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Article: Intracerebral clysis in a rat glioma model

TitleIntracerebral clysis in a rat glioma model
Authors
Issue Date2000
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.neurosurgery-online.com
Citation
Neurosurgery, 2000, v. 46 n. 3, p. 683-691 How to Cite?
AbstractOBJECTIVE: Intracerebral clysis (ICC) is a new term we use to describe convection-enhanced microinfusion into the brain. This study establishes baseline parameters for preclinical, in vivo, drug investigations using ICC in a rat glioma model. METHODS: Intracranial pressure was measured, with an intraparenchymal fiber-optic catheter, in male Fischer rats 10, 15, 20, and 25 days after implantation of C6 glioma cells in the right frontal lobe (n = 80) and in control rats without tumor (n = 20), before and during ICC. A 25% albumin solution (100 μl) was infused through an intratumoral catheter at 0.5, 1.0, 2.0, 3.0, and 4.0 μl/min. Infusate distribution was assessed by infusion of fluorescein isothiocyanate-dextran (M(r) 20,000), using the aforementioned parameters (n = 36). Brains were sectioned and photographed under ultraviolet light, and distribution was calculated by computer analysis (NIH Image for Macintosh). Safe effective drug distribution was demonstrated by measuring tumor sizes and apoptosis in animals treated with N,N'-bis(2- chloroethyl)-N-nitrosourea via ICC, compared with untreated controls. Magnetic resonance imaging noninvasively confirmed tumor growth before treatment. RESULTS: Intracranial pressure increased with tumor progression, from 5.5 mm Hg at baseline to 12.95 mm Hg on Day 25 after tumor cell implantation. Intracranial pressure during ICC ranged from 5 to 21 mm Hg and was correlated with increasing infusion volumes and increasing rates of infusion. No toxicity was observed, except at the higher ends of the tumor size and volume ranges. Fluorescein isothiocyanate-dextran distribution was greater with larger infusion volumes (30 μl versus 10 μl, n = 8, P<0.05). No significant differences in distribution were observed when different infusion rates were compared while the volume was kept constant. At tolerated flow rates, the volumes of distribution were sufficient to promote adequate drug delivery to tumors. N,N'-Bis(2-chloroethyl)-N-nitrosourea treatment resulted in significant decreases in tumor size, compared with untreated controls. CONCLUSION: The C6 glioma model can be easily modified to study aspects of interstitial delivery via ICC and the application of ICC to the screening of potential antitumor agents for safety and efficacy.
Persistent Identifierhttp://hdl.handle.net/10722/155126
ISSN
2015 Impact Factor: 3.78
2015 SCImago Journal Rankings: 1.414
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorBruce, JNen_US
dc.contributor.authorFalavigna, Aen_US
dc.contributor.authorJohnson, JPen_US
dc.contributor.authorHall, JSen_US
dc.contributor.authorBirch, BDen_US
dc.contributor.authorYoon, JTen_US
dc.contributor.authorWu, EXen_US
dc.contributor.authorFine, RLen_US
dc.contributor.authorParsa, ATen_US
dc.date.accessioned2012-08-08T08:31:58Z-
dc.date.available2012-08-08T08:31:58Z-
dc.date.issued2000en_US
dc.identifier.citationNeurosurgery, 2000, v. 46 n. 3, p. 683-691en_US
dc.identifier.issn0148-396Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/155126-
