Brain region-specific immune responses driving concussion-related injury

大脑区域特异性免疫反应导致脑震荡相关损伤

• 批准号: MR/V032925/1
• 负责人: Andrew Greenhalgh
• 金额: $ 175.44万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV032925%2F1
• 关键词: Brain; region; specific; immune; responses

Concussion - just a bang on the head?The term concussion is part of everyday vocabulary. People know that it refers to a pretty severe bang on the head, that may leave the person unconscious for a short period, with a headache and possibly even some memory loss. Many people may have seen a concussion occur, if they watch sports such as rugby and football, but they may not know that most concussions occur due to car accidents and domestic violence. The other thing people may not know is that, in the long-term, concussion may cause mood swings and anxiety, or even problems like dementia in later life. We are beginning to understand that concussion is more dangerous than we thought, though we still don't know why. One issue for scientists is that normal brain scans are not sensitive enough to show any major problems in the brains of people concussion. However, using models of brain injury in mice, our research suggests that we may have been looking in the wrong places. We have seen that a protective membrane around the brain, called the meninges, becomes inflamed after a concussion, as does another area called the cerebellum (latin for 'littlebrain'). We do not usually look at these brain areas when someone has a head injury. Therefore, our work has two major aims:1) Test in animal models if the inflammation in these two understudied places (the meninges and cerebellum) are responsible for increases in anxiety and reduced brain function after concussion 2) Develop new types of brain scans in people, so we can see these processes in those who have suffered a concussionWe will do this work at the University of Manchester within the world leading Lydia Becker Institute of Immunology and Inflammation in collaboration with neurosurgeons and neuroimaging experts at Salford Royal NHS Foundation Trust. If successful we hope to find new ways to image the brains of patients and new target areas for therapies against the effects of concussion. This is extremely important as, at the moment, we have little understanding of these processes no treatment options for those affected.

脑震荡——只是头部受到撞击？脑震荡一词是日常词汇的一部分。人们知道，它指的是头部受到相当严重的撞击，可能会导致人短时间失去知觉，伴有头痛，甚至可能会丧失记忆。许多人可能在观看橄榄球和足球等体育运动时见过脑震荡的发生，但他们可能不知道大多数脑震荡是由于车祸和家庭暴力而发生的。人们可能不知道的另一件事是，从长远来看，脑震荡可能会导致情绪波动和焦虑，甚至在以后的生活中出现痴呆等问题。我们开始认识到脑震荡比我们想象的更危险，尽管我们仍然不知道为什么。科学家面临的一个问题是，正常的脑部扫描不够灵敏，无法显示脑震荡患者大脑中的任何重大问题。然而，通过使用小鼠脑损伤模型，我们的研究表明我们可能找错了地方。我们已经看到，大脑周围的保护膜（称为脑膜）在脑震荡后会发炎，另一个称为小脑（拉丁语“小脑”）的区域也会发炎。当某人头部受伤时，我们通常不会观察这些大脑区域。因此，我们的工作有两个主要目标：1）在动物模型中测试这两个未研究部位（脑膜和小脑）的炎症是否会导致脑震荡后焦虑增加和大脑功能下降2）开发新型人类脑部扫描，以便我们可以在遭受脑震荡的人身上看到这些过程我们将在曼彻斯特大学世界领先的莉迪亚贝克尔免疫学和炎症研究所进行这项工作 与索尔福德皇家 NHS 基金会信托基金的神经外科医生和神经影像专家合作。如果成功，我们希望找到对患者大脑进行成像的新方法以及针对脑震荡影响的治疗的新目标区域。这非常重要，因为目前我们对这些过程知之甚少，也没有针对受影响者的治疗选择。

项目成果

N-3 PUFA Deficiency Affects the Ultrastructural Organization and Density of White Matter Microglia in the Developing Brain of Male Mice.

• DOI: 10.3389/fncel.2022.802411
• 发表时间: 2022
• 期刊: Frontiers in cellular neuroscience
• 影响因子: 5.3
• 作者: Decoeur F;Picard K;St-Pierre MK;Greenhalgh AD;Delpech JC;Sere A;Layé S;Tremblay ME;Nadjar A
• 通讯作者: Nadjar A

Microglia states and nomenclature: A field at its crossroads.

• DOI: 10.1016/j.neuron.2022.10.020
• 发表时间: 2022-11-02
• 期刊: NEURON
• 影响因子: 16.2
• 作者: Paolicelli, Rosa C.;Sierra, Amanda;Stevens, Beth;Tremblay, Marie-Eve;Aguzzi, Adriano;Ajami, Bahareh;Amit, Ido;Audinat, Etienne;Bechmann, Ingo;Bennett, Mariko;Bennett, Frederick;Bessis, Alain;Biber, Knut;Bilbo, Staci;Blurton-Jones, Mathew;Boddeke, Erik;Brites, Dora;Brone, Bert;Brown, Guy C.;Butovsky, Oleg;Carson, Monica J.;Castellano, Bernardo;Colonna, Marco;Cowley, Sally A.;Cunningham, Colm;Davalos, Dimitrios;De Jager, Philip L.;de Strooper, Bart;Denes, Adam;Eggen, Bart J. L.;Eyo, Ukpong;Galea, Elena;Garel, Sonia;Ginhoux, Florent;Glass, Christopher K.;Gokce, Ozgun;Gomez-Nicola, Diego;Gonzalez, Berta;Gordon, Siamon;Graeber, Manuel B.;Greenhalgh, Andrew D.;Gressens, Pierre;Greter, Melanie;Gutmann, David H.;Haass, Christian;Heneka, Michael T.;Heppner, Frank L.;Hong, Soyon;Hume, David A.;Jung, Steffen;Kettenmann, Helmut;Kipnis, Jonathan;Koyama, Ryuta;Lemke, Greg;Lynch, Marina;Majewska, Ania;Malcangio, Marzia;Malm, Tarja;Mancuso, Renzo;Masuda, Takahiro;Matteoli, Michela;McColl, Barry W.;Miron, Veronique E.;Molofsky, Anna Victoria;Monje, Michelle;Mracsko, Eva;Nadjar, Agnes;Neher, Jonas J.;Neniskyte, Urte;Neumann, Harald;Noda, Mami;Peng, Bo;Peri, Francesca;Perry, V. Hugh;Popovich, Phillip G.;Pridans, Clare;Priller, Josef;Prinz, Marco;Ragozzino, Davide;Ransohoff, Richard M.;Salter, Michael W.;Schaefer, Anne;Schafer, Dorothy P.;Schwartz, Michal;Simons, Mikael;Smith, Cody J.;Streit, Wolfgang J.;Tuan Leng Tay;Tsai, Li-Huei;Verkhratsky, Alexei;von Bernhardi, Rommy;Wake, Hiroaki;Wittamer, Valerie;Wolf, Susanne A.;Wu, Long-Jun;Wyss-Coray, Tony
• 通讯作者: Wyss-Coray, Tony