A specific dietary intervention to restore brain structure and function after ischemic stroke

Abstract

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.

Effect of a multinutrient intervention after ischemic stroke in female C57Bl/6 mice

“…Group sizes were calculated based on the effect sizes (Type I error: 0.05, statistical power: 0.80), exclusion and mortality rates determined in our previous study (Wiesmann et al . ).…”

“…Furthermore, the Fortasyn diet contained a specific multinutrient composition comprising uridine, omega‐3 polyunsaturated fatty acids (PUFAs), choline, B vitamins, phospholipids, and antioxidants (the specific composition is specified in (Wiesmann et al . ). Both diets were manufactured and pelleted by Ssniff (Soest, Germany) and stored at −20°C until use.…”

“…; Wiesmann et al . ). In short, mice were anesthetized with isoflurane (Abbott Animal Health; 3.5% for induction and 1.8% for maintenance) in a 2 : 1 oxygen and N 2 O mixture and placed in a stereotactic holder.…”

“…; Wiesmann et al . ). In short, three regions of interest [ROI; cerebral cortex, hippocampus, and thalamus according to the atlas of Paxinos and Franklin (Paxinos and Franklin )] were analyzed by two researchers that were blinded to the treatment conditions.…”

“…In this study, the same batches of the diets as given to the mice in our previous study (Wiesmann et al . ) were used. Food intake was measured two times a week to calculate the average daily food intake per mouse.…”