{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:12:03Z","timestamp":1777396323877,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T00:00:00Z","timestamp":1537315200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2018,10,16]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Cerebral hypoperfusion and degeneration of the noradrenergic locus coeruleus (LC) occur early in Alzheimer\u2019s disease (AD). Cerebral blood vessels are densely innervated by noradrenergic projections from the LC suggesting a functional role for the regulation of cerebral blood flow (CBF). Experimental LC stimulation, however, has provided no clarity as decreases or increases in CBF were reported from different experimental settings and investigators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To find out with pharmacological methods whether endogenously released norepinephrine (NE) increases or decreases carotid artery blood flow (CABF) in anesthetized pigs by investigating the effect of centrally acting alpha-2 adrenergic drugs, which increase (atipamezole) or decrease (xylazine) NE in the brain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>CABF was measured by a Doppler-flow probe placed around the left carotid artery in pentobarbital anesthetized young pigs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Neither current antihypertensive drugs nor pharmacological stimulation of dopamine, histamine, serotonin or acetylcholine receptors changed CABF. The alpha-2 adrenergic-receptor agonist xylazine decreased, while the antagonist atipamezole raised CABF. This rise was abolished by a combined treatment with endothelial NO-synthase inhibitor N\n                      <jats:italic>\u03c9<\/jats:italic>\n                      -Nitro-L-arginine methyl ester (L-NAME) and the non-selective \u03b2-receptor antagonist propranolol. Propranolol alone did not decrease CABF in contrast to L-NAME but decreased CABF after L-NAME, surprisingly.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Pharmacological evidence suggests that NE released in the brain of anesthetized pigs raises CABF involving \u03b2-adrenergic mechanisms and nitric oxide. If in awake humans NE released from the LC had vasodilator effects early LC degeneration could be involved in early cerebral hypoperfusion of AD. Moreover, a cerebral adrenergic vascular innervation deficit, possibly resulting from LC degeneration, and systemic endothelial dysfunction together may act synergistically to reduce CBF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-180340","type":"journal-article","created":{"date-parts":[[2018,9,21]],"date-time":"2018-09-21T13:43:54Z","timestamp":1537537434000},"page":"407-419","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Role of Noradrenergic Brain Nuclei in the Regulation of Carotid Artery Blood Flow: Pharmacological Evidence from Anesthetized Pigs with Alpha-2 Adrenergic Receptor Modulator Drugs"],"prefix":"10.1177","volume":"66","author":[{"given":"Klaus J.","family":"Wirth","sequence":"first","affiliation":[{"name":"Sanofi-Aventis Deutschland GmbH, R&amp;D TA Immunology, Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,9,19]]},"reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(03)00143-7"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(81)90031-9"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2006.02.007"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318232a379"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12289"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-142682"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13447"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00220"},{"key":"e_1_3_1_10_2","first-page":"1155","article-title":"Longitudinal evaluation of early Alzheimer\u2019s disease using brain perfusion","volume":"41","author":"Kogure D","year":"2000","unstructured":"KogureD, MatsudaH, OhnishiT, AsadaT, UnoM, KunihiroT, NakanoS, TakasakiM (2000) Longitudinal evaluation of early Alzheimer\u2019s disease using brain perfusion. SPECT J Nucl Med 41, 1155\u20131162.","journal-title":"SPECT J Nucl Med"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02988596"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00137-8"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhs381"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-015-0261-z"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.027448"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-2012-120793"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-015-0308-1"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.48"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2015.08.014"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.1993.11740127"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb05572.x"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00068-X"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(89)90164-X"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2017.12.027."},{"key":"e_1_3_1_25_2","first-page":"367","article-title":"Alterations in adrenergic receptors of frontal cortex and cerebral microvessels in Alzheimer\u2019s disease and aging","volume":"317","author":"Kalaria RN","year":"1989","unstructured":"KalariaRN, AndornAC, HarikSI (1989) Alterations in adrenergic receptors of frontal cortex and cerebral microvessels in Alzheimer\u2019s disease and aging. Prog Clin Biol Res 317, 367\u2013374.","journal-title":"Prog Clin Biol Res"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3346-12.2013"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(76)90096-8"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(89)91537-0"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.9.3726"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-012-0278-3"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.2344\/0003-3006-62.1.31"},{"issue":"7","key":"e_1_3_1_32_2","first-page":"1149","article-title":"Effect of cilostazol, a new antithrombotic drug, on cerebral circulation","volume":"35","author":"Kawamura K","year":"1985","unstructured":"KawamuraK, WatanabeK, KimuraY (1985) Effect of cilostazol, a new antithrombotic drug, on cerebral circulation. Arzneimittelforschung 35(7A), 1149\u20131154.","journal-title":"Arzneimittelforschung"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1447-0594.2012.00866.x"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2010.551431"},{"key":"e_1_3_1_35_2","first-page":"615","article-title":"An overview of the influence of anesthesia on cerebral blood flow and cerebral metabolism","volume":"59","author":"Van Aken H","year":"1993","unstructured":"Van Aken H, Van Hemelrijck J (1993) An overview of the influence of anesthesia on cerebral blood flow and cerebral metabolism. Minerva Anestesiol 59, 615\u2013620.","journal-title":"Minerva Anestesiol"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00321"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2007.038588"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1097\/ACO.0b013e32833020be"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.115"},{"key":"e_1_3_1_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-017-2059-y"},{"key":"e_1_3_1_41_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-16-0423"}],"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-180340","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JAD-180340","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-180340","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:08:07Z","timestamp":1777370887000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-180340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,19]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,10,16]]}},"alternative-id":["10.3233\/JAD-180340"],"URL":"https:\/\/doi.org\/10.3233\/jad-180340","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,19]]}}}