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

被引:19
作者
Badner, Anna [1 ,2 ]
Vidal, Pia M. [1 ]
Hong, James [1 ,2 ]
Hacker, Justin [1 ]
Fehlings, Michael G. [1 ,2 ]
机构
[1] Univ Hlth Network, Krembil Res Inst, Div Genet & Dev, Toronto, ON, Canada
[2] Univ Toronto, Inst Med Sci, Toronto, ON, Canada
基金
加拿大健康研究院;
关键词
interleukin-10; spinal cord injury; vasculature; GRAY-MATTER DAMAGE; RECOVERY; MODEL; EXPRESSION;
D O I
10.1089/neu.2018.6081
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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-1 beta, tumor necrosis factor (TNF)-alpha, 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.
引用
收藏
页码:2298 / 2307
页数:10
相关论文
共 42 条
  • [1] The effects of endogenous interleukin-10 on gray matter damage and the development of pain behaviors following excitotoxic spinal cord injury in the mouse
    Abraham, KE
    Mcmillen, D
    Brewer, KL
    [J]. NEUROSCIENCE, 2004, 124 (04) : 945 - 952
  • [2] A bilateral cervical contusion injury model in mice: Assessment of gripping strength as a measure of forelimb motor function
    Aguilar, Roberto M.
    Steward, Oswald
    [J]. EXPERIMENTAL NEUROLOGY, 2010, 221 (01) : 38 - 53
  • [3] Bilateral cervical contusion spinal cord injury in rats
    Anderson, Kim D.
    Sharp, Kelli G.
    Steward, Oswald
    [J]. EXPERIMENTAL NEUROLOGY, 2009, 220 (01) : 9 - 22
  • [4] [Anonymous], 2015, F1000RESEARCH
  • [5] Early Intravenous Delivery of Human Brain Stromal Cells Modulates Systemic Inflammation and Leads to Vasoprotection in Traumatic Spinal Cord Injury
    Badner, Anna
    Vawda, Reaz
    Laliberte, Alex
    Hong, James
    Mikhail, Mirriam
    Jose, Alejandro
    Dragas, Rachel
    Fehlings, Michael
    [J]. STEM CELLS TRANSLATIONAL MEDICINE, 2016, 5 (08) : 991 - 1003
  • [6] Barbaric Ivana, 2007, Briefings in Functional Genomics & Proteomics, V6, P91, DOI 10.1093/bfgp/elm008
  • [7] Basso mouse scale for locomotion detects differences in recovery after spinal cord in ury in five common mouse strains
    Basso, DM
    Fisher, LC
    Anderson, AJ
    Jakeman, LB
    McTigue, DM
    Popovich, PG
    [J]. JOURNAL OF NEUROTRAUMA, 2006, 23 (05) : 635 - 659
  • [8] The Need for Speed in Rodent Locomotion Analyses
    Batka, Richard J.
    Brown, Todd J.
    McMillan, Kathryn P.
    Meadows, Rena M.
    Jones, Kathryn J.
    Haulcomb, Melissa M.
    [J]. ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, 2014, 297 (10): : 1839 - 1864
  • [9] Recovery of forepaw gripping ability and reorganization of cortical motor control following cervical spinal cord injuries in mice
    Blanco, Jennifer E.
    Anderson, Kim D.
    Steward, Oswald
    [J]. EXPERIMENTAL NEUROLOGY, 2007, 203 (02) : 333 - 348
  • [10] Detection of subtle neurological alterations by the Catwalk XT gait analysis system
    Chen, Ying-Ju
    Cheng, Fu-Chou
    Sheu, Meei-Ling
    Su, Hong-Lin
    Chen, Chun-Jung
    Sheehan, Jason
    Pan, Hung-Chuan
    [J]. JOURNAL OF NEUROENGINEERING AND REHABILITATION, 2014, 11