title: Neurotoxicity screening test for deep brain stimulation leads.
abstract: A description of qualitative and quantitative cell-culture studies using in vitro human cerebellar, cortical and glial cell lines developed to screen a deep brain stimulation lead for neurotoxicity potential is presented. Preclinical neurotoxicity testing requirements for implantable medical devices have historically been met by expensive long-term large animal testing. To decrease large animal killing, expense and time to human trials, an in vitro human tissue testing process was developed and compared to standard animal testing. A permanently implantable deep brain stimulation lead was subjected to both qualitative and quantitative cell culture studies using in vitro human cerebellar, cortical and glial cell lines. Materials were extracted in both saline (72 h at 50 degrees C) and minimum essential medium (24 h at 37 degrees C) environments. All cytotoxicity and cell proliferation testing resulted in positive controls (Tygon) F-4040-A) showing severe cytotoxicity in all cell lines, negative controls (high-density polyethylene) and both extraction media above showing non-cytotoxic results in all cell lines. In vitro human neuronal cell specific cytotoxicity testing in combination with ISO-10993 biological and materials characterization testing is an efficient, practical means of screening a device for preclinical safety for use in humans.
authors.affiliation: Advanced Neuromodulation Systems Inc., 6901 Preston Road, Plano, TX 75024, USA. s.hooper@ans-medical.com
authors.forename: Sandy
authors.initials: S
authors.lastname: Hooper
authors.forename: Tracy
authors.initials: T
authors.lastname: Cameron
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D018929:Cell Culture Techniques; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D046690:Deep Brain Stimulation; D005260:Female; D006801:Humans; D008297:Male; D023421:Models, Animal; D009474:Neurons / Q000378:metabolism*; D009498:Neurotoxins / Q000032:analysis / Q000378:metabolism; D020959:Polyethylene / Q000737:chemistry; D011140:Polyurethanes / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature
chemical_list: D009498:Neurotoxins; D011140:Polyurethanes; D020959:Polyethylene