ABSTRACT
Doxorubicin (DOX) is a widely used chemotherapy drug for various cancers and it is known to induce cognitive impairment. The aim of this study was to investigate the effect of treadmill exercise on chemotherapy-induced memory impairment. We assessed whether DOX affects inflammation, mitochondrial Ca2+ retention capacity, and Wnt/ß-catenin signaling. Male Sprague-Dawley rats were divided into control group, exercise group, DOX-injection group, and DOX-injection and exercise group. To create a DOX-induced memory impairment model, animals were injected intraperitoneally with DOX (2 mg/kg) dissolved in saline solution once a week for 4 weeks. Treadmill exercise was performed once a day, 5 days a week, for 8 consecutive weeks. Short-term memory was determined using the step-down avoidance test. Western blot was performed for the proinflammatory cytokines, Wnt/ß-catenin signaling, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) in the hippocampus. Mitochondrial Ca2+ retention capacity in the hippocampus was also measured. DOX-injection rats showed deterioration of short-term memory along with decreased expression of BDNF and TrkB in the hippocampus. Levels of the proinflammatory cytokines, tumor necrosis factor-α and interleukin-6, were increased in the DOX-injection rats. Wnt/ß-catenin signaling was activated and mitochondrial Ca2+ retention capacity was decreased in the DOX-injection rats. However, treadmill exercise alleviated short-term memory impairment, decreased proinflammatory cytokines, increased BDNF and TrkB expression, and enhanced mitochondrial Ca2+ retention capacity. Treadmill exercise restorated Wnt/ß-catenin signaling pathway. This study demonstrated that treadmill exercise can be used for patients undergoing chemotherapy with DOX.
ABSTRACT
Percutaneous vertebroplasty (PVP) is an efficient procedure to treat pain due to osteoporotic vertebral compression fractures (OVCFs). However, some patient populations experience recurrent vertebral fracture after initial successful procedure. There are a lot of literatures about the effectiveness of this procedure but few concerning the development of recurrent, new compression fracture. This is a retrospective review of all PVPs performed in author's institution from September 1999 to December 2001 to investigate the factors related to the development of new symptomatic OVCFs after PVPs. A retrospective review of 244 cases of PVP for symptomatic OVCFs at 382 levels was performed. Sociodemographic, clinical, radiologic, and procedural data were analyzed and compared between the two patient groups (control group : no further symptomatic OVCFs after the initial PVP, "new symptomatic fracture" group: with newly developed symptomatic OVCF). Statistical analysis was performed between the variables of the two groups. Survival analysis was performed using the Kaplan-Meier method. Over all, 38 among 244 treated patients (15.6%) had experienced newly developed symptomatic OVCF(s) during the follow up period (mean 52.5 months). Old age and the presence of multiple treated vertebrae at the initial PVP were assessed as a strong parameter for predicting new symptomatic OVCF. With increasing preoperative wedging deformity the risk of developing new symptomatic OVCF decreased. The Kaplan-Meier estimate of the 1 year fracture-free rate was 92.2%. The Kaplan-Meier curve showed that 7.8% of the patients would experience new symptomatic OVCF within 1 year after initial PVP. A preoperative only mild wedge deformity of the fractured vertebra(e) could indicate the increased risk of developing new symptomatic OVCF after vertebroplasty.
