatic drainage pathway. Enhanced cerebrospinal fluid clearance by blood pressure lowering\u00a0may have therapeutic potential in diseases with dysregulated cerebrospinal fluid\u00a0 flow.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12987-024-00509-9","type":"journal-article","created":{"date-parts":[[2024,1,26]],"date-time":"2024-01-26T16:01:58Z","timestamp":1706284918000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Blood pressure lowering enhances cerebrospinal fluid efflux to the systemic circulation primarily via the lymphatic vasculature"],"prefix":"10.1186","volume":"21","author":[{"given":"Jari","family":"Jukkola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Kaakinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadegh","family":"Moradi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hany","family":"Ferdinando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teemu","family":"Myllyl\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesa","family":"Kiviniemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauri","family":"Eklund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,26]]},"reference":[{"key":"509_CR1","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1086\/394447","volume":"8","author":"LB Flexner","year":"1933","unstructured":"Flexner LB. 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