Skip to main content
Journal cover image

Bone Marrow-Derived Monocytes Drive the Inflammatory Microenvironment in Local and Remote Regions after Thoracic Spinal Cord Injury.

Publication ,  Journal Article
Norden, DM; Faw, TD; McKim, DB; Deibert, RJ; Fisher, LC; Sheridan, JF; Godbout, JP; Basso, DM
Published in: J Neurotrauma
March 19, 2019

Spinal cord injury (SCI) produces a toxic inflammatory microenvironment that negatively affects plasticity and recovery. Recently, we showed glial activation and peripheral myeloid cell infiltration extending beyond the epicenter through the remote lumbar cord after thoracic SCI. The presence and role of infiltrating monocytes is important, especially in the lumbar cord where locomotor central pattern generators are housed. Therefore, we compared the inflammatory profile of resident microglia and peripheral myeloid cells after SCI. Bone marrow chimeras received midthoracic contusive SCI, and trafficking was determined 1-7 days later. Fluorescence-activated cell (FAC) sorting showed similar infiltration timing of both neutrophils and macrophages in epicenter and lumbar regions. While neutrophil numbers were attenuated by day 3, macrophages remained unchanged at day 7, suggesting that macrophages have important long-term influence on the microenvironment. Nanostring gene array identified a strong proinflammatory profile of infiltrating macrophages relative to microglia at both epicenter and lumbar sites. Macrophages had elevated expression of inflammatory cytokines (IL-1β, IFNγ), chemokines (CCL2, CXCL2), mediators (COX-1, MMP-9), and receptors (CCR2, Ly6C), and decreased expression of growth promoting genes (GDNF, BDNF). Importantly, lumbar macrophages had elevated expression of active trafficking genes (CCR2, l-selectin, MMP-9) compared with epicenter macrophages. Further, acute rehabilitation exacerbated the inflammatory profile of infiltrated macrophages in the lumbar cord. Such high inflammatory potential and negative response to rehabilitation of infiltrating macrophages within lumbar locomotor central pattern generators likely impedes activity-dependent recovery. Therefore, limiting active trafficking of macrophages into the lumbar cord identifies a novel target for SCI therapies to improve locomotion.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Neurotrauma

DOI

EISSN

1557-9042

Publication Date

March 19, 2019

Volume

36

Issue

6

Start / End Page

937 / 949

Location

United States

Related Subject Headings

  • Spinal Cord Injuries
  • Spinal Cord
  • Neurology & Neurosurgery
  • Monocytes
  • Mice, Inbred C57BL
  • Mice
  • Macrophages
  • Inflammation
  • Female
  • Chemotaxis, Leukocyte
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Norden, D. M., Faw, T. D., McKim, D. B., Deibert, R. J., Fisher, L. C., Sheridan, J. F., … Basso, D. M. (2019). Bone Marrow-Derived Monocytes Drive the Inflammatory Microenvironment in Local and Remote Regions after Thoracic Spinal Cord Injury. J Neurotrauma, 36(6), 937–949. https://doi.org/10.1089/neu.2018.5806
Norden, Diana M., Timothy D. Faw, Daniel B. McKim, Rochelle J. Deibert, Lesley C. Fisher, John F. Sheridan, Jonathan P. Godbout, and D Michele Basso. “Bone Marrow-Derived Monocytes Drive the Inflammatory Microenvironment in Local and Remote Regions after Thoracic Spinal Cord Injury.J Neurotrauma 36, no. 6 (March 19, 2019): 937–49. https://doi.org/10.1089/neu.2018.5806.
Norden DM, Faw TD, McKim DB, Deibert RJ, Fisher LC, Sheridan JF, et al. Bone Marrow-Derived Monocytes Drive the Inflammatory Microenvironment in Local and Remote Regions after Thoracic Spinal Cord Injury. J Neurotrauma. 2019 Mar 19;36(6):937–49.
Norden, Diana M., et al. “Bone Marrow-Derived Monocytes Drive the Inflammatory Microenvironment in Local and Remote Regions after Thoracic Spinal Cord Injury.J Neurotrauma, vol. 36, no. 6, Mar. 2019, pp. 937–49. Pubmed, doi:10.1089/neu.2018.5806.
Norden DM, Faw TD, McKim DB, Deibert RJ, Fisher LC, Sheridan JF, Godbout JP, Basso DM. Bone Marrow-Derived Monocytes Drive the Inflammatory Microenvironment in Local and Remote Regions after Thoracic Spinal Cord Injury. J Neurotrauma. 2019 Mar 19;36(6):937–949.
Journal cover image

Published In

J Neurotrauma

DOI

EISSN

1557-9042

Publication Date

March 19, 2019

Volume

36

Issue

6

Start / End Page

937 / 949

Location

United States

Related Subject Headings

  • Spinal Cord Injuries
  • Spinal Cord
  • Neurology & Neurosurgery
  • Monocytes
  • Mice, Inbred C57BL
  • Mice
  • Macrophages
  • Inflammation
  • Female
  • Chemotaxis, Leukocyte