Temporal profiles of apoptosis-related markers and locomotor recovery during repetitive transcranial magnetic stimulation after spinal cord injury in female rats.

Abstract

Spinal cord injury (SCI) triggers a cascade of secondary injury processes, among which apoptosis contributes to neuronal loss and functional deterioration. Repetitive transcranial magnetic stimulation (rTMS) is a promising non-invasive neuromodulatory intervention for SCI, but the temporal profiles of apoptosis-related markers during a defined treatment course have not been fully characterized. An SCI model was established in female rats using a modified Allen's method, and active rTMS or sham stimulation was initiated on post-injury day 2. Animals received the assigned intervention once daily until the prespecified endpoint. Molecular, immunofluorescence, TUNEL, histopathological, and locomotor outcomes were assessed after 3, 7, and 14 consecutive days of intervention. SCI was associated with increased Bax and cleaved caspase-3 expression and reduced Bcl-2 expression. Compared with sham-stimulated SCI animals, the SCI+rTMS group showed lower Bax expression at all examined intervention endpoints and lower cleaved caspase-3 expression and higher Bcl-2 expression after 7 and 14 days of intervention. Caspase-8 findings differed between western blotting and immunofluorescence and did not support consistent regulation by rTMS. These molecular differences were accompanied by lower mean counts of TUNEL-positive nuclei per field and morphometric evidence of smaller cavity areas and greater preserved tissue areas at all examined intervention endpoints, as well as higher BBB locomotor scores at the 14-day intervention endpoint. Overall, the findings describe temporally evolving associations between rTMS, apoptosis-related markers, lesion-area DNA strand-break labeling, and locomotor recovery after SCI, while causal involvement of a specific signaling pathway remains to be established.