Deficiency in Complement C1q Improves Histological and Functional Locomotor Outcome after Spinal Cord Injury

Galvan, Manuel; Luchetti, Sabina; Burgos, Adrian M; Nguyen, Hal X.; Hooshmand, Mitra J.; Hamers, Frank P.T.; Anderson, Aileen J.

doi:10.1523/jneurosci.2823-08.2008

Cited by 71 publications

(75 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[42][43][44][45] For this reason, we sought to evaluate by 14 dpi, when we observed that fibronectin immunolabeling in the injured tissue was clearly…”

Section: Ryk Expression After Moderate Contusive Spinal Cord Damagementioning

confidence: 99%

“…Several reports have demonstrated the presence of fibronectin in the injury core, even in non-penetrating injuries where meningeal fibroblast invasion and proliferation are minimal. [42][43][44][45] Different sources have been proposed for this fibronectin + scar, including vascular extravasation of plasma fibronectin. 42,45 However, this intriguing issue has not been completely explored as, for example, there are meningeal-like cells that surround the blood vessels in the CNS, but the extent to which they participate in CNS injuries is not yet clear.…”

Section: Fig 7 Ryk Is Expressed In Fibronectinmentioning

confidence: 99%

See 1 more Smart Citation

The Ryk Receptor Is Expressed in Glial and Fibronectin-Expressing Cells after Spinal Cord Injury

González

Fernández-Martos

Arenas

et al. 2013

Journal of Neurotrauma

View full text Add to dashboard Cite

Wnt proteins play a critical role in central nervous system development and have been implicated in several neuropathologies, including spinal cord injury (SCI). Ryk, an unconventional Wnt receptor, regulates axonal regeneration after SCI, although its expression pattern in this neuropathology remains unclear. Therefore, we sought to define the spatiotemporal and cellular pattern of Ryk expression after a contusive SCI in adult rats using quantitative reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemical analysis. Under physiological conditions, Ryk is expressed in neurons, astrocytes, and blood vessels, but not in oligodendrocytes, microglia, NG2+ glial precursor cells, or axonal projections. Following SCI, we observed an increase in Ryk mRNA expression from 24 h post-injury until 7 days post-injury, whereas its protein levels were significantly augmented at 7 and 14 days post-injury. Moreover, the spatial and cellular Ryk expression pattern was altered in the damaged tissue, where this receptor was observed in reactive astrocytes and microglia/macrophages, NG2+ glial precursors, fibronectin + cells, oligodendrocytes, and axons. In conclusion, we demonstrate that Ryk is expressed in the unlesioned spinal cord and that, after SCI, its spatiotemporal and cellular expression pattern changed dramatically, being expressed in cells involved in the spinal cord response to damage.

show abstract

“…[42][43][44][45] For this reason, we sought to evaluate by 14 dpi, when we observed that fibronectin immunolabeling in the injured tissue was clearly…”

Section: Ryk Expression After Moderate Contusive Spinal Cord Damagementioning

confidence: 99%

Section: Fig 7 Ryk Is Expressed In Fibronectinmentioning

confidence: 99%

The Ryk Receptor Is Expressed in Glial and Fibronectin-Expressing Cells after Spinal Cord Injury

González

Fernández-Martos

Arenas

et al. 2013

Journal of Neurotrauma

View full text Add to dashboard Cite

show abstract

“…Conversely, in SCI WT mice, intraspinal antibody deposits were found in conjunction with C1q labeling. Recently, a deficiency in C1q was shown to be neuroprotective and promote functional recovery after SCI or traumatic brain injury (34)(35)(36). C3 deficiency also confers neuroprotection with reduced inflammation and improved functional recovery after SCI (37).…”

Section: Figurementioning

confidence: 99%

B cells produce pathogenic antibodies and impair recovery after spinal cord injury in mice

