Cytokine profile and glial activation following brachial plexus roots avulsion injury in mice

Ke Zhong,Yingqin Li,Ying Tang,Guangyin Yu,Prince Last Mudenda Zilundu,Yaqiong Wang,Yingying Zhou,Xiaoying Xu,Rao Fu,Lihua Zhou

doi:10.1016/j.jneuroim.2021.577517

Abstract

Inflammation and tissue infiltration by various immune cells play a significant role in the pathogenesis of neurons suffering the central nervous systems diseases. Although brachial plexus root avulsion (BPRA) leads to dramatic motoneurons (MNs) death and permanent loss of function, however, the knowledge gap on cytokines and glial reaction in the spinal cord injury is still existing. The current study is sought to investigate the alteration of specific cytokine expression patterns of the BPRA injured spinal cord during an acute and subacute period. The cytokine assay, transmission electron microscopy, and histological staining were utilized to assess cytokine network alteration, ultrastructure morphology, and glial activation and MNs loss within two weeks post-injury on a mouse unilateral BPRA model. The BPRA injury caused a progressively spinal MNs loss, reduced the alpha-(α) MNs synaptic inputs, whereas enhanced glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule-1 (IBA-1), F4/80 expression in ipsilateral but not the contralateral spinal segments. Additionally, cytokine assays revealed BPRA significantly altered the level of CXCL1, ICAM1, IP10, MCP-5, MIP1-α, and CD93. Notably, the elevated MIP1-α was mainly expressed in the injured spinal MNs. While the re-distribution of CD93 expression, from the cytoplasm to the nucleus, occasionally occurred at neurons of the ipsilateral spinal segment after injury. Overall, these findings suggest that the inflammatory cytokines associated with glial cell activation might contribute to the pathophysiology of the MNs death caused by nerve roots injury.

Highlights

Inflammation and tissue infiltration by various immune cells play a significant role in the pathogenesis of neurons suffering the central nervous systems diseases
We found that brachial plexus root avulsion (BPRA) significantly changed the level of CXCL1, IL12 p70, ICAM1, IP10, MCP-5, MIP1-α and CD93
The cytokines are proteins that coordinate the immune response throughout the central nervous system (CNS), recruiting phagocytic cells, like peripheral neutrophils and macrophages into the injured spinal cord [13][14], which are considered to be the first wave of infiltrating immune cells [15]

Summary

Introduction

Inflammation and tissue infiltration by various immune cells play a significant role in the pathogenesis of neurons suffering the central nervous systems diseases. Brachial plexus root avulsion (BPRA) leads to dramatic motoneurons (MNs) death and permanent loss of function, the crosstalk between cytokines and glial reaction in the spinal cord during injury is far beyond our knowledge. The current study is sought to investigate the alteration of specific cytokine expression patterns of BPRA injured spinal cord during an acute and subacute period. It has been well documented that the neuroinflammation plays a causal role for the MNs degeneration and death associated with spinal cord injury, including avulsion injury [4][5][6][7]. It has been reported that the neuroinflammation is characteristic of the infiltration of leukocytes [8] and glial activation during the acute and subacute period after spinal cord injury [9] [10][11]. The cytokines are proteins that coordinate the immune response throughout the CNS, recruiting phagocytic cells, like peripheral neutrophils and macrophages into the injured spinal cord [13][14], which are considered to be the first wave of infiltrating immune cells [15]

Results

Discussion

Conclusion