Preclinical mechanistic study
Therapeutic Effect of Nicotinamide Mononucleotide for Hypoxic–Ischemic Brain Injury in Neonatal Mice
Takuya Kawamura, Gagandeep Singh Mallah, Maryam Ardalan, Tetyana Chumak, Pernilla Svedin, Lina Jonsson, Seyedeh Marziyeh Jabbari Shiadeh, Fanny Goretta, Tomoaki Ikeda, Henrik Hagberg, Mats Sandberg, Carina Mallard
ASN Neuro · 2023 · 15:17590914231198983
Study at a glance
- Design
- Randomized-within-litter, blinded preclinical neonatal mouse hypoxia–ischemia intervention with acute biochemical, histologic, developmental, motor, and memory assessments.
- Population or model
- Postnatal-day-9 male and female mice exposed to unilateral carotid ligation and hypoxia; naïve animals provided reference values.
- Sample size
- Varied by endpoint, generally 6–21 mice per group; main long-term behavioral groups were approximately 18–21 per group
- Intervention
- A single intraperitoneal NMN dose immediately after hypoxia–ischemia; 50, 150, and 300 mg/kg were used in dose-ranging work and 50 mg/kg in the main long-term experiments, versus saline.
- Publication type
- Animal intervention study
- Evidence class
- preclinical-mechanistic
- Research area
- Neonatal hypoxic–ischemic brain injury
- Trial registration
- Not reported (animal study)
Study endpoints
- Hippocampal NAD+, SIRT1, and SIRT6
- Caspase-3 activity and HMGB1 release
- Brain tissue loss and neuroinflammation
- Early developmental behavior
- Motor and memory function at approximately six weeks
Plain-language summary
Key findings
Limitations
Funding and transparency
Funding
Swedish Research Council (VR2021-01872 to Carina Mallard and VR2019-01320 to Henrik Hagberg); Public Health Service at Sahlgrenska University Hospital (ALFGBG-966107 to Carina Mallard and ALFGBG-965174 to Henrik Hagberg); Swedish Brain Foundation (FO2022-0110 to Carina Mallard and FO2021-0056 to Henrik Hagberg); Åhlen Foundation to Carina Mallard; Stiftelsen Wilhelm och Martina Lundgrens Vetenskapsfond (2022-3947 to Seyedeh Marziyeh Jabbari Shiadeh); and Lundbeck Foundation (R322-2019-2721 to Maryam Ardalan).
Competing interests
The authors declared no potential conflicts of interest with respect to the research, authorship, or publication of the article.
HealthspanX observation
The treatment was administered immediately after an experimentally induced injury in neonatal mice and was not combined with therapeutic hypothermia, the current clinical standard of care.
Interpretive weight
Mechanistic context
Randomized and blinded animal experiments provide mechanistic context, but neonatal mouse injury, immediate intraperitoneal dosing, and absence of human data sharply limit clinical translation.
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