Yazdani Armin, Khoja Zehra, Johnstone Aaron, Dale Laura, Rampakakis Emmanouil, Wintermark Pia
Division of Newborn Medicine, Department of Pediatrics, Montreal Children's Hospital, Montreal, Que., Canada.
Dev Neurosci. 2016;38(4):251-263. doi: 10.1159/000448327. Epub 2016 Sep 10.
Term asphyxiated newborns remain at risk of developing brain injury despite available neuropreventive therapies such as hypothermia. Neurorestorative treatments may be an alternative. This study investigated the effect of sildenafil on brain injury induced by neonatal hypoxia-ischemia (HI) at term-equivalent age. Neonatal HI was induced in male Long-Evans rat pups at postnatal day 10 (P10) by left common carotid ligation followed by a 2-hour exposure to 8% oxygen; sham-operated rat pups served as the control. Both groups were randomized to oral sildenafil or vehicle twice daily for 7 consecutive days. Gait analysis was performed on P27. At P30, the rats were sacrificed, and their brains were extracted. The surfaces of both hemispheres were measured on hematoxylin and eosin-stained brain sections. Mature neurons and endothelial cells were quantified near the infarct boundary zone using immunohistochemistry. HI caused significant gait impairment and a reduction in the size of the left hemisphere. Treatment with sildenafil led to an improvement in the neurological deficits as measured by gait analysis, as well as an improvement in the size of the left hemisphere. Sildenafil, especially at higher doses, also caused a significant increase in the number of neurons near the infarct boundary zone. In conclusion, sildenafil administered after neonatal HI may improve brain injury recovery by promoting neuronal populations.
足月窒息新生儿尽管有亚低温等可用的神经预防疗法，但仍有发生脑损伤的风险。神经修复治疗可能是一种替代方法。本研究调查了西地那非对足月等效年龄新生儿缺氧缺血（HI）所致脑损伤的影响。在出生后第10天（P10）对雄性Long-Evans大鼠幼崽进行左侧颈总动脉结扎，然后暴露于8%氧气中2小时，诱导新生儿HI；假手术大鼠幼崽作为对照。两组均随机分为每日两次口服西地那非或赋形剂，连续7天。在P27进行步态分析。在P30处死大鼠并取出大脑。在苏木精和伊红染色的脑切片上测量两个半球的表面。使用免疫组织化学对梗死边界区附近的成熟神经元和内皮细胞进行定量。HI导致明显的步态障碍和左半球大小减小。西地那非治疗导致步态分析测量的神经功能缺损得到改善，以及左半球大小得到改善。西地那非，尤其是高剂量时，还导致梗死边界区附近神经元数量显著增加。总之，新生儿HI后给予西地那非可能通过促进神经元群体来改善脑损伤恢复。
