Effect of Soluble Complement Receptor-1 on Neutrophil Accumulation after Traumatic Brain Injury in Rats

Kaczorowski, Susan L.; Schiding, Joanne K.; Toth, Carol A.; Kochanek, Patrick M.

doi:10.1038/jcbfm.1995.107

Cited by 122 publications

(61 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, posttraumatic brain neutrophil accumulation, known to be C3-dependent (Kaczorowski et al, 1995;You et al, 2007), was similar in MBL KO and WT mice. Thus, MBL A/C, and hence the lectin pathway, appears to be dispensable for terminal complement activation after CCI, in agreement with previous reports from our group and others that indicate a predominant role for the alternative pathway in TBI (Rancan et al, 2003;You et al, 2007).…”

Section: Discussionmentioning

confidence: 78%

“…Activation of complement plays a role in posttraumatic brain inflammation. Intracerebral complement activation occurs in traumatic human brain (Bellander et al, 2001;Schmidt et al, 2005;Stahel et al, 1998), and genetic or pharmacological inhibition of terminal complement components reduce brain neutrophil accumulation, blood-brain barrier damage, apoptosis, and neurologic dysfunction in experimental TBI models (Kaczorowski et al, 1995;Leinhase et al, 2006;Rancan et al, 2003). Complement activation may be mediated by three distinct pathways: The classical pathway (initiated by antigen-antibody aggregates and proceeding through C1q, C4, and C2), the alternative pathway (initiated by C3b and proceeding through factor B and factor D), and the lectin pathway (initiated by mannose binding lectin (MBL) and proceeding through C4 and C2).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mannose Binding Lectin Gene Deficiency Increases Susceptibility to Traumatic Brain Injury in Mice

Yager

You

Qin

et al. 2008

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Mannose binding lectin (MBL) initiates complement activation and exacerbates tissue damage after systemic ischemia/reperfusion. We tested the hypothesis that MBL activates complement and worsens outcome using two levels of controlled cortical impact (CCI) in mice. After moderate CCI (0.6 mm depth), MBL immunostaining was detected on injured endothelial cells of wild-type (WT) mice and C3d was detected in MBL KO (deficient in MBL A/C) and WT mice, suggesting that MBL is dispensable for terminal complement activation after CCI. Brain neutrophils, edema, blood-brain barrier permeability, gross histopathology, and motor dysfunction were similar in injured MBL KO and WT mice. In mice subjected to mild CCI (0.2 mm), MBL KO mice had almost two-fold increased acute CA3 cell degeneration at 6 h (P < 0.01 versus WT). Naive MBL KO mice had decreased brain volume but performed similar to WT mice in two distinct Morris water maze (MWM) paradigms. However, injured MBL KO mice had impaired performance in cued platform trials (P < 0.05 versus WT), suggesting a transient nonspatial learning deficit in injured MBL KO mice. The data suggest that MBL deficiency increases susceptibility to CCI through C3-independent mechanisms and that MBL-deficient patients may be at increased risk of poor outcome after traumatic brain injury.

show abstract

Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Mannose Binding Lectin Gene Deficiency Increases Susceptibility to Traumatic Brain Injury in Mice

Yager

You

Qin

et al. 2008

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…posttraumatic brain neutrophil accumulation was not decreased in C4 À/À mice compared with WT. We and others found that brain neutrophil accumulation after cerebral contusion in rodents is C3-dependent, as shown in rats using a pharmacologic C3 convertase inhibitor (Kaczorowski et al, 1995) and in mice deficient in C3 in this study. Collectively, these findings imply that C3-independent mechanism(s) mediate the biologic effects of C4 in our CCI model.…”

Section: Discussionmentioning

confidence: 82%

“…The investigators showed beneficial effects on histopathologic or functional outcome of pharmacologic C3 convertase inhibitors (Kaczorowski et al, 1995;Leinhase et al, 2006b), genetic inhibition of factor B (a component of the alternative pathway) (Leinhase et al, 2006a), or of astrocyte-specific overexpression of an endogenous C3 convertase inhibitor (Rancan et al, 2003). These studies suggested that terminal complement activation may induce secondary injury after TBI; however, the pathway(s) that initiate complement activation after TBI have not been completely defined (Leinhase et al, 2006a).…”

mentioning

confidence: 99%

Reduced Tissue Damage and Improved Recovery of Motor Function after Traumatic Brain Injury in Mice Deficient in Complement Component C4

