Lumbar Myeloid Cell Trafficking into Locomotor Networks after Thoracic Spinal Cord Injury

Exp Neurol. 2016 Aug;282:86-98. doi: 10.1016/j.expneurol.2016.05.019. Epub 2016 May 16.

Abstract

Spinal cord injury (SCI) promotes inflammation along the neuroaxis that jeopardizes plasticity, intrinsic repair and recovery. While inflammation at the injury site is well-established, less is known within remote spinal networks. The presence of bone marrow-derived immune (myeloid) cells in these areas may further impede functional recovery. Previously, high levels of the gelatinase, matrix metalloproteinase-9 (MMP-9) occurred within the lumbar enlargement after thoracic SCI and impeded activity-dependent recovery. Since SCI-induced MMP-9 potentially increases vascular permeability, myeloid cell infiltration may drive inflammatory toxicity in locomotor networks. Therefore, we examined neurovascular reactivity and myeloid cell infiltration in the lumbar cord after thoracic SCI. We show evidence of region-specific recruitment of myeloid cells into the lumbar but not cervical region. Myeloid infiltration occurred with concomitant increases in chemoattractants (CCL2) and cell adhesion molecules (ICAM-1) around lumbar vasculature 24h and 7days post injury. Bone marrow GFP chimeric mice established robust infiltration of bone marrow-derived myeloid cells into the lumbar gray matter 24h after SCI. This cell infiltration occurred when the blood-spinal cord barrier was intact, suggesting active recruitment across the endothelium. Myeloid cells persisted as ramified macrophages at 7days post injury in parallel with increased inhibitory GAD67 labeling. Importantly, macrophage infiltration required MMP-9.

Keywords: Blood brain barrier; Inflammation; MMP-9; Macrophage; Spinal cord injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • CD11b Antigen / metabolism
  • Capillary Permeability / physiology
  • Cell Movement / physiology*
  • Cell Tracking
  • Chemokine CCL2 / metabolism
  • Chemokine CXCL12 / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Glutamate Decarboxylase / metabolism
  • Green Fluorescent Proteins
  • Intercellular Adhesion Molecule-1 / metabolism
  • Locomotion / physiology*
  • Lumbosacral Region / physiology*
  • Lumbosacral Region / physiopathology
  • Matrix Metalloproteinase 9 / deficiency
  • Matrix Metalloproteinase 9 / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myeloid Cells / physiology*
  • Sacrococcygeal Region / pathology
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord Injuries / pathology*
  • Spinal Cord Injuries / physiopathology*
  • Time Factors

Substances

  • CD11b Antigen
  • Chemokine CCL2
  • Chemokine CXCL12
  • Intercellular Adhesion Molecule-1
  • Green Fluorescent Proteins
  • Matrix Metalloproteinase 9
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1