Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury

Abstract

Trauma to the central nervous system (CNS) triggers intraparenchymal inflammation and activation of systemic immunity with the capacity to exacerbate neuropathology and stimulate mechanisms of tissue repair. Despite our incomplete understanding of the mechanisms that control these divergent functions, immune-based therapies are becoming a therapeutic focus. This review will address the complexities and controversies of post-traumatic neuroinflammation, particularly in spinal cord. In addition, current therapies designed to target neuroinflammatory cascades will be discussed.

Figure 1

Temporal correlation between inflammatory cascades, secondary neurodegenerative events and functional recovery in SCI rodents. A) Anatomical and functional outcomes, including de- and remyelination, axonal sprouting/plasticity and locomotor recovery. B) Activation of resident microglia and intraspinal accumulation of circulating leukocytes. Dashed lines departing from solid curves depict data from SCI mice whereas continuing solid curves indicate data from SCI rats. Solid curves before these break points are from both species. C) Expression of proinflammatory cytokines and reactive oxygen species (ROS). D) Expression of neurotrophic cytokines. E) Blood-brain barrier permeability to α-aminoisobutyric acid (AIB; 104 Da), horseradish peroxidase (HRP; 44000 Da), and luciferase (61000 Da). All AIB and HRP data were obtained from rat SCI models while luciferase data was from mice. Dashed curve departing from AIB solid curve indicates secondary rise in AIB permeability in white matter whereas continuing solid curve indicates permeability in gray matter. Solid curve before this break point represents permeability in both white and gray matter. Values on the vertical axis represent relative changes and are not to scale. Curves were generated using data from the following references: A) (11;67;169); B) (81;132;136;159;188): C) (129;163;180); D) (24;59;72;108); E) (120;133;179).