Laparotomy-Induced Peripheral Inflammation Activates NR2B Receptors on the Brain Mast Cells and Results in Neuroinflammation in a Vagus Nerve-Dependent Manner.
Laparotomy-Induced Peripheral Inflammation Activates NR2B Receptors on the Brain Mast Cells and Results in Neuroinflammation in a Vagus Nerve-Dependent Manner.
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剖腹手术引起的外周炎症激活脑肥大细胞上的 NR2B 受体，并以迷走神经依赖性方式导致神经炎症
DOI：
10.3389/fncel.2022.771156
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发表时间：
2022
影响因子：
5.3
通讯作者：
Li NN
中科院分区：
文献类型：
--
作者：
Yang J;Dong HQ;Liu YH;Ji MH;Zhang X;Dai HY;Sun ZC;Liu L;Zhou J;Sha HH;Qian YN;Li QG;Yao H;Li NN
背景：多年来，术后认知功能障碍(POCD)的病理生理机制仍不清楚。手术引起的神经炎症已被认为是POCD发生发展的重要因素。许多研究还表明，迷走神经在将周围损伤信号传递到中枢神经系统(CNS)以及由此引起的神经炎症中发挥着重要作用。以前，我们已经证明，脑肥大细胞(BMC)作为第一反应者，在神经炎症和POCD中起着至关重要的作用。然而，在POCD中，迷走神经与骨髓细胞之间的联系尚不清楚。方法：在目前的研究中，我们首次强调了迷走神经在手术引起的神经炎症中作为传导高速公路的作用。在我们的模型中，我们测试了早期接受单侧颈迷走神经切断术(VGX)的小鼠是否比剖腹手术(LP)后的假手术小鼠有更少的神经炎症。为了进一步研究肥大细胞和谷氨酸在这一过程中的作用，我们利用KitW-sh小鼠和原代骨髓来源的MC再次验证了MC上的谷氨酸-NR2B轴。结果：Lp后4h即有较高水平的谷氨酸和BMCs活性。同时，迷走神经切断术可部分阻断急性期外周炎症引起的神经炎症反应，部分阻断炎症反应。令人兴奋的是，抑制NR2B受体和敲除肥大细胞可以减轻谷氨酸诱导的神经炎症。结论：迷走神经是外周炎症向中枢神经系统传递的高速通道。骨髓细胞的激活引发了一系列神经炎性反应。抑制BMCs上NR2B受体可以减少谷氨酸诱导的BMCs活化、神经炎症和记忆障碍，为POCD提供了一种新的治疗策略。
Background: The pathophysiological mechanisms underlying postoperative cognitive dysfunction (POCD) remain unclear over the years. Neuroinflammation caused by surgery has been recognized as an important element in the development of POCD. Many studies also suggest that the vagus nerve plays an important role in transmitting peripheral injury signals to the central nervous system (CNS) and the resultant neuroinflammation. Previously, we have demonstrated that brain mast cells (BMCs), as the “first responders”, play a vital role in neuroinflammation and POCD. However, how the vagus nerve communicates with BMCs in POCD has not yet been clarified. Methods: In the current study, we highlighted the role of the vagus nerve as a conduction highway in surgery-induced neuroinflammation for the first time. In our model, we tested if mice underwent unilateral cervical vagotomy (VGX) had less neuroinflammation compared to the shams after laparotomy (LP) at an early stage. To further investigate the roles of mast cells and glutamate in the process, we employed KitW-sh mice and primary bone marrow-derived MCs to verify the glutamate-NR2B axis on MCs once again. Results: Our results demonstrated that there were higher levels of glutamate and BMCs activation as early as 4 h after LP. Meanwhile, vagotomy could partially block the increases and reduce neuroinflammation caused by peripheral inflammation during the acute phase. Excitingly, inhibition of NR2B receptor and knockout of mast cells can attenuateneuroinflammation induced by glutamate. Conclusion: Taken together, our findings indicate that the vagus is a high-speed pathway in the transmission of peripheral inflammation to the CNS. Activation of BMCs triggered a neuroinflammatory cascade. Inhibition of NR2B receptor on BMCs can reduce glutamate-induced BMCs activation, neuroinflammation, and memory impairment, suggesting a novel treatment strategy for POCD.
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影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
Glyx-13，NMDA受体甘氨酸位点功能性局部激动剂可增强认知并产生抗抑郁作用，而没有NMDA受体拮抗剂的心理副作用。
影响因子：
6.1
作者：
Moskal JR;Burch R;Burgdorf JS;Kroes RA;Stanton PK;Disterhoft JF;Leander JD
通讯作者：
Leander JD
影响因子：
4.2
作者：
Kamat, Pradip K.;Rai, Shivika;Nath, Chandishwar
通讯作者：
Nath, Chandishwar
影响因子：
3.7
作者：
Broncel A;Bocian R;Kłos-Wojtczak P;Konopacki J
通讯作者：
Konopacki J
影响因子：
2.9
作者：
Mawhinney LJ;de Rivero Vaccari JP;Alonso OF;Jimenez CA;Furones C;Moreno WJ;Lewis MC;Dietrich WD;Bramlett HM
通讯作者：
Bramlett HM