Ankeny¹,

Guan²,

Popovich³

2009

J. Clin. Invest.

170

174

View full text Add to dashboard Cite

IntroductionThe consequences of neuroinflammation caused by spinal cord injury (SCI) have been inferred mostly from the results of studies that manipulate the function or survival of neutrophils, monocytes/macrophages or T lymphocytes (T cells) (1-9). Less is known about the role played by antibody-producing B cells. In humans with SCI, elevated titers of myelin-reactive antibodies in serum and cerebrospinal fluid (CSF) suggest that SCI activates T and B cells that recognize CNS proteins (10-12). Using a clinically relevant murine model of SCI, we have shown that SCI induces a long-lasting B cell response, characterized by enhanced lymphopoiesis in bone marrow and spleen, with increased levels of circulating IgM and IgG antibodies (13). Activated B cells also accumulate in the injured spinal cord, in which they persist indefinitely (13). Accumulation of intraspinal B cells also is associated with de novo expression of mRNA that encodes a range of autoantibodies (14).Currently, the breadth of self/auto antigens recognized by SCIinduced antibodies is not known; however, some will bind CNS proteins and the potential exists for antibody-mediated neurodegeneration (10, 11, 13). Previously, we showed that microinjection of sera containing SCI antibodies into the intact CNS caused focal inflammation and neurotoxicity (13). Conversely, sera from SCI B cell-knockout mice (BCKO mice), which cannot make antibodies, was innocuous (13). Collectively, these data suggest that activated B cells contribute to the pathological sequelae of SCI, presumably via production of autoantibodies and activation of downstream inflammatory cascades. Here, we prove there is a causal role for B cells as effectors of post-SCI pathology. Specifically, we show that behavioral and anatomical indices of recovery from SCI are improved in BCKO mice and that B cell-mediated pathology is caused by the antibodies they produce. Indeed, antibodies purified from SCI mice cause axon and myelin pathology with transient impairment of motor function. Antibody-mediated pathology is dependent on activation of complement and cells bearing Fc-receptors in the spinal cord. Collectively, these data suggest that con-

show abstract

“…[57,58,59] The complement system is also becoming increasingly implicated in diseases of the central nervous system such as Alzheimer's disease and other neurodegenerative conditions such as spinal cord injuries. [60] It is thought that the complement system might play a role in many diseases with an immune component, such as Barraquer-Simons Syndrome, asthma, glomerulonephritis, various forms of arthritis, autoimmune heart disease, multiple sclerosis, inflammatory bowel disease, paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome [61,62] and rejection of transplanted organs. [63] Mutations in the complement regulators factor H and membrane cofactor protein have been associated with atypical hemolytic uremic syndrome.…”

Section: Selected Diseases Related To Dysfunction Of Complement Systemmentioning

confidence: 99%

Complement Activation: The role in Health and Disease and Strategies of Therapeutic Complement Inhibition

Akhtar¹,

Rahman²,

Sultana³

et al. 2014

AJMSM

View full text Add to dashboard Cite

The multiple interconnections among complement proteins, immune cells, and mediators provide an excellent mechanism to protect the organism against infections and support the repair of damaged tissues. However, disturbances in this "defense machinery" contribute to the pathogenesis of various diseases. The role of complement in various inflammatory disorders is multifaceted; for example, the activation of complement can significantly contribute to inflammation-mediated tissue damage, whereas inherited or acquired complement deficiencies highly favor the development of autoimmunity. Complement as an essential component of the immune system is of substantial relevance for the destruction of invading microorganisms and for maintaining tissue homeostasis including the protection against autoimmune diseases. The involvement of complement in the pathogenesis of a great number of partly life threatening diseases defines the importance to develop inhibitors which specifically interfere with its deleterious action. Endogenous soluble complement-inhibitors, antibodies or low molecular weight antagonists, either blocking key proteins of the cascade reaction or neutralizing the action of the complementderived anaphylatoxins have successfully been tested in various animal models over the past years.

show abstract

Deficiency in Complement C1q Improves Histological and Functional Locomotor Outcome after Spinal Cord Injury

Cited by 71 publications

References 112 publications

The Ryk Receptor Is Expressed in Glial and Fibronectin-Expressing Cells after Spinal Cord Injury

The Ryk Receptor Is Expressed in Glial and Fibronectin-Expressing Cells after Spinal Cord Injury

B cells produce pathogenic antibodies and impair recovery after spinal cord injury in mice

Complement Activation: The role in Health and Disease and Strategies of Therapeutic Complement Inhibition

Contact Info

Product

Resources

About