| Background:Spinal cord injury (SCI) is a serious clinical problem that lead to a series of complications, including paralysis, pain and progressing neurological dysfunction. This is not only a huge blow for the patients, but also a heavy financial burden for the community. Preclinical studies, case reports, and small clinical trials suggest that early treatment may improve neurological recovery. To date, no proven therapeutic modality exists that has demonstrated a positive effect on neurological outcome, so we have to continue to explore new methods of treatment. Specifically, current researches are aimed at preventing secondary injury and promoting regeneration. Theses studies provide us with a better understanding of the complex interaction of pathophysiologic events after SCI, and a clear direction for future research.Objectives:To determine the impact of tanshione IIA (TIIA) on the recovery of hindlimb neurological disorders and lower urinary tract dysfunction, and to explore the possible mechanisms.Methods:Adult female Sprague-Dawley rats (n=64) were randomly divided into 4 groups: Sham group (laminectomy only), SCI group (T9 spinal cord contusive injury), SCI/TIIA group (SCI with intravenously injection of TIIA [20mg/kg] from 1 to 7 days post-injury at the same time), SCI/MP group (SCI with intravenously injection of methylprednisolone [30mg/kg] once post-injury). SCI was generated by using MASCIS injury device with a 10-g weight dropped from a height of 25 mm. Sham group and SCI group are administrated with intravenously injection of lml normal saline from 1 to 7 days post-injury at the same time. (1) Spontaneous locomotion of all animals were assessed by using the Basso, Beattie, and Bresnahan (BBB) open field locomotor test. (2) Using the hot plate test to evaluate sensory function of hindlimb of all animals. (3) Transcardiac perfusion fixation were done at 1,4 and 8 weeks post-SCI. Sections of T9 spinal cord, L6-S1 dorsal root ganglia (DRG) and the bladder tissue were collected. The T9 spinal cord and L6-S1 DRG stained with Cresyl Violet for Nissl staining and stained with hematoxylin and eosin for HE staining. Then the cross-sectional areas of L6-S1 DRG cell profiles were measured using Image Pro Plus 6.0. (4) The bladder was removed 4 weeks post-SCI, and the bladder tissue stained with Masson’s trichrome. (5) Microglia in the injured spinal cord were marked by immunohistochemistry at 7 days and 8 weeks post-SCI. (6) Urodynamic assessments were performed at 4 weeks after SCI.Results:(1) Hindlimb motor function of TIIA group and MP group had significantly improved but MP group was more effective. (2) Sensory function of MP group recovered faster than TIIA group 3 days post-surgery, and the difference was statistically significant. But TIIA group recovered nearly as fast as MP group at 7 days post-surgery. And TIIA group showed a trend that sensory function recovers faster than MP group at 4 weeks post-surgery, almost reached to statistical significance. (3) In each group, except sham group, microglia contract their processes and transformed from a ramified to an ameboid morphology at 3 days post-surgery. Changes of morphology in TIIA group and MP group were relatively smaller, but the number of macrophage/microglia reduced significantly compared with SCI group. (4) In each group, except sham group, microglia transformed from an ameboid to a ramified morphology at 8 weeks post-surgery. The number of macrophage/microglia in SCI group reduced dramatically compared with sham group. But the number of macrophage/microglia increased in TIIA group than SCI group. However, the number of macrophage/microglia increased dramatically in MP group compare with SCI group.Conclusion:(1) TIIA possibly promotes the recovery of motor and sensory function of hindlimb of rats after SCI. (2) TIIA may improve pathology progress of injured spinal cord, bladder and L6-S1 DRG, and may play a positive role in the recovery of neurological disorder by influencing the macrophage/microglia. (3) TIIA may improve the voiding efficiency and reduce the number of no-voiding contractions in rats after SCI. Thus, TIIA may promote the recovery of lower urinary tract dysfunction. (4) Urodynamic study is an effective means to evaluate lower urinary tract function in rats. |
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