Neuroproteomics and systems biology‐based discovery of protein biomarkers for traumatic brain injury and clinical validation

The rapidly growing field of neuroproteomics has expanded to track global proteomic changes underlying various neurological conditions such as traumatic brain injury (TBI), stroke, and Alzheimer's disease. TBI remains a major health problem with approximately 2 million incidents occurring annually in the United States, yet no affective treatment is available despite several clinical trials. The absence of brain injury diagnostic biomarkers was identified as a significant road‐block to therapeutic development for brain injury. Recently, the field of neuroproteomics has undertaken major advances in the area of neurotrauma research, where several candidate markers have been identified and are being evaluated for their efficacy as biological biomarkers in the field of TBI. One scope of this review is to evaluate the current status of TBI biomarker discovery using neuroproteomics techniques, and at what stage we are at in their clinical validation. In addition, we will discuss the need for strengthening the role of systems biology and its application to the field of neuroproteomics due to its integral role in establishing a comprehensive understanding of specific brain disorder and brain function in general. Finally, to achieve true clinical input of these neuroproteomic findings, these putative biomarkers should be validated using preclinical and clinical samples and linked to clinical diagnostic assays including ELISA or other high‐throughput assays.

[1]  Jing Zhang,et al.  Identification of Proteins Involved in Microglial Endocytosis of α-Synuclein , 2007 .

[2]  B. Romner,et al.  Biochemical serum markers for brain damage: a short review with emphasis on clinical utility in mild head injury. , 2003, Restorative neurology and neuroscience.

[3]  B. Rowlands,et al.  Neuron-specific enolase as an aid to outcome prediction in head injury. , 1996, British journal of neurosurgery.

[4]  F. Tortella,et al.  Comparing calpain- and caspase-3-mediated degradation patterns in traumatic brain injury by differential proteome analysis. , 2006, The Biochemical journal.

[5]  R. L. Hayes,et al.  Maitotoxin Induces Calpain But Not Caspase-3 Activation and Necrotic Cell Death in Primary Septo-Hippocampal Cultures , 1999, Neurochemical Research.

[6]  C. Price,et al.  The early fall in levels of S-100 beta in traumatic brain injury. , 2000, Clinical chemistry and laboratory medicine.

[7]  A. Ebert,et al.  Temporal profile of release of neurobiochemical markers of brain damage after traumatic brain injury is associated with intracranial pathology as demonstrated in cranial computerized tomography. , 2000, Journal of neurotrauma.

[8]  C. Oliveira,et al.  Mitochondrial Dysfunction and Reactive Oxygen Species in Excitotoxicity and Apoptosis: Implications for the Pathogenesis of Neurodegenerative Diseases , 2003, Neurochemical Research.

[9]  D. Jo,et al.  Proapoptotic Effects of Tau Cleavage Product Generated by Caspase-3 , 2001, Neurobiology of Disease.

[10]  A. Brawanski,et al.  S-100B Protein Serum Levels After Controlled Cortical Impact Injury in the Rat , 2000, Acta Neurochirurgica.

[11]  Cooper Eh Neuron-Specific Enolase , 1994, The International journal of biological markers.

[12]  J. Trojanowski,et al.  Protein accumulation in traumatic brain injury , 2007, NeuroMolecular Medicine.

[13]  O. Alonso,et al.  Monoubiquitination and Cellular Distribution of XIAP in Neurons after Traumatic Brain Injury , 2003, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[14]  B. Romner,et al.  Renal elimination of protein S-100beta in pigs with acute encephalopathy. , 2001, Scandinavian journal of clinical and laboratory investigation.

[15]  D. Daly,et al.  ELISA microarray technology as a high-throughput system for cancer biomarker validation , 2006, Expert review of proteomics.

[16]  G. Clifton,et al.  Immunohistochemical study of calpain-mediated breakdown products to alpha-spectrin following controlled cortical impact injury in the rat. , 1997, Journal of neurotrauma.

