The complement membrane attack complex and the bystander effect in cerebral vasospasm

Park, CC; Ml, Shin; Jm, Simard

doi:10.3171/jns.1997.87.2.0294

Cited by 36 publications

(14 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The higher CSF levels of C3a and C4a in patients with DIND indicated a relationship between these components and the pathogenesis of cerebral vasospasms. Another earlier study showed that complement activation by aged erythrocytes can result in MAC insertion into “innocent bystander” smooth-muscle cell membranes and that this mechanism may contribute to development of vasospasm after subarachnoid hemorrhage (Park et al, 1997). The earlier dogma that MAC could only attack non-nucleated cells (Whaley, 1987) now seems to be overturned, although it is still not clear what the final contribution of the MAC is to complement-mediated brain injury.…”

Section: The Role Of Complement In Strokementioning

confidence: 99%

Neuroprotection in stroke by complement inhibition and immunoglobulin therapy

et al. 2009

View full text Add to dashboard Cite

Activation of the complement system occurs in a variety of neuroinflammatory diseases and neurodegenerative processes of the CNS. Studies in the last decade have demonstrated that essentially all of the activation components and receptors of the complement system are produced by astrocytes, microglia, and neurons. There is also rapidly growing evidence to indicate an active role of the complement system in cerebral ischemic injury. In addition to direct cell damage, regional cerebral ischemia and reperfusion (I/R) induces an inflammatory response involving complement activation and generation of active fragments, such as C3a and C5a anaphylatoxins, C3b, C4b, and iC3b. The use of specific inhibitors to block complement activation or their mediators such as C5a, can reduce local tissue injury after I/R. Consistent with therapeutic approaches that have been successful in models of autoimmune disorders, many of the same complement inhibition strategies are proving effective in animal models of cerebral I/R injury. One new form of therapy, which is less specific in its targeting of complement than monodrug administration, is the use of immunoglobulins. Intravenous immunoglobulin (IVIG) has the potential to inhibit multiple components of inflammation, including complement fragments, pro-inflammatory cytokine production and leukocyte cell adhesion. Thus, IVIG may directly protect neurons, reduce activation of intrinsic inflammatory cells (microglia) and inhibit transendothelial infiltration of leukocytes into the brain parenchyma following an ischemic stroke. The striking neuroprotective actions of IVIG in animal models of ischemic stroke suggest a potential therapeutic potential that merits consideration for clinical trials in stroke patients.

show abstract

Section: The Role Of Complement In Strokementioning

confidence: 99%

Neuroprotection in stroke by complement inhibition and immunoglobulin therapy

et al. 2009

View full text Add to dashboard Cite

show abstract

“…It has been estimated that the range for bystander-induced complement cytotoxicity is ~2.5 µm [8], which would allow injury of closely intermingled oligodendrocytes following complement activation on astrocytes. There is precedent for complement bystander cytotoxicity for astrocyte injury in Rasmussen’s encephalitis following complement activation by glutamate receptor GluR3 autoantibodies in neurons [36], and for a large increase in membrane conductance of rat cerebral artery smooth-muscle cells caused by complement activation on aged erythrocytes [18]. The experimental evidence here includes cytotoxicity and immunofluorescence in astrocyte-oligodendrocyte cocultures exposed to AQP4-IgG and complement, as well as in rat brain following intracerebral AQP4-IgG administration.…”

Section: Introductionmentioning

confidence: 99%

Bystander mechanism for complement-initiated early oligodendrocyte injury in neuromyelitis optica

Tradtrantip

Yao

et al. 2017

Acta Neuropathol

View full text Add to dashboard Cite

Neuromyelitis optica spectrum disorder (herein called NMO) is an autoimmune inflammatory disease of the central nervous system in which immunoglobulin G antibodies against astrocyte water channel aquaporin-4 (AQP4-IgG) cause demyelination and neurological deficit. Injury to oligodendrocytes, which do not express AQP4, links the initiating pathogenic event of AQP4-IgG binding to astrocyte AQP4 to demyelination. Here, we report evidence for a complement ‘bystander mechanism’ to account for early oligodendrocyte injury in NMO in which activated, soluble complement proteins following AQP4-IgG binding to astrocyte AQP4 result in deposition of the complement membrane attack complex (MAC) on nearby oligodendrocytes. Primary cocultures of rat astrocytes and mature oligodendrocytes exposed to AQP4-IgG and complement showed early death of oligodendrocytes in close contact with astrocytes, which was not seen in pure oligodendrocyte cultures, in cocultures exposed to AQP4-IgG and C6-depleted serum, or when astrocytes were damaged by a complement-independent mechanism. Astrocyte-oligodendrocyte cocultures exposed to AQP4-IgG and complement showed prominent MAC deposition on oligodendrocytes in contact with astrocytes, whereas C1q, the initiating protein in the classical complement pathway, and C3d, a component of the alternative complement pathway, were deposited only on astrocytes. Early oligodendrocyte injury with MAC deposition was also found in rat brain following intracerebral injection of AQP4-IgG, complement and a fixable dead-cell stain. These results support a novel complement bystander mechanism for early oligodendrocyte injury and demyelination in NMO.

show abstract

“…Platelets are also susceptible to immune destruction and may be particularly prone to ‘bystander destruction’, whereby membrane attack complexes non‐specifically injure nearby cells . There is also growing evidence implicating direct platelet interaction with complement proteins as an important regulator of the classical and alternative pathways .…”

Section: Discussionmentioning

confidence: 99%