Promoting functions of microRNA-29a/199B in neurological recovery in rats with spinal cord injury through inhibition of the RGMA/STAT3 axis

Abstract Background The prognostic and therapeutic potential of microRNAs (miRNAs) in spinal cord injury (SCI) has aroused increasing concerns. This study aims to research the functions of miR-29a/199B in the neurological function recovery after SCI and the mechanical mechanism. Methods A rat model with SCI was induced with sham-operated ones as control. The locomotor function and coordination of rat hindlimbs were determined by a Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and a ladder-climbing test, respectively. Expression of a neurofilament protein NF-200 and synaptophysin in gray matter of rats was determined to evaluate neuronal recovery in a cellular perspective. Binding relationships between miR-29a/199B with RGMA were predicted and validated using luciferase assays. Altered expression of miR-29a/199B and RGMA was introduced to explore their functions in rat neurological functions. The protein level and phosphorylation of STAT3 in gray matter were measured by western blot analysis. Results miR-29a and miR-199B were poorly expressed, while RGMA was abundantly expressed in gray matter at injury sites. Either miR-29a or miR-199B could bind to RGMA. Overexpression of miR-29a/199B or silencing of RGMA led to an increase in BBB locomotor scores, hindlimb coordination ability, and the expression of NF-200 and synaptophysin in gray matter. Further inhibition in miR-29a/199B blocked the promoting roles of RGMA silencing in neurological recovery. Upregulation of miR-29a/199B or downregulation of RGMA suppressed the phosphorylation of STAT3. Conclusion This study evidenced that miR-29a and miR-199B negatively regulated RGMA to suppress STAT3 phosphorylation, therefore promoting the neurological function recovery in rats following SCI.

Download Full-text

Blocking of BDNF-TrkB signaling inhibits the promotion effect of neurological function recovery after treadmill training in rats with spinal cord injury

Spinal Cord ◽

10.1038/s41393-018-0173-0 ◽

2018 ◽

Vol 57 (1) ◽

pp. 65-74 ◽

Cited By ~ 12

Author(s):

Xiangzhe Li ◽

Qinfeng Wu ◽

Caizhong Xie ◽

Can Wang ◽

Qinghua Wang ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Neurological Function ◽

Treadmill Training ◽

Promotion Effect ◽

Function Recovery ◽

Cord Injury

Download Full-text

Coadministration of Methylprednisolone with Hypertonic Saline Solution Improves Overall Neurological Function and Survival Rates in a Chronic Model of Spinal Cord Injury

Neurosurgery ◽

10.1097/00006123-200112000-00022 ◽

2001 ◽

Vol 49 (6) ◽

pp. 1427-1433 ◽

Cited By ~ 17

Author(s):

Jeffrey J. Legos ◽

Kurt R. Gritman ◽

Ronald F. Tuma ◽

William F. Young

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Hypertonic Saline ◽

Intravenous Injection ◽

Rating Scale ◽

Survival Rates ◽

Isotonic Saline ◽

Neurological Function ◽

Control Group ◽

Cord Injury

ABSTRACT OBJECTIVE We previously demonstrated that administration of 7.5% hypertonic saline (HS) significantly improved spinal cord blood flow and neurological outcomes after spinal cord injury. The aim of this study was to determine whether hypertonicity would enhance the effects of methylprednisolone (MP), further improving neurological function. METHODS Rat spinal cords were compressed for 10 minutes with 50 g of weight, and neurological function was assessed for 28 days, using the Basso-Beattie-Bresnahan locomotor rating scale. The control group received an intravenous injection of isotonic saline (IS) (5 ml/kg). Group 1 received an intravenous injection of 7.5% HS (5 ml/kg). Group 2 received an intravenous injection of MP (30 mg/kg) and IS (5 ml/kg). Group 3 received an intravenous injection of MP (30 mg/kg) administered with 7.5% HS (5 ml/kg). RESULTS At 24 hours after spinal cord injury, the combination of MP plus HS provided significant (P < 0.01) neurological improvements, compared with all other treatment groups. At 10 days after injury, the animals that had received MP plus HS exhibited significantly (P < 0.01) higher Basso-Beattie-Bresnahan scores, compared with the MP plus IS and control groups. The median survival time was significantly (P < 0.01) increased for the MP plus HS group (28 d), compared with the MP plus IS group (16 d). Because of the dramatic decrease in survival rates at 28 days after injury, there was a significant (P < 0.01) difference in neurological function only between the MP plus HS group and the control group. CONCLUSION The results indicate that the administration of HS may enhance the delivery of MP and prevent immunosuppression, leading to improvements in overall neurological function and survival rates after spinal cord injury.

Download Full-text