[17]  S. Sealfon,et al.  Structure of the GnRH receptor-stimulated signaling network: insights from genomics , 2003, Frontiers in Neuroendocrinology.

[18]  J. Bazarian,et al.  Serum S-100B and cleaved-tau are poor predictors of long-term outcome after mild traumatic brain injury , 2006, Brain injury.

[19]  D. Menon,et al.  Discordant temporal patterns of S100 β and cleaved tau protein elevation after head injury: a pilot study , 2002, British journal of neurosurgery.

[20]  Eckart D Gundelfinger,et al.  Proteomics Analysis of Rat Brain Postsynaptic Density , 2004, Journal of Biological Chemistry.

[21]  S. Grant,et al.  Proteomics in Neuroscience: From Protein to Network , 2001, The Journal of Neuroscience.

[22]  R. Gilbertsen,et al.  Non-erythroid alpha-spectrin breakdown by calpain and interleukin 1 beta-converting-enzyme-like protease(s) in apoptotic cells: contributory roles of both protease families in neuronal apoptosis. , 1996, The Biochemical journal.

[23]  Laszlo Prokai,et al.  Proteomic analysis of the synaptic plasma membrane fraction isolated from rat forebrain. , 2003, Brain research. Molecular brain research.

[24]  B. Pike,et al.  Temporal relationships between de novo protein synthesis, calpain and caspase 3‐like protease activation, and DNA fragmentation during apoptosis in septo‐hippocampal cultures , 1998, Journal of neuroscience research.

[25]  MartinWiesmann,et al.  S-100 Protein and Neuron-Specific Enolase Concentrations in Blood as Indicators of Infarction Volume and Prognosis in Acute Ischemic Stroke , 1997 .

[26]  T. Dóczi,et al.  Spectrin breakdown products in the cerebrospinal fluid in severe head injury – preliminary observations , 2005, Acta Neurochirurgica.

[27]  Trey Ideker,et al.  Building with a scaffold: emerging strategies for high- to low-level cellular modeling. , 2003, Trends in biotechnology.

[28]  V. Seifert,et al.  Protein S-100B as a serum marker of brain damage in severe head injury: preliminary results , 2000, Neurosurgical Review.

[29]  R. Hayes,et al.  A novel marker for traumatic brain injury: CSF alphaII-spectrin breakdown product levels. , 2004, Journal of neurotrauma.

[30]  P. Svenningsson,et al.  Peptidomics-based discovery of novel neuropeptides. , 2003, Journal of proteome research.

[31]  J. Hoheisel,et al.  Antibody microarrays: promises and problems. , 2002, BioTechniques.

[32]  J. Rafols,et al.  Disruption of MAP-2 immunostaining in rat hippocampus after traumatic brain injury. , 1998, Journal of neurotrauma.

[33]  V. Seifert,et al.  Correlation of Computed Tomography Findings and Serum Brain Damage Markers Following Severe Head Injury , 1998, Acta Neurochirurgica.

[34]  A. Usui,et al.  S-100ao protein in blood and urine during open-heart surgery. , 1989, Clinical chemistry.

[35]  J. Olney,et al.  Sensitivity of the developing rat brain to hypobaric/ischemic damage parallels sensitivity to N-methyl-aspartate neurotoxicity , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  Sophia Ananiadou,et al.  Text mining and its potential applications in systems biology. , 2006, Trends in biotechnology.

[37]  G. Opiteck,et al.  Biomarker discovery in biological fluids. , 2005, Methods.

[38]  G. Tomei,et al.  Traumatic Intracerebellar Hemorrhage: Clinicoradiological Analysis of 81 Patients , 2002, Neurosurgery.

[39]  M. Sjögren,et al.  The Use of Proteomics in Biomarker Discovery in Neurodegenerative Diseases , 2005, Disease markers.

[40]  B. Pike,et al.  Concurrent Assessment of Calpain and Caspase-3 Activation after Oxygen–Glucose Deprivation in Primary Septo-Hippocampal Cultures , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[41]  B. Romner,et al.  Traumatic brain damage: serum S-100 protein measurements related to neuroradiological findings. , 2000, Journal of neurotrauma.

