Figure 5.

Metformin promotes neurological functional recovery and tissue repair after SCI in aged mice.

(A, B) Functional evaluation of locomotor recovery in aged mice treated with PBS or metformin and in the sham group as determined by BMS scoring over 56 days. Metformin markedly promoted hindlimb functional recovery in aged mice after SCI compared with the PBS group. (C) Sensory function analysis based on withdrawal threshold in aged mice treated with PBS or metformin and the sham group post-injury. Metformin markedly promoted hindlimb sensory recovery in aged mice after SCI compared with the PBS group. (D) Representative electrophysiological traces from aged mice treated with PBS or metformin and the sham group post-injury at 56 days. Metformin markedly enhanced MEP amplitude and latency in aged mice after SCI compared with the PBS group. (E, F) Quantification of amplitudes and the latency period in aged mice treated with PBS or metformin and the sham group. (G) Representative H&E-stained transverse sections from the injury epicenter from the different groups. The aged mice exhibited smaller lesions and more healthy tissue compared with the PBS group after SCI. Red lines indicate the lesion area. Scale bar: 200 μm. (H, I) Quantification of the health and lesioned tissue area data shown in G. (J) Representative images of footprint analysis of aged mice before surgery and 56 days post-SCI treated with PBS or metformin. Longer stride length and less paw rotation were observed after metformin administration. (K, L) Quantification of the stride length and paw rotation data shown in J. The data are presented as the mean ± SEM (n = 6 per group). #P < 0.05, ##P < 0.01; †P < 0.05, ††P < 0.01, vs. aged mice post-SCI with PBS treatment (two-tailed Student’s t-test [A–C], or one-way analysis of variance followed by Tukey’s multiple comparisons test [E, F, H, I, K, and L]). BMS: Basso Mouse Scale; H&E: hematoxylin-eosin; MEP: motor evoked potential; PBS: phosphate buffer saline; SCI: spinal cord injury.