NAD⁺ depletion drives age-related monocyte hyperinflammation after stroke and is reversed by nicotinamide riboside

Mica Cabrera^#^{1

2}, Brent Eastman^#³, Hannah Ennerfelt¹, Abrar I Alsaadi⁴, Ludmila Alexandrova⁵, Yeonglong Albert Ay¹, Jolie Huang^{1

6}, Qian Wang¹, Eran Blacher^{1

7}, Melanie R McReynolds⁴, Katrin I Andreasson^{1

8}, Chinyere Agbaegbu Iweka^{9

10}

Affiliations

¹ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
² Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
³ Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁴ Department of Biochemistry and Molecular Biology, Huck Institutes of the Life Sciences, Pennsylvania State University University Park, PA, USA.
⁵ Mass Spectrometry Center, Stanford University, Stanford, CA, USA.
⁶ Stanford Neurosciences Graduate Program, Stanford University, Stanford, CA, USA.
⁷ Department of Biological Chemistry,, The Hebrew University of Jerusalem, Jerusalem, Israel.
⁸ Chan Zuckerberg Biohub, San Francisco, CA, USA.
⁹ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA. cxi60@case.edu.
¹⁰ Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. cxi60@case.edu.

^# Contributed equally.

Free article

Mica Cabrera et al. J Neuroinflammation. 2025.

Free article

. 2025 Nov 27.

doi: 10.1186/s12974-025-03638-6. Online ahead of print.

¹ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
² Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
³ Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁴ Department of Biochemistry and Molecular Biology, Huck Institutes of the Life Sciences, Pennsylvania State University University Park, PA, USA.
⁵ Mass Spectrometry Center, Stanford University, Stanford, CA, USA.
⁶ Stanford Neurosciences Graduate Program, Stanford University, Stanford, CA, USA.
⁷ Department of Biological Chemistry,, The Hebrew University of Jerusalem, Jerusalem, Israel.
⁸ Chan Zuckerberg Biohub, San Francisco, CA, USA.
⁹ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA. cxi60@case.edu.
¹⁰ Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. cxi60@case.edu.

^# Contributed equally.

No abstract available

Keywords: Aging; Gut; Inflammation; Metabolism; Monocytes; NAD+; Nicotinamide riboside; Quinolinic acid; Stroke.

Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

1. Offner H, Subramanian S, Parker SM, Afentoulis ME, Vandenbark AA, Hurn PD. Experimental stroke induces massive, rapid activation of the peripheral immune system. J Cereb Blood Flow Metab. 2006;26(5):654–65. PubMed PMID: 16121126. Epub 2005/08/27.
1. Ritzel RM, Lai YJ, Crapser JD, Patel AR, Schrecengost A, Grenier JM, et al. Aging alters the immunological response to ischemic stroke. Acta Neuropathol. 2018;136(1):89–110. PubMed PMID: 29752550. PMCID: PMC6015099. Epub 20180511.
1. Androvic P, Kirdajova D, Tureckova J, Zucha D, Rohlova E, Abaffy P, et al. Decoding the transcriptional response to ischemic stroke in young and aged mouse brain. Cell Rep. 2020;31(11):107777. PubMed PMID: 32553170.
1. O’Neill LA, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists. Nat Rev Immunol. 2016;16(9):553–65. PubMed PMID: 27396447. PMCID: PMC5001910. Epub 20160711.
1. Minhas PS, Liu L, Moon PK, Joshi AU, Dove C, Mhatre S, et al. Macrophage de Novo NAD(+) synthesis specifies immune function in aging and inflammation. Nat Immunol. 2019;20(1):50–63. PubMed PMID: 30478397. PMCID: PMC6768398. Epub 2018/11/28.