[42]  E. Cooper Neuron-specific enolase. , 1994, The International journal of biological markers.

[43]  B. Pike,et al.  Temporal Profile and Cell Subtype Distribution of Activated Caspase‐3 Following Experimental Traumatic Brain Injury , 2000, Journal of neurochemistry.

[44]  J. Pickard,et al.  Jugular venous and arterial concentrations of serum S-100B protein in patients with severe head injury: a pilot study , 1998, Journal of neurology, neurosurgery, and psychiatry.

[45]  R. Hayes,et al.  Biomarkers of Proteolytic Damage Following Traumatic Brain Injury , 2004, Brain pathology.

[46]  C. Lee,et al.  Mitochondrial dysfunction and calcium perturbation induced by traumatic brain injury. , 1997, Journal of neurotrauma.

[47]  H. Joller,et al.  S-100 beta reflects the extent of injury and outcome, whereas neuronal specific enolase is a better indicator of neuroinflammation in patients with severe traumatic brain injury. , 2001, Journal of neurotrauma.

[48]  Henry L. Lew,et al.  Rehabilitation needs of an increasing population of patients: Traumatic brain injury, polytrauma, and blast-related injuries. , 2005, Journal of rehabilitation research and development.

[49]  F. Michetti,et al.  S100B protein in biological fluids: a tool for perinatal medicine. , 2002, Clinical chemistry.

[50]  S. Budd,et al.  Mitochondria and neuronal survival. , 2000, Physiological reviews.

[51]  D. Hovda,et al.  Mitochondrial damage and dysfunction in traumatic brain injury. , 2004, Mitochondrion.

[52]  A. Brawanski,et al.  Early S-100B serum level correlates to quality of life in patients after severe head injury , 2002, Brain injury.

[53]  S. Hanash,et al.  Proteomics Approaches to Uncover the Repertoire of Circulating Biomarkers for Breast Cancer , 2002, Journal of Mammary Gland Biology and Neoplasia.

[54]  H. Kitano,et al.  Computational systems biology , 2002, Nature.

[55]  P. Johnsson Markers of cerebral ischemia after cardiac surgery. , 1996, Journal of cardiothoracic and vascular anesthesia.

[56]  A. Marini,et al.  Genomics and variation of ionotropic glutamate receptors: implications for neuroplasticity , 2005, Amino Acids.

[57]  A. Brawanski,et al.  Comparison of serial S-100 and NSE serum measurements after severe head injury , 2005, Acta Neurochirurgica.

[58]  G. Fiskum,et al.  Mitochondrial dysfunction early after traumatic brain injury in immature rats , 2007, Journal of neurochemistry.

[59]  R. Vink,et al.  Mitochondrial metabolism following traumatic brain injury in rats. , 1990, Journal of neurotrauma.

[60]  T. Mathiesen,et al.  Characterization of Bax and Bcl-2 in apoptosis after experimental traumatic brain injury in the rat , 2003, Acta Neuropathologica.

[61]  M Aldea,et al.  The nucleotide sequence of Saccharomyces cerevisiae chromosome XV. , 1997, Nature.

[62]  Frank Vitzthum,et al.  Proteomics: from basic research to diagnostic application. A review of requirements & needs. , 2005, Journal of proteome research.

[63]  T. Beems,et al.  Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury , 2004, Neurology.

[64]  S. Scheff,et al.  Cyclosporin A significantly ameliorates cortical damage following experimental traumatic brain injury in rodents. , 1999, Journal of neurotrauma.

[65]  E. Davidov,et al.  Advancing drug discovery through systems biology. , 2003, Drug discovery today.

[66]  B. Pike,et al.  Accumulation of non-erythroid alpha II-spectrin and calpain-cleaved alpha II-spectrin breakdown products in cerebrospinal fluid after traumatic brain injury in rats. , 2001, Journal of neurochemistry.

