Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the rat cerebellum

Bénard, Magalie; Raoult, Emilie; Vaudry, David; Leprince, Jérôme; Falluel‐Morel, Anthony; Gonzalez, Bruno J.; Galas, Ludovic; Vaudry, Hubert; Fontaine, Marc

doi:10.1016/j.molimm.2008.05.027

Cited by 66 publications

(63 citation statements)

References 35 publications

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“…It has been found that the inflammatory cascade is activated due to SIRI, including neutrophil and neuroglia mobilization and infiltration, as well as elevated levels of inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6. 11 The complement system, a major component of the innate immune system, is constituted by a series of complement components and involved in synapse elimination, 12 development 13 and maturation of neural systems. 14 A range of pathologies in the brain or the spinal cord, including ischemia-reperfusion injury (IRI), 15 stroke, traumatic brain injury and spinal cord injury, 16 potently trigger complement activation following the disruption of neuronal homeostasis.…”

Section: Introductionmentioning

confidence: 99%

PMX53 protects spinal cord from ischemia-reperfusion injury in rats in the short term

et al. 2015

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Study design: Experimental study. Objectives: To investigate the effect of pre-treatment with PMX53, a C5aR antagonist, on spinal cord ischemia-reperfusion injury (IRI) in rat. Setting: Department of Neurosurgery, Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi Province, China. Methods: IRI was induced in the lumbar spinal cord by applying a mini aneurysm clamp to the abdominal aorta for 60 min in adult Sprague-Dawley rats. PMX53 (1 mg kg − 1 ) was administered through femoral vein injection 30 min before ischemia on the rats in the PMX53 group (n = 18). The saline group (n = 18) was given saline at the same volume through femoral vein injection. The neurologic outcome of the posterior limbs was assessed by the Basso-Beattie-Bresnahan (BBB) score at 1, 6, 12, 24 and 48 h after reperfusion. Histologic changes of the spinal cord were detected with hematoxylin-eosin (H-E) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect myeloperoxidase (MPO) activity in the spinal cord. Immunohistochemistry was used to investigate the quantity of activated astrocytes and microglia. Results: After pre-treatment with PMX53, neurologic function improved gradually after 6, 12, 24 and 48 h reperfusion. The BBB score of the PMX53 group increased significantly (Po0.05) compared with the saline group. H-E staining showed that pathologic damage in the PMX53 group was reduced. Moreover, administration of PMX53 significantly inhibited neutrophil infiltration in the spinal cord. Levels of MPO activity in the spinal cord were remarkably lower in the PMX53 group (Po0.05). There were also more activated microglia and astrocytes in the spinal cord of the PMX53 group than in the saline group (Po0.05). INTRODUCTIONSpinal cord ischemia-reperfusion injury (SIRI) mainly occurs after operations on the descending thoracic or thoracoabdominal aorta, such as thoracoabdominal aneurysm. 1 SIRI causes various complications, including paraparesis and paraplegia. 2 These complications have been attributed to temporary or permanent ischemia of the spinal cord caused by interruption of the blood supply during aortic cross-clamping. The incidence of paraplegia has been correlated with dissection, rupture and prolonged clamp times. 3 Systemic hypothermia, spinal fluid drainage and preconditioning ischemia were considered to prevent paraplegia, 4 but the effect was limited. Recent studies indicated that pathophysiological mechanisms underlying SIRI are complicated, including the release of inflammatory factors, 5 calcium overload, 6 oxidative stress, 7 excitotoxicity 8 and neuronal apoptosis. 9,10 In addition, there are more mechanisms that remain unclear. It has been found that the inflammatory cascade is activated due to SIRI, including neutrophil and neuroglia mobilization and infiltration, as well as elevated levels of inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6. 11 The complement system, a major component of the innate immune system, is

