Figure 4.
Sustained STAT3 expression promotes functional recovery following pyramidotomy. (A) Schematic representation of the pyramidotomy paradigm used for assessing behavioural recovery. (B) Quantification of the number of pellets eaten by mice injected with Control rAAV (grey line, n=23) or rAAV-STAT3 (red line, n=28) at different test intervals up to 10 w following pyramidotomy and at 3 days following lesion of the contralateral CST tract (contralateral PTX, n=13). (C) Schematic representation of the cortical stimulations and EMG recordings that we used to quantify circuit reconnection after pyramidotomy. (D) Trace of a forelimb EMG recording after cortical stimulation. (E) Quantification of the percentage of responsive sites contralateral to the lesion in unlesioned mice (black bar, n=6 mice) and ipsilateral to the lesion acutely following pyramidotomy (white bar) and 12 w following pyramidotomy in mice injected with Control rAAV (grey bar) or rAAV-STAT3 (red bar, n=6–8 mice per group). A contralateral pyramidotomy 12 w following the initial lesion and injection of rAAV-STAT3 abolishes the ipsilateral responses (red bar, contralateral PTX; n=5 mice). (F,G) Quantification of the stimulation thresholds (F) and latencies (G) of the forelimb responses in unlesioned mice (black bars, contralateral to lesion) in mice injected with Control rAAV (grey bars, ipsilateral to the lesion) or rAAV-STAT3 (red bars, ipsilateral to the lesion) at 12 w following pyramidotomy (n=5–8 mice per group). All bars and error bars in this figure represent mean±s.e.m. Statistical analysis was performed using a repeated one-way ANOVA followed by Tukey test in B and a one-way ANOVA followed by Tukey test in E, F, G. *P<0.05; **P<0.01; ***P<0.001. ##P<0.01 10 w re-lesion vs 10 w. ANOVA, analysis of variance; CST, corticospinal tract; EMG, electromyography; SCI, spinal cord injury; STAT3, signal transducer and activator of transcription 3.