Endogenous Interleukin-10 Deficiency Exacerbates Vascular Pathology in Traumatic Cervical Spinal Cord Injury

J Neurotrauma. 2019 Aug 1;36(15):2298-2307. doi: 10.1089/neu.2018.6081. Epub 2019 Apr 24.

Abstract

Although the majority of traumatic spinal cord injuries (SCIs) take place at the cervical level, pre-clinical studies have been disproportionally focused on thoracic insults. With differences in anatomy, physiology, and immune response between spinal cord levels, there is evidence that injury pathophysiology may vary, requiring tailored treatment paradigms. Further, as only a few therapies have been successfully translated to the clinic, cervical models are increasingly recognized as essential for the characterization of trauma and therapy. Using a novel and clinically relevant cervical contusion-compression mouse model of bilateral incomplete injury, this study aimed to assess the role of interleukin10 (IL-10), a potent cytokine with broad anti-inflammatory effects, in SCI vascular pathology. While the effects of IL-10 loss have been previously evaluated, the vascular changes are poorly characterized. Here, using in vivo high-resolution ultrasound imaging, we demonstrate that IL-10 deficiency is associated with increased acute vascular damage. Importantly, the loss of endogenous IL-10 led to significant differences in the acute systemic response to SCI, specifically the circulating levels of IL-12 (p70), LIX (CXCL5), IL-1β, tumor necrosis factor (TNF)-α, and IL-6 relative to genotype sham controls. These effects also fostered modest impairments in long-term functional recovery, assessed by the Basso Mouse Scale, as well as histological outcomes.

Keywords: interleukin-10; spinal cord injury; vasculature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cervical Cord / injuries*
  • Interleukin-10 / blood*
  • Interleukin-10 / deficiency*
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Spinal Cord Injuries / blood*
  • Spinal Cord Injuries / diagnostic imaging
  • Vascular Diseases / blood*
  • Vascular Diseases / diagnostic imaging

Substances

  • Interleukin-10

Grants and funding