Abstract
With modern advances in life support and resuscitation medicine, neurologic injury in critical illness has become the new and the last frontier in critical care medicine. In addition to preserving life, the “holy grail” of modern critical care is to preserve function and quality of life. Molecular biomarkers have revolutionalized modern medicine, leading to novel gold standard diagnostics such as troponin for myocardial infarction, new disease monitors such as tumor markers, and new “personalized medicine” tools for selecting patient likely to respond to certain therapy such as Imatinib (Gleevec) use in Philadelphina chromosome chronic myelogenous leukemia. The central nervous system (CNS) poses a special challenge for diagnostic and therapeutic treatments due to the skull being a barrier to brain monitoring and tissue sampling, the presence of the blood–brain barrier (BBB), the complex relationship between localization and function, and the frequently poor reflection of clinical disease in animal models. Novel molecular biomarkers may help reflect underlying pathophysiology, monitor disease progression, identify intermediate phenotypes for clinical trials, and improve prognostic accuracy and thereby revolutionize clinical practice in neurocritical care.
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References
Suarez JI (2006) Outcome in neurocritical care: advances in monitoring and treatment and effect of a specialized neurocritical care team. Crit Care Med 34:S232–S238
Maier B, Lehnert M, Laurer HL et al (2007) Biphasic elevation in cerebrospinal fluid and plasma concentrations of endothelin 1 after traumatic brain injury in human patients. Shock 27:610–614
Mattsson N, Zetterberg H, Hansson O et al (2009) CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 302:385–393
Mitchell RM, Freeman WM, Randazzo WT et al (2009) A CSF biomarker panel for identification of patients with amyotrophic lateral sclerosis. Neurology 72:14–19
Maurer MH (2010) Proteomics of brain extracellular fluid (ECF) and cerebrospinal fluid (CSF). Mass Spectrom Rev 29:17–28
Reiber H (2001) Dynamics of brain-derived proteins in cerebrospinal fluid. Clin Chim Acta 310:173–186
Bloomfield SM, McKinney J, Smith L et al (2007) Reliability of S100B in predicting severity of central nervous system injury. Neurocrit Care 6:121–138
Michetti F, Corvino V, Geloso MC et al (2012) The S100B protein in biological fluids: more than a lifelong biomarker of brain distress. J Neurochem 120:644–659
Blennow M, Savman K, Ilves P et al (2001) Brain-specific proteins in the cerebrospinal fluid of severely asphyxiated newborn infants. Acta Paediatr 90:1171–1175
Bottiger BW, Mobes S, Glatzer R et al (2001) Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage and outcome after cardiac arrest in humans. Circulation 103:2694–2698
Rosen H, Sunnerhagen KS, Herlitz J et al (2001) Serum levels of the brain-derived proteins S-100 and NSE predict long-term outcome after cardiac arrest. Resuscitation 49:183–191
Pelinka LE, Toegel E, Mauritz W et al (2003) Serum S 100 B: a marker of brain damage in traumatic brain injury with and without multiple trauma. Shock 19:195–200
Berger RP, Adelson PD, Pierce MC et al (2005) Serum neuron-specific enolase, S100B, and myelin basic protein concentrations after inflicted and noninflicted traumatic brain injury in children. J Neurosurg 103:61–68
Woertgen C, Rothoerl RD, Metz C et al (1999) Comparison of clinical, radiologic, and serum marker as prognostic factors after severe head injury. J Trauma 47:1126–1130
Raabe A, Grolms C, Keller M et al (1998) Correlation of computed tomography findings and serum brain damage markers following severe head injury. Acta Neurochir (Wien) 140:787–791, discussion 791–792
Wiesmann M, Missler U, Hagenstrom H et al (1997) S-100 protein plasma levels after aneurysmal subarachnoid haemorrhage. Acta Neurochir (Wien) 139:1155–1160
Herrmann M, Vos P, Wunderlich MT et al (2000) Release of glial tissue-specific proteins after acute stroke: a comparative analysis of serum concentrations of protein S-100B and glial fibrillary acidic protein. Stroke 31:2670–2677
