Department of Anesthesiology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
J Alzheimers Dis. 2021;81(4):1685-1699. doi: 10.3233/JAD-201590.
Accumulating evidence has demonstrated that aging is associated with an exaggerated response to surgical trauma together with cognitive impairments. This has significant implications for the development of clinical phenotype such as perioperative neurocognitive disorders (PND), which is a common complication following surgery, especially for the elderly. However, the mechanism by which aging brain is vulnerable to surgical trauma remains to be elucidated.
To test whether age-related alterations in hippocampal network activities contribute to increased risk of PND following surgery.
Thirty-two adult and seventy-two aged male C57BL/6 mice undergone sevoflurane anesthesia and exploratory laparotomy were used to mimic human abdominal surgery. For the interventional study, mice were treated with minocycline. Behavioral tests were performed post-surgery with open field, novel object recognition and fear conditioning tests, respectively. The brain tissues were then harvested and subjected to biochemistry studies. Local field potential (LFP) recording was performed in another separate experiment.
Aged mice displayed signs of neuroinflammation, as reflected by significantly increased proinflammatory mediators in the hippocampus. Also, aged mice displayed persistently decreased oscillation activities under different conditions, both before and after surgery. Further correlation analysis suggested that theta power was positively associated with time with novel object, while γ oscillation activity was positively associated with freezing time to context. Of note, downregulation of neuroinflammation by microglia inhibitor minocycline reversed some of these abnormities.
Our study highlights that age-related hippocampal oscillation dysregulation increases the risk of PND incidence, which might provide diagnostic/prognostic biomarkers for PND and possible other neurodegenerative diseases.
越来越多的证据表明，衰老与手术创伤后的过度反应以及认知障碍有关。这对临床表型的发展有重要影响，例如围手术期神经认知障碍（PND），这是手术后的常见并发症，尤其是老年人。然而，衰老大脑易受手术创伤影响的机制仍有待阐明。
测试海马网络活动的年龄相关性改变是否导致手术后 PND 风险增加。
32 只成年和 72 只老年雄性 C57BL/6 小鼠接受七氟醚麻醉和剖腹探查术，以模拟人类腹部手术。在干预研究中，小鼠用米诺环素治疗。手术后分别进行旷场、新物体识别和恐惧条件反射测试。然后采集脑组织进行生化研究。在另一个单独的实验中进行局部场电位（LFP）记录。
老年小鼠表现出神经炎症的迹象，反映出海马体中促炎介质显著增加。此外，老年小鼠在手术前后的不同条件下表现出持续降低的振荡活动。进一步的相关分析表明，θ功率与新物体的时间呈正相关，而γ 振荡活动与上下文的冻结时间呈正相关。值得注意的是，小胶质细胞抑制剂米诺环素下调神经炎症可逆转其中一些异常。
我们的研究强调，与年龄相关的海马体振荡失调增加了 PND 发生率的风险，这可能为 PND 及其他可能的神经退行性疾病提供诊断/预后生物标志物。