[67]  H. Kitano Systems Biology: A Brief Overview , 2002, Science.

[68]  R. Aebersold,et al.  Mass spectrometry-based proteomics , 2003, Nature.

[69]  W Ansorge,et al.  The nucleotide sequence of Saccharomyces cerevisiae chromosome XII. , 1997, Nature.

[70]  Jeremy J. Flint,et al.  Accumulation of non‐erythroid αII‐spectrin and calpain‐cleaved αII‐spectrin breakdown products in cerebrospinal fluid after traumatic brain injury in rats , 2001 .

[71]  Adriana B Ferreira,et al.  The Generation of a 17 kDa Neurotoxic Fragment: An Alternative Mechanism by which Tau Mediates β-Amyloid-Induced Neurodegeneration , 2005, The Journal of Neuroscience.

[72]  J. Langlois,et al.  The Incidence of Traumatic Brain Injury Among Children in the United States: Differences by Race , 2005, The Journal of head trauma rehabilitation.

[73]  Kevin K W Wang,et al.  Evidence for Activation of Caspase‐3‐Like Protease in Excitotoxin‐ and Hypoxia/Hypoglycemia‐Injured Neurons , 1998, Journal of neurochemistry.

[74]  Robert W. Williams,et al.  Informatics center for mouse genomics , 2007, Neuroinformatics.

[75]  M. Mattson,et al.  Traumatic brain injury alters synaptic homeostasis: implications for impaired mitochondrial and transport function. , 1998, Journal of neurotrauma.

[76]  W. Mauritz,et al.  Serum S 100 B: A Marker of Brain Damage in Traumatic Brain Injury with and without Multiple Trauma , 2003, Shock.

[77]  S. Scheff,et al.  Cleaved-tau: a biomarker of neuronal damage after traumatic brain injury. , 2005, Journal of neurotrauma.

[78]  A. Raabe,et al.  Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma. , 2004, The Journal of trauma.

[79]  S. Grant,et al.  Proteomics in postgenomic neuroscience: the end of the beginning , 2004, Nature Neuroscience.

[80]  B. Pike,et al.  Stretch injury causes calpain and caspase-3 activation and necrotic and apoptotic cell death in septo-hippocampal cell cultures. , 2000, Journal of neurotrauma.

[81]  Kathryn Saatman,et al.  Application of proteomics technology to the field of neurotrauma. , 2003, Journal of neurotrauma.

[82]  J. García,et al.  Functional and quantitative proteomics using SILAC in cancer research , 2008 .

[83]  Bernard Dujon,et al.  The nucleotide sequence of Saccharomyces , 1997 .

[84]  C. Alling,et al.  Elimination of S100B and renal function after cardiac surgery. , 2000, Journal of cardiothoracic and vascular anesthesia.

[85]  P. Kochanek,et al.  Serum neuron-specific enolase, S100B, and myelin basic protein concentrations after inflicted and noninflicted traumatic brain injury in children. , 2005, Journal of neurosurgery.

[86]  F. Tortella,et al.  Novel Differential Neuroproteomics Analysis of Traumatic Brain Injury in Rats* , 2006, Molecular & Cellular Proteomics.

[87]  TBI State Demonstration Grants , 1998, The Journal of head trauma rehabilitation.

[88]  K. Blennow,et al.  Proteome studies of human cerebrospinal fluid and brain tissue using a preparative two‐dimensional electophoresis approach prior to mass spectrometry , 2001, Proteomics.

[89]  R. Anderson,et al.  High serum S100B levels for trauma patients without head injuries. , 2001, Neurosurgery.

[90]  R. Hayes,et al.  Identification and preliminary validation of novel biomarkers of acute hepatic ischaemia/reperfusion injury using dual-platform proteomic/degradomic approaches , 2006, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[91]  B. Romner,et al.  Serial S-100 protein serum measurements related to early magnetic resonance imaging after minor head injury. Case report. , 1996, Journal of neurosurgery.

