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The aim of the present study was to investigate the protective effects of miconazole on myelin sheaths following cerebral white matter damage (WMD) in premature infant rats. Sprague Dawley rats (3-days-old) were randomly divided into four groups (n=30 each) as follows: Sham surgery group, WMD model group, 10 mg/kg/day treatment group and 40 mg/kg/day treatment group. A cerebral white matter lesion model was created by ligating the right common carotid artery for 80 min. Treatment groups were administered with 10 or 40 mg/kg miconazole at 4–8 days following birth (early treatment group) or 5–11 days following birth (late treatment group). Rats in the model group received the same concentration of dimethylsulfoxide. Myelin basic protein (MBP) immunohistochemical staining and western blotting were used to detect the expression of cerebral white matter-specific MBP, and changes in myelin structure were observed using transmission electron microscopy. No swelling or necrosis was observed in the corpus callosum of the sham group rats, whereas rats in the model group demonstrated edema, loose structure, fiber disorder, inflammatory gliocytes and selective white matter lesions. Following treatment with miconazole, MBP expression in the corpus callosum was significantly higher compared with the model group. Furthermore, in the model group, myelin sheaths in the corpus callosum were loose with small vacuoles, there was a marked decrease in thickness and structural damage was observed. Conversely, a marked improvement in myelination was observed in the treatment group. The results of the present study suggest that miconazole is able to promote formation of the myelin sheath to ameliorate premature cerebral white matter lesions caused by ischemia or hypoxia in rats.

<b><i>Introduction:</i></b> White matter injury (WMI) is the most common brain injury in preterm infants and can result in life-long neurological deficits. The main cause of WMI is damage to the oligodendrocyte precursor cells (OPC) in the brain that results in delayed myelin sheath formation, or the destruction of existing myelin sheaths. OPC undergo highly regulated and strictly timed developmental changes that result in their transformation to mature oligodendrocytes capable of myelin production. <b><i>Objective:</i></b> Studies have shown that clobetasol strongly promotes differentiation of OPC into myelin sheaths. Therefore, we hypothesized that clobetasol may be a therapeutic option for the treatment of preterm WMI. <b><i>Methods:</i></b> We induced a WMI rat model and observed white matter damage under an optical microscope. Rats subjected to WMI were injected intraperitoneally with clobetasol (2 or 5 mg/kg daily) from day 1 to day 5 in the early treatment groups, or from day 6 to day 10 in the late treatment groups. After 17 days, the rats were sacrificed and the expression of myelin basic protein (MBP) was visualized using immunofluorescence. In addition, we evaluated myelin sheath formation using electron microscopy. The rats were also subjected to the suspension test, ramp test, and open field test to evaluate neurobehavioral functions. <b><i>Results:</i></b> A rat model of WMI was successfully induced. It was found that clobetasol significantly induced MBP expression and myelin sheath formation and improved neurobehavioral function in the rats subjected to WMI. <b><i>Conclusions:</i></b> Our results indicate that clobetasol attenuates WMI by promoting OPC differentiation, and it may be an effective therapeutic agent for the treatment of preterm WMI.

Incidence of white matter injury (WMI), which is featured as softening of white matter tissues, has recently increased. Previous studies have demonstrated a close correlation between T helper cell 1 and T helper cell 2 (Th1/Th2) imbalance and nuclear factor‑κB (NF‑κB) with brain disease. Their role in premature WMI, however, remains to be illustrated. Serum samples were collected from 60 premature WMI neonates, plus another control group of 60 premature babies without WMI. Patients were further divided into mild, moderate and severe WMI groups. Reverse transcription quantitative polymerase chain reaction was used to test mRNA expression levels of Th1/Th2 cytokines, including interleukin 2 (IL)‑2, tumor necrosis factor‑α (TNF‑α), IL‑4, IL‑10 and nuclear factor (NF)‑κB, whilst their serum levels were measured by ELISA. Their correlation with disease occurrence and progression were further analysed, to illustrate the effect of Th1/Th2 balance and NF‑κB on pathology of premature WMI. Serum levels of IL‑4 and IL‑10 were significantly decreased in premature WMI babies, whilst IL‑2, TNF‑α and NF‑κB were upregulated (P<0.05 vs. control group). With aggravated disease, IL‑4 and IL‑10 expression was further decreased while IL‑2, TNF‑α and NF‑κB were increased (P<0.05 vs. mild WMI group). Th1 cytokines IL‑2 and TNF‑α and NF‑κB were negatively correlated with Th2 cytokines IL‑4 and IL‑10. Disease severity was positively correlated with IL‑2, TNF‑α and NF‑κB expression, and was negatively correlated with IL‑4 and IL‑10 (P<0.05). Th1/Th2 imbalance and NF‑κB upregulation were observed in WMI pathogenesis, with elevated secretion of Th1 cytokines and decreased Th2 cytokines, suggesting that Th1/Th2 imbalance and NF‑κB upregulation may be a potential indicator for the early diagnosis and treatment of WMI pathogenesis and progression.