1000 Section - Tetrahedral Framework Nucleic Acids Promote Functional Recovery after Spinal Cord Injury by Stabilizing Mitochondrial Dynamics

Spinal cord injury (SCI) involves primary mechanical damage followed by secondary destructive processes, including inflammation and glial scar formation, which exacerbate neuronal loss and hinder recovery. Tetrahedral framework nucleic acids (tFNAs), a DNA nanomaterial known for its anti-inflammatory and mitochondrial regulatory properties, show therapeutic potential; however, their effect on neural regeneration in SCI and the underlying mechanisms remain largely unexplored.

Design:

This study investigates the therapeutic potential of tFNAs in spinal cord injury (SCI) through integrated in vitro and in vivo experiments. In vitro, primary neurons or NSC-34 cells subjected to oxygen-glucose deprivation (OGD) were treated with tFNAs. Neuronal apoptosis and mitochondrial function—assessed via TUNEL, immunofluorescence, JC-1, ATP quantification, GO/KEGG analysis, and mitochondrial functions were evaluated to explore the underlying mechanisms. For in vivo validation, a T10 complete SCI model in SD rats was established, including sham, SCI, SCI+NGF, and SCI+tFNAs groups. Recovery was monitored at 4 and 8 weeks post-injury using BBB scoring, video analysis, and histological examination.

Results:

tFNAs treatment regulated mitochondrial outer membrane permeabilization (MOMP), preserved mitochondrial dynamics, and reversed dysfunction. It elevated ATP production while reducing MDA and SOD levels, indicating suppressed oxidative stress and efficient ROS clearance in OGD-injured NSC-34 cells. PCR revealed that tFNAs stabilized mitochondrial dynamics by counteracting the SCI-induced increase in fission (Drp1, FIS) and decrease in fusion (Mfn1/2). Furthermore, walking video analysis and BBB scores confirmed significant functional recovery, with tFNAs-treated rats exhibiting extensive hindlimb movement and ankle dorsiflexion after 4 weeks, contrasting sharply with the limited joint movement in the NGF group and no response in SCI controls.

Conclusion:

In conclusion, tFNAs were effective in neural regeneration and movement rehabilitation. tFNAs could be a promising treatment option for spinal cord injury.