Hem Santiago, Albite Romina, Loresi Monica, Rasmussen Jorge, Ajler Pablo, Yampolsky Claudio, Chabot Joseph D, Gerszten Peter C, Goldschmidt Ezequiel
Department of Neurosurgery, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Institute of Basic Sciences and Experimental Medicine, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
Acta Neurochir (Wien). 2016 Nov;158(11):2163-2171. doi: 10.1007/s00701-016-2938-6. Epub 2016 Sep 8.
Postoperative cognitive dysfunction (POCD) is a known complication after intracranial surgery. Impaired hippocampal neurogenesis has been associated with cognitive dysfunction in animal models.
In order to assess hippocampal changes after brain surgery, a frontal lobe corticectomy was performed in ten adult Wistar rats (group 4). Three different control groups (n = 10 each) included no treatment (G1), general anesthesia alone (G2), and craniectomy without dural opening (G3). Twenty-four hours after surgery, half of the animals were killed, and the mRNA levels for IL-6, TNF-α, and brain-derived growth factor (BDNF) in the contralateral hippocampus were assessed by qPCR. Seven days later, the remaining animals underwent anxiety and memory testing. Afterwards, the number of immature neurons in the hippocampal cortex was measured by doublecortin (DCX) staining.
Twenty-four hours after surgery, mRNA levels of IL-6 and TNF-α increased and BDNF decreased in both surgical groups G3 and G4 (p = 0.012). Cognitive tests demonstrated an increase in anxiety levels and memory impairment in surgical groups compared with non-surgical animals. These changes correlated with an inhibition of hippocampal neurogenesis evidenced by a decreased number of new neurons (mean ± SD for G1-4: 66.4 ± 24; 57.6 ± 22.2; 21.3 ± 3.78; 5.7 ± 1.05, p < 0.001, non-parametric ANOVA).
Intracranial surgery was demonstrated to induce an inflammatory reaction within the hippocampus that compromised neurogenesis and impaired normal cognitive processing. Corticectomy had a greater effect than craniotomy alone, indicating a central trigger for hippocampal inflammatory changes. POCD after craniotomy may originate from a central inflammatory response resulting from surgical trauma to the brain parenchyma.
术后认知功能障碍（POCD）是颅内手术后已知的并发症。在动物模型中，海马神经发生受损与认知功能障碍有关。
为了评估脑部手术后海马的变化，对十只成年Wistar大鼠进行了额叶皮质切除术（第4组）。三个不同的对照组（每组n = 10）包括不进行治疗（G1）、仅进行全身麻醉（G2）和开颅但不打开硬脑膜（G3）。手术后24小时，处死一半动物，通过qPCR评估对侧海马中白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和脑源性神经营养因子（BDNF）的mRNA水平。七天后，其余动物接受焦虑和记忆测试。之后，通过双皮质素（DCX）染色测量海马皮质中未成熟神经元的数量。
手术后24小时，手术组G3和G4中IL-6和TNF-α的mRNA水平升高，BDNF水平降低（p = 0.012）。认知测试表明，与非手术动物相比，手术组的焦虑水平增加且记忆受损。这些变化与海马神经发生的抑制相关，新神经元数量减少证明了这一点（G1 - 4的平均值±标准差：66.4±24；57.6±22.2；21.3±3.78；5.7±1.05，p < 0.001，非参数方差分析）。
颅内手术被证明会在海马内引发炎症反应，损害神经发生并损害正常认知过程。皮质切除术的影响比单纯开颅手术更大，表明是海马炎症变化的一个主要触发因素。开颅术后的POCD可能源于手术对脑实质造成创伤引起的中枢炎症反应。
