Characterization of the Early Neuroinflammation After Spinal Cord Injury in Mice

Abstract

The occurrence of neuroinflammation after spinal cord injury (SCI) is well established, but its function is debated, with both beneficial and detrimental consequences ascribed. A discriminate of the role of neuroinflammation may be the time period after SCI, and there is evidence to favor early neuroinflammation being undesirable, whereas the later evolving phase may have useful roles. Here, we have focused on the inflammatory response in the first 24 hours of SCI in mice. We found elevation of interleukin (IL)-1beta and other cytokines and chemokines within 15 minutes to 3 hours of injury. The early neuroinflammation in SCI is likely to be CNS-derived and involves microglia, as demonstrated by in situ hybridization for IL-1beta in microglia, by an in vitro model of SCI in which elevation of inflammatory cytokines occurs in the absence of a dynamic source of infiltrating leukocytes, and by the correlation of decreased levels of inflammatory molecules and microglia activity in IL-1beta-null mice. Nonetheless, as there are no specific immunohistochemical markers that clearly differentiate microglia from their peripheral counterparts, macrophages, the latter cannot be definitively excluded as participants in early neuroinflammation in mouse SCI. These results of an instantaneous inflammatory response validate approaches to modulate microglia/macrophage activity to improve recovery from SCI.

Depletion of Ly6G/Gr-1 Leukocytes after Spinal Cord Injury in Mice Alters Wound Healing and Worsens Neurological Outcome

“…These early responses to injury include the activation of endogenous CNS cells, microglia and astrocytes, that produce proinflammatory mediators such as cytokines, chemokines, and lipid mediators that drive leukocyte recruitment to the injured tissue (Bartholdi and Schwab, 1997;Pineau and Lacroix, 2007;Rice et al, 2007). Although the precise signals are yet unknown, SCI leads to a rapid and marked mobilization of circulating neutrophils within the first few hours after injury and their entry into the injured spinal cord that peaks at 12-24 h (Dusart and Schwab, 1994;Carlson et al, 1998;Stirling and Yong, 2008).…”

Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK2) Contributes to Secondary Damage after Spinal Cord Injury

“…The localized immune response after SCI, involving neutrophils, microglia/macrophages, and reactive astrocytes, contributes to this secondary damage (Giulian and Robertson, 1990;Taoka et al, 1997;Popovich et al, 1999Popovich et al, , 2002Tonai et al, 2001;Gris et al, 2004). Under such conditions, these cells release various cytotoxic mediators, including proinflammatory chemokines/cytokines (McTigue et al, 1998;Rice et al, 2007), reactive oxygen species (Bao et al, 2004), and proteases (Noble et al, 2002;Wells et al, 2003b).…”

Transcriptional and Epigenetic Regulation in Injury-Mediated Neuronal Dendritic Plasticity

“…Following CNS injury, the primary mechanical insult and especially the temporo-spatial spread of secondary biochemical inflammatory, oxidative, and other events, cause glial, vascular, and neuronal damage and death surrounding the injury site, [7][8][9] and induce surviving cells to produce and release a variety of cytokines, chemokines, neurotransmitters, and trophic factors [10][11][12]. These released agents signal local cells to trigger a variety of responses to the changing microenvironment induced by injury.…”