Low-dose metformin treatment in the subacute phase improves the locomotor function of a mouse model of spinal cord injury.

Metformin, a first-line drug for type-2 diabetes, has been shown to improve locomotor recovery after spinal cord injury. However, there are studies reporting no beneficial effect. Recently, we found that high dose of metformin (200 mg/kg, intraperitoneal) and acute phase administration (immediately after injury) led to increased mortality and limited locomotor function recovery. Consequently, we used a lower dose (100 mg/kg, i.p.) metformin in mice, and compared the effect of immediate administration after spinal cord injury (acute phase) with that of administration at 3 days post-injury (subacute phase). Our data showed that metformin treatment starting at the subacute phase significantly improved mouse locomotor function evaluated by Basso Mouse Scale (BMS) scoring. Immunohistochemical studies also revealed significant inhibitions of microglia/macrophage activation and astrogliosis at the lesion site. Furthermore, metformin treatment at the subacute phase reduced neutrophil infiltration. These changes were in parallel with the increased survival rate of spinal neurons in animals treated with metformin. These findings suggest that low-dose metformin treatment for subacute spinal cord injury can effectively improve the functional recovery possibly through anti-inflammation and neuroprotection. This study was approved by the Institute Animal Care and Use Committee at the University of Texas Medical Branch (approval No. 1008041C) in 2010.

Epidemiology of traumatic spinal cord injury in Tianjin, China: An 18-year retrospective study of 735 cases.

Study Design: Hospital-based retrospective studyObjectives: To evaluate the pathogenetic features of traumatic spinal cord injury (TSCI) during 1999-2016 according to changed injury etiology with time, explore different characteristics of patients suffered a TSCI during 1999-2007 and 2008-2016 in Tianjin, China.Setting: Tianjin Medical University General HospitalMethods: In this study, the medical records of TSCI patients were obtained from Tianjin Medical University General Hospital (TMUGH) from 1st January 1999 to 31th December 2016. Variables were recorded, including age, gender occupation, etiology, the level of injury, America Spinal Injury Association (ASIA) impairment scale, the severity, concomitant injuries, death and its cause. To explore the differences in characteristics by etiology and by two periods, related statistical methods were used to calculate the correlation of some variables. Differences in etiology of TSCI during 1999-2016 were evaluated and differences in epidemiological characteristics were separately compared and analyzed between the 1999-2007 period and the 2008-2016 period.Results: From 1999-2016, 831 TSCI cases were identified and 96 cases were excluded from analyses. The male-to-female ratio was 2.9:1 and the mean age was 49.7±15.2 years, which changed significantly between 1999-2007 (45.1±14.2) and 2008-2016 (51.6±15.2). Traffic accidents (45.8%) were the leading cause of TSCI during the 1999-2007 period, followed by low falls (30.7%). However, the opposite result was observed during the 2008-2016 period. Significant difference was observed compared with thoracic, lumbar and sacral levels, cervical level was the most commonly affected levels and the percentage decreased to a certain degree between 1999-2007 and 2008-2016 (from 84.4% to 68.9%). The proportions of ASIA grades A, B, C, and D were 20.5%, 10.3%, 23.3%, and 45.9%, respectively. The percentage of complete tetraplegia decreased from 22.9% in 1999-2007 to 13.2% in 2008-2016, and the percentage of incomplete paraplegia increased from 9.7% to 27.9%.Conclusion: According to the changes in the epidemiological characteristics of TSCI, relevant health service, laws and regulations, preventative strategies should be readjusted to follow up the changing situation and epidemiological characteristics of TSCI.

Bone marrow mesenchymal stem cells stimulated with low-intensity pulsed ultrasound: Better choice of transplantation treatment for spinal cord injury: Treatment for SCI by LIPUS-BMSCs transplantation.

Stem cell transplantation, especially treatment with bone marrow mesenchymal stem cells (BMSCs), has been considered a promising therapy for the locomotor and neurological recovery of spinal cord injury (SCI) patients. However, the clinical benefits of BMSCs transplantation remain limited because of the considerably low viability and inhibitory microenvironment. In our research, low-intensity pulsed ultrasound (LIPUS), which has been widely applied to clinical applications and fundamental research, was employed to improve the properties of BMSCs. The most suitable intensity of LIPUS stimulation was determined. Furthermore, the optimized BMSCs were transplanted into the epicenter of injured spinal cord in rats, which were randomized into four groups: (a) Sham group (n = 10), rats received laminectomy only and the spinal cord remained intact. (b) Injury group (n = 10), rats with contused spinal cord subjected to the microinjection of PBS solution. (c) BMSCs transplantation group (n = 10), rats with contused spinal cord were injected with BMSCs without any priming. (d) LIPUS-BMSCs transplantation group (n = 10), BMSCs stimulated with LIPUS were injected at the injured epicenter after contusion. Rats were then subjected to behavioral tests, immunohistochemistry, and histological observation. It was found that BMSCs stimulated with LIPUS obtained higher cell viability, migration, and neurotrophic factors expression in vitro. The rate of apoptosis remained constant. After transplantation of BMSCs and LIPUS-BMSCs postinjury, locomotor function was significantly improved in LIPUS-BMSCs transplantation group with higher level of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the epicenter, and the expression of neurotrophic receptor was also enhanced. Histological observation demonstrated reduced cavity formation in LIPUS-BMSCs transplantation group when comparing with other groups. The results suggested LIPUS can improve BMSCs viability and neurotrophic factors expression in vitro, and transplantation of LIPUS-BMSCs could promote better functional recovery, indicating possible clinical application for the treatment of SCI.