Abstract: Abstract：Objective To investigate the effect of adipose-derived mesenchymal stem cells (ASC-ST) on the secondary brain edema of rats after traumatic brain injury (TBI) and its potential mechanisms. Methods Seventy SD rats were randomly divided into three groups: Sham group (n=18), TBI group (n=26) and TBI + ST group (n=26). TBI models were established by electric cortical contusion impactor (eCCI). Rats from sham group only received the craniectomy without impact. Rats from TBI + ST group were injected with 0.2 mL ASC-ST and 0.1 mL normal saline, while rats from TBI group were injected with 0.3 mL normal saline through tail veins after TBI. The injection was persisted for 7 days. Modified neurological function scores (mNSS) were performed on 8 rats from TBI and TBI+ST groups at 3, 7 and 14 days after TBI. Six rats of each groups accepted magnetic resonance imaging (MRI) at 3, 7 and 14 days after TBI. The water content of brain was measured, and total RNA was exacted from brain tissue of the injured lesions. The mRNA expression levels of TNF-α, IL- 1β and IL-6 were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Results At 14 and 21 days after TBI, rats from TBI + ST group got lower mNSS scores than those from TBI group (P＜0.05). At 3 days after TBI, compared with those in Sham group, the ADC values of ipsilateral cortex (IC) and contralateral cortex (CC) were higher in both TBI and TBI+ST groups (P＜0.05). At 7 days after TBI, the ADC values of IC and ipsilateral hippocampus (IH) were lower in TBI + ST group than those in TBI group (P＜0.05). At 14 days after TBI, ADC values of IC and CC were lower in TBI + ST group than those in TBI group (P＜0.05). At 3 and 7 days after TBI, the water content of brain tissue of TBI group was similar with TBI+ST group (P＞0.05). At 14 days after TBI, the water content of brain tissue was lower in TBI+ST group than that of TBI group (P＜0.05). At 3 days after TBI, the expression of IL-6 was extremely lower in Sham group than that in TBI and TBI+ST groups, while expression of TNF-α was higher in TBI+ST group than that in TBI and Sham groups, and expression of TNF-α was higher in TBI group than that of Sham group (P＜0.05). At 7 days after TBI, expressed levels of IL- 6 were lower in TBI+ST and Sham groups than those of TBI group, and the expression was lower in TBI+ST group than that in Sham group; The more mRNA expression of TNF-α was found in TBI group than Sham group, and more IL-1β than other groups; The more IL-1β expression was found in Sham group than TBI+ST group (all P＜0.05). At 14 days after TBI, both TBI+ST and Sham groups were found less mRNA of IL-6 than TBI group, TBI+ST group was found less TNF-α expression than other two groups, but the expression of IL-1β in TBI group was still higher than that in other groups (all P＜0.05). Conclusion ASC-ST can significantly reduce the brain edema of rats after TBI and improve the prognosis of neurological function by mitigating the inflammatory responses. It is a promising kind of biotherapeutic drug with high clinical value.

Key words: mesenchymal stem cells, brain injuries, brain edema, secretome of stem cells, traumatic brain injury, inflammation