Raabe A (2001) High serum S100B levels for trauma patients without head injuries. Neurosurgery 49:1491–1492; author reply 1492–1493
Lins H, Wallesch CW, Wunderlich MT (2005) Sequential analyses of neurobiochemical markers of cerebral damage in cerebrospinal fluid and serum in CNS infections. Acta Neurol Scand 112:303–308
Foerch C, Otto B, Singer OC et al (2004) Serum S100B predicts a malignant course of infarction in patients with acute middle cerebral artery occlusion. Stroke 35:2160–2164
Castellanos M, Leira R, Serena J et al (2004) Plasma cellular-fibronectin concentration predicts hemorrhagic transformation after thrombolytic therapy in acute ischemic stroke. Stroke 35:1671–1676
Biberthaler P, Linsenmeier U, Pfeifer KJ et al (2006) Serum S-100B concentration provides additional information for the indication of computed tomography in patients after minor head injury: a prospective multicenter study. Shock 25:446–453
Romner B, Ingebrigtsen T (2001) High serum S100B levels for trauma patients without head injuries. Neurosurgery 49:1490; author reply 1492–1493
Pelinka LE, Hertz H, Mauritz W et al (2005) Nonspecific increase of systemic neuron-specific enolase after trauma: clinical and experimental findings. Shock 24:119–123
Missler U, Wiesmann M, Friedrich C et al (1997) S-100 protein and neuron-specific enolase concentrations in blood as indicators of infarction volume and prognosis in acute ischemic stroke. Stroke 28:1956–1960
Einav S, Kaufman N, Algur N et al (2012) Modeling serum biomarkers S100 beta and neuron-specific enolase as predictors of outcome after out-of-hospital cardiac arrest: an aid to clinical decision making. J Am Coll Cardiol 60:304–311
Chabok SY, Moghadam AD, Saneei Z et al (2012) Neuron-specific enolase and S100BB as outcome predictors in severe diffuse axonal injury. J Trauma Acute Care Surg 72:1654–1657
Vos PE, Lamers KJ, Hendriks JC et al (2004) Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury. Neurology 62:1303–1310
Yamazaki Y, Yada K, Morii S et al (1995) Diagnostic significance of serum neuron-specific enolase and myelin basic protein assay in patients with acute head injury. Surg Neurol 43:267–270, discussion 270–271
Herrmann M, Curio N, Jost S et al (1999) Protein S-100B and neuron specific enolase as early neurobiochemical markers of the severity of traumatic brain injury. Restor Neurol Neurosci 14:109–114
Ross SA, Cunningham RT, Johnston CF et al (1996) Neuron-specific enolase as an aid to outcome prediction in head injury. Br J Neurosurg 10:471–476
Meynaar IA, Oudemans-van Straaten HM, van der Wetering J et al (2003) Serum neuron-specific enolase predicts outcome in post-anoxic coma: a prospective cohort study. Intensive Care Med 29:189–195
Rossetti AO, Oddo M, Logroscino G et al (2010) Prognostication after cardiac arrest and hypothermia: a prospective study. Ann Neurol 67:301–307
Schmitt B, Bauersfeld U, Schmid ER et al (1998) Serum and CSF levels of neuron-specific enolase (NSE) in cardiac surgery with cardiopulmonary bypass: a marker of brain injury? Brain Dev 20:536–539
Nylen K, Ost M, Csajbok LZ et al (2006) Increased serum-GFAP in patients with severe traumatic brain injury is related to outcome. J Neurol Sci 240:85–91
Thomas DG, Palfreyman JW, Ratcliffe JG (1978) Serum-myelin-basic-protein assay in diagnosis and prognosis of patients with head injury. Lancet 1:113–115
Ingebrigtsen T, Romner B (2002) Biochemical serum markers of traumatic brain injury. J Trauma 52:798–808
Coplin WM, Longstreth WT Jr, Lam AM et al (1999) Cerebrospinal fluid creatine kinase-BB isoenzyme activity and outcome after subarachnoid hemorrhage. Arch Neurol 56:1348–1352
Papa L, Akinyi L, Liu MC et al (2010) Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury. Crit Care Med 38:138–144
Mondello S, Papa L, Buki A et al (2011) Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury: a case control study. Crit Care 15:R156
Morganti-Kossmann MC, Rancan M, Otto VI et al (2001) Role of cerebral inflammation after traumatic brain injury: a revisited concept. Shock 16:165–177
Lenzlinger PM, Morganti-Kossmann MC, Laurer HL et al (2001) The duality of the inflammatory response to traumatic brain injury. Mol Neurobiol 24:169–181
