Proteomic Biomarker Discovery in Cerebrospinal Fluid for Cerebral Vasospasm Following Subarachnoid Hemorrhage

Lad, Shivanand P.; Hegen, Harald; Gupta, Gaurav; Deisenhammer, Florian; Steinberg, Gary K.

doi:10.1016/j.jstrokecerebrovasdis.2010.04.004

Cited by 83 publications

(76 citation statements)

References 44 publications

(70 reference statements)

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“…11,12,29 There is broad consensus that SAH changes cerebrovascular function by inducing an inflammatory reaction within the vascular wall. 9,[30][31][32] Although several cytokines may be involved, [33][34][35][36] TNFα has garnered special attention because (1) cerebrospinal 33 and interstitial fluid 34 TNFα levels rise and peak between 4 and 10 days post-SAH (ie, a time-frame consistent with a role in DCI); (2) elevated TNFα levels associate with angiographic vasospasm, abnormal cerebral flow velocities, and poor clinical outcome [35][36][37] ; and (3) anti-TNFα therapy (infliximab) prevents basilar artery vasospasm in experimental SAH. 9 Our results demonstrate that TNFα augments olfactory artery myogenic tone in vitro; targeted disruption of TNFα signaling (TNFα and TNFα receptor 1 knockout models) confirmed this function in vivo after SAH.…”

Section: Discussionmentioning

confidence: 99%

Therapeutically Targeting Tumor Necrosis Factor-α/Sphingosine-1-Phosphate Signaling Corrects Myogenic Reactivity in Subarachnoid Hemorrhage

Yagi

Lidington

Wan

et al. 2015

Stroke

148

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S ubarachnoid hemorrhage (SAH) affects ≈10 in 100 000 people/y.1 Although SAH accounts for only 5% to 10% of all strokes, it is particularly devastating: half of all SAH patients die within 1 month and half of those who survive will require life-long assistance for daily living (ie, ≈75% of patients die or are seriously debilitated).2,3 The poor clinical outcome can be attributed to the biphasic course of the disease, characterized by an initial hemorrhagic stroke that is frequently followed by delayed cerebral ischemia (DCI) within 4 to 12 days. 4,5 The latter is a primary therapeutic concern when treating SAH, because DCI causes at least half of the morbidity and mortality in SAH. 2The transition from the hemorrhagic insult to secondary ischemia is driven by prominent changes in cerebrovascular reactivity, which compromises cerebral autoregulation 6,7 and evokes angiographic vasospasm (ie, radiographically identifiable arterial narrowing in the proximal cerebrovascular circulation).2,8 Conceptually, both events originate from augmentedBackground and Purpose-Subarachnoid hemorrhage (SAH) is a complex stroke subtype characterized by an initial brain injury, followed by delayed cerebrovascular constriction and ischemia. Current therapeutic strategies nonselectively curtail exacerbated cerebrovascular constriction, which necessarily disrupts the essential and protective process of cerebral blood flow autoregulation. This study identifies a smooth muscle cell autocrine/paracrine signaling network that augments myogenic tone in a murine model of experimental SAH: it links tumor necrosis factor-α (TNFα), the cystic fibrosis transmembrane conductance regulator, and sphingosine-1-phosphate signaling. Methods-Mouse olfactory cerebral resistance arteries were isolated, cannulated, and pressurized for in vitro vascular reactivity assessments. Cerebral blood flow was measured by speckle flowmetry and magnetic resonance imaging. Standard Western blot, immunohistochemical techniques, and neurobehavioral assessments were also used. Results-We demonstrate that targeting TNFα and sphingosine-1-phosphate signaling in vivo has potential therapeutic application in SAH. Both interventions (1) eliminate the SAH-induced myogenic tone enhancement, but otherwise leave vascular reactivity intact; (2) ameliorate SAH-induced neuronal degeneration and apoptosis; and (3) improve neurobehavioral performance in mice with SAH. Furthermore, TNFα sequestration with etanercept normalizes cerebral perfusion in SAH. Conclusions-Vascular smooth muscle cell TNFα and sphingosine-1-phosphate signaling significantly enhance cerebral artery tone in SAH; anti-TNFα and anti-sphingosine-1-phosphate treatment may significantly improve clinical outcome.

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Section: Discussionmentioning

confidence: 99%

Therapeutically Targeting Tumor Necrosis Factor-α/Sphingosine-1-Phosphate Signaling Corrects Myogenic Reactivity in Subarachnoid Hemorrhage

Yagi

Lidington

Wan

et al. 2015

Stroke

148

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“…[40][41][42][43] Cytokine inhibition, in animal models of SAH, has been associated with improved outcome. 44 DCI typically occurs between days 4 and 14 after the initial hemorrhage.…”

Section: Strokementioning

confidence: 99%

“…Inflammatory mediators, such as interleukin-6, tumor necrosis factor, intracellular adhesion molecule, matrix metalloproteinase 9, and C-reactive protein, have been linked to DCI and are downregulated through preconditioning. [40][41][42][43][48][49][50][51][52][53][54] In addition, tissue is rendered more tolerant to ischemia through reduction of excitotoxicity and metabolic protection by enhancing mitochondrial function. Preconditioning also affects several other pathways that have been implicated in vasospasm and DCI.…”

Section: Preconditioning To Ameliorate Vasospasm and DCImentioning

confidence: 99%

Preconditioning the Human Brain

Koch

Gonzalez

2013

Stroke

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“…14,15 None of these grading scales meet all the constitutive criteria for an ideal SAH grading scale, additionally; there is a paucity of validation studies. 16,17 Therefore, there is a principal requirement to supplement these radiological and/or clinical assessments with properly validated biological based marker(s) that predict either the ensuing complications, or the overall patient outcome itself. A significant complication of SAH is cerebral vasospasm (CV).…”

Section: Prognosismentioning

confidence: 99%

“…Not all CV manifests clinically, studies report that in at-least two-thirds of patients with SAH who undergo cerebral angiography between days 4e14, will experience a certain degree of vessel narrowing. 16 Symptomatic CV clinically manifests itself as fresh focal neurological deficits whereby the aetiology cannot be attributed to other structural or metabolic processes. 19 This is particularly difficult to diagnose in the unconscious sedated patient in critical care; here diagnosis of CV relies upon Middle Cerebral Artery Doppler studies.…”

Section: Prognosismentioning

confidence: 99%