Hyperacute Detection of Neurofilament Heavy Chain in Serum Following Stroke: A Transient Sign

Sellner, Johann; Patel, Amit; Dassan, Pooja; Brown, Martin M.; Petzold, Axel

doi:10.1007/s11064-011-0553-8

Cited by 35 publications

(31 citation statements)

References 26 publications

(36 reference statements)

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“…The perturbation of the axonal membrane expels neurofilaments to the interstitial space and eventually to the cerebrospinal fluid and the blood. In this manner, the levels of neurofilaments in the blood can be used for both the prediction and monitoring of the progress of a disease and the evaluation of the efficacy and/or toxicity of neuroprotective treatments [67–70]. The phosphorylated form of NF-H is axon-specific and is used as a specific marker for neuronal damage and degeneration [71].…”

Section: Discussionmentioning

confidence: 99%

Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin-2 Administration

Romero

Holubiec

Tornatore

et al. 2017

Oxidative Medicine and Cellular Longevity

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The general disruption of redox signaling following an ischemia-reperfusion episode has been proposed as a crucial component in neuronal death and consequently brain damage. Thioredoxin (Trx) family proteins control redox reactions and ensure protein regulation via specific, oxidative posttranslational modifications as part of cellular signaling processes. Trx proteins function in the manifestation, progression, and recovery following hypoxic/ischemic damage. Here, we analyzed the neuroprotective effects of postinjury, exogenous administration of Grx2 and Trx1 in a neonatal hypoxia/ischemia model. P7 Sprague-Dawley rats were subjected to right common carotid ligation or sham surgery, followed by an exposure to nitrogen. 1 h later, animals were injected i.p. with saline solution, 10 mg/kg recombinant Grx2 or Trx1, and euthanized 72 h postinjury. Results showed that Grx2 administration, and to some extent Trx1, attenuated part of the neuronal damage associated with a perinatal hypoxic/ischemic damage, such as glutamate excitotoxicity, axonal integrity, and astrogliosis. Moreover, these treatments also prevented some of the consequences of the induced neural injury, such as the delay of neurobehavioral development. To our knowledge, this is the first study demonstrating neuroprotective effects of recombinant Trx proteins on the outcome of neonatal hypoxia/ischemia, implying clinical potential as neuroprotective agents that might counteract neonatal hypoxia/ischemia injury.

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Section: Discussionmentioning

confidence: 99%

Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin-2 Administration

Romero

Holubiec

Tornatore

et al. 2017

Oxidative Medicine and Cellular Longevity

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“…Data on GFAP levels in ischaemic stroke (Martinez-Morillo et al, 2014;Foerch et al, 2006Foerch et al, , 2012Dvorak et al, 2009;Sellner et al, 2011), subarachnoid haemorrhage (SAH) (Martinez-Morillo et al, 2014;Petzold et al, 2006;Vos et al, 2006;Nylen et al, 2006a;Kaneda et al, 2010), cerebral vasculitis (Nylen et al, 2002) and intracranial haemorrhage ( Data from the ICH studies suggest that blood GFAP levels may be b r a i n r e s e a r c h 1 6 0 0 ( 2 0 1 5 ) 1 7 -3 1 of diagnostic value if taken within 1-6 h after onset of ICH (Foerch et al, 2006(Foerch et al, , 2012Dvorak et al, 2009;Sun et al, 2013;Zhang et al, 2013). Likewise, longitudinal data from SAH indicates a wash-out time of 7-10 days for CSF GFAP levels (Petzold et al, 2006).…”

Section: Cerebrovascular Pathologymentioning

confidence: 99%

Glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease

Petzold

2015

Brain Research

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This review on the role of glial fibrillary acidic protein (GFAP) as a biomarker for astroglial pathology in neurological diseases provides background to protein synthesis, assembly, function and degeneration. Qualitative and quantitative analytical techniques for the investigation of human tissue and biological fluid samples are discussed including partial lack of parallelism and multiplexing capabilities. Pathological implications are reviewed in view of immunocytochemical, cell-culture and genetic findings. Particular emphasis is given to neurodegeneration related to autoimmune astrocytopathies and to genetic gain of function mutations. The current literature on body fluid levels of GFAP in human disease is summarised and illustrated by disease specific meta-analyses. In addition to the role of GFAP as a diagnostic biomarker for chronic disease, there are important data on the prognostic value for acute conditions. The published evidence permits to classify the dominant GFAP signatures in biological fluids. This classification may serve as a template for supporting diagnostic criteria of autoimmune astrocytopathies, monitoring disease progression in toxic gain of function mutations, clinical treatment trials (secondary outcome and toxicity biomarker) and provide prognostic information in neurocritical care if used within well defined time-frames.

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“…This ionic flux destabilizes the axolemma and activates calcium-dependent proteases, such as calpain, that chew up neurofilament proteins and other structural components [48]. Notably, neurofilament proteins can be detected in the blood within hours after acute stroke [49,50]. This immediate early phase of axonal injury has rarely been studied using animal models of stroke but rather using ex-vivo axonal and myelinated nerve preps or other models of axonal injury [51–54].…”

Section: The Back: Progressive Axonal Degeneration After Strokementioning

confidence: 99%

The back and forth of axonal injury and repair after stroke

Hinman¹

2014

Current Opinion in Neurology

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Purpose of review The axon plays a central role in both the injury and repair phases after stroke. This review highlights emerging principles in the study of axonal injury in stroke and the role of the axon in neural repair after stroke. Recent findings Ischemic stroke produces a rapid and significant loss of axons in the acute phase. This early loss of axons results from a primary ischemic injury that triggers a wave of calcium signaling, activating proteolytic mechanisms and downstream signaling cascades. A second progressive phase of axonal injury occurs during the subacute period and damages axons that survive the initial ischemic insult but go on to experience a delayed axonal degeneration driven in part by changes in axoglial contact and axonal energy metabolism. Recovery from stroke is dependent on axonal sprouting and reconnection that occurs during a third degenerative/regenerative phase. Despite this central role played by the axon, comparatively little is understood about the molecular pathways that contribute to early and subacute axonal degeneration after stroke. Recent advances in axonal neurobiology and signaling suggest new targets that hold promise as potential molecular therapeutics including axonal calcium signaling, axoglial energy metabolism and cell adhesion as well as retrograde axonal mitogen-activated protein kinase pathways. These novel pathways must be modeled appropriately as the type and severity of axonal injury vary by stroke subtype. Summary Stroke-induced injury to axons occurs in three distinct phases each with a unique molecular underpinning. A wealth of new data about the molecular organization and molecular signaling within axons is available but not yet robustly applied to the study of axonal injury after stroke. Identifying the spatiotemporal patterning of molecular pathways within the axon that contribute to injury and repair may offer new therapeutic strategies for the treatment of stroke.

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Hyperacute Detection of Neurofilament Heavy Chain in Serum Following Stroke: A Transient Sign

Cited by 35 publications

References 26 publications

Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin-2 Administration

Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin-2 Administration

Glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease

The back and forth of axonal injury and repair after stroke

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