Complement activation in the injured central nervous system: another dual-edged sword?

Brennan, Faith H.; Anderson, Aileen J.; Taylor, Stephen M.; Woodruff, Trent M.; Ruitenberg, Marc J.

doi:10.1186/1742-2094-9-137

Cited by 110 publications

(101 citation statements)

References 148 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These studies indicated that the acute phase of inflammation might exacerbate the secondary injury after SCI, while the chronic phase could have a protective effect. Even C5a could probably have an opposite role during this second phase, as Beck et al [30] predicted that the blocking of subacute to chronic inflammation by the C5a receptor antagonist would reduce functional recovery after SCI, which was confirmed in CD88 −/− mice by Brennan et al [9]. Perhaps for this reason, in our study the functional recovery of control mice started from 15 days after injury.…”

Section: Discussionsupporting

confidence: 69%

“…However, it was reported recently that complement activation had another neuroprotective role [6][7][8][9] in addition to that involving the secondary injury [10,11], and C5a was thought to be the most important factor in this respect. Although C5a can induce the chemotactic response and mediate the early phase of inflammation that is harmful to cells at the lesion site [12,13], it can exert its neuroprotective effect by inhibiting neurone apoptosis [6,7,14] and promoting microglial phagocytosis [15,16], which is beneficial in alleviating the secondary injury.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Delayed post-injury administration of C5a improves regeneration and functional recovery after spinal cord injury in mice

Guo

Cheng

Zhang

et al. 2013

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummaryThe activation of a complement system can aggravate the secondary injury after spinal cord injury (SCI). However, it was reported recently that the activation of a complement could have both a secondary injury and a neuroprotective effect, in which C5a is the most important factor, but there is no direct evidence for this dual effect of C5a after SCI. In order to investigate the potential neuroprotective effect of C5a after SCI, in this study ectogenic C5a was injected intraperitoneally before/after SCI in vivo, or administrated to mechanically injured neurones in vitro; following this, neurone apoptosis, neurite outgrowth, axonal regeneration and functional recovery were investigated. The in-vivo experiments indicated that, following treatment with C5a 24 h before or immediately after injury, locomotor function was impaired significantly. However, when treatment with C5a took place 24 h after injury, locomotor function improved significantly. In-vitro experiments indicated that a certain concentration of C5a (50-100 nM) could inhibit caspase-3-mediated neurone apoptosis by binding to its receptor CD88, and that it could even promote the neurite outgrowth of uninjured neurones. In conclusion, delayed post-injury administration of C5a within a certain concentration could exert its neuroprotective effect through inhibiting caspase-3-mediated neurone apoptosis and promoting neurite outgrowth of uninjured neurones as well. These data suggest that C5a may have opposite functions in a time-and concentration-dependent manner after SCI. The dual roles of C5a have to be taken into account when measures are taken to inhibit complement activation in order to promote regeneration after SCI.

show abstract

Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Delayed post-injury administration of C5a improves regeneration and functional recovery after spinal cord injury in mice

Guo

Cheng

Zhang

et al. 2013

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…In particular, C3a protects neurons against N-methyl-D-aspartate (NMDA)-induced excitotoxicity in a dose-and astrocyte-dependent manner (Van Beek et al, 2001), while C5a exposure causes upregulation of nerve growth factor (NGF) in astrocytes, with similar neuroprotective effects in vitro (Jauneau et al, 2006). The role of the complement after ischemic stroke in vivo is yet to be fully elucidated, and the complexity of experimental animal studies suggests that complement activation could be a "dual edged sword" exerting beneficial or detrimental effects depending on its timing and context (Brennan et al, 2012).…”

Section: Neuronal Functional Plasticitymentioning

confidence: 99%

The role of the immune system in central nervous system plasticity after acute injury

Peruzzotti-Jametti¹,

Donegá²,

Giusto³

et al. 2014

Neuroscience

View full text Add to dashboard Cite

Acute brain injuries cause rapid cell death that activates bidirectional crosstalks between the injured brain and the immune system.In the acute phase, the damaged central nervous system (CNS) activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, which would ultimately bring the inflammatory reaction to a close. In the chronic phase, a sustained immune activation is described in many CNS disorders, and the degree of this prolonged response has variable effects on the spontaneous brain regenerative processes. The challenge for treating acute CNS damages is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury.Here we have reviewed the available information about the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of recovery after injury. We have examined how CNS damage evolves along the activation of main Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Europe PMC Funders Group

show abstract

“…A number of animal and human studies [29][30][31][32][33][34][35][36][37][38][39] , including our own [40][41][42] , demonstrated that activation of the complement system play a decisive role in the pathophysiology of IS. No study has reported data on functional state of FH and FL in this disorder.…”

Section: Discussionmentioning

confidence: 99%

Collectins, C3 complement protein, annexin V and C-reactive protein in acute ischemic stroke: interrelation and implication to upregulated apoptosis and inflammation

Boyajyan

Tsakanova

Sim

2014

Inflamm Cell Signal

View full text Add to dashboard Cite

Upregulated inflammatory response and apoptosis, both triggered by ischemia, are the most destructive pathologic processes developed after acute ischemic stroke (IS) at both central and peripheral levels. Identification of molecular mediators of these processes and understanding of their pathomechanisms will support the development of therapies, which can significantly improve outcomes of IS-affected subjects.Mannan-binding lectin (MBL), ficolin L (FL), ficolin H (FH) and C3 complement proteins participate in apoptotic cells recognition and clearance through various mechanisms. In the present study we performed comparative determination of the blood levels of MBL, FL and FH, and hemolytic activity of C3 protein (C3H50) as well as apoptosis marker protein, circulating annexin V (cANXV), and inflammatory marker C-reactive protein (CRP) in 99 patients with acute IS on the first day of stroke onset and 110 healthy subjects. Potential correlation between all measured parameters was analyzed. Methods included enzyme-linked immunosorbent, hemolytic, and immunonephelometric assays; statistics were performed by Student's t-test and Pearson's correlation analysis. The obtained data demonstrated significantly increased and correlated with each other blood levels of MBL and C3H50, cANXV and CRP in patients compared to controls. Slight, while significant, changes in the blood levels of FL and FH were also observed. We concluded that post-ischemic response at the first day of IS onset is characterized by sufficiently elevated and positively correlated with each other blood levels of MBL, C3H50, cANXV and CRP as well as by slightly increased blood levels of FH and FL. The obtained results suggest that MBL and C3 protein are implicated in upregulated inflammatory response and apoptosis developed after IS onset at a peripheral level, and that these pathological processes are interrelated and interdependent.

show abstract

Complement activation in the injured central nervous system: another dual-edged sword?

Cited by 110 publications

References 148 publications

Delayed post-injury administration of C5a improves regeneration and functional recovery after spinal cord injury in mice

Delayed post-injury administration of C5a improves regeneration and functional recovery after spinal cord injury in mice

The role of the immune system in central nervous system plasticity after acute injury

Collectins, C3 complement protein, annexin V and C-reactive protein in acute ischemic stroke: interrelation and implication to upregulated apoptosis and inflammation

Contact Info

Product

Resources

About