title: Paclitaxel improves outcome from traumatic brain injury.
abstract: Pharmacologic interventions for traumatic brain injury (TBI) hold promise to improve outcome. The purpose of this study was to determine if the microtubule stabilizing therapeutic paclitaxel used for more than 20 years in chemotherapy would improve outcome after TBI. We assessed neurological outcome in mice that received direct application of paclitaxel to brain injury from controlled cortical impact (CCI). Magnetic resonance imaging was used to assess injury-related morphological changes. Catwalk Gait analysis showed significant improvement in the paclitaxel group on a variety of parameters compared to the saline group. MRI analysis revealed that paclitaxel treatment resulted in significantly reduced edema volume at site-of-injury (11.92 ± 3.0 and 8.86 ± 2.2mm(3) for saline vs. paclitaxel respectively, as determined by T2-weighted analysis; p ≤ 0.05), and significantly increased myelin tissue preservation (9.45 ± 0.4 vs. 8.95 ± 0.3, p ≤ 0.05). Our findings indicate that paclitaxel treatment resulted in improvement of neurological outcome and MR imaging biomarkers of injury. These results could have a significant impact on therapeutic developments to treat traumatic brain injury.
authors.affiliation: Department of Radiology, University of Washington, 1959 N.E. Pacific Street, Seattle, WA, 98195-7115, USA. Electronic address: dcross@uw.edu.
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Cross
authors.affiliation: Department of Radiology, University of Washington, 1959 N.E. Pacific Street, Seattle, WA, 98195-7115, USA.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Garwin
authors.affiliation: Department of Radiology, University of Washington, 1959 N.E. Pacific Street, Seattle, WA, 98195-7115, USA.
authors.forename: Marcella M
authors.initials: MM
authors.lastname: Cline
authors.affiliation: Department of Radiology, University of Washington, 1959 N.E. Pacific Street, Seattle, WA, 98195-7115, USA.
authors.forename: Todd L
authors.initials: TL
authors.lastname: Richards
authors.affiliation: Department of Radiology, University of Washington, 1959 N.E. Pacific Street, Seattle, WA, 98195-7115, USA.
authors.forename: Vasily
authors.initials: V
authors.lastname: Yarnykh
authors.affiliation: Department of Neurological Surgery, University of Washington, 1959 N.E. Pacific Street, Seattle, WA 98195-7115, USA.
authors.forename: Pierre D
authors.initials: PD
authors.lastname: Mourad
authors.affiliation: Department of Pharmaceutics, University of Washington, 1959 N.E. Pacific Street, Seattle, WA 98195-7115, USA.
authors.forename: Rodney J Y
authors.initials: RJ
authors.lastname: Ho
authors.affiliation: Department of Radiology, University of Utah, 30 North 1900 East, Salt Lake City, UT 84132, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Minoshima
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D020233:Gait Disorders, Neurologic / Q000188:drug therapy / Q000209:etiology; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000627:therapeutic use*; D016896:Treatment Outcome; D050257:Tubulin Modulators / Q000627:therapeutic use*
chemical_list: D050257:Tubulin Modulators; D017239:Paclitaxel
keywords: MR imaging; Microtubule stabilization; Neurological function; Traumatic brain injury