Microtubule Stabilization Promotes Microcirculation Reconstruction After Spinal Cord Injury

J Mol Neurosci. 2021 Mar;71(3):583-595. doi: 10.1007/s12031-020-01679-5. Epub 2020 Sep 8.

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 β, 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.

Keywords: Endothelial cells; Microcirculation; Microtubule; Pericytes; Spinal cord injury.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Hypoxia
  • Cell Movement
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Epothilones / pharmacology*
  • Epothilones / therapeutic use
  • Female
  • Glucose / deficiency
  • Microcirculation*
  • Microtubules / drug effects
  • Microtubules / metabolism*
  • Pericytes / drug effects
  • Pericytes / metabolism
  • Platelet-Derived Growth Factor / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Spinal Cord / blood supply
  • Spinal Cord / metabolism
  • Spinal Cord Injuries / drug therapy*
  • Tubulin Modulators / pharmacology*
  • Tubulin Modulators / therapeutic use
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Epothilones
  • Platelet-Derived Growth Factor
  • Tubulin Modulators
  • Vascular Endothelial Growth Factor A
  • Receptors, Platelet-Derived Growth Factor
  • Receptors, Vascular Endothelial Growth Factor
  • Glucose
  • epothilone B