Systemic Effects of Dietary n‐3 PUFA Supplementation Accompany Changes of CNS Parameters in Cerebral Hypoperfusion

Abstract

Dietary supplementation with long-chain polyunsaturated fatty acids (PUFAs) has become an attractive possibility to alleviate or prevent cerebrovascular pathophysiology. To characterize the potentially beneficial cerebrovascular action of n-3 PUFAs that predominantly occur in fish oil, we set up an experimental paradigm where rats with chronic cerebral hypoperfusion were supplied with n-3 PUFA-enriched diets. Cerebral hypoperfusion was created by a permanent, bilateral occlusion of the common carotid arteries (2VO) of rats at the age of 4 months, with a survival of 3 months. Simultaneously, the rats were provided with experimental diets from the time of weaning until the termination of the experiments. The control diet was comparable to standard rat chow, while diet 1 contained additional n-3 PUFAs and diet 2 was further enriched with structural phospholipids and neurotransmitter precursors. In summary, the data show that diet 2 improved spatial learning of 2VO rats in the Morris water maze. Both diet 1 and diet 2 augmented blood-brain barrier parameters and increased the density of the M1-type muscarinic cholinergic receptors in the hippocampus independent of the rate of cerebral perfusion. In addition to an overview of these results, changes that were supportive or accompanying those described in the CNS are also presented. Briefly, plasma corticosterone concentration was elevated most explicitly by 2VO, while the relative weight of the liver and spleen increased due to the diets. The data draw attention to changes not only in the CNS, but also in the periphery as a consequence of chronic supplementation with n-3 PUFA-enriched diets.

Interactive Effects of Dietary Resistant Starch and Fish Oil on Short-Chain Fatty Acid Production and Agonist-Induced Contractility in Ileum of Young Rats

“…In this regard, fish oil feeding of specifically DHA has been reported to augment the muscarinic agonist-induced chloride secretion in human intestinal T84 cells (31). Further, n-3 PUFA has been also been found to increase brain blood flow by increasing the density of hippocampal M 1 muscarinic cholinergic receptors (32). It has been reported that there are maturational changes of muscarinic receptor subtypes and their coupling to G proteins in rat colonic and ovine ileal smooth muscle (33).…”

The neuron-astrocyte-microglia triad in CA3 after chronic cerebral hypoperfusion in the rat: Protective effect of dipyridamole

“…The high motility of microglia that effectively monitor the status of the local surroundings may explain the decrease of microglia in CA3 SP and the increase in CA3 SL and SR where it endocytoses small cellular debris derived from apoptotic cells (Neumann et al 2009). Therefore, post-ischemic production of cytokines and recruitment of microglia to the damaged tissue (Farkas et al 2002) can facilitate tissue repair by increasing phagocytosis or phagoptosis, promoting the resolution of inflammation and exerting direct cytoprotective effects on surviving cells in the ischemic area. It would be of interest to investigate the modification of the number of microglia in the acute phase of brain chronic hypoperfusion, taking hippocampal sections at earlier times after 2VO-vehicle and make a comparison between CA3 and CA1 areas.…”

The neuron-astrocyte-microglia triad in a rat model of chronic cerebral hypoperfusion: protective effect of dipyridamole

“…The production of these cytokines is promoted by phagocytosis, occurs in concert with the removal of dead cells (Nathan and Ding, 2010), and may have both neuroprotective properties and anti-inflammatory effects (Liesz et al, 2009). Therefore, post-ischemic production of cytokines and/or endogenous glucocorticoids (Farkas et al, 2002) can facilitate tissue repair by promoting the resolution of inflammation and exerting direct cytoprotective effects on surviving cells in the ischemic area. The effect of the anti-inflammatory cytokines could also explain the lack of modification in the percentage of resting/reactive microglia in 2VO-vehicle rats in comparison to sham rats.…”