Isoflurane Differentially Affects Neurogenesis and Long-term Neurocognitive Function in 60-day-old and 7-day-old Rats
Isoflurane Differentially Affects Neurogenesis and Long-term Neurocognitive Function in 60-day-old and 7-day-old Rats
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DOI：
10.1097/aln.0b013e31819c463d
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发表时间：
2009-04-01
期刊：
影响因子：
8.8
通讯作者：
Dai, Ran
中科院分区：
文献类型：
--
作者：
Stratmann, Greg;Sall, Jeffrey W.;Dai, Ran
背景：麻醉剂导致发育中的啮齿类动物脑细胞死亡和长期的，主要是大脑依赖性的神经认知功能障碍。然而，这些发现之间的因果关系尚未得到证实。出生后海马神经发生影响海马功能直至成年;因此，作者检验了异氟烷通过影响齿状回神经发生影响长期神经认知功能的假设。在给予出生后第60天和第7天（P）的大鼠异氟烷4小时之前、期间和之后的不同时间给予S期标记物5-溴脱氧尿苷以评估齿状回祖细胞增殖，早期神经元谱系选择和新颗粒细胞神经元的长期存活。恐惧条件反射和空间参考记忆进行了测试，在不同的时间间隔从2周到8个月后anesthes.Results：在1160大鼠，异氟烷增加早期神经元分化评估BrdU/NeuroD costaining，祖细胞增殖减少1天，随后增加祖细胞增殖5-10天后麻醉。在P7大鼠中，异氟烷没有诱导神经元谱系选择，但降低祖细胞增殖，直到麻醉后至少5天。异氟醚改善P60大鼠的空间参考记忆的长期，但它造成了延迟发作，进行性，持续性海马赤字P7大鼠在恐惧条件反射和空间参考memorytasks.Conclusion：作者得出结论，异氟醚差异影响;神经发生;和长期的神经认知功能在P60和P7大鼠。不同年龄异氟醚给药后，神经发生可能介导长期神经认知结果。
Background: Anesthetic agents cause cell death in the developing rodent brain and long-term, mostly hippocampal-dependent, neurocognitive dysfunction. However, a causal link between these findings has not been shown. Postnatal hippocampal neurogenesis affects hippocampal function into adulthood; therefore, the authors tested the hypothesis that isoflurane affects long-term neurocognitive function via an effect on dentate gyrus neurogenesis.Methods: The S-phase marker 5-bromodeoxyuridine was administered at various times before, during, and after 4 h of isoflurane given to postnatal day (P)60 and P7 rats to assess dentate gyrus progenitor proliferation, early neuronal lineage selection, and long-term survival of new granule cell neurons. Fear conditioning and spatial reference memory was tested at various intervals from 2 weeks until 8 months after anesthesia.Results: in 1160 rats, isoflurane increased early neuronal differentiation as assessed by BrdU/NeuroD costaining, decreased progenitor proliferation for 1 day, and subsequently increased progenitor proliferation 5-10 days after anesthesia. In P7 rats, isoflurane did not induce neuronal lineage selection but decreased progenitor proliferation until at least 5 days after anesthesia. Isoflurane improved spatial reference memory of P60 rats long-term, but it caused a delayed-onset, progressive, persistent hippocampal deficit in P7 rats in fear conditioning and spatial reference memory tasks.Conclusion: The authors conclude that isoflurane differentially affects; both neurogenesis; and long-term neurocognitive function in P60 and P7 rats. Neurogenesis might mediate the long-term neurocognitive outcome after isoflurane at different ages.