Buyang huanwu decoction combined with BMSCs transplantation promotes recovery after spinal cord injury by rescuing axotomized red nucleus neurons

Abstract

Ethnopharmacological relevance: Buyang huanwu decoction (BYHWD) is a classic recipe in traditional Chinese medicine (TCM) to supplement Qi and activate blood. It has been used to recover the neural function after the injury of central nervous system for hundreds of years in China.

Aim of the study: This study investigated whether Buyang huanwu decoction (BYHWD) combined with bone marrow mesenchymal stem cells (BMSCs) transplantation had synergistic effect on neuroprotection of red nucleus neurons after spinal cord injury (SCI).

Materials and methods: Rubrospinal tract (RST) transection model was established and BMSCs were collected. The forelimb locomotor function was recorded using inclined plate test and spontaneous vertical exploration. cAMP level in red nucleus was detected with Enzyme-linked immunosorbent assay (ELISA). Morphology and number of red nucleus neurons was observed using Nissl's staining. Expression of cAMP-response element binding protein (CREB), ras homolog gene family member A (RhoA) and nerve growth factor (NGF) in red nucleus was detected using immunohistochemistry, qRT-PCR and Western-blotting.

Results: The combination of BYHWD and BMSCs transplantation could improve the forelimb locomotor function significantly and give the red nucleus somas a better protection. Meanwhile, cAMP level, CREB and NGF increased, while RhoA decreased remarkably in the BYHWD+BMSCs group.

Conclusions: BYHWD combined with BMSCs transplantation had synergistic effect on neuroprotection of red nucleus neurons after SCI; the mechanism may be related to up-regulating cAMP level, activating the cAMP/CREB/RhoA signaling pathway, and promoting expression of NGF.

Keywords: Bone marrow mesenchymal stem cells (BMSCs); Buyang huanwu decoction (BYHWD); Cyclic adenosine monophosphate (cAMP); Rubrospinal tract (RST); Spinal cord injury (SCI).