Cederberg D, Siesjo P (2010) What has inflammation to do with traumatic brain injury? Childs Nerv Syst 26:221–226
Helmy A, De Simoni MG, Guilfoyle MR et al (2011) Cytokines and innate inflammation in the pathogenesis of human traumatic brain injury. Prog Neurobiol 95:352–372
Zhou Y, Martin RD, Zhang JH (2011) Advances in experimental subarachnoid hemorrhage. Acta Neurochir Suppl 110:15–21
Mashaly HA, Provencio JJ (2008) Inflammation as a link between brain injury and heart damage: the model of subarachnoid hemorrhage. Cleve Clin J Med 75(suppl 2):S26–S30
Dumont AS, Dumont RJ, Chow MM et al (2003) Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery 53:123–133, discussion 133–135
Ostrowski RP, Colohan AR, Zhang JH (2006) Molecular mechanisms of early brain injury after subarachnoid hemorrhage. Neurol Res 28:399–414
Heiss WD (2012) The ischemic penumbra: how does tissue injury evolve? Ann N Y Acad Sci 1268:26–34
Kamel H, Iadecola C (2012) Brain-immune interactions and ischemic stroke: clinical implications. Arch Neurol 69:576–581
Xing C, Arai K, Lo EH et al (2012) Pathophysiologic cascades in ischemic stroke. Int J Stroke 7:378–385
Lo EH, Wang X, Cuzner ML (2002) Extracellular proteolysis in brain injury and inflammation: role for plasminogen activators and matrix metalloproteinases. J Neurosci Res 69:1–9
Petty MA, Lo EH (2002) Junctional complexes of the blood–brain barrier: permeability changes in neuroinflammation. Prog Neurobiol 68:311–323
Hayakawa K, Qiu J, Lo EH (2010) Biphasic actions of HMGB1 signaling in inflammation and recovery after stroke. Ann N Y Acad Sci 1207:50–57
Lo EH, Dalkara T, Moskowitz MA (2003) Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 4:399–415
Xing C, Hayakawa K, Lok J et al (2012) Injury and repair in the neurovascular unit. Neurol Res 34:325–330
Chou SH-Y, Ning MM, Konigsberg RG, Loesch EC, Alpargu G, Chibnik L, De Jager PH, Feske SK, Lo EH (2010) Peripheral leukocyte count and matrix metalloproteinase-2 in cerebral vasospasm following subarachnoid hemorrhage. Neurology 74:A131
Sadamasa N, Yoshida K, Narumi O et al (2011) Prediction of mortality by hematological parameters on admission in patients with subarachnoid hemorrhage. Neurol Med Chir (Tokyo) 51:745–748
McGirt MJ, Mavropoulos JC, McGirt LY et al (2003) Leukocytosis as an independent risk factor for cerebral vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg 98:1222–1226
Dhar R, Diringer MN (2008) The burden of the systemic inflammatory response predicts vasospasm and outcome after subarachnoid hemorrhage. Neurocrit Care 8:404–412
Yoshimoto Y, Tanaka Y, Hoya K (2001) Acute systemic inflammatory response syndrome in subarachnoid hemorrhage. Stroke 32:1989–1993
Weir B, Disney L, Grace M et al (1989) Daily trends in white blood cell count and temperature after subarachnoid hemorrhage from aneurysm. Neurosurgery 25:161–165
Maiuri F, Gallicchio B, Donati P et al (1987) The blood leukocyte count and its prognostic significance in subarachnoid hemorrhage. J Neurosurg Sci 31:45–48
Niikawa S, Hara S, Ohe N et al (1997) Correlation between blood parameters and symptomatic vasospasm in subarachnoid hemorrhage patients. Neurol Med Chir (Tokyo) 37:881–884, discussion 884–885
Spallone A, Acqui M, Pastore FS et al (1987) Relationship between leukocytosis and ischemic complications following aneurysmal subarachnoid hemorrhage. Surg Neurol 27:253–258
Kim J, Song TJ, Park JH et al (2012) Different prognostic value of white blood cell subtypes in patients with acute cerebral infarction. Atherosclerosis 222:464–467
Nardi K, Milia P, Eusebi P et al (2011) Admission leukocytosis in acute cerebral ischemia: influence on early outcome. J Stroke Cerebrovasc Dis 21:819–824
Gurkanlar D, Lakadamyali H, Ergun T et al (2009) Predictive value of leucocytosis in head trauma. Turk Neurosurg 19:211–215
Rovlias A, Kotsou S (2001) The blood leukocyte count and its prognostic significance in severe head injury. Surg Neurol 55:190–196
McKeating EG, Andrews PJ (1998) Cytokines and adhesion molecules in acute brain injury. Br J Anaesth 80:77–84
Provencio JJ, Vora N (2005) Subarachnoid hemorrhage and inflammation: bench to bedside and back. Semin Neurol 25:435–444
