Interstitial infusion of IL13-PE38QQR, a tumor specific, chimeric cytotoxin, into the rat brain stem was performed in an effort to assess safety. Six rats underwent stereotaxic cannula placement into the pontine segment of the brain stem followed by a 24-h infusion of IL13-PE38QQR (volume of infusion (Vi) 200 microl) at a concentration of 10 microg/ml. The animals were assessed neurologically and then sacrificed either immediately or after 2 weeks. All animals tolerated the infusions without exhibiting any neurological changes. Postmortem examination of the brains revealed no significant histological changes beyond the site of the cannula tract. These findings indicate that supratherapeutic concentrations of IL13-PE38QQR administered by interstitial infusion into the rat brain stem is well tolerated and may serve as a potential therapeutic strategy for children with diffuse pontine gliomas.
Interstitial infusion of carmustine (BCNU) into the rat brain stem in conjunction with systemic administration of O6-benzylguanine (O6-BG) was performed in an effort to assess clinical tolerance. A total of 12 rats underwent stereotactic cannula placement into the pontine segment of the brain stem. Six of the rats underwent a 24-h infusion of BCNU (Volume of infusion [Vi] 200 microl) at its maximal concentrated dose (3.3 mg/ml) in 5% dextrose water. Six additional rats underwent 24-h infusion of BCNU preceded by an intraperitoneal injection of O6-BG at a dose of 50 mg/kg. Serial neurological examinations were performed on all animals. Histologic analyses were performed immediately or 2 weeks following sacrifice. Postoperatively, there were no neurological changes in any of the animals. Postmortem histological examination of the brains showed small pontine cavitary lesions (ranging from 20 to 250 microm) containing variable numbers of macrophages or neutrophils consistent with an inflammatory response. No changes beyond these findings indicated any histological evidence of injury. These finding were limited only to the cannula site and no changes beyond region of the cannula tract were found. These findings indicate that interstitial infusion of BCNU into the brain stem in conjunction with systemic administration of O6-BG is safe in a small animal and may serve as a potential investigative strategy for children with diffuse pontine gliomas.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.