Ketogenic diet and quercetin promote the recovery of motor function in rats with spinal cord injury

Spinal cord injury (SCI) is a devastating neurological disorder, and currently, there are no effective therapeutic options to promote the recovery of motor function. Therefore, exploring safe and effective post-SCI repair strategies is crucial. In our study, we investigated the therapeutic effects of ketogenic diet (KD) and quercetin, both separately and in combination, on the recovery of motor and neurological functions in rats with SCI. Female Sprague-Dawley rats were randomly assigned to five groups: (i) sham-operated surgery (sham), (ii) spinal cord injury (injury), (iii) ketogenic diet (KD), (iv) quercetin (Que), and (v) ketogenic diet+quercetin (KD + Que). We used thoracic cord clamp compression to create the SCI model and studied the potential synergistic effects of quercetin and KD on functional restoration. The Basso, Beattie, and Bresnahan (BBB) tests were conducted to assess motor performance, while motor-evoked potentials (MEPs) were used to evaluate neurophysiological function. 4 weeks post-SCI, magnetic resonance imaging (MRI), histological examination, immunofluorescence staining, and western blotting were performed to investigate the mechanisms underlying the synergistic repair effects. Our findings revealed that the combined treatment significantly decreased cavity volume, reduced glial scarring, attenuated local inflammatory infiltration, and enhanced neurite structural preservation and myelin integrity compared to either the KD or quercetin alone. Additionally, the synergistic effect of the KD and quercetin on SCI recovery may be mediated through the NF-κB/NLRP3 pathway. In conclusion, a KD in conjunction with quercetin can facilitate the regaining of motor function following SCI by inhibiting the NF-κB/NLRP3 pathway.