Hanafy KA, Grobelny B, Fernandez L et al (2010) Brain interstitial fluid TNF-alpha after subarachnoid hemorrhage. J Neurol Sci 291:69–73
Fassbender K, Hodapp B, Rossol S et al (2001) Inflammatory cytokines in subarachnoid haemorrhage: association with abnormal blood flow velocities in basal cerebral arteries. J Neurol Neurosurg Psychiatry 70:534–537
Mathiesen T, Edner G, Ulfarsson E et al (1997) Cerebrospinal fluid interleukin-1 receptor antagonist and tumor necrosis factor-alpha following subarachnoid hemorrhage. J Neurosurg 87:215–220
Chou SH, Feske SK, Atherton J, Konigsberg RG, De Jager PL, Du R, Ogilvy CS, Lo EH, Ning M (2012) Early elevation of serum tumor necrosis factor-α is associated with poor outcome in subarachnoid hemorrhage. J Investig Med 60(7):1054–8. PMID: 22918199
Beeftink MM, Ruigrok YM, Rinkel GJ et al (2011) Relation of serum TNF-alpha and TNF-alpha genotype with delayed cerebral ischemia and outcome in subarachnoid hemorrhage. Neurocrit Care 15:405–409
Gruber A, Rossler K, Graninger W et al (2000) Ventricular cerebrospinal fluid and serum concentrations of sTNFR-I, IL-1ra, and IL-6 after aneurysmal subarachnoid hemorrhage. J Neurosurg Anesthesiol 12:297–306
Graetz D, Nagel A, Schlenk F et al (2010) High ICP as trigger of proinflammatory IL-6 cytokine activation in aneurysmal subarachnoid hemorrhage. Neurol Res 32:728–735
Dietmann A, Lackner P, Fischer M et al (2012) Soluble endoglin and transforming growth factor-beta(1) and the development of vasospasm after spontaneous subarachnoid hemorrhage: a pilot study. Cerebrovasc Dis 33:16–22
Stein DM, Lindel AL, Murdock KR et al (2012) Use of serum biomarkers to predict secondary insults following severe traumatic brain injury. Shock 37:563–568
Perez-Barcena J, Ibanez J, Brell M et al (2011) Lack of correlation among intracerebral cytokines, intracranial pressure, and brain tissue oxygenation in patients with traumatic brain injury and diffuse lesions. Crit Care Med 39:533–540
Rhind SG, Crnko NT, Baker AJ et al (2010) Prehospital resuscitation with hypertonic saline-dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients. J Neuroinflammation 7:5
Cuzner ML, Opdenakker G (1999) Plasminogen activators and matrix metalloproteases, mediators of extracellular proteolysis in inflammatory demyelination of the central nervous system. J Neuroimmunol 94:1–14
Guo ZD, Sun XC, Zhang JH (2011) Mechanisms of early brain injury after SAH: matrix metalloproteinase 9. Acta Neurochir Suppl 110:63–65
Gu Z, Kaul M, Yan B et al (2002) S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death. Science 297:1186–1190
Ning M, Furie KL, Koroshetz WJ et al (2006) Association between tPA therapy and raised early matrix metalloproteinase-9 in acute stroke. Neurology 66:1550–1555
Castellanos M, Sobrino T, Millan M et al (2007) Serum cellular fibronectin and matrix metalloproteinase-9 as screening biomarkers for the prediction of parenchymal hematoma after thrombolytic therapy in acute ischemic stroke: a multicenter confirmatory study. Stroke 38:1855–1859
Montaner J, Molina CA, Monasterio J et al (2003) Matrix metalloproteinase-9 pretreatment level predicts intracranial hemorrhagic complications after thrombolysis in human stroke. Circulation 107:598–603
Heo JH, Kim SH, Lee KY et al (2003) Increase in plasma matrix metalloproteinase-9 in acute stroke patients with thrombolysis failure. Stroke 34:e48–e50
Graham CA, Chan RW, Chan DY et al (2012) Matrix metalloproteinase 9 mRNA: an early prognostic marker for patients with acute stroke. Clin Biochem 45:352–355
Serena J, Blanco M, Castellanos M et al (2005) The prediction of malignant cerebral infarction by molecular brain barrier disruption markers. Stroke 36:1921–1926
Rosell A, Ortega-Aznar A, Alvarez-Sabin J et al (2006) Increased brain expression of matrix metalloproteinase-9 after ischemic and hemorrhagic human stroke. Stroke 37:1399–1406
Silva Y, Leira R, Tejada J et al (2005) Molecular signatures of vascular injury are associated with early growth of intracerebral hemorrhage. Stroke 36:86–91
Abilleira S, Montaner J, Molina CA et al (2003) Matrix metalloproteinase-9 concentration after spontaneous intracerebral hemorrhage. J Neurosurg 99:65–70
