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NAD( + ) precursor nutritional supplements sensitize the brain to future ischemic events

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单位： [1]Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [2]Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA [3]Division of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA [4]Division of Nephrology and Department of Medicine, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA [5]Peritz Scheinberg Cerebral Vascular Disease Laboratories, Department of Neurology, The University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA [6]Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX, USA [7]Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

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关键词： Cerebral ischemia nicotinamide adenine dinucleotide oxidative phosphorylation sirtuin-1 proliferator-activated receptor-gamma coactivator 1

摘要：

Nicotinamide adenine dinucleotide (NAD(+)) is a redox cofactor critical for oxidative phosphorylation. Nicotinamide (NAM) and nicotinamide riboside (NR) are NAD(+) precursors widely used as nutritional supplements to augment oxidative phosphorylation. Indeed, NAD(+) precursors have been reported to improve outcomes in ischemic stroke when administered as a rescue therapy after stroke onset. However, we have also reported that enhanced reliance on oxidative phosphorylation before ischemia onset might worsen outcomes. To address the paradox, we examined how NAD(+) precursors modulate the outcome of middle cerebral artery occlusion in mice, when administered either 20 minutes after reperfusion or daily for three days before ischemia onset. A single post-ischemic dose of NAM or NR indeed improved tissue and neurologic outcomes examined at 72 hours. In contrast, pre-ischemic treatment for three days enlarged the infarcts and worsened neurological deficits. As a possible explanation for the diametric outcomes, a single dose of NAM or NR augmented tissue AMPK, PGC1 alpha, SIRT1, and ATP in both naive and ischemic brains, while the multiple-dose paradigm failed to do so. Our data suggest that NAD(+) precursor supplements may sensitize the brain to subsequent ischemic events, despite their neuroprotective effect when administered after ischemia onset.

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出版当年[2022]版：

大类 | 1 区

医学

小类 | 1 区神经科学 1 区内分泌学与代谢 2 区血液学

最新[2025]版：

大类 | 2 区医学

小类 | 2 区内分泌学与代谢 2 区血液学 2 区神经科学

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出版当年[2021]版：

Q1 ENDOCRINOLOGY & METABOLISM Q1 NEUROSCIENCES Q2 HEMATOLOGY

最新[2024]版：

Q1 HEMATOLOGY Q1 NEUROSCIENCES Q2 ENDOCRINOLOGY & METABOLISM

影响因子： 4.5 最新[2024版] 6.3 最新五年平均 6.597 出版当年[2021版] 7.261 出版当年五年平均 6.2 出版前一年[2020版] 6.3 出版后一年[2022版]

第一作者：

第一作者单位： [1]Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [2]Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA

通讯作者：

通讯机构： [2]Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA [4]Division of Nephrology and Department of Medicine, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA [6]Division of Nephrology, Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX, USA [7]Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA [*1]Massachusetts General Hospital, Harvard Medical School, Boston, MA USA. [*2]University of Texas Southwestern Medical School, Dallas, TX, USA.

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NAD( + ) precursor nutritional supplements sensitize the brain to future ischemic events

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