[92]  S. Itohara,et al.  Glial protein S100B modulates long-term neuronal synaptic plasticity , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[93]  B. Romner,et al.  The clinical value of serum S-100 protein measurements in minor head injury: a Scandinavian multicentre study. , 2000, Brain injury.

[94]  F. Lecky,et al.  Rapid elimination of protein S-100B from serum after minor head trauma. , 2006, Journal of neurotrauma.

[95]  R. Raghupathi,et al.  Cell Death Mechanisms Following Traumatic Brain Injury , 2004, Brain pathology.

[96]  V. Seifert,et al.  Serum S-100B protein as a molecular marker in severe traumatic brain injury. , 2003, Restorative neurology and neuroscience.

[97]  R. Neumar,et al.  Proteins released from degenerating neurons are surrogate markers for acute brain damage , 2004, Neurobiology of Disease.

[98]  D. Choi,et al.  Bench to bedside: the glutamate connection. , 1992, Science.

[99]  R. Wells,et al.  Serum neuron-specific enolase as a predictor of short-term outcome in children with closed traumatic brain injury. , 2005, Academic emergency medicine : official journal of the Society for Academic Emergency Medicine.

[100]  R. Schmidhammer,et al.  Circulating S100B is increased after bilateral femur fracture without brain injury in the rat. , 2003, British journal of anaesthesia.

[101]  D. Choi Excitotoxic cell death. , 1992, Journal of neurobiology.

[102]  B. Romner,et al.  High Serum S100B Levels for Trauma Patients without Head Injuries. , 2001, Neurosurgery.

[103]  B. Pike,et al.  Regional calpain and caspase‐3 proteolysis of α‐spectrin after traumatic brain injury , 1998, Neuroreport.

[104]  M. Plotkine,et al.  Characterization of a rat model to study acute neuroinflammation on histopathological, biochemical and functional outcomes , 2005, Journal of Neuroscience Methods.

[105]  Alexander Sasha Rabchevsky,et al.  Mitochondrial permeability transition in CNS trauma: Cause or effect of neuronal cell death? , 2005, Journal of neuroscience research.

[106]  A. Raabe,et al.  GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome. , 2004, Journal of neurotrauma.

[107]  W Ansorge,et al.  The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI. , 1997, Nature.

[108]  H. Joller,et al.  S-100β reflects the extent of injury and outcome, whereas neuronal specific enolase is a better indicator of neuroinflammation in patients with severe traumatic brain injury , 2001 .

[109]  David Botstein,et al.  The nucleotide sequence of yeast chromosome XVI , 1997 .

[110]  E. Hall,et al.  Attenuation of acute mitochondrial dysfunction after traumatic brain injury in mice by NIM811, a non-immunosuppressive cyclosporin A analog , 2008, Experimental Neurology.

[111]  V. Seifert,et al.  Serum markers of brain damage and outcome prediction in patients after severe head injury. , 1999, British journal of neurosurgery.

[112]  M. Wunderlich,et al.  Release of glial fibrillary acidic protein is related to the neurovascular status in acute ischemic stroke , 2006, European journal of neurology.

[113]  S. Margulies,et al.  Traumatic axonal injury is exacerbated following repetitive closed head injury in the neonatal pig. , 2004, Journal of neurotrauma.

[114]  Marcus Svensson,et al.  A neuroproteomic approach to targeting neuropeptides in the brain , 2002, Proteomics.

[115]  H. Xiong,et al.  [Pathophysiological alterations in cultured astrocytes exposed to hypoxia/reoxygenation]. , 2000, Sheng li ke xue jin zhan [Progress in physiology].

[116]  T. Wieloch,et al.  Mitochondrial permeability transition in acute neurodegeneration. , 2002, Biochimie.

[117]  V. Seifert,et al.  Fatal secondary increase in serum S-100B protein after severe head injury. Report of three cases. , 1999, Journal of neurosurgery.