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Section: Introductionmentioning

confidence: 99%

PMX53 protects spinal cord from ischemia-reperfusion injury in rats in the short term

et al. 2015

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“…MMP-9, Collagenase, Gelatinase, Elastase (Fang et al, 1999;Bao Dang et al, 2013), MPO (Baldus et al, 2001;Shechter et al, 2011) Elastase (Kitson et al, 1998;Jacobsen et al, 2007) Tryptase Chymase (Weerth et al, 2003;Tchougounova et al, 2005), MMP-2, MMP-9 (Fang et al, 1999;Stirling et al, 2009) (Rahpeymai et al, 2006;Hao et al, 2010), BDNF, NT-3 (Hammarberg, et al 2000;Shinjyo et al, 2009) Sema4A, NT-3 (Bénard et al, 2008;Ishii et al, 2012) NAA (modulation of H 2 O 2 -induced apoptosis) (Warrington et al, 2004;Mantovani et al, 2011) Angiogenesis C5 (Norrby, 2002;Langer et al, 2010) VEGF (Scapini et al, 2004;Ribatti et al, 2011), MMP-9 (Justicia et al, 2003;Riboldi et al, 2005) PDGF, TNF-α and VEGF (Horiuchi and Weller, 1997) VEGF, TNF-α and β, FGF, MMP (Norrby et al, 2002) tryptase and chymase (Ribatti et al, 2011) VEGF (Riboldi et al, 2005), TNF-α, transdifferentiation in ELCs (Fernandez Pujol et al, 2001), trogocytosis of VEGF receptor …”

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confidence: 99%

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

Peruzzotti-Jametti¹,

Donegá²,

Giusto³

et al. 2014

Neuroscience

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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

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“…The use of this antagonist, albeit one of controversy, supports the assumption that the effects demonstrated through the application of C3a to neural progenitors is indeed through C3aR, a question that was not fully answered in the work of Shinjyo and colleagues (2009). In vivo, the subdural administration of C3a caused a reduction in the thickness of the proliferative external granule cell layer and a increase in thickness of the post-mitotic internal granule cell layer, suggesting that C3a acts to promote exit from the cell cycle and migration to form functional neurons 125 . In addition to a purported role in basal neurogenesis, C3aR also functions to accelerate neurogenesis in mouse models of stroke 8 .…”

Section: Emerging Novel Rolesmentioning

confidence: 99%

“…This effect can also be elicited with administration of the controversial C3aR antagonist, SB290157 8,56 . In rat postnatal cerebellar development C3a is also a chemoattractant for cerebellar granule neurons of the external granule cell layer and this effect can be blocked by SB290157 125 . The use of this antagonist, albeit one of controversy, supports the assumption that the effects demonstrated through the application of C3a to neural progenitors is indeed through C3aR, a question that was not fully answered in the work of Shinjyo and colleagues (2009).…”

Section: Emerging Novel Rolesmentioning

confidence: 99%

The anaphylatoxin receptors in neural progenitor physiology

Coulthard¹

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The complement cascade is phylogenically ancient pathogen recognition and response system that forms the initial frontier of mammalian innate immunity. Complement forms the bridge between humoural and cellular immunity through the generation of the anaphylatoxins, C3a and C5a, to recruit leukocytes to a pathogenic insult. However, in recent years, novel roles for the complement system outside of innate immunity have been demonstrated, especially in the developing embryo.To add to these novel roles, this thesis explores the role of the complement anaphylatoxin receptors in neural development.Previous studies in our laboratory have indicated a novel role for C5aR1 in the prevention of neural tube defects in folate-deficient dams. In these studies, C5aR1 was localised to the neuroepithelium throughout the period of neural tube closure and the precursor to C5a, C5, was also shown to be present. It has previously been unclear, both in this study and others, what other components of the complement system are present in the developing embryo that may lead to the generation ofanaphylatoxins. Here we demonstrate that the classical and alternative pathways, at the time of murine neural tube closure, lack expression of key propagators. Our data demonstrate the C2/4-independent and extrinsic pathways remain patent as a plausible means of C5a generation.In order to trace C5aR1-expressing cells within the developing embryo, a transgenic mouse was

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Role of complement anaphylatoxin receptors (C3aR, C5aR) in the development of the rat cerebellum

Cited by 66 publications

References 35 publications

PMX53 protects spinal cord from ischemia-reperfusion injury in rats in the short term

PMX53 protects spinal cord from ischemia-reperfusion injury in rats in the short term

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

The anaphylatoxin receptors in neural progenitor physiology

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