Alvarez-Sabin J, Delgado P, Abilleira S et al (2004) Temporal profile of matrix metalloproteinases and their inhibitors after spontaneous intracerebral hemorrhage: relationship to clinical and radiological outcome. Stroke 35:1316–1322
McGirt MJ, Lynch JR, Blessing R et al (2002) Serum von Willebrand factor, matrix metalloproteinase-9, and vascular endothelial growth factor levels predict the onset of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurgery 51:1128–1134, discussion 1134–1135
Chou SH-Y, Feske SK, Simmons SL, Konigsberg RG, Orzell SC, Marckmann A, Bourget G, Bauer DJ, De Jager PL, Du R, Arai K, Lo EH, Ning MM (2011) Elevated peripheral neutrophils and matrix metalloproteinase 9 as biomarkers of functional outcome following subarachnoid hemorrhage. Transl Stroke Res 2(4):600–607
Barr TL, Latour LL, Lee KY et al (2010) Blood–brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9. Stroke 41:e123–e128
Kazmierski R, Michalak S, Wencel-Warot A et al (2012) Serum tight-junction proteins predict hemorrhagic transformation in ischemic stroke patients. Neurology 79:1677–1685
Rubanyi GM, Polokoff MA (1994) Endothelins: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. Pharmacol Rev 46:325–415
Lo AC, Chen AY, Hung VK et al (2005) Endothelin-1 overexpression leads to further water accumulation and brain edema after middle cerebral artery occlusion via aquaporin 4 expression in astrocytic end-feet. J Cereb Blood Flow Metab 25:998–1011
Fernandez-Patron C, Radomski MW, Davidge ST (1999) Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a novel vasoconstrictor. Circ Res 85:906–911
Fernandez-Patron C, Zouki C, Whittal R et al (2001) Matrix metalloproteinases regulate neutrophil-endothelial cell adhesion through generation of endothelin-1[1–32]. FASEB J 15:2230–2240
Moldes O, Sobrino T, Millan M et al (2008) High serum levels of endothelin-1 predict severe cerebral edema in patients with acute ischemic stroke treated with t-PA. Stroke 39:2006–2010
Ziv I, Fleminger G, Djaldetti R et al (1992) Increased plasma endothelin-1 in acute ischemic stroke. Stroke 23:1014–1016
Lampl Y, Fleminger G, Gilad R et al (1997) Endothelin in cerebrospinal fluid and plasma of patients in the early stage of ischemic stroke. Stroke 28:1951–1955
Haapaniemi E, Tatlisumak T, Hamel K et al (2000) Plasma endothelin-1 levels neither increase nor correlate with neurological scores, stroke risk factors, or outcome in patients with ischemic stroke. Stroke 31:720–725
Kobayashi H, Hayashi M, Kobayashi S et al (1991) Cerebral vasospasm and vasoconstriction caused by endothelin. Neurosurgery 28:673–678, discussion 678–679
Seifert V, Loffler BM, Zimmermann M et al (1995) Endothelin concentrations in patients with aneurysmal subarachnoid hemorrhage. Correlation with cerebral vasospasm, delayed ischemic neurological deficits, and volume of hematoma. J Neurosurg 82:55–62
Masaoka H, Suzuki R, Hirata Y et al (1989) Raised plasma endothelin in aneurysmal subarachnoid haemorrhage. Lancet 2:1402
Suzuki R, Masaoka H, Hirata Y et al (1992) The role of endothelin-1 in the origin of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 77:96–100
Fujimori A, Yanagisawa M, Saito A et al (1990) Endothelin in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage. Lancet 336:633
Gaetani P, Rodriguez y Baena R, Grignani G et al (1994) Endothelin and aneurysmal subarachnoid haemorrhage: a study of subarachnoid cisternal cerebrospinal fluid. J Neurol Neurosurg Psychiatry 57:66–72
Macdonald RL, Higashida RT, Keller E et al (2012) Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (CONSCIOUS-2). Lancet Neurol 10:618–625
Chou SH, Kuruppu S, Feske SK et al (2013) Increased big endothelin-1 in human cerebrospinal fluid is associated with vasospasm and poor 3-month outcome following subarachnoid hemorrhage. Stroke 44:AWMP114
Mascia L, Fedorko L, Stewart DJ et al (2001) Temporal relationship between endothelin-1 concentrations and cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. Stroke 32:1185–1190
Park SM, Hwang IK, Kim SY et al (2006) Characterization of plasma gelsolin as a substrate for matrix metