Wiesmann Maximilian, Zinnhardt Bastian, Reinhardt Dirk, Eligehausen Sarah, Wachsmuth Lydia, Hermann Sven, Dederen Pieter J, Hellwich Marloes, Kuhlmann Michael T, Broersen Laus M, Heerschap Arend, Jacobs Andreas H, Kiliaan Amanda J
Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition & Behaviour, Nijmegen, The Netherlands; Department of Geriatric Medicine, Radboud university medical center, Donders Institute for Brain, Cognition & Behaviour, Nijmegen, The Netherlands.
European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms University Münster, Münster, Germany.
Theranostics. 2017 Jan 6;7(2):493-512. doi: 10.7150/thno.17559. eCollection 2017.
Occlusion of the middle cerebral artery (MCAo) is among the most common causes of ischemic stroke in humans. Cerebral ischemia leads to brain lesions existing of an irreversibly injured core and an ischemic boundary zone, the penumbra, containing damaged but potentially salvageable tissue. Using a transient occlusion (30 min) of the middle cerebral artery (tMCAo) mouse model in this cross-institutional study we investigated the neurorestorative efficacy of a dietary approach (Fortasyn) comprising docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium as therapeutic approach to counteract neuroinflammation and impairments of cerebral (structural+functional) connectivity, cerebral blood flow (CBF), and motor function. Male adult C57BL/6j mice were subjected to right tMCAo using the intraluminal filament model. Following tMCAo, animals were either maintained on Control diet or switched to the multicomponent Fortasyn diet. At several time points after tMCAo, behavioral tests, and MRI and PET scanning were conducted to identify the impact of the multicomponent diet on the elicited neuroinflammatory response, loss of cerebral connectivity, and the resulting impairment of motor function after experimental stroke. Mice on the multicomponent diet showed decreased neuroinflammation, improved functional and structural connectivity, beneficial effect on CBF, and also improved motor function after tMCAo. Our present data show that this specific dietary intervention may have beneficial effects on structural and functional recovery and therefore therapeutic potential after ischemic stroke.
大脑中动脉闭塞(MCAo)是人类缺血性中风最常见的病因之一。脑缺血会导致脑损伤,包括一个不可逆损伤的核心区域和一个缺血半暗带,即缺血边界区,其中包含受损但可能可挽救的组织。在这项跨机构研究中,我们使用大脑中动脉短暂闭塞(30分钟)的小鼠模型(tMCAo),研究了一种饮食方案(Fortasyn)的神经修复功效,该方案包含二十二碳六烯酸、二十碳五烯酸、尿苷、胆碱、磷脂、叶酸、维生素B12、B6、C和E以及硒,作为一种治疗方法来对抗神经炎症以及脑(结构+功能)连接性、脑血流量(CBF)和运动功能的损害。成年雄性C57BL/6j小鼠采用腔内栓线模型进行右侧tMCAo手术。tMCAo术后,动物要么维持对照饮食,要么改为多成分的Fortasyn饮食。在tMCAo后的几个时间点,进行行为测试、MRI和PET扫描,以确定多成分饮食对实验性中风后引发的神经炎症反应、脑连接性丧失以及由此导致的运动功能损害的影响。采用多成分饮食的小鼠在tMCAo后显示神经炎症减轻、功能和结构连接性改善、对CBF有有益影响,并且运动功能也得到改善。我们目前的数据表明,这种特定的饮食干预可能对缺血性中风后的结构和功能恢复具有有益作用,因此具有治疗潜力。