Motor Recovery and Anatomical Evidence of Axonal Regrowth in Spinal Cord-Repaired Adult Rats

Abstract

Behavioral assessments of hindlimb motor recovery and anatomical assessments of extended axons of long spinal tracts were conducted in adult rats following complete spinal cord transection. Rats were randomly divided into 3 groups: 1) sham control group (laminectomy only; n = 12); 2) transection-only group, spinal cord transection at T8 (n = 20); and 3) experimental treatment group, spinal cord transection at T8, with peripheral nerve grafts (PNG) and application of acidic fibroblast growth factor (aFGF) (n = 14). The locomotor behavior and stepping of all rats were analyzed over a 6-month survival time using the Basso, Beattie, Bresnahan (BBB) open field locomotor test and the contact placing test. Immunohistochemistry for serotonin (5-HT), anterograde tracing with biotinylated dextran amine (BDA), and retrograde tracing with fluoro-gold were used to evaluate the presence of axons below the damage site following treatment. When compared with the transection-only group, the nerve graft with the aFGF group showed 1) significant improvement in hindlimb locomotion and stepping, 2) the presence of 5-HT-labeled axons below the lesion site at lumbar cord level (these were interpreted as regenerated axons from the raphe nuclei), 3) the presence of anterograde BDA labeling of corticospinal tract axons at the graft site and below, and 4) fluoro-gold retrograde labeling of neuron populations in motor cortex and in red nucleus, reticulospinal nuclei, raphe nuclei, and vestibular nuclei. We conclude that peripheral nerve grafts and aFGF treatments facilitate the regrowth of the spinal axons and improve hindlimb function in a T-8 spinal cord-transected rat model.

Expression of Suppressor of Cytokine Signaling-3 (SOCS3) and its role in neuronal death after complete spinal cord injury

“…In addition, we have identified significant neuronal death within areas 4 mm rostral and caudal to the injured site. We have previously demonstrated functional recovery and regenerative nerve fibers within 5 mm areas beyond the lesion site with our peripheral nerve bridging strategy after complete SCI (Lee et al, 2002; Lee et al, 2004; Lee et al, 2006; Lee et al, 2013). Therefore, promoting neuronal survival within a 4 mm range could be critical for improving functional outcomes when combined with a nerve regenerative strategy.…”

Acid Fibroblast Growth Factor and Peripheral Nerve Grafts Regulate Th2 Cytokine Expression, Macrophage Activation, Polyamine Synthesis, and Neurotrophin Expression in Transected Rat Spinal Cords

“…An SCI repair strategy using peripheral nerve grafts and acidic fibroblast growth factor (aFGF, FGF-1) improves hindlimb locomotor function in spinal cord-transected rats (Cheng et al, 1996;Lee et al, 2002Lee et al, , 2004Tsai et al, 2005). Repaired spinal cords induce the expression of the M2 macrophage marker arginase I (Arg I) 6 -14 d after repair and recruited large numbers of M2 macrophages to the graft area 10 d after repair .…”

Transplantation of porous tubes following spinal cord transection improves hindlimb function in the rat

“…The Tx group finished with a mean BBB score of 1.4 and these results are consistent with other spinal cord transection studies. 12,27,28 The TxTp group finished with a mean score of 7.1 after 4 weeks, and was significantly greater than the Tx group. The main differences in locomotor behavior between the two groups was that the TxTp group showed extensive movement of all three joints of the hindlimbs (ankle, knee and hip) compared to slight movement of one or two joints in the Tx group.…”

“…Cellular damage to the cord resulting in myelin debris and scar tissue has been shown to impede locomotor recovery significantly. [10][11][12][13] The amount and type of preserved tissue following a spinal cord injury is highly correlated to recovery and function. 1,[14][15][16] Small amounts of preserved spinal cord tissue can facilitate large amounts of recovery and locomotor behavior.…”