{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T09:16:08Z","timestamp":1778318168358,"version":"3.51.4"},"reference-count":32,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1]]},"abstract":"\n OBJECTIVE<\/jats:title>\n \n Convection-enhanced delivery (CED) and osmotic pump delivery both have been promoted as promising techniques to deliver drugs to pediatric diffuse intrinsic pontine gliomas (DIPGs). Correspondingly, the aim of this study was to understand how infusate molecular weight (MW), duration of delivery, and mechanism of delivery (CED or osmotic pump) affect volume of distribution (V\n d<\/jats:sub>\n ) in the brainstem, to better inform drug selection and delivery in future DIPG investigations.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n A series of in vivo experiments were conducted using rat models. CED and osmotic pump delivery systems were surgically implanted in the brainstem, and different MW fluorescent dextran beads were infused either once (acute) or daily for 5 days (chronic) in a volume infused (V\n i<\/jats:sub>\n ). Brainstems were harvested after the last infusion, and V\n d<\/jats:sub>\n was quantified using serial sectioning and fluorescence imaging.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Fluorescence imaging showed infusate uptake within the brainstem for both systems without complication. A significant inverse relationship was observed between infusate MW and V\n d<\/jats:sub>\n in all settings, which was distinctly exponential in nature in the setting of acute delivery across the 570-Da to 150-kDa range. Chronic duration and CED technique resulted in significantly greater V\n d<\/jats:sub>\n compared to acute duration or osmotic pump delivery, respectively. When accounting for V\n i<\/jats:sub>\n , acute infusion yielded significantly greater V\n d<\/jats:sub>\n \/V\n i<\/jats:sub>\n than chronic infusion. The distribution in CED versus osmotic pump delivery was significantly affected by infusate MW at higher weights.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n \n Here the authors demonstrate that infusate MW, duration of infusion, and infusion mechanism all impact the V\n d<\/jats:sub>\n of an infused agent and should be considered when selecting drugs and infusion parameters for novel investigations to treat DIPGs.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3171\/2019.10.focus19703","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T18:29:41Z","timestamp":1578076181000},"page":"E2","source":"Crossref","is-referenced-by-count":25,"title":["Evaluating infusate parameters for direct drug delivery to the brainstem: a comparative study of convection-enhanced delivery versus osmotic pump delivery"],"prefix":"10.3171","volume":"48","author":[{"given":"Julian S.","family":"Rechberger","sequence":"first","affiliation":[{"name":"Department of Neurologic Surgery, Mayo Clinic;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica A.","family":"Power","sequence":"additional","affiliation":[{"name":"Department of Neurologic Surgery, Mayo Clinic;"},{"name":"Mayo Clinic Graduate School of Biomedical Sciences;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor M.","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurologic Surgery, Mayo Clinic;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurologic Surgery, Mayo Clinic;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jann N.","family":"Sarkaria","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Daniels","sequence":"additional","affiliation":[{"name":"Department of Neurologic Surgery, Mayo Clinic;"},{"name":"Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1754","reference":[{"key":"b1","series-title":"Nat Rev Neurosci","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nrn1824","article-title":"Astrocyte-endothelial interactions at the blood-brain barrier","volume":"7","author":"Abbott NJ","year":"2006","unstructured":"Abbott NJ, R\u00f6nnb\u00e4ck L, Hansson E: Astrocyte-endothelial interactions at the blood-brain barrier. 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