The ability to perform stepping and standing can be reacquired after complete thoracic spinal cord transection in adult cats with appropriate, repetitive training. We now compare GAD(67)A levels in the spinal cord of cats that were trained to step or stand. We confirmed that a complete spinal cord transection at approximately T12 increases glutamic acid decarboxylase (GAD)(67) in both the dorsal and ventral horns of L5-L7. We now show that step training decreases these levels toward control. Kinematic analyses show that this downward modulation is correlated inversely with stepping ability. Compared with intact cats, spinal cord-transected cats had increased punctate GAD(67) immunoreactivity around neurons in lamina IX at cord segments L5-L7. Compared with spinal nontrained cats, those trained to stand on both hindlimbs had more GAD(67) puncta bilaterally in a subset of lamina IX neurons. In cats trained to stand unilaterally, this elevated staining pattern was limited to the trained side and extended for at least 4 mm in the L6 and L7 segments. The location of this asymmetric GAD(67) staining corresponded to the motor columns of primary knee flexors, which are minimally active during standing, perhaps because of extensor-activated inhibitory interneuron projections. The responsiveness to only a few days of motor training, as well as the GABA-synthesizing potential in the spinal cord, persists for at least 25 months after the spinal cord injury. This modulation is specific to the motor task that is performed repetitively and is closely linked to the ability of the animal to perform a specific motor task.

Conus medullaris and/or cauda equina forms of spinal cord injury commonly result in a permanent loss of bladder function. Here, we developed a cauda equina injury and repair rodent model to investigate whether surgical implantation of avulsed lumbosacral ventral roots into the spinal cord can promote functional recovery of the lower urinary tract. Adult female rats underwent sham surgery (n ϭ 6), bilateral L5-S2 ventral root avulsion (VRA) injury (n ϭ 5), or bilateral L5-S2 VRA followed by an acute implantation of the avulsed L6 and S1 ventral roots into the conus medullaris (n ϭ 6). At 12 weeks after operation, the avulsed group demonstrated urinary retention, absence of bladder contractions and external urethral sphincter (EUS) electromyographic (EMG) activation during urodynamic recordings, increased bladder size, and retrograde death of autonomic and motoneurons in the spinal cord. In contrast, the implanted group showed reduced urinary retention, return of reflexive bladder voiding contractions coincident with EUS EMG activation, anatomical reinnervation of the EUS demonstrated by retrograde neuronal labeling, normalization of bladder size, and a significant neuroprotection of both autonomic and motoneurons. In addition, a positive correlation between motoneuronal survival and voiding efficiency was observed in the implanted group. Our results show that implantation of avulsed lumbosacral ventral roots into the spinal cord promotes reinnervation of the urinary tract and return of functional micturition reflexes, suggesting that this surgical repair strategy may also be of clinical interest after conus medullaris and cauda equina injuries.

Injuries to the cauda equina of the spinal cord result in autonomic and motor neuron dysfunction. We developed a rodent lumbosacral ventral root avulsion injury model of cauda equina injury to investigate the lesion effect in the spinal cord. We studied the retrograde effects of a unilateral L5-S2 ventral root avulsion on efferent preganglionic parasympathetic neurons (PPNs) and pelvic motoneurons in the L6 and S1 segments at 1, 2, 4, and 6 weeks postoperatively in the adult male rat. We used Fluoro-Gold-prelabeling techniques, immunohistochemistry, and quantitative stereologic analysis to show an injury-induced progressive and parallel death of PPNs and motoneurons. At 6 weeks after injury, only 22% of PPNs and 16% of motoneurons remained. Furthermore, of the neurons that survived at 6 weeks, the soma volume was reduced by 25% in PPNs and 50% in motoneurons. Choline acetyltransferase (ChAT) protein was expressed in only 30% of PPNs, but 80% of motoneurons remaining at 1 week postoperatively, suggesting early differential effects between these two neuronal types. However, all remaining PPNs and motoneurons were ChAT positive at 4 weeks postoperatively. Nuclear condensation and cleaved caspase-3 were detected in axotomized PPNs and motoneurons, suggesting apoptosis as a contributing mechanism of the neural death. We conclude that lumbosacral ventral root avulsions progressively deplete autonomic and motor neurons. The findings suggest that early neuroprotection will be an important consideration in future attempts of treating acute cauda equina injuries.

Neuropathic pain is common after traumatic injuries to the cauda equina/conus medullaris and brachial plexus. Clinically, this pain is difficult to treat and its mechanisms are not well understood. Lesions to the ventral roots are common in these injuries, but are rarely considered as potential contributors to pain. We examined whether a unilateral L6-S1 ventral root avulsion (VRA) injury in adult female rats might elicit pain within the dermatome projecting to the adjacent, uninjured L5 spinal segment. Additionally, a subset of subjects had the avulsed L6-S1 ventral roots reimplanted (VRA+Imp) into the lateral funiculus post-avulsion to determine whether this neural repair strategy elicits or ameliorates pain. Behavioral tests for mechanical allodynia and hyperalgesia were performed weekly over 7 weeks post-injury at the hind paw plantar surface. Allodynia developed early and persisted post-VRA, whereas VRA+Imp rats exhibited allodynia only at 1 week postoperatively. Hyperalgesia was not observed at any time in any experimental group. Quantitative immunohistochemistry showed increased levels of inflammatory markers in laminae III-V and in the dorsal funiculus of the L5 spinal cord of VRA, but not VRA+Imp rats, specific to areas that receive projections from mechanoreceptive, but not nociceptive, primary afferents. These data suggest that sustained at-level neuropathic pain can develop following a pure motor lesion, whereas the pain may be ameliorated by acute root reimplantation. We believe that our findings are of translational research interest, as root implantation surgery is emerging as a potentially useful strategy for the repair of cauda equina/conus medullaris injuries.

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