Background: Traumatic spinal cord injury (SCI) is a major clinical concern, and it is a life-changing neurological condition with substantial socioeconomic implications. Muscone has been widely used in traditional Chinese medicinal formulations for its anti-inflammatory activity. However, its protective effects on traumatic SCI have not been explored. This study investigated whether muscone plays a protective role in SCI and compared its effects with those of methylprednisolone sodium succinate (MPSS).Methods: Rats were divided into five groups: normal saline (NS; n=24), methylprednisolone (MP; w=24), and muscone 1 (MO1), muscone 2 (MO2), and muscone 3 (MO3) (n=24 in each group, collectively called the MOx groups). The SCI rat model was established by the modified Allen's method. The rats were administered muscone (MO1: 2.5 mg/kg, MO2: 5 mg/kg, and MO3: 10 mg/kg) or MP (30 mg/kg), or an equivalent volume of saline. The rats were kept under observation for 4 weeks. Malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA). The expression of glial fibrillary acidic protein (GFAP), B-cell lymphoma-2 (BCL-2), and caspase3 was detected by western blot analysis. Hematoxylin-eosin (HE), Nissl, and immunocytochemistry (ICC) staining was performed for pathological observation. Basso-Beattie-Bresnahan motor function scores were evaluated for assessment of neural functions after acute SCI.Results: Muscone inhibited immune-inflammatory reactions, neuronal necrosis, and apoptosis. The lower limb function recovery was better in the MOx groups compared with NS and MP groups according to Basso-Beattie-Bresnahan scores. The changes were remarkable in the MO2 group compared with the other groups.Conclusions: Muscone alleviates secondary injury after SCI by reducing immune-inflammatory reactions, neuronal necrosis, and apoptosis.

Background Traumatic spinal cord injury (SCI) is a major clinical concern and a life-changing neurological condition with substantial socioeconomic implications. The initial mechanical force applied to the spinal cord at the time of injury is known as the primary injury. After the primary injury, ischemia and hypoxia induce cell death and autolysis, which are associated with the release of a group of inflammatory factors and biologically active substances, such as superoxide dismutase (SOD), malonaldehyde (MDA), lactate dehydrogenase (LDH), and tumor necrosis factor-α (TNF-α). These processes are called the secondary injury, and may lead to an excess of extracellular glutamate (Glu), which in turn promotes the neuronal injuries. Muscone has been shown to have anti-inflammatory effects in the treatment of brain diseases and other diseases. However, to date, no study has examined the effects of muscone in the treatment of SCI. Methods Astrocytes were separated and purified by the method of short-term exposure combining with differential sticking wall. Astrocyte was identified by glial fibers acidic protein (GFAP) selecting cell immunochemical staining. A mechanical-chemical damage (MCD) model was established via the primary spinal astrocytes of rats, and treatment was administered with different concentrations of muscone. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) was detected at 6, 12, 24, 48 and 72 h. SOD, MDA, LDH, TNF-alpha and intracellular calcium was detected at 3, 6 and 12 h. Glu in supernatant was detected respectively at 3, 6 and 12 h by enzyme-linked immunosorbent assay (ELISA) method. Intracellular calcium was detected respectively at 3, 6 and 12 h by flow cytometry method. MRNA expression of excitatory amino acid transporters (EAATs) and GFAP were detected by the quantitative reverse transcription polymerase chain reaction (qRT-PCR) method and protein expression of those by western blot at 6 h. Results Muscone reduced the levels of LDH, TNF-α, and MDA after injury, and upregulated the level of SOD. Muscone also reduced the density of extracellular Glu and suppressed the intracellular calcium level. Additionally, it decreased the expression levels of EAATs and GFAPs. Conclusions Muscone has a protective effect on astrocytes in a MCD and inhibits astrocytes’ proliferation.