Involvement of acute neuroinflammation in postoperative delirium-like cognitive deficits in rats
Involvement of acute neuroinflammation in postoperative delirium-like cognitive deficits in rats
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DOI：
10.1007/s00540-018-2504-x
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发表时间：
2018-08-01
影响因子：
2.8
通讯作者：
Yokoyama, Masataka
中科院分区：
文献类型：
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作者：
Kawano, Takashi;Yamanaka, Daiki;Yokoyama, Masataka
本研究的目的是研究大鼠术后年龄、时间和脑区域依赖性神经炎症轨迹及其与神经认知结果的关系。成年和老年大鼠随机分为三组：对照组、单独异氟醚麻醉组和异氟醚麻醉合并腹部手术组。在术后第2天（早期）或第7天（后期），所有大鼠在获得痕量恐惧条件反射后进行痕量和情境恐惧记忆保留测试。冻结行为被用作恐惧记忆的一个指标。认知测试后，使用酶联免疫吸附法测量几个脑区域的促炎细胞因子水平（每组n = 8）。术后早期，异氟醚麻醉下的手术可引起急性神经炎症，并伴有相关的痕迹和情境记忆功能障碍。这种急性神经炎症反应在成年和老年动物中都可以比较地观察到，而老年大鼠更有可能表现出行为变化。另一方面，在术后后期，成年动物在所有测试的大脑区域都没有发现神经炎症，也没有发现伴随的记忆衰退。仅在老年大鼠海马中检测到显著的神经炎症，这与环境有关，但不存在痕迹记忆功能障碍。我们的研究结果表明，手术引起的急性、短暂性、全脑神经炎症可能参与了大鼠术后谵妄样认知缺陷的发病机制。此外，神经炎症可能以年龄和海马特异性的方式从急性转变为慢性，可能导致持续认知功能障碍的发展。
The purpose of this study was to investigate the age-, time-, and brain region-dependent postoperative neuroinflammatory trajectory, and its association with neurocognitive outcomes in rats.Adult and aged rats were randomly assigned to one of three groups: control, isoflurane anesthesia alone, and isoflurane anesthesia with abdominal surgery. On either postoperative day 2 (early phase) or 7 (late phase), all rats were tested for trace and context fear memory retention after acquisition of trace fear conditioning. Freezing behavior was used as an index of fear memory. Following the cognitive testing, the levels of pro-inflammatory cytokines in several brain regions were measured using enzyme-linked immunosorbent assay (n = 8 in each group).In the early postoperative period, surgery under isoflurane anesthesia induced acute neuroinflammation along with related trace and context memory dysfunction. Such acute neuroinflammatory responses were comparably observed in both adult and aged animals, whereas the aged rats were more likely to exhibit behavioral changes. On the other hand, in the late postoperative period, neither neuroinflammation in all tested brain regions nor concomitant memory decline were found in adult animals. Significant neuroinflammation was detected only in the hippocampus of aged rats, which was associated with context, but not trace memory dysfunction.Our findings indicate that surgery-induced acute, transient, brain-wide neuroinflammation may be involved in the pathogenesis of the postoperative delirium-like cognitive deficits in rats. Furthermore, neuroinflammation may convert from acute to chronic in an age- and hippocampal-specific manner, likely resulting in the development of sustained cognitive dysfunction.