{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T07:29:51Z","timestamp":1768289391395,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,2,15]],"date-time":"2013-02-15T00:00:00Z","timestamp":1360886400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Niemann\u2010Pick type C disease is an inherited autosomal recessive neurodegenerative disorder characterised by the accumulation of unesterified cholesterol and sphingolipids within the endosomal\/lysosomal compartments. It has been observed that the administration of hydroxypropyl\u2010\u03b2\u2010cyclodextrin (HPBCD) delays onset of clinical symptoms and reduces accumulation of cholesterol and gangliosides within neuronal cells. It was assumed that HPBCD exerts its action by readily entering the CNS and directly interacting with neurones and other brain cells to facilitate removal of stored cholesterol from the late endosomal\/lysosomal compartment. Here, we present evidence that refutes this hypothesis. We use two well established techniques for accurately measuring brain uptake of solutes from blood and show that there is no significant crossing of HPBCD into the brain. The two techniques are brain in situ perfusion and intraperitoneal injection followed by multi\u2010time\u2010point regression analysis. Neither study demonstrates significant, time\u2010dependent uptake of HPBCD in either adult or neonatal mice. However, the volume of distribution available to HPBCD (0.113\u2009\u00b1\u20090.010 ml\/g) exceeds the accepted values for plasma and vascular volume of the brain. In fact, it is nearly three times larger than that for sucrose (0.039\u2009\u00b1\u20090.006 ml\/g). We propose that this indicates cell surface binding of HPBCD to the endothelium of the cerebral vasculature and may provide a mechanism for the mobilisation and clearance of cholesterol from the CNS.<\/jats:p>","DOI":"10.1007\/s10545-012-9583-x","type":"journal-article","created":{"date-parts":[[2013,2,14]],"date-time":"2013-02-14T13:47:06Z","timestamp":1360849626000},"page":"491-498","source":"Crossref","is-referenced-by-count":74,"title":["Cyclodextrin alleviates neuronal storage of cholesterol in Niemann\u2010Pick C disease without evidence of detectable blood\u2013brain barrier permeability"],"prefix":"10.1002","volume":"36","author":[{"given":"Charles C.","family":"Pontikis","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Science, Blood\u2013brain Barrier Group Kings College London Franklin\u2010Wilkins Building, 150, Stamford Street London SE1 9NH UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristin D.","family":"Davidson","sequence":"additional","affiliation":[{"name":"Dominick D. Purpura Department of Neuroscience, Rose F Kennedy Intellectual and Developmental Disabilities Research Center Albert Einstein College of Medicine Bronx NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven U.","family":"Walkley","sequence":"additional","affiliation":[{"name":"Dominick D. Purpura Department of Neuroscience, Rose F Kennedy Intellectual and Developmental Disabilities Research Center Albert Einstein College of Medicine Bronx NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frances M.","family":"Platt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford Mansfield Road Oxford OX1 3QT UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Begley","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Science, Blood\u2013brain Barrier Group Kings College London Franklin\u2010Wilkins Building, 150, Stamford Street London SE1 9NH UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,2,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1317-11.2011"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119223"},{"key":"e_1_2_8_4_1","first-page":"91","volume-title":"Brain barrier systems. 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