Department of Cardiothoracic Surgery, Heart Center, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Cardiothoracic Surgery, Heart Center, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
J Thorac Cardiovasc Surg. 2018 Dec;156(6):2271-2280. doi: 10.1016/j.jtcvs.2018.06.038. Epub 2018 Jul 18.
Periventricular leukomalacia is a common white-matter injury after neonatal cardiac surgery; however, its potential cellular mechanism remains uncertain. There is limited study regarding periventricular leukomalacia treatment.
A neonatal rat brain slice perfusion model was used for reproducing the condition of cardiopulmonary bypass, and oxygen glucose deprivation simulated circulatory arrest. Seven-day-old Sprague-Dawley rats were randomly divided into 7 groups: (1) control group with 36°C; (2) 60 minutes of oxygen glucose deprivation group on 15°C, 25°C, 36°C, respectively; and (3) 60 minutes of oxygen glucose deprivation group on 15°C, 25°C, 36°C, plus minocycline (10 μmol/L), respectively. Immunohistochemistry, Western blot, and inflammatory mediators were compared after the perfusion procedures in the different groups.
This neonatal rat brain slice perfusion with oxygen glucose deprivation model could replicate the pathophysiologic process and injury after cardiopulmonary bypass and hypothermic circulatory arrest. With the increase of oxygen glucose deprivation perfusion temperature, we found that both microglia activation and preoligodendrocyte loss increased. The application of minocycline can significantly inhibit microglial activation and preoligodendrocyte cells loss in the normothermic (36°C) and moderate hypothermia (25°C) oxygen glucose deprivation groups (P < .05), with accompanying significant decreasing microglial inflammatory productions; however, no significant improvement was found in the deep hypothermia (15°C) group.
The microglial activation may play a key role in preoligodendrocyte injury in the ex vivo neonatal rat brain slice perfusion and circulatory arrest model. Inhibition of microglial activation with minocycline may be an attractive target for white-matter protection during cardiopulmonary bypass and hypothermic circulatory arrest.
脑室周围白质软化症是新生儿心脏手术后常见的白质损伤，但潜在的细胞机制尚不确定。关于脑室周围白质软化症的治疗研究有限。
使用新生大鼠脑片灌流模型模拟体外循环，并模拟氧葡萄糖剥夺性循环停止。将 7 日龄 Sprague-Dawley 大鼠随机分为 7 组：（1）对照组，温度为 36°C；（2）分别在 15°C、25°C、36°C 下进行 60 分钟氧葡萄糖剥夺组；（3）分别在 15°C、25°C、36°C 下进行 60 分钟氧葡萄糖剥夺组，加用米诺环素（10 μmol/L）。比较各组灌流后免疫组织化学、Western blot 和炎症介质的变化。
该新生大鼠脑片氧葡萄糖剥夺灌流模型可复制体外循环和低温循环停止后的病理生理过程和损伤。随着氧葡萄糖剥夺灌流温度的升高，我们发现小胶质细胞激活和前少突胶质细胞丢失均增加。米诺环素的应用可显著抑制正常体温（36°C）和中度低温（25°C）氧葡萄糖剥夺组小胶质细胞激活和前少突胶质细胞丢失（P <.05），并伴随小胶质细胞炎症产物显著减少；然而，在深低温（15°C）组未见明显改善。
小胶质细胞激活可能在体外新生大鼠脑片灌流和循环停止模型中前少突胶质细胞损伤中起关键作用。用米诺环素抑制小胶质细胞激活可能是体外循环和低温循环停止期间保护白质的一个有吸引力的靶点。
