Su Xuewen, Yuan Haifeng, Bai Yuxin, Chen Junlong, Sui Mingze, Zhang Xiaomei, Liang Yanyan, Feng Wanyu, Dou Zhongxia, Zhu Hua
Inner Mongolia People's Hospital, Hohhot, China.
Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
Pediatr Neurosurg. 2020;55(4):188-196. doi: 10.1159/000509521. Epub 2020 Oct 9.
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.
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.
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.
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.
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.
白质损伤（WMI）是早产儿中最常见的脑损伤，可导致终身神经功能缺损。WMI的主要原因是脑内少突胶质前体细胞（OPC）受损，导致髓鞘形成延迟或现有髓鞘破坏。OPC经历高度调控且严格定时的发育变化，从而转化为能够产生髓鞘的成熟少突胶质细胞。
研究表明氯倍他索能强烈促进OPC分化为髓鞘。因此，我们假设氯倍他索可能是治疗早产儿WMI的一种治疗选择。
我们诱导建立了WMI大鼠模型，并在光学显微镜下观察白质损伤情况。早期治疗组从第1天至第5天，晚期治疗组从第6天至第10天，对遭受WMI的大鼠腹腔注射氯倍他索（每日2或5mg/kg）。17天后，处死大鼠，采用免疫荧光法观察髓鞘碱性蛋白（MBP）的表达。此外，我们使用电子显微镜评估髓鞘形成情况。还对大鼠进行悬吊试验、斜坡试验和旷场试验以评估神经行为功能。
成功诱导建立了WMI大鼠模型。发现氯倍他索能显著诱导遭受WMI大鼠的MBP表达和髓鞘形成，并改善其神经行为功能。
我们的结果表明氯倍他索通过促进OPC分化减轻WMI，它可能是治疗早产儿WMI的一种有效治疗药物。