You

Yang

Takahashi

et al. 2007

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Complement component C4 mediates C3-dependent tissue damage after systemic ischemiareperfusion injury. Activation of C3 also contributes to the pathogenesis of experimental and human traumatic brain injury (TBI); however, few data exist regarding the specific pathways (classic, alternative, and lectin) involved. Using complement knockout mice and a controlled cortical impact (CCI) model, we tested the hypothesis that the classic pathway mediates secondary damage after TBI. After CCI, C4c and C3d immunostaining were detected in cortical vascular endothelial cells in wild-type (WT) mice; however, C4c and C3d immunostaining were also detected in C1q À/À mice, and C3d immunostaining was detected in C4 À/À mice. After CCI, WT and C1q À/À mice had similar motor deficits, Morris water maze performance, and brain lesion size. Naive C4 À/À and WT mice did not differ in baseline motor performance, but C4 À/À mice had reduced postinjury motor deficits (days 1 to 7, P < 0.05) and decreased brain tissue damage (days 14 and 35, P < 0.05) versus WT. Reconstitution of C4 À/À mice with human C4 (hC4) reversed their protection against postinjury motor deficits (P < 0.05 versus vehicle), but administration of hC4 did not impair postinjury motor performance (versus vehicle) in WT mice. The protective effects of C4 À/À were functionally distinct from the classic pathway and terminal complement, as C1q À/À and C3 À/À mice had postinjury tissue damage and motor dysfunction similar to WT. Thus, C4 contributes to motor deficits and brain tissue damage after CCI by mechanism(s) fundamentally different from those involved in experimental systemic ischemia-reperfusion injury.Journal of Cerebral Blood Flow & Metabolism (2007) 27, 1954-1964 doi:10.1038/sj.jcbfm.9600497; published online 25 April 2007 Keywords: complement; mice; behavior; traumatic brain injury; inflammation; genetics Introduction Traumatic brain injury induces an acute inflammatory response that contributes to posttraumatic cell death and functional neurologic deficits (Schmidt et al, 2005). Activation of complement amplifies local inflammation and exacerbates tissue damage and organ dysfunction after systemic and central nervous system ischemia-reperfusion injury (Chan et al, 2003;del Zoppo, 1999;Zhou et al, 2000), and studies in humans and in experimental animal models provide convincing evidence that Stahel et al, 2000). Complement signaling in injured brain parenchyma may also be contributed by serum components that enter the brain through a compromised blood-brain barrier.To date, only four published studies have examined a role for complement in traumatic cerebral contusion models. The investigators showed beneficial effects on histopathologic or functional outcome of pharmacologic C3 convertase inhibitors (Kaczorowski et al, 1995;Leinhase et al, 2006b), genetic inhibition of factor B (a component of the alternative pathway) (Leinhase et al, 2006a), or of astrocyte-specific overexpression of an endogenous C3 convertase inhibitor (Rancan et al, 2003). These studies...

show abstract

“…In a study of traumatic brain injury model in rat, recombinant sCR1 reduced tissue neutrophil infiltration and relieved local immune inflammation by inhibiting activation of the complement system. 17 Dobschuetz et al 18 have shown that sCR1 effectively improved the pancreatic ischemia-reperfusion-induced microcirculation in rats and they also described the possibility of treatment after post-ischemic pancreatitis. Li et al 19 showed that recombinant sCR1 effectively inhibited complement activation during cardiopulmonary bypass in humans, and referred the tolerance and improvement of vascular functions in infant's case.…”

Section: Discussionmentioning

confidence: 99%

Soluble complement receptor type 1 inhibits complement system activation and improves motor function in acute spinal cord injury

Zhu

et al. 2009

Spinal Cord

View full text Add to dashboard Cite

Study design: Spinal cord injured rat model, treated with soluble complement receptor type 1 (sCR1). Setting: Experimental Animal Department of China Medical University, Shenyang, China. Objectives: Soluble CR1 is a powerful inhibitor of complement activation. In this study, we investigate the effectiveness of sCR1 on spinal cord injury (SCI) in rats. Methods: Spinal cord injury was induced in Sprague-Dawley rats. Three experimental groups were examined; the sCR1 group was administered sCR1 at 1 h after the SCI, whereas the control group was administered saline at 1 h after SCI and the sham group underwent a sham operation without SCI or administration. The expressions of C9 and CD59 in the injured spinal cords were evaluated by immunohistochemistry, and numbers of positive cells counted. Furthermore, myeloperoxidase (MPO) activity and motor function were evaluated in each group. Results: At all postoperative time points, the numbers of C9-and CD59-positive cells in the sCR1 group were reduced compared with the control group and MPO activity was significantly decreased compared with both other groups. Moreover, the Basso, Beattie and Bresnahan score for the sCR1 group was significantly improved as compared with that of the control group after 7 days postoperatively. Conclusion: Soluble CR1 decreases inflammation reactions by inhibiting activation of the complement system and improves motor function after acute SCI.

show abstract

Effect of Soluble Complement Receptor-1 on Neutrophil Accumulation after Traumatic Brain Injury in Rats

Cited by 122 publications

References 20 publications

Mannose Binding Lectin Gene Deficiency Increases Susceptibility to Traumatic Brain Injury in Mice

Mannose Binding Lectin Gene Deficiency Increases Susceptibility to Traumatic Brain Injury in Mice

Reduced Tissue Damage and Improved Recovery of Motor Function after Traumatic Brain Injury in Mice Deficient in Complement Component C4

Soluble complement receptor type 1 inhibits complement system activation and improves motor function in acute spinal cord injury

Contact Info

Product

Resources

About