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Scholarly Works (4 results)

  • Thesis
  • Peer Reviewed
UC Davis Electronic Theses and Dissertations (2021)

Spinal cord injury (SCI) is a debilitating condition often resulting in motor deficits and loss of tactile sensation below the injury. The brain needs to relearn strategies to regain motor control after SCI. This ability of the brain to adapt after injury/rehabilitation is defined as neuroplasticity. Neuroplasticity in the motor cortex (M1) required to gain cortical control of trunk muscles below the injury level is not well understood after a clinically relevant incomplete mid-thoracic spinal contusion injury. After an incomplete SCI, there is a substantial spontaneous recovery of function that can be further facilitated by physical rehabilitation. The difference in cortical neuroplasticity associated with rehabilitation-assisted recovery and spontaneous recovery of function is unknown.

This thesis aimed to understand whether neuroplasticity in trunk M1 after rehabilitation is a mere enhancement of the learning strategy adopted by the cortex during spontaneous recovery or whether they represent a different strategy to regain control of muscle groups below the level of the lesion.

Regions within trunk M1 that control lower thoracic trunk muscle (LTM1) were specialized in the neuronal encoding of posture in intact animals. After an incomplete mid-thoracic spinal contusion injury, the network and cellular neuroplasticity in trunk M1 differed between animals that received physical rehabilitation and animals that spontaneously recovered. In animals that received the therapy, the lower thoracic trunk motor cortex (LTM1) maintained some control of trunk muscles below the injury, in addition to recruiting trunk muscles at/above the level of injury. Exercise therapy also prevented the degradation of neuronal responsiveness in the reorganized cortex to unexpected postural perturbation as well as during treadmill locomotion. This knowledge can help design activity-based therapy paradigms that improve cortical plasticity in the LTM1, relevant for postural control.

    Cover page: Role of trunk sensorimotor cortex in supporting rehabilitation assisted functional recovery of locomotion after spinal contusion injury
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2021)
    Sensorimotor integration in the trunk system is poorly understood despite its importance for functional recovery after neurological injury. To address this, a series of mapping studies were performed in the rat. First, the receptive fields (RFs) of cells recorded from thoracic dorsal root ganglia were identified. Second, the RFs of cells recorded from trunk primary sensory cortex (S1) were used to assess the extent and internal organization of trunk S1. Finally, the trunk motor cortex (M1) was mapped using intracortical microstimulation to assess coactivation of trunk muscles with hindlimb and forelimb muscles, and integration with S1. Projections from trunk S1 to trunk M1 were not anatomically organized, with relatively weak sensorimotor integration between trunk S1 and M1 compared to extensive integration between hindlimb S1/M1 and trunk M1. Assessment of response latency and anatomical tracing suggest that trunk M1 is abundantly guided by hindlimb somatosensory information that is derived primarily from the thalamus. Finally, neural recordings from awake animals during unexpected postural perturbations support sensorimotor integration between hindlimb S1 and trunk M1, providing insight into the role of the trunk system in postural control that is useful when studying recovery after injury.
      Cover page: Hindlimb Somatosensory Information Influences Trunk Sensory and Motor Cortices to Support Trunk Stabilization.
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2021)

      Background

      The rat mid-thoracic contusion model has been used to study at-level tactile allodynia, a common type of pain that develops after spinal cord injury (SCI). An important advantage of this model is that not all animals develop hypersensitivity. Therefore, it can be used to examine mechanisms that are strictly related to the development of pain-like behaviour separately from mechanisms related to the injury itself. However, how to separate animals that develop hypersensitivity from those that do not is unclear.

      Methods

      The aims of the current study were to identify where hypersensitivity and spasticity develop and use this information to identify metrics to separate animals that develop hypersensitivity from those that do not to study differences in their behaviour. To accomplish these aims, a grid was used to localize hypersensitivity on the dorsal trunk relative to thoracic dermatomes and supraspinal responses to tactile stimulation were tallied. These supraspinal responses were used to develop a hypersensitivity score to separate animals that develop hypersensitivity, or pain-like response to nonpainful stimuli.

      Results

      Similar to humans, the development of hypersensitivity could occur with the development of spasticity or hyperreflexia. Moreover, the time course and prevalence of hypersensitivity phenotypes (at-, above-, or below level) produced by this model were similar to that observed in humans with SCI.

      Conclusion

      However, the amount of spared spinal matter in the cord did not explain the development of hypersensitivity, as previously reported. This approach can be used to study the mechanisms underlying the development of hypersensitivity separately from mechanisms related to injury alone.
        Cover page: Modelling at‐level allodynia after mid‐thoracic contusion in the rat
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2019)

        Aim

        The activation of the TNFR2 receptor is beneficial in several pathologies of the central nervous system, and this study examines whether it can ameliorate the recovery process following spinal cord injury.

        Methods

        EHD2-sc-mTNFR2 , an agonist specific for TNFR2, was used to treat neurons exposed to high levels of glutamate in vitro. In vivo, it was infused directly to the spinal cord via osmotic pumps immediately after a contusion to the cord at the T9 level. Locomotion behavior was assessed for 6 weeks, and the tissue was analyzed (lesion size, RNA and protein expression, cell death) after injury. Somatosensory evoked potentials were also measured in response to hindlimb stimulation.

        Results

        The activation of TNFR2 protected neurons from glutamate-mediated excitotoxicity through the activation of phosphoinositide-3 kinase gamma in vitro and improved the locomotion of animals following spinal cord injury. The extent of the injury was not affected by infusing EHD2-sc-mTNFR2 , but higher levels of neurofilament H and 2', 3'-cyclic-nucleotide 3'-phosphodiesterase were observed 6 weeks after the injury. Finally, the activation of TNFR2 after injury increased the neural response recorded in the cortex following hindlimb stimulation.

        Conclusion

        The activation of TNFR2 in the spinal cord following contusive injury leads to enhanced locomotion and better cortical responses to hindlimb stimulation.
          Cover page: Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injuryCreative Commons 'BY' version 4.0 license
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