Changes in depressive-like behaviors induced by spinal cord injury based on the hypothalamic-pituitary-adrenal axis and hippocampal neurogenesis.

A reduction in sucrose preference is a key characteristic of depressive-like behaviors after spinal cord injury as judged by the sucrose preference test, the hypothalamic-pituitary-adrenal axis and adult hippocampal neurogenesis. Male rats were divided into three groups: control, sham and spinal cord injury groups. The spinal cord injury rats received a severe mid-thoracic contusion. The Basso, Beattie and Bresnahan score was used to assess motor function. The sucrose preference test and forced swim test were used to evaluate depressive-like behaviors. Serum corticosterone levels were examined by enzyme-linked immunosorbent assay and hippocampal glucocorticoid receptor levels were examined by Western blot to evaluate the function of the hypothalamic-pituitary-adrenal axis. Adult hippocampal neurogenesis was assessed by testing hippocampal brain-derived neurotrophic factor and tropomyosin receptor kinase B levels by Western blot and doublecortin levels by immunohistochemistry. Data showed that spinal cord injury impaired motor function. The spinal cord injury rats exhibited decreased sucrose preference on day six, which continued to decrease until day twelve, followed by a plateau phase. Additionally, the immobility time of the spinal cord injury rats was increased on day thirty-four. Moreover, serum corticosterone levels in the spinal cord injury group peaked on day seven, was decreased by day twenty-one and was increased again on day thirty-five. Serum corticosterone levels were significantly negatively correlated with sucrose preference and positively correlated with immobility time. Finally, hippocampal doublecortin levels on days twenty-one and thirty-five were lower in the spinal cord injury group than in the other groups. These results suggest that hyperactivation of the hypothalamic-pituitary-adrenal axis and the inhibition of adult hippocampal neurogenesis may be part of the underlying mechanism responsible for depressive-like behaviors after spinal cord injury.

Inhibition of UDP-Glucuronosyltransferases (UGTs) Activity by constituents of Schisandra chinensis.

Structure-activity relationship for the inhibition of Schisandra chinensis's ingredients toward (Uridine-Diphosphate) UDP-glucuronosyltransferases (UGTs) activity was performed in the present study. In vitro incubation system was employed to screen the inhibition capability of S. chinensis's ingredients, and in silico molecular docking method was carried out to explain possible mechanisms. At 100 µM of compounds, the activity of UGTs was inhibited by less than 90% by schisandrol A, schisandrol B, schisandrin, schisandrin C, schisantherin A, gomisin D, and gomisin G. Schisandrin A exerted strong inhibition toward UGT1A1 and UGT1A3, with the residual activity to be 7.9% and 0% of control activity. Schisanhenol exhibited strong inhibition toward UGT2B7, with the residual activity to be 7.9% of control activity. Gomisin J of 100 µM inhibited 91.8% and 93.1% of activity of UGT1A1 and UGT1A9, respectively. Molecular docking prediction indicated different hydrogen bonds interaction resulted in the different inhibition potential induced by subtle structure alteration among schisandrin A, schisandrin, and schisandrin C toward UGT1A1 and UGT1A3: schisandrin A > schisandrin > schisandrin C. The detailed inhibition kinetic evaluation showed the strong inhibition of gomisin J toward UGT1A9 with the inhibition kinetic parameter (Ki ) to be 0.7 µM. Based on the concentrations of gomisin J in the plasma of the rats given with S. chinensis, high herb-drug interaction existed between S. chinensis and drugs mainly undergoing UGT1A9-mediated metabolism. In conclusion, in silico-in vitro method was used to give the inhibition information and possible inhibition mechanism for S. chinensis's components toward UGTs, which guide the clinical application of S. chinensis.

Calcium supplementation reducing the risk of hypertensive disorders of pregnancy and related problems: A meta-analysis of multicentre randomized controlled trials.

Hypertensive disorders of pregnancy are closely related to maternal mortality and morbidity. Calcium supplementation during pregnancy seems to reduce the risk of hypertensive disorders. No systematic review on multicentre RCTs of calcium supplementation during pregnancy has been published. The purpose of this study was to report a quantitative systematic review of the effectiveness of calcium supplementation during pregnancy on reducing the risk of hypertensive disorders of pregnancy and related problems. Publications over the years of 1991-2012 were searched through PubMed, Science Direct, EMBASE, CINAHL and Web of Science. The literatures were selected of the multicentre RCTs on calcium supplementation during pregnancy in prevention of hypertensive disorders and related problems. Reference lists from the studies were also examined for additional references. Studies were critically appraised by three independent reviewers, and the Cochrane Handbook was used to assess the quality of those included trials. Four studies were included in this systematic review. All included studies were high quality, with low risk of bias. There was an observed risk reduction in hypertension in calcium group. However, there was no reduction in the risk of severe gestational hypertension, pre-eclampsia, severe pre-eclampsia, preterm birth and low birthweight. Calcium supplementation appears to reduce the risk of hypertension in pregnancy.

Effects of body weight-supported treadmill training at different speeds on the motor function and depressive behaviors after spinal cord injury in rats.

