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Microtubule Stabilization Promotes Microcirculation Reconstruction After Spinal Cord Injury.

ABSTRACT: Spinal cord microcirculation plays an important role in maintaining the function of spinal cord neurons and other cells. Previous studies have largely focused on the ability of microtubule stabilization to inhibit the fibroblast migration and promote axon regeneration after spinal cord injury (SCI). However, the effect of microtubule stabilization treatment on microcirculation reconstruction after SCI remains unclear. By using immunofluorescence, we found that microtubule stabilization treatment improved microcirculation reconstruction via increasing the number of microvessels, pericytes, and the perfused microvessels after SCI. To clarify the underlying mechanisms, rat brain microvascular endothelial cells and pericytes were subjected to glucose oxygen deprivation. By using flow cytometry and western blotting, we found that microtubule stabilization treatment inhibited apoptosis and migration of endothelial cells and pericytes but promoted proliferation and survival of endothelial cells and pericytes through upregulated expression of vascular endothelial growth factor A (VEGFA), VEGF receptor 2, platelet-derived growth factor-B (PDGFB), PDGF receptor ?, and angiopoietin-1 after SCI. Taken together, this study provides evidence for the mechanisms underlying the promotion of microcirculation reconstruction after SCI by microtubule stabilization treatment. Importantly, this study suggests the potential of microtubule stabilization as a therapeutic target to reduce microcirculation dysfunction after SCI in the clinic.

SUBMITTER: Duan YY

PROVIDER: S-EPMC7851021 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Microtubule Stabilization Promotes Microcirculation Reconstruction After Spinal Cord Injury.

Duan Yang-Yang YY Chai Yong Y Zhang Nai-Li NL Zhao Dong-Mei DM Yang Cheng C

Journal of molecular neuroscience : MN 20200908 3

Spinal cord microcirculation plays an important role in maintaining the function of spinal cord neurons and other cells. Previous studies have largely focused on the ability of microtubule stabilization to inhibit the fibroblast migration and promote axon regeneration after spinal cord injury (SCI). However, the effect of microtubule stabilization treatment on microcirculation reconstruction after SCI remains unclear. By using immunofluorescence, we found that microtubule stabilization treatment ...[more]

PMID: 32901373

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Project description:Functional recovery after spinal cord injury (SCI) often proves difficult as physical and mental barriers bar survivors from enacting their designated rehabilitation programs. We recently demonstrated that adult mice administered gabapentinoids, clinically approved drugs prescribed to mitigate chronic neuropathic pain, recovered upper extremity function following cervical SCI. Given that rehabilitative training enhances neuronal plasticity and promotes motor recovery, we hypothesized that the combination of an aerobic-based rehabilitation regimen like treadmill training with gabapentin (GBP) administration will maximize recovery in SCI mice by strengthening synaptic connections along the sensorimotor axis. Whereas mice administered GBP recovered forelimb functions over the course of weeks and months following SCI, no additive forelimb recovery as the result of voluntary treadmill training was noted in these mice. To our surprise, we also failed to find an additive effect in mice administered vehicle. As motivation is crucial in rehabilitation interventions, we scored active engagement toward the rehabilitation protocol and found that mice administered GBP were consistently participating in the rehabilitation program. In contrast, mice administered vehicle exhibited a steep decline in participation, especially at chronic time points. Whereas neuroinflammatory gene expression profiles were comparable between experimental conditions, we discovered that mice administered GBP had increased hippocampal neurogenesis and exhibited less anxiety-like behavior after SCI. We also found that an external, social motivator effectively rescues participation in mice administered vehicle and promotes forelimb recovery after chronic SCI. Thus, not only does a clinically relevant treatment strategy preclude the deterioration of mental health after chronic SCI, but group intervention strategies may prove to be physically and emotionally beneficial for SCI individuals.

Project description:Gait rehabilitation following incomplete spinal cord injury (iSCI) often aims to enhance speed and stability. Concurrently increasing both may be difficult though as certain stabilization strategies will be compromised at faster speeds. To evaluate the interaction between speed and lateral stability, we examined individuals with (n = 12) and without (n = 12) iSCI as they performed straight walking and lateral maneuvers at Preferred and Fast treadmill speeds. To better detect the effects of speed on stability, we challenged lateral stability with a movement amplification force field. The Amplification field, created by a cable-driven robot, applied lateral forces to the pelvis that were proportional to the real-time lateral center of mass (COM) velocity. While we expected individuals to maintain stability during straight walking at the Fast speed in normal conditions, we hypothesized that both groups would be less stable in the Amplification field at the Fast speed compared to the Preferred. However, we found no effects of speed or the interaction between speed and field on straight-walking stability [Lyapunov exponent or lateral margin of stability (MOS)]. Across all trials at the Fast speed compared to the Preferred, there was greater step width variability (p = 0.031) and a stronger correlation between lateral COM state at midstance and the subsequent lateral foot placement. These observations suggest that increased stepping variability at faster speeds may be beneficial for COM control. We hypothesized that during lateral maneuvers in the Amplification field, MOS on the Initiation and Termination steps would be smaller at the Fast speed than at the Preferred. We found no effect of speed on the Initiation step MOS within either field (p > 0.350) or group (p > 0.200). The Termination step MOS decreased at the Fast speed within the group without iSCI (p < 0.001), indicating a trade-off between lateral stability and forward walking speed. Unexpectedly, participants took more steps and time to complete maneuvers at the Fast treadmill speed in the Amplification field. This strategy prioritizing stability over speed was especially evident in the group with iSCI. Overall, individuals with iSCI were able to maintain lateral stability when walking fast in balance-challenging conditions but may have employed more cautious maneuver strategies.

Dataset Information

Microtubule Stabilization Promotes Microcirculation Reconstruction After Spinal Cord Injury.

Publications

Microtubule Stabilization Promotes Microcirculation Reconstruction After Spinal Cord Injury.

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