Open Access

Neuroprotective effect of combining tanshinone IIA with low‑dose methylprednisolone following acute spinal cord injury in rats

  • Authors:
    • Nian‑Wei Yao
    • Yuan Lu
    • Li‑Qi Shi
    • Feng Xu
    • Xian‑Hua Cai
  • View Affiliations

  • Published online on: March 28, 2017     https://doi.org/10.3892/etm.2017.4271
  • Pages: 2193-2202
  • Copyright: © Yao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study compared the potential neuroprotective effect of tanshinone IIA (TIIA) monotherapy, methylprednisolone (MP) monotherapy and combined treatment in an adult acute spinal cord injury (ASCI) rat model. The current study used the weight‑drop method (Allen's Impactor) in the rat model and the mechanical scratch method in primary spinal cord neuron culture to determine whether the combined treatment was able to reduce the required dosage of MP in the treatment of ASCI to produce a similar or improved therapeutic effect. In vivo male Sprague Dawley rats (n=60) were randomly divided into 5 groups, of which 12 rats were selected for the sham group and T9‑T11 laminectomies, leading to ASCI, were performed on 48 of the 60 rats using a 10 g x25 mm weight‑drop at the level of T10 spinal cord. Therefore, the ASCI group (n=12) included the ‘laminectomy and weight‑drop’. The remaining 36 ASCI model animals were subdivided into 3 groups (n=12 each group): TIIA group (30 mg/kg/day), MP group (30 mg/kg) and combined treatment group (TIIA 30 mg/kg/day + MP 20 mg/kg). Neuronal function following ASCI was evaluated using the Basso Beattie Bresnahan (BBB) locomotor rating scale. Levels of the anti‑apoptotic factor B‑cell lymphoma‑2 (Bcl‑2), the pro‑apoptotic factors Bcl‑2 associated protein X (Bax) and caspase‑3, and the inflammatory associated factor nuclear factor‑κB, were analyzed by western blot analysis. Immunohistochemistry was used to detect caspase‑3. To investigate the underlying mechanism, the anti‑oxidative effect of combination TIIA and MP treatment was assessed by measuring the activity of malondialdehyde (MDA) and superoxide dismutase (SOD) in ASCI. In agreement with the experiment in vivo, primary neurons were prepared from the spinal cord of one‑day‑old Sprague‑Dawley rats' and co‑cultured with astrocytes from the brain cortex. The injury of neurons was induced by mechanical scratch and levels of apoptosis factors were analyzed by western blot analysis. The results of the current study indicated that injured animals in the combined treatment group exhibited a significant increase in BBB scores (P<0.05). TIIA + MP combined treatment and MP treatment was observed to reduce the expression of pro‑apoptotic factors and promote neuron survival in vivo and in vitro. Combined treatment may promote neuroprotection through reduced apoptosis and inflammation caused by ASCI, similar to MP alone. Combined treatment reversed the decrease of SOD and the increase of MDA level caused by ASCI. In addition, combined treatment decreased the expression of caspase‑3 in the neurons following ASCI in rats, as indicated by immunofluorescence double labeling. Overall, the present study indicates that the combined treatment of TIIA and MP may protect the neurons by stimulating the rapid initiation of neuroprotection following ASCI and reduce the dosage of MP in the treatment of ASCI required to produce the same or improved neuroprotective effects in vivo and in vitro.
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May-2017
Volume 13 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Yao NW, Lu Y, Shi LQ, Xu F and Cai XH: Neuroprotective effect of combining tanshinone IIA with low‑dose methylprednisolone following acute spinal cord injury in rats. Exp Ther Med 13: 2193-2202, 2017.
APA
Yao, N., Lu, Y., Shi, L., Xu, F., & Cai, X. (2017). Neuroprotective effect of combining tanshinone IIA with low‑dose methylprednisolone following acute spinal cord injury in rats. Experimental and Therapeutic Medicine, 13, 2193-2202. https://doi.org/10.3892/etm.2017.4271
MLA
Yao, N., Lu, Y., Shi, L., Xu, F., Cai, X."Neuroprotective effect of combining tanshinone IIA with low‑dose methylprednisolone following acute spinal cord injury in rats". Experimental and Therapeutic Medicine 13.5 (2017): 2193-2202.
Chicago
Yao, N., Lu, Y., Shi, L., Xu, F., Cai, X."Neuroprotective effect of combining tanshinone IIA with low‑dose methylprednisolone following acute spinal cord injury in rats". Experimental and Therapeutic Medicine 13, no. 5 (2017): 2193-2202. https://doi.org/10.3892/etm.2017.4271