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. 2021 Jul 15;38(15):2186–2191. doi: 10.1089/neu.2020.7504

FIG. 2.

FIG. 2.

Inhibition of central soluble tumor necrosis factor-alpha (sTNFα) signaling via intrathecal XPro1595 starting 2 weeks post-spinal cord injury (SCI) does not affect colorectal distension (CRD)-induced autonomic dysreflexia. (a, b) Continuous basal hemodynamic activity was measured prior to injury and at biweekly time points post-complete transection at the T3 spinal segment (T3Tx). In both groups, baseline mean arterial pressure (MAP) was significantly reduced following injury and persisted up to 8 weeks post-injury (wpi) (a). Injury also significantly increased heart rate (HR) and persisted in both groups (b). No differences between treatment groups were observed at any time point. (c, d) Representative traces of beat-to-beat arterial pressure (mm Hg) before, during, and after CRD in T3Tx-Saline (n = 11) and T3Tx-XPro1595 (n = 15) treated rats 8 wpi. The 1 min CRD event is indicated by the red line and MAP is indicated by the white line in the traces. Both T3Tx-Saline (c) and -XPro1595 (d) treated animals exhibit a sharp spike in MAP in response to CRD. (e) The severity of these CRD-induced MAP spikes significantly increases over 2–8 weeks post-SCI in both treatment groups. XPro1595 treatment initiated 2 wpi did not attenuate this sharp spike in MAP compared with saline-treated controls. (f) There was no difference within groups or across time in the duration of CRD-induced AD events, measured as time (seconds) to return to baseline MAP after the 1-min CRD period. (g) Inhibition of sTNFα beginning 2 wpi also had no significant effect on attenuating concomitant CRD-induced bradycardia, indicated as change (Δ) in HR beats per minute (bpm), compared with controls. In both treatment groups, such reflexive bradycardia significantly worsened over 2–8 weeks post-SCI, further demonstrating that AD worsens over time (e, g). Values represent mean ± standard error of the mean (S.E.M.). *p < 0.05; **p < 0.01; ****p < 0.0001. P values were determined by two-way mixed-analysis of variance (ANOVA) and post-hoc Fisher's Least Significant Difference (LSD) tests. Color image is available online.