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Updated: Jul 23, 2025
07:52
Remote Limb Ischemic Preconditioning: A Neuroprotective Technique in Rodents
Published on: June 2, 2015
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NAD precursor nutritional supplements sensitize the brain to future ischemic events
Wensheng Qu1,2, Kenneth M Ralto3,4, Tao Qin2
1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Summary
Nicotinamide adenine dinucleotide (NAD+) precursors like NAM and NR show neuroprotective effects when given after ischemic stroke. However, pre-stroke treatment with these supplements may worsen outcomes by altering cellular metabolism.
Area of Science:
- Neuroscience
- Biochemistry
- Metabolism
Background:
- Nicotinamide adenine dinucleotide (NAD+) is vital for cellular energy production.
- NAD+ precursors, nicotinamide (NAM) and nicotinamide riboside (NR), are popular supplements.
- Previous studies show conflicting results regarding NAD+ precursor efficacy in ischemic stroke.
Purpose of the Study:
- To investigate the dual effects of NAD+ precursors on ischemic stroke outcomes.
- To compare the impact of post-ischemic administration versus pre-ischemic administration of NAM and NR.
Main Methods:
- Middle cerebral artery occlusion (MCAO) model in mice.
- Administration of NAM or NR either 20 minutes after reperfusion or daily for three days before MCAO.
- Assessment of infarct volume, neurological deficits, and key metabolic markers (AMPK, PGC1α, SIRT1, ATP).
Main Results:
- A single post-ischemic dose of NAM or NR improved neurological and tissue outcomes.
- Pre-ischemic treatment with NAM or NR for three days worsened stroke outcomes, increasing infarct size.
- Post-ischemic NAD+ precursor administration upregulated AMPK, PGC1α, SIRT1, and ATP, an effect not observed with pre-ischemic treatment.
Conclusions:
- NAD+ precursors exhibit neuroprotective effects when administered therapeutically after ischemic stroke.
- Pre-treatment with NAD+ precursors may sensitize the brain to ischemia, potentially worsening outcomes.
- The timing of NAD+ precursor administration is critical for determining their impact on ischemic stroke. The underlying metabolic changes induced by NAD+ precursors may explain these differential effects.
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