Abstract
BACKGROUND: Neonatal hypoxic-ischemic brain damage (Hypoxic‑Ischemic Brain Damage, HIBD) is a severe neurological disorder caused by perinatal asphyxia. Its severe long-term sequelae impose a heavy burden on families and society. Therefore, effective early diagnosis and intervention for HIBD are crucial for improving prognosis. OBJECTIVE: To investigate the correlation between serum levels of interleukin-6 (IL-6), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) and the severity of hypoxic-ischemic brain damage (HIBD) in neonatal SD rats, as well as the effects of mesenchymal stem cells (MSCs) on serum cytokine levels and the repair of HIBD in rats. METHODS: 250 7-day-old SD rats were selected and a HIBD model was established using the Rice-Vannucci method. The rats were randomly divided into 5 groups: 1) control group; 2) mild HIBD group; 3) severe HIBD group; 4) mild HIBD + MSCs group; 5) severe HIBD + MSCs group. The MSCs intervention group rats were injected with MSCs into the lumbar spine 1 and 8 days after modeling. Longa scores were evaluated at 0, 3, 7, 11, and 15 days after modeling, and serum levels of IL-6, IL-18, and TNF-α were detected. Brain tissue was stained with hematoxylin-eosin (HE) for Longa scoring. The correlation between serum cytokines and the severity of brain injury was analyzed, and the regulatory effect of MSCs intervention on cytokine expression levels and its role in neural injury repair were further explored. RESULTS: (1) The Longa scores and serum levels of IL-6, IL-18, and TNF-α in the mild HIBD group and severe HIBD group were significantly higher than those in the control group at all stages (P < 0.05), and the severe HIBD group had significantly higher levels than the mild HIBD group at all stages (P < 0.05). (2) After treatment, HE staining showed that the brain tissue damage in the mild HIBD group and mild HIBD + MSCs group improved, and the Longa scores and serum levels of IL-6, IL-18, and TNF-α decreased significantly at all time points (D3, D7, D11, D15) after treatment compared to those before treatment (D0). The Longa scores and serum levels of IL-6, IL-18, and TNF-α in the mild HIBD + MSCs group and severe HIBD + MSCs group decreased significantly at each time point (D3, D7, D11, D15) after treatment compared to those before treatment (D0). CONCLUSION: The serum levels of IL-6, IL-18, and TNF-α in rats are positively correlated with the severity of HIBD and can reflect the degree of brain tissue injury. They can be used for disease assessment; mesenchymal stem cell treatment can significantly reduce the serum levels of IL-6, IL-18, and TNF-α in HIBD rats, alleviate inflammatory responses, improve symptoms, and repair brain injury.