[Effect of Herba Lycopodii Alcohol Extracted Granule Combined Methylprednisolone on Expression Levels of BDNF and NMDA and Behavior of Traumatic Spinal Cord Injury Rats].

OBJECTIVE: To study different effects of Herba Lycopodii (HL) Alcohol Extracted Granule combined methylprednisolone on behavioral changes, brain derived neurotrophic factor (BDNF) expression levels, and N-methyl-D-aspartate (NMDA) receptor levels in rats with spinal cord injury (SCI). METHODS: Male adult SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the HL treatment group, the methylprednisolone treatment group, the HL + methylprednisolone treatment group. Rats in the HL treatment group were intragastrically administered with HL at the daily dose of 50 mg/kg for 5 successive days. Rats in the methylprednisolone treatment group were intramuscularly injected with 50 mg/kg methylprednisolone within 8 h after spinal cord contusion, and then the dose of methylprednisolone was reduced for 10 mg/kg for 5 successive days. Rats in the HL + methylprednisolone treatment group received the two methods used for the aforesaid two groups. Basso Beattie and Bresnahan (BBB) score (for hindlimb motor functions) were assessed at day 0, 3, 7, and 28 after operation. At day 13 after SCI, injured spinal T8-10 was taken from 8 rats of each group and stored in liquid nitrogen. The N-methyl-D-aspartate (NMDA) receptor affinity (Kd) and the maximal binding capacity (Bmax) were determined using [3H]MK-801 radioactive ligand assay. Rats' injured spinal cords were taken for immunohistochemical assay at day 28 after SCI. Expression levels of BDNF in the ventral and dorsal horn of the spinal cord were observed. RESULTS: Compared with the sham-operation group, the number of BDNF positive neurons in the ventral and dorsal horn of the spinal cord increased in the model group, Bmax increased (470 ± 34), Kd decreased, and BBB scores decreased at day 3 -28 (all P <0. 05). Compared with the SCI model group, the number of BDNF positive neurons and Kd increased, BBB scores at day 3 -28 increased (P <0. 05) in each medicated group. Bmax was (660 ± 15) in the methylprednisolone treatment group, (646 ± 25) in the HL treatment group, and (510 ± 21) in the HL +methylprednisolone treatment group (P <0. 05). Compared with the methylprednisolone treatment group, the number of BDNF positive neurons and Kd increased, BBB scores at day 7 -28 increased, and Bmax decreased in the HL treatment group and the HL + methylprednisolone treatment group (all P <0. 05). Compard with the HL treatment group, the number of BDNF positive neurons and Kd increased, and Bmax decreased (all P < 0.05). CONCLUSIONS: HL could effectively improve motor functions of handlimbs, increase expression levels of BDNF in the spinal cord, and lessen secondary injury by affecting spinal levels of NMDA receptors. It showed certain therapeutic and protective roles in treating SCI. Its effect was better than that of methylprednisolone with synergism.

[Effect of gold belt on the BDNF and NMDA receptor expression and behaviour changes in rats following traumatic spinal cord injury].

OBJECTIVE: To study the effects of gold belt (GB), a Chinese Herbal, on behavioral changes and brain derived neutrophic factor (BDNF) expression and N-methyl-D-aspartic acid (NMDA) receptor level in rats subjected to spinal cord injury (SCI). METHODS: Adult male SD rats were randomly divided into three groups: (1) Sham group; (2) Spinal cord injury group (SCI group); (3) Spinal cord injury followed with gold belt treatment (gold belt 50 mg/(kg x d), intragastric gavage once daily for 7 days) group (GB group). The Basso, Beattie and Bresnahan (BBB) locomotor scale method was performed to evaluate the hindlimb motor function in the days 0, 3, 10 and 28. After 13 days, 8 rats in each group were treated with 1% sodium pentobarbital (30 mg/kg), myoloid tissue in T10 position was taken and stored in liquid nitrogen to detect NMDA receptor affinity and maximum binding amount (Bmax) with radioligand binding assay. After 28 days, rats were sacrificed and the spinal cords were harvested for immunohistochemistry to observe the localization of BDNF in the ventral and dorsal horn of the spinal cord. RESULTS: After spinal cord contusion, GB resulted in a significant increase on the number of BDNF positive neurons compared with traumatic group, and increased BBB score and decreased NMDA receptor were also found in GB group. Whereas decreased BDNF expression, NMDA receptor affininty (Kd) were observed in traumatic injury group. CONCLUSION: The gold belt treatment could effectively improve motor function, increase expression of BDNF, reduce the level of NMDA receptors in SCI rats. These data suggested that the gold belt played a role in the neuroplasticity after spinal cord injury.

Generalized propensity score for estimating the average treatment effect of multiple treatments.

The propensity score method is widely used in clinical studies to estimate the effect of a treatment with two levels on patient's outcomes. However, due to the complexity of many diseases, an effective treatment often involves multiple components. For example, in the practice of Traditional Chinese Medicine (TCM), an effective treatment may include multiple components, e.g. Chinese herbs, acupuncture, and massage therapy. In clinical trials involving TCM, patients could be randomly assigned to either the treatment or control group, but they or their doctors may make different choices about which treatment component to use. As a result, treatment components are not randomly assigned. Rosenbaum and Rubin proposed the propensity score method for binary treatments, and Imbens extended their work to multiple treatments. These authors defined the generalized propensity score as the conditional probability of receiving a particular level of the treatment given the pre-treatment variables. In the present work, we adopted this approach and developed a statistical methodology based on the generalized propensity score in order to estimate treatment effects in the case of multiple treatments. Two methods were discussed and compared: propensity score regression adjustment and propensity score weighting. We used these methods to assess the relative effectiveness of individual treatments in the multiple-treatment IMPACT clinical trial. The results reveal that both methods perform well when the sample size is moderate or large.