dc.description.abstractOBJECTIVE: Intracerebral clysis (ICC) is a new term we use to describe convection-enhanced microinfusion into the brain. This study establishes baseline parameters for preclinical, in vivo, drug investigations using ICC in a rat glioma model. METHODS: Intracranial pressure was measured, with an intraparenchymal fiber-optic catheter, in male Fischer rats 10, 15, 20, and 25 days after implantation of C6 glioma cells in the right frontal lobe (n = 80) and in control rats without tumor (n = 20), before and during ICC. A 25% albumin solution (100 μl) was infused through an intratumoral catheter at 0.5, 1.0, 2.0, 3.0, and 4.0 μl/min. Infusate distribution was assessed by infusion of fluorescein isothiocyanate-dextran (M(r) 20,000), using the aforementioned parameters (n = 36). Brains were sectioned and photographed under ultraviolet light, and distribution was calculated by computer analysis (NIH Image for Macintosh). Safe effective drug distribution was demonstrated by measuring tumor sizes and apoptosis in animals treated with N,N'-bis(2- chloroethyl)-N-nitrosourea via ICC, compared with untreated controls. Magnetic resonance imaging noninvasively confirmed tumor growth before treatment. RESULTS: Intracranial pressure increased with tumor progression, from 5.5 mm Hg at baseline to 12.95 mm Hg on Day 25 after tumor cell implantation. Intracranial pressure during ICC ranged from 5 to 21 mm Hg and was correlated with increasing infusion volumes and increasing rates of infusion. No toxicity was observed, except at the higher ends of the tumor size and volume ranges. Fluorescein isothiocyanate-dextran distribution was greater with larger infusion volumes (30 μl versus 10 μl, n = 8, P<0.05). No significant differences in distribution were observed when different infusion rates were compared while the volume was kept constant. At tolerated flow rates, the volumes of distribution were sufficient to promote adequate drug delivery to tumors. N,N'-Bis(2-chloroethyl)-N-nitrosourea treatment resulted in significant decreases in tumor size, compared with untreated controls. CONCLUSION: The C6 glioma model can be easily modified to study aspects of interstitial delivery via ICC and the application of ICC to the screening of potential antitumor agents for safety and efficacy.en_US
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.neurosurgery-online.comen_US
dc.relation.ispartofNeurosurgeryen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntineoplastic Agents, Alkylating - Administration & Dosageen_US
dc.subject.meshBrain - Metabolism - Pathologyen_US
dc.subject.meshBrain Neoplasms - Drug Therapy - Physiopathologyen_US
dc.subject.meshCarmustine - Administration & Dosageen_US
dc.subject.meshDextrans - Pharmacokineticsen_US
dc.subject.meshDrug Delivery Systemsen_US
dc.subject.meshFluorescein-5-Isothiocyanate - Analogs & Derivatives - Pharmacokineticsen_US
dc.subject.meshGlioma - Drug Therapy - Physiopathologyen_US
dc.subject.meshImage Processing, Computer-Assisteden_US
dc.subject.meshInjectionsen_US
dc.subject.meshIntracranial Pressureen_US
dc.subject.meshMagnetic Resonance Imagingen_US
dc.subject.meshMaleen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Inbred F344en_US
dc.subject.meshRats, Wistaren_US
dc.subject.meshTissue Distributionen_US
dc.titleIntracerebral clysis in a rat glioma modelen_US
dc.typeArticleen_US
dc.identifier.emailWu, EX:ewu1@hkucc.hku.hken_US
dc.identifier.authorityWu, EX=rp00193en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid10719865-
dc.identifier.scopuseid_2-s2.0-0034016827en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034016827&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume46en_US
dc.identifier.issue3en_US
dc.identifier.spage683en_US
dc.identifier.epage691en_US
dc.identifier.isiWOS:000085684200079-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridBruce, JN=7201835650en_US
dc.identifier.scopusauthoridFalavigna, A=7003862473en_US
dc.identifier.scopusauthoridJohnson, JP=7406813015en_US
dc.identifier.scopusauthoridHall, JS=25936062100en_US
dc.identifier.scopusauthoridBirch, BD=7005297631en_US
dc.identifier.scopusauthoridYoon, JT=7403587752en_US
dc.identifier.scopusauthoridWu, EX=7202128034en_US
dc.identifier.scopusauthoridFine, RL=7201538355en_US
dc.identifier.scopusauthoridParsa, AT=7003634163en_US

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