This study evaluated the effects of intraperitoneal injections of NMN after spinal cord injury in mice.
Key Points:
Treatment with NMN injections showed several benefits after SCI:
- Restored NAD+ levels
- Improved motor function
- Reduced pain levels
- Controlled inflammatory response
- Demonstrated efficacy of i.p. NMN injection, bypassing gastrointestinal (GI) metabolism
Study Evaluates NMN Injection on Spinal Cord Injury in Mice
The researchers used a surgical procedure to induce moderate-to-severe spinal cord injury (SCI) in the mice.
Mice were injected with 500 mg/kg of NMN (equivalent to approximately 40 mg/kg in humans) or saline immediately after surgery, followed by daily injections for seven days.
Twenty-four mice were divided into four groups (n = 6 per group):
- Sham group: surgery without injury
- Sham + NMN group: surgery without injury + NMN
- SCI group: surgery with injury
- SCI + NMN group: surgery with injury + NMN
Restored NAD+ Levels After Injury
The levels of NAD+ were measured in the spinal cord tissue of the mice.
In the figure below, untreated mice with SCI displayed a decline in spinal cord NAD+ levels (pink bar on the right). However, mice treated with NMN (blue bar on the right) did not experience this drop; instead, their NAD+ levels resembled those of healthy mice (bars on the left).
“After spinal cord injury in mice, the NAD + content in spinal cord tissue decreases, and this deficiency can be compensated by supplementation with NMN.”
Promoted Motor Function Recovery
NMN treatment markedly enhanced motor function in mice with spinal cord injury, starting at the 3-week mark post-injury and persisting throughout the entire 8-week study period.
The figure below depicts motor function scores (BMS) of mice
The upper lines represent healthy mice receiving saline (black line) or NMN (yellow line). Motor function (BMS) scores in injured mice show a quick decline on Day 3 after injury. From Day 21 onward, NMN-treated injured mice (blue line) consistently have improved scores compared to untreated injured mice (red line).
Alleviated Pain
Administration of NMN significantly alleviated pain in mice with SCI, beginning two weeks after the injury and sustaining this effect throughout the entire 8-week study.
Pain was not apparent in healthy mice on a standard diet (black line) or treated with NMN (yellow line). In mice with SCI-induced pain, NMN treatment significantly improved pain scores (blue line) compared to untreated mice with SCI (red line) at each time point.
Controlled Inflammatory Response
The researchers used a specialized technique to look at the effects of NMN on a wide range of genes.
“NMN exerts neuroprotective effects after SCI by the regulation of certain genes acting on signaling pathways related to neurological diseases.”
In particular, NMN modulated genes related to inflammation and cell death. The inflammatory molecules IL-1β, TNF-α, IL-17A, IRF7, CCL3, and Cxcl10 were reduced in SCI mice treated with NMN.
This figure shows the levels of the inflammatory molecule, TNF-α, were significantly elevated in untreated SCI mice (blue bar) compared to healthy mice on a standard diet (black bar) or treated with NMN (gray bar). Treatment with NMN in mice with SCI (pink bar) significantly reduced the levels of TNF-α.
Demonstrated Efficacy of NMN Injection, Bypassing GI Metabolism
This study demonstrated the effectiveness of i.p. NMN injection (500 mg/kg) on SCI when administered immediately after injury and for the following seven days.
Importantly, i.p. injections delivers NMN directly to the bloodstream, bypassing the metabolism in the gut often associated with oral administration.
This method tends to yield different results compared to oral delivery because the injected molecule is not susceptible to degradation during administration.
Conclusion
Treatment with NMN injections restored NAD+ levels and significantly improved motor function and pain severity in mice with SCI.
“The reduction of NAD+ levels after SCI can be compensated by NMN supplementation, which can significantly restore motor function and relieve pain in a mouse model.”
NMN modulated the inflammatory response after SCI and promoted cellular health.
“NMN exerted neuroprotective effects and inhibited inflammatory response by regulating gene expression levels.”