Cross Donna J, Garwin Gregory G, Cline Marcella M, Richards Todd L, Yarnykh Vasily, Mourad Pierre D, Ho Rodney J Y, Minoshima Satoshi
Department of Radiology, University of Washington, 1959 N.E. Pacific Street, Seattle, WA, 98195-7115, USA.
Department of Radiology, University of Washington, 1959 N.E. Pacific Street, Seattle, WA, 98195-7115, USA.
Brain Res. 2015 Aug 27;1618:299-308. doi: 10.1016/j.brainres.2015.06.006. Epub 2015 Jun 15.
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.
针对创伤性脑损伤（TBI）的药物干预有望改善治疗结果。本研究的目的是确定化疗中使用了20多年的微管稳定治疗药物紫杉醇是否能改善TBI后的治疗结果。我们评估了直接将紫杉醇应用于可控皮质撞击（CCI）所致脑损伤小鼠的神经学结果。采用磁共振成像评估与损伤相关的形态学变化。Catwalk步态分析显示，与生理盐水组相比，紫杉醇组在各种参数上均有显著改善。MRI分析显示，紫杉醇治疗导致损伤部位水肿体积显著减小（T2加权分析确定，生理盐水组和紫杉醇组分别为11.92±3.0和8.86±2.2mm³；p≤0.05），髓鞘组织保存显著增加（9.45±0.4对8.95±0.3，p≤0.05）。我们的研究结果表明，紫杉醇治疗可改善神经学结果和损伤的磁共振成像生物标志物。这些结果可能会对创伤性脑损伤治疗的研发产生重大影响。
