1. Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition & Behaviour, Nijmegen, The Netherlands
2. Department of Geriatric Medicine, Radboud university medical center, Donders Institute for Brain, Cognition & Behaviour, Nijmegen, The Netherlands
3. European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms University Münster, Münster, Germany
4. Department of Clinical Radiology of the University Hospital, Westfälische Wilhelms University Münster, Münster, Germany
5. Advanced Medical Nutrition, Nutricia Research, Utrecht, The Netherlands
6. Department of Radiology & Nuclear Medicine, Radboud university medical center, Nijmegen, The Netherlands
7. Department of Geriatrics, Johanniter Hospital, Evangelische Kliniken, Bonn, Germany
† Bastian Zinnhardt and Maximilian Wiesmann contributed equally to the present work and share first authorship.
‡ Andreas H Jacobs and Amanda J Kiliaan share last authorship.
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.
Keywords: Cerebral Ischemia, Neuroinflammation, Cerebral Connectivity, Cerebral Blood Flow, MRI, PET, Animal Model