[118]  W. Geraerts,et al.  Protein synthesis in synaptosomes: a proteomics analysis , 2002, Journal of neurochemistry.

[119]  B. Dujon,et al.  The nucleotide sequence of Saccharomyces cerevisiae chromosome VII. , 1997, Nature.

[120]  Steven A Carr,et al.  Protein biomarker discovery and validation: the long and uncertain path to clinical utility , 2006, Nature Biotechnology.

[121]  C. Vorhees,et al.  Methamphetamine enhances the cleavage of the cytoskeletal protein tau in the rat brain , 2003, Neuroscience.

[122]  Eric Boerwinkle,et al.  Gene expression profiling and functional proteomic analysis reveal perturbed kinase-mediated signaling in genetic stroke susceptibility. , 2003, Physiological genomics.

[123]  J. James Unproven diagnostic and therapeutic techniques , 2002, Current Allergy and Asthma Reports.

[124]  D. Goldman,et al.  Genomics and Variation of Ionotropic Glutamate Receptors , 2003, Annals of the New York Academy of Sciences.

[125]  D. Prough,et al.  Analysis of long-term gene expression in neurons of the hippocampal subfields following traumatic brain injury in rats , 2005, Neuroscience.

[126]  D. Thompson,et al.  Application of proteomic technologies in the drug development process. , 2003, Toxicology letters.

[127]  F. Tortella,et al.  Accumulation of Calpain and Caspase-3 Proteolytic Fragments of Brain-Derived αII-Spectrin in Cerebral Spinal Fluid after Middle Cerebral Artery Occlusion in Rats , 2004, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[128]  A. Raabe High serum S100B levels for trauma patients without head injuries. , 2001, Neurosurgery.

[129]  R. Hayes,et al.  Rapid discovery of putative protein biomarkers of traumatic brain injury by SDS-PAGE-capillary liquid chromatography-tandem mass spectrometry. , 2005, Journal of neurotrauma.

[130]  D. Desiderio,et al.  Analysis of the human lumbar cerebrospinal fluid proteome , 2002, Electrophoresis.

[131]  K. Johnson,et al.  Chronic phencyclidine increases NMDA receptor NR1 subunit mRNA in rat forebrain , 1999, Journal of neuroscience research.

[132]  A. Can,et al.  Attenuation of microtubule associated protein-2 degradation after mild head injury by mexiletine and calpain-2 inhibitor , 2007, British journal of neurosurgery.

[133]  D. Wallace Mitochondrial diseases in man and mouse. , 1999, Science.

[134]  K. Sandelin,et al.  Proteomic Characterization of the Interstitial Fluid Perfusing the Breast Tumor Microenvironment , 2004, Molecular & Cellular Proteomics.

[135]  R. Neumar,et al.  Comparison of Calpain and Caspase Activities in the Adult Rat Brain after Transient Forebrain Ischemia , 2002, Neurobiology of Disease.

[136]  T. Neumann-Haefelin,et al.  Serum glial fibrillary acidic protein as a biomarker for intracerebral haemorrhage in patients with acute stroke , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[137]  R. Ergün,et al.  Prognostic value of serum neuron-specific enolase levels after head injury. , 1998, Neurological research.

[138]  I. Zagon,et al.  Brain spectrin(240/235) and brain spectrin(240/235E): two distinct spectrin subtypes with different locations within mammalian neural cells , 1986, The Journal of cell biology.

[139]  J. Yates,et al.  Shotgun Proteomics and Biomarker Discovery , 2002, Disease markers.

[140]  山崎 義矩 Diagnostic significance of serum neuron-specific enolase and myelin basic protein assay in patients with acute head injury , 1994 .

[141]  R. Hayes,et al.  Concurrent calpain and caspase-3 mediated proteolysis of alpha II-spectrin and tau in rat brain after methamphetamine exposure: a similar profile to traumatic brain injury. , 2005, Life sciences.

[142]  Firas Kobeissy,et al.  Proteomics studies of traumatic brain injury. , 2004, International review of neurobiology.

