Loss of hindlimb function after ablation of reactive astrocytes adjacent to stab SCI. A, Time course of left hindlimb (HL) locomotor performance in an open field over 14 d after ipsilateral stab SCI in control mice and GFAP-TK transgenic mice given GCV (Tg+GCV). Three groups of control mice were evaluated: nontransgenic mice not given GCV, nontransgenic mice given GCV, and transgenic mice not given GCV. No significant difference was detected among these control groups (ANOVA), and their values were pooled to a single control value. Control mice (n = 14) exhibited no visibly detectable impairment of ipsilateral hindlimb performance after stab SCI, whereas transgenic mice given GCV (n = 7) exhibited a gradual but ultimately substantial and significant impairment during and after ablation of reactive astrocytes. ***Significantly different from control, p < 0.001 (ANOVA plus post hoc pair-wise analysis). B, Time course of rotorod performance after SCI of control mice and GFAP-TK transgenic mice given GCV. Control mice (n = 9; pooled values of three groups not significantly different by ANOVA) exhibited an initial mild impairment of rotorod performance after stab SCI that was fully reversible by 14 d. In contrast, transgenic mice given GCV (n = 5) failed to recover rotorod performance during and after ablation of reactive astrocytes and by 14 d exhibited a substantial and significant impairment. ***Significantly different from control, p < 0.001 (ANOVA plus post hoc pair-wise analysis). C, Representative footprint analysis at 14 d after stab SCI of a control mouse and a GFAP-TK transgenic mouse given GCV. Footprints of a control mouse illustrate normal plantar placement of forepaws and hindpaws. In contrast, footprints of a transgenic mouse given GCV show no plantar placement of the left (L, ipsilateral) hindpaw (circles show placement of only the left forepaw), which is indicative of foot dragging on the dorsal surface. In addition, the right (R, contralateral) hindpaw shows smears (arrow) indicative of toe dragging.