Reduced brain edema after traumatic brain injury in mice deficient in P-selectin and intercellular adhesion molecule-1

Whalen, Michael J.; Carlos, Timothy M.; Dixon, C. Edward; Robichaud, Paul; Clark, Robert S. B.; Marion, Donald W.; Kochanek, Patrick M.

doi:10.1002/jlb.67.2.160

Cited by 58 publications

(50 citation statements)

References 62 publications

(131 reference statements)

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“…However, histopathology, brain edema, and functional outcome tests used in this study can be influenced after CCI by targeting inflammation (Sinz et al, 1999;Whalen et al, 2000). Alternatively, offtarget effects of Ig-Crry fusion protein on neuroprotective gene expression may have mitigated cell death and improved functional outcome in previous reports (Leinhase et al, 2006b).…”

Section: Discussionmentioning

confidence: 93%

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

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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...

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Section: Discussionmentioning

confidence: 93%

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

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“…In this regard, our model may be particularly clinically relevant if early decompressive craniectomy becomes standard of care in the management of patients with severe focal TBI. Significant histopathology and functional deficits are characteristics of CCI models with or without replacement of the craniotomy (Bermpohl et al, 2006;Whalen et al, 2000). Nonetheless, whether TNFa/Fas inhibition would be similarly protective in a CCI (or other TBI) model featuring significant intracranial hypertension is an important question for future studies.…”

Section: Discussionmentioning

confidence: 99%

“…Lesion volume was expressed in cubic meters. Brain tissue loss was calculated by obtaining the total volume of remaining tissue in the right (uninjured) (Bermpohl et al, 2006;Clark et al, 2000), mutant mice were always subjected to CCI concomitantly with WT controls.…”

Section: Assessment Of Injury After Tissue Damagementioning

confidence: 99%

TNF Alpha and Fas Mediate Tissue Damage and Functional Outcome after Traumatic Brain Injury in Mice

Bermpohl

You

et al. 2007

J Cereb Blood Flow Metab

113

116

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Tumor necrosis factor-alpha (TNFa) and Fas are induced after traumatic brain injury (TBI); however, their functional roles are incompletely understood. Using controlled cortical impact (CCI) and mice deficient in TNFa, Fas, or both (TNFa/FasÀ/À), we hypothesized that TNFa and Fas receptor mediate secondary TBI in a redundant manner. Compared with wild type (WT), TNFa/FasÀ/À mice had improved motor performance from 1 to 4 days (P < 0.05), improved spatial memory acquisition at 8 to 14 days (P < 0.05), and decreased brain lesion size at 2 and 6 weeks after CCI (P < 0.05). Protection in TNFa/FasÀ/À mice from histopathological and motor deficits was reversed by reconstitution with recombinant TNFa before CCI, and TNFaÀ/À mice administered anti-Fas ligand antibodies had improved spatial memory acquisition versus similarly treated WT mice (P < 0.05). Tumor necrosis factor-alpha/FasÀ/À mice had decreased the numbers of cortical cells with plasmalemma damage at 6 h (P < 0.05 versus WT), and reduced matrix metalloproteinase-9 activity in injured brain at 48 and 72 h after CCI. In immature mice subjected to CCI, genetic inhibition of TNFa and Fas conferred beneficial effects on histopathology and spatial memory acquisition in adulthood (both P < 0.05 versus WT), suggesting that the beneficial effects of TNFa/Fas inhibition may be permanent. The data suggest that redundant signaling pathways initiated by TNFa and Fas play pivotal roles in the pathogenesis of TBI, and that biochemical mechanisms downstream of TNFa/Fas may be novel therapeutic targets to limit neurological sequelae in children and adults with severe TBI.

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“…The evidence of increased serum levels of sICAM-1 during acute relapses are in accordance with recently reported data 11,14,[24][25][26] showing elevated expression of adhesion molecules (ICAM-1) on the luminal surface of endothelial cells in active MS lesions. In this sense, high concentrations of sICAM-1 and VCAM-1 in the peripheral blood during active disease would reflect BBB damage and may further serve as an adhesion ligand during extravasation of activated leukocytes into the brain tissue 24,27 . Indeed the extent of ICAM-1 activation may vary within different regions of the inflamed brain tissue which ultimately may account for the varying degrees of neurological deficit 2,4,28,29 .…”

Section: Discussionmentioning

confidence: 99%

Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis

Alves-Leon

Batista²,

Papais-Alvarenga

et al. 2001

Arq. Neuro-Psiquiatr.

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Cytokines and adhesion molecules have been implicated in the pathogenesis of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. In this study we analyzed intrathecal (CSF) and serum levels of soluble intercellular adhesion molecule (ICAM-1) and TNFalphaR (60kD) from 20 patients with clinically definite MS during acute relapse or stable disease. Comparing to control groups of healthy individuals and patients with intervertebral herniated disc, MS patients showed increased levels (p< 0.001) of sICAM-1 and TNFalphaR in both serum and CSF samples. Regardless stage of disease there was no significant difference in the levels of sICAM-1 during acute relapse (657±124.9 ng/ml) or remission (627±36.2 ng/ml). A steady increase of TNFalphaR (60kD) in both serum and CSF, indicate the existence of a continuous inflammatory process within the brain tissue of MS patients despite absence of clinical signs of disease activity.

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Reduced brain edema after traumatic brain injury in mice deficient in P-selectin and intercellular adhesion molecule-1

Cited by 58 publications

References 62 publications

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

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

TNF Alpha and Fas Mediate Tissue Damage and Functional Outcome after Traumatic Brain Injury in Mice

Determination of soluble ICAM-1 and TNFalphaR in the cerebrospinal fluid and serum levels in a population of Brazilian patients with relapsing-remitting multiple sclerosis

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