Background Neonatal caffeine treatment might affect brain development. Long-term studies show conflicting results on brain-related outcomes. Herein we aimed to investigate the long-term effects of neonatal caffeine administration in a rabbit model of preterm birth. Methods Preterm (born day 29) and term (day 32) pups were raised by wet nurses and allocated to treatment with saline or caffeine for 7 or 17 days. At pre-puberty, neurobehavioral tests were performed and brains were harvested for immunostaining of neurons, synapses, myelin, and astrocytes. Results Survival was lower in preterm saline pups than in controls, whereas caffeine-treated preterm pups did not differ from term control pups. Preterm saline pups covered less distance compared to controls and were more likely to stay in the peripheral zone of the open field. Corresponding differences were not seen in preterm caffeine pups. Preterm animals had lower neuron density compared to controls, which was not influenced by caffeine treatment. Synaptic density, astrocytes, and myelin were not different between groups. Conclusion Caffeine appeared to be safe. All preterm rabbits had lower neuron density but anxious behavior seen in preterm saline rabbits was not seen in caffeine-treated preterm pups.

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新生儿咖啡因治疗对早产兔模型的长期神经学影响

背景 新生儿咖啡因治疗可能会影响大脑发育。长期研究显示与大脑相关的结果相互矛盾。在此，我们旨在研究在早产兔模型中给予新生儿咖啡因的长期影响。方法 早产（出生第 29 天）和足月（第 32 天）幼崽由奶妈抚养，并分配给生理盐水或咖啡因治疗 7 或 17 天。在青春期前，进行神经行为测试并收获大脑用于神经元、突触、髓鞘和星形胶质细胞的免疫染色。结果 早产盐水幼崽的存活率低于对照组，而咖啡因处理的早产幼崽与足月对照组幼崽没有差异。与对照组相比，早产盐水幼崽覆盖的距离更短，更有可能留在开阔场地的外围区域。在早产的咖啡因幼崽中没有看到相应的差异。与对照组相比，早产动物的神经元密度较低，这不受咖啡因治疗的影响。突触密度、星形胶质细胞和髓鞘在各组之间没有差异。结论 咖啡因似乎是安全的。所有早产兔都有较低的神经元密度，但在早产盐水兔中观察到的焦虑行为在咖啡因处理的早产幼崽中未观察到。