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，只是头部受到重击吗？脑震荡这个术语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，可能会让人在短时间内失去意识，头疼，甚至可能有些失忆。如果观看橄榄球和足球等运动，很多人可能见过脑震荡的发生，但他们可能不知道大多数脑震荡是由车祸和家庭暴力引起的。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引发痴呆等问题。我们开始明白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主要问题。然而，使用小鼠脑损伤模型，我们的研究表明，我们可能一直在寻找错误的地方。我们已经看到，在脑震荡后，大脑周围被称为脑膜的保护膜会发炎，另一个区域被称为小脑（拉丁语为“小脑”）。当一个人头部受伤时，我们通常不会去看这些大脑区域。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被研究的部位（脑膜和小脑）的炎症是否导致脑震荡后焦虑增加和大脑功能下降；2)开发新型的人类脑部扫描，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与索尔福德皇家NHS基金会信托的神经外科医生和神经成像专家合作开展这项工作。如果成功，我们希望找到新的方法来对患者的大脑进行成像，并找到新的目标区域来治疗脑震荡的影响。这是非常重要的，因为目前，我们对这些过程知之甚少，对受影响的人没有治疗选择。

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