Puls Robert, von Haefen Clarissa, Bührer Christoph, Endesfelder Stefanie
Department of Neonatology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.
Antioxidants (Basel). 2023 Apr 21;12(4):980. doi: 10.3390/antiox12040980.
Impaired cerebellar development of premature infants and the associated impairment of cerebellar functions in cognitive development could be crucial factors for neurodevelopmental disorders. Anesthetic- and hyperoxia-induced neurotoxicity of the immature brain can lead to learning and behavioral disorders. Dexmedetomidine (DEX), which is associated with neuroprotective properties, is increasingly being studied for off-label use in the NICU. For this purpose, six-day-old Wistar rats (P6) were exposed to hyperoxia (80% O) or normoxia (21% O) for 24 h after DEX (5 µg/kg, i.p.) or vehicle (0.9% NaCl) application. An initial detection in the immature rat cerebellum was performed after the termination of hyperoxia at P7 and then after recovery in room air at P9, P11, and P14. Hyperoxia reduced the proportion of Calb1+-Purkinje cells and affected the dendrite length at P7 and/or P9/P11. Proliferating Pax6+-granule progenitors remained reduced after hyperoxia and until P14. The expression of neurotrophins and neuronal transcription factors/markers of proliferation, migration, and survival were also reduced by oxidative stress in different manners. DEX demonstrated protective effects on hyperoxia-injured Purkinje cells, and DEX without hyperoxia modulated neuronal transcription in the short term without any effects at the cellular level. DEX protects hyperoxia-damaged Purkinje cells and appears to differentially affect cerebellar granular cell neurogenesis following oxidative stress.
早产儿小脑发育受损以及小脑功能在认知发育中的相关损害可能是神经发育障碍的关键因素。麻醉和高氧诱导的未成熟脑神经毒性可导致学习和行为障碍。右美托咪定（DEX）具有神经保护特性，越来越多地被研究用于新生儿重症监护病房（NICU）的超说明书用药。为此，在应用DEX（5μg/kg，腹腔注射）或赋形剂（0.9%氯化钠）后，将6日龄的Wistar大鼠（P6）暴露于高氧（80%氧气）或常氧（21%氧气）环境中24小时。在P7高氧结束后，然后在P9、P11和P14在室内空气中恢复后，对未成熟大鼠小脑进行初步检测。高氧降低了Calb1+浦肯野细胞的比例，并在P7和/或P9/P11影响了树突长度。高氧后直至P14，增殖的Pax6+颗粒祖细胞数量持续减少。神经营养因子以及增殖迁移和存活的神经元转录因子/标志物的表达也因氧化应激以不同方式降低。DEX对高氧损伤的浦肯野细胞具有保护作用，且无高氧环境时DEX在短期内调节神经元转录，但在细胞水平无任何影响。DEX保护高氧损伤的浦肯野细胞，并且在氧化应激后似乎对小脑颗粒细胞神经发生有不同影响。
