==== Front EBioMedicineEBioMedicineEBioMedicine2352-3964Elsevier S2352-3964(18)30232-910.1016/j.ebiom.2018.06.023CommentaryThe injured brain might need more fat! Hyacinth Hyacinth I. Laney Graduate School Neuroscience Program and The Aflac Cancer and Blood Disorder Center of Children's Healthcare of Atlanta and Emory Department of Pediatrics Atlanta, GA, USA29 6 2018 7 2018 29 6 2018 33 12 13 21 6 2018 21 6 2018 © 2018 The Author2018This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Keywords MicroinfarctsCognitive declineOmega-3 polyunsaturated fatty acids ==== Body One of the benefits of medical and technological advances is the increase in life expectancy and thus, an increase in the proportion of the “oldest (≥80 years)” individuals in the general population [1]. The increase in number and proportion of “oldest” individuals has resulted in an increase in the incidence and prevalence of dementia and other age-related cognitive impairment [1]. A common observation in the brains of individuals with dementia, especially vascular cognitive dementias (VCIDs), are microinfarcts [9, 10]. Cerebral microinfarcts result from the loss of blood flow through cortical-penetrating micro-vessels (arteriole or venule) supplying or draining a neurovascular unit [3, 4]. These microinfarcts are usually asymptomatic until cognitive symptoms develop decades later when the individual is much older. As such, identifying at-risk individuals and providing neuroprotective protective molecules is required to reduce the impact, and thus complications resulting from the presence and burden of cerebral microinfarcts. Studies have suggested a neuroprotective role for the omega-3 polyunsaturated fatty acids (PUFAs) (Lo Van [5]). A recently published study [6] hypothesized that omega-3 PUFAs will protect against the development of cerebral microinfarcts and association symptoms. This study utilized an endogenous and exogenous model/approach and showed that omega-3 PUFAs not only protected the development and severity of cerebral microinfarcts but also ameliorated cerebral microinfarct-associated neurological symptoms such as learning and anxiety. A potential mechanism proposed by the authors was that omega-3 PUFAs inhibit and thus prevented receptor-interacting serine/threonine protein kinase 1 (RIPK1)-dependent apoptosis of neurons after a cerebral microinfarction [6]. While preclinical and some clinical studies indicate that omega-3 PUFAs have a health benefit with regards to neuroprotection and/or cardio-protection, the overall evidence has been inconclusive. For instance, in a systematic review and meta-analysis, Rizos et al. [8] reported that use of omega-3 PUFAs was not associated with significant reduction in all-cause mortality, reduction in the incidence of stroke or cardiovascular endpoint. But a recent report issued by the American Heart Association (AHA), indicated otherwise, reporting a benefit in reduction of cardiovascular and cerebrovascular outcomes with consistent intake (at least once-a-week consumption of seafood) of omega-3 PUFAs [7]. The conclusions from this AHA report [7] directly contradicted Rizos et al. [8], but supports the findings of the study recently published by Luo et al. [6]. The exact reason for this inconsistency in results and thus conclusions from these studies is unclear. But the report from the AHA indicates that the benefits of omega-3 PUFAs might be dependent on a consistent intake. Furthermore, although omega-3 PUFAs and their derivatives make up an integral portion of neural and other cellular membranes, they cannot be endogenously synthesized by humans and thus have to be consumed in the diet. In two separate clinical studies which also agreed with the conclusion of Luo et al., the benefits of omega-3 PUFAs on neuroprotection evidenced by improvement in cognition and reduction in the burden of subclinical microinfarcts [2, 11] were dependent on daily intake. This strict regimen might be responsible for some of the inconsistent result since it is well understood that medications requiring daily intake tend to be associated with significant non-compliance, which affects efficacy and thus the overall therapeutic benefits of the medication. Most omega-3 PUFAs are available over the counter with little to no information on how to use them for maximum benefit. It is the conclusion of the editorial commentary that more education is needed for both doctors and consumers in the most effective way to use medications containing omega-3 PUFAs. Disclosure The author declares no conflict of interest. ==== Refs References 1 Alzheimer's Association 2016 Alzheimer's disease facts and figures Alzheimers Dement 12 2016 459 509 27570871 2 Gao Q. omega-3 polyunsaturated fatty acid supplements and cognitive decline: Singapore longitudinal aging studies J Nutr Health Aging 15 2011 32 35 21267519 3 Hartmann D.A. Does pathology of small venules contribute to cerebral microinfarcts and dementia? J Neurochem 144 2018 517 526 28950410 4 Hyacinth H.I. Higher prevalence of spontaneous cerebral vasculopathy and cerebral infarcts in a mouse model of sickle cell disease J Cereb Blood Flow Metab 2017 [271678X17732275] (Epub Ahead of Print) 5 Lo Van A. Targeting the brain with a neuroprotective omega-3 fatty acid to enhance neurogenesis in hypoxic condition in culture Mol Neurobiol 2018 (Epub Ahead of Print) 6 Luo C. Enriched brain omega-3 polyunsaturated fatty acids confer neuroprotection against microinfarction 2018 [EBioMedicine] 7 Rimm E.B. Seafood long-chain n-3 polyunsaturated fatty acids and cardiovascular disease: a science advisory from the American Heart Association Circulation 2018 (Epub Ahead of Print) 8 Rizos E.C. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis JAMA 308 2012 1024 1033 22968891 9 Shih A.Y. Rodent models of cerebral microinfarct and microhemorrhage Stroke 49 2018 803 810 29459393 10 van Veluw S.J. Detection, risk factors, and functional consequences of cerebral microinfarcts Lancet Neurol 16 2017 730 740 28716371 11 Virtanen J.K. Circulating omega-3 polyunsaturated fatty acids and subclinical brain abnormalities on MRI in older adults: the cardiovascular health study J Am Heart Assoc 2 2013 e000305