[143]  J. Rossier,et al.  Identification of brain cell death associated proteins in human post-mortem cerebrospinal fluid. , 2006, Journal of proteome research.

[144]  T. Emanuelli,et al.  Neurochemical characterization of traumatic brain injury in humans. , 2001, Journal of neurotrauma.

[145]  C. Alling,et al.  Neuron-specific enolase increases in plasma during and immediately after extracorporeal circulation. , 2000, The Annals of thoracic surgery.

[146]  T. Boyer,et al.  Identification of a short form of ubiquitin-specific protease 3 that is a repressor of rat glutathione S-transferase gene expression. , 2006, The Biochemical journal.

[147]  Vidya N. Nukala,et al.  Proteomic identification of oxidized mitochondrial proteins following experimental traumatic brain injury. , 2007, Journal of neurotrauma.

[148]  T. Ideker,et al.  Network genomics. , 2007, Ernst Schering Research Foundation workshop.

[149]  P. Urdal,et al.  Increased serum creatine kinase BB and neuron specific enolase following head injury indicates brain damage , 2005, Acta Neurochirurgica.

[150]  L. Liotta,et al.  CSF proteome: a protein repository for potential biomarker identification , 2005, Expert review of proteomics.

[151]  A. Brawanski,et al.  S-100 serum levels after minor and major head injury. , 1998, The Journal of trauma.

[152]  Jean-Paul Noben,et al.  Proteomic analysis of cerebrospinal fluid from multiple sclerosis patients , 2004, Proteomics.

[153]  Roger E Bumgarner,et al.  Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. , 2001, Science.

[154]  S. Orencole,et al.  Array-based ELISAs for high-throughput analysis of human cytokines. , 2001, BioTechniques.

[155]  W. Hermens,et al.  Fatty acid-binding proteins as plasma markers of tissue injury. , 2005, Clinica chimica acta; international journal of clinical chemistry.

[156]  A. Sikorski,et al.  Spectrin and calpain: a ‘target’ and a ‘sniper’ in the pathology of neuronal cells , 2005, Cellular and Molecular Life Sciences CMLS.

[157]  Manfred Herrmann,et al.  Release of Glial Tissue–Specific Proteins After Acute Stroke: A Comparative Analysis of Serum Concentrations of Protein S-100B and Glial Fibrillary Acidic Protein , 2000, Stroke.

[158]  S. Grant,et al.  Systems biology in neuroscience: bridging genes to cognition , 2003, Current Opinion in Neurobiology.

[159]  S. Hunsucker,et al.  Proteomic analysis of multiple sclerosis cerebrospinal fluid , 2004, Multiple sclerosis.

[160]  I. Zagon,et al.  Brain spectrin: Of mice and men , 1995, Brain Research Bulletin.

[161]  T. Ideker,et al.  A new approach to decoding life: systems biology. , 2001, Annual review of genomics and human genetics.

[162]  R. Donato,et al.  Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type. , 1999, Biochimica et biophysica acta.

[163]  Takashi Yamauchi,et al.  Molecular constituents of the postsynaptic density fraction revealed by proteomic analysis using multidimensional liquid chromatography‐tandem mass spectrometry , 2003, Journal of neurochemistry.

[164]  A. Brawanski,et al.  Comparison of clinical, radiologic, and serum marker as prognostic factors after severe head injury. , 1999, The Journal of trauma.

[165]  A. Twijnstra,et al.  S‐100B and neuron‐specific enolase in serum of mild traumatic brain injury patients
A comparison with healthy controls , 2001, Acta neurologica Scandinavica.

[166]  Jing Zhang,et al.  Identification of proteins involved in microglial endocytosis of alpha-synuclein. , 2007, Journal of proteome research.

[167]  C. Price,et al.  The Early Fall in Levels of S-100 β in Traumatic Brain Injury , 2000 .

[168]  L. Lv,et al.  High-throughput antibody microarrays for quantitative proteomic analysis , 2007, Expert review of proteomics.