Spinal cord injury (SCI) causes motor dysfunction and depression, which hinders the recovery of motor function. Body weight-supported treadmill training (BWSTT) should be considered an effective method for functional rehabilitation after SCI, as it is an efficacious intervention in healthcare with no side effects. Because exercise exerts different effects on motor function recovery and inhibiting depression after SCI, we aimed to determine the appropriate intensity of BWSTT. In this study, fixed durations, frequencies, and percentages of BWSTT with different speeds of BWSTT (7, 15, and 21 cm/s) were chosen to explore the appropriate intensity, which affected the recovery of motor function and antidepressant effects on SCI rats. Based on our results, BWSTT at 21 cm/s produced the best outcomes for motor function recovery and the spinal cord levels of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB). The antidepressant effects of BWSTT at 15 and 21 cm/s were confirmed based on the increasing sucrose preference, the time spent in the central area and social time, and reduced immobility time. BWSTT at 15 and 21 cm/s improved the modulation of the hypothalamic-pituitary-adrenal axis by decreasing serum corticosterone levels and increasing hippocampal glucocorticoid receptor levels. In addition, higher levels of neurogenesis-related proteins were observed in the hippocampus of the group subjected to BWSTT at 21 cm/s than in the other groups. Thus, BWSTT at 21 cm/s is a potentially favorable treatment that synchronously improves motor function recovery and exerts an antidepressant effect.

Design and Evaluation of a Novel Laminectomy Auxiliary Device Based on Rats.

Most types of spinal cord injury (SCI) observed in humans can be replicated in adult rat models, which are widely used for laboratory studies of SCI rehabilitation. To ensure the effectiveness and efficiency of an SCI rat model, the minimal time spent performing the laminectomy procedure and the damage caused to the body are of great importance. We describe and evaluate the effectiveness and advantages of a laminectomy auxiliary device (LAD) for removing the rat vertebral lamina without injuring the spinal cord. The incision size, success rate, operation duration, body weight, BBB score, step detection, latency and amplitude of transcranial electrical motor-evoked potentials (tceMEPs), and serum MDA and SOD levels were recorded in 8 normal rats, 8 rats treated with traditional laminectomy and 8 rats treated with LAD laminectomy. Compared with traditional laminectomy, in our LAD, the surgical incision was smaller (approximately 2.2 and 1.3 cm, respectively), the success rate was higher (88.89% and 100%, respectively) and the duration shorter (14.644±1.617 and 4.821±0.668 minutes, respectively). Compared with normal rats, those treated with either laminectomy using LAD or the traditional method showed slower body weight gain and temporarily increased oxidative stress levels. However, there were no significant differences between these two groups. Our results show that laminectomy using this LAD provides three main advantages in rats: a high success rate, time savings, small incisions and reduced trauma. We believe this LAD can be used as an effective assistant tool for rodent laminectomy.

Effective robotic assistive pattern of treadmill training for spinal cord injury in a rat model.

The purpose of the present study was to establish an effective robotic assistive stepping pattern of body-weight-supported treadmill training based on a rat spinal cord injury (SCI) model and assess the effect by comparing this with another frequently used assistive stepping pattern. The recorded stepping patterns of both hind limbs of trained intact rats were edited to establish a 30-sec playback normal rat stepping pattern (NRSP). Step features (step length, step height, step number and swing duration), BBB scores, latencies, and amplitudes of the transcranial electrical motor-evoked potentials (tceMEPs) and neurofilament 200 (NF200) expression in the spinal cord lesion area during and after 3 weeks of body-weight-supported treadmill training (BWSTT) were compared in rats with spinal contusion receiving NRSP assistance (NRSPA) and those that received manual assistance (MA). Hind limb stepping performance among rats receiving NRSPA during BWSTT was greater than that among rats receiving MA in terms of longer step length, taller step height, and longer swing duration. Furthermore a higher BBB score was also indicated. The rats in the NRSPA group achieved superior results in the tceMEPs assessment and greater NF200 expression in the spinal cord lesion area compared with the rats in the MA group. These findings suggest NRSPA was an effective assistive pattern of treadmill training compared with MA based on the rat SCI model and this approach could be used as a new platform for animal experiments for better understanding the mechanisms of SCI rehabilitation.

Comparison of three different time points of starting treadmill training in spinal cord injured rats.

OBJECTIVE: It has been widely acknowledged that early treadmill training plays an important role in rewiring neurons in a functionally meaningful manner in spinal cord injury (SCI) treatment. However, it is still unclear how early to start treadmill training to obtain the most efficacious results after SCI. The purpose of this study was to find the earliest time point when treadmill training was most effective in rewiring neurons. METHODS: The rats were randomly divided into five groups: a sham group, control group, and three treadmill groups based on training start time post-injury: a 24 h group, 48 h group, and 72 h group. RESULTS: The results revealed that in the 72 h group, Basso, Beattie, and Bresnaham scores increased and apoptotic cells decreased significantly compared to the other groups. There were no statistically differences in neuron counting and 5-bromo-2V-deoxyuridine assays between the groups. CONCLUSION: These results indicated that the best start time for treadmill training is 72 h after SCI.