Figure 5.

Thoracic contusion or staggered hemisection injury induces chronic hypoxia that impairs locomotion. (a) Schematic of thoracic staggered-hemisection SCI, which transects all descending axons from the brain, including those containing monoaminergic neurons. (b) Video image sequence of a rat walking one month after receiving a staggered hemisection injury. Impaired hindlimb function while walking is evident from poor weight support (quantified as torso height above ground), leg extensor spasms (quantified as spasm time relative to step-cycle duration), slow steps (number of hindlimb plantar steps per step-cycle of front leg) and poor foot placement (caudal to behind hip). Hip (iliac crest), knee and ankle joints are shown with dots and lines. Arrow shows foot movement. (c) Effects of intrathecal application of GR127935 (10 mM in 30 μl) on locomotion, with locomotion phases annotated above. (d) Plots of mean locomotor parameters for each rat (circles) with staggered hemisection injury (3 - 5 weeks post injury), including body height, extensor spasm time, number of successful hindlimb steps and foot placement error, before and after application of GR127935 or transient breathing of 95% O₂ (90 s; with 5% CO₂; measured 10–15 min post treatment). n = 7 rats per treatment group. Error bars: s.e.m, bars: group means (e) Plots of mean locomotor parameters for each rats with contusion injury, in a similar format as d. Effects 1 and 24 h after treatment with NSD1015 (100 mM in 30 μl i.t.; NSD) were also measured. n = 9 rats for GR127935 and oxygen, and n = 6 for NSD. (f-g) Plots of pO₂ in uninjured (normal) rats (lumbar cord) and in SCI rats (caudal [lumbar] and rostral [thoracic] to the site of injury), before and 10-15 min after treatments with transient oxygen (95%, 90 s), GR127935 (GR, topically applied 30 μM), or RX821002 (RX, topical 5 μM). *P < 0.05: difference relative to normal cord or change with treatment.