Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA.
PLoS One. 2013 Apr 18;8(4):e61241. doi: 10.1371/journal.pone.0061241. Print 2013.
We assessed the effects of low dose methamphetamine treatment of traumatic brain injury (TBI) in rats by employing MRI, immunohistology, and neurological functional tests. Young male Wistar rats were subjected to TBI using the controlled cortical impact model. The treated rats (n = 10) received an intravenous (iv) bolus dose of 0.42 mg/kg of methamphetamine at eight hours after the TBI followed by continuous iv infusion for 24 hrs. The control rats (n = 10) received the same volume of saline using the same protocol. MRI scans, including T2-weighted imaging (T2WI) and diffusion tensor imaging (DTI), were performed one day prior to TBI, and at 1 and 3 days post TBI, and then weekly for 6 weeks. The lesion volumes of TBI damaged cerebral tissue were demarcated by elevated values in T2 maps and were histologically identified by hematoxylin and eosin (H&E) staining. The fractional anisotropy (FA) values within regions-of-interest (ROI) were measured in FA maps deduced from DTI, and were directly compared with Bielschowsky's silver and Luxol fast blue (BLFB) immunohistological staining. No therapeutic effect on lesion volumes was detected during 6 weeks after TBI. However, treatment significantly increased FA values in the recovery ROI compared with the control group at 5 and 6 weeks after TBI. Myelinated axons histologically measured using BLFB were significantly increased (p<0.001) in the treated group (25.84±1.41%) compared with the control group (17.05±2.95%). Significant correlations were detected between FA and BLFB measures in the recovery ROI (R = 0.54, p<0.02). Methamphetamine treatment significantly reduced modified neurological severity scores from 2 to 6 weeks (p<0.05) and foot-fault errors from 3 days to 6 weeks (p<0.05) after TBI. Thus, the FA data suggest that methamphetamine treatment improves white matter reorganization from 5 to 6 weeks after TBI in rats compared with saline treatment, which may contribute to the observed functional recovery.
我们通过 MRI、免疫组织化学和神经功能测试评估了小剂量冰毒治疗创伤性脑损伤（TBI）对大鼠的影响。使用皮质撞击模型对年轻雄性 Wistar 大鼠进行 TBI。治疗组大鼠（n=10）在 TBI 后 8 小时接受静脉（iv）推注 0.42mg/kg 冰毒，然后连续 iv 输注 24 小时。对照组大鼠（n=10）以相同的方案接受相同体积的生理盐水。在 TBI 前一天以及 TBI 后 1 天和 3 天进行 MRI 扫描，包括 T2 加权成像（T2WI）和弥散张量成像（DTI），然后每周进行一次，共 6 周。TBI 损伤脑组织的病变体积通过 T2 图中升高的值来划定，并通过苏木精和伊红（H&E）染色进行组织学鉴定。从 DTI 推导出的 FA 图中测量 ROI 内的各向异性分数（FA）值，并与 Bielschowsky 银染和 Luxol 快速蓝（BLFB）免疫组织化学染色直接比较。在 TBI 后 6 周内未检测到对病变体积的治疗效果。然而，与对照组相比，在 TBI 后 5 周和 6 周时，治疗组在恢复 ROI 中的 FA 值显著增加。用 BLFB 测量的有髓轴突在治疗组（25.84±1.41%）显著增加（p<0.001），而在对照组（17.05±2.95%）中显著减少（p<0.001）。在恢复 ROI 中检测到 FA 与 BLFB 测量值之间存在显著相关性（R=0.54，p<0.02）。冰毒治疗可从 TBI 后 2 周到 6 周（p<0.05）显著降低改良神经严重程度评分，从 TBI 后 3 天到 6 周（p<0.05）显著降低足误。因此，FA 数据表明，与生理盐水治疗相比，冰毒治疗可在 TBI 后 5 周至 6 周改善大鼠的白质重组，这可能有助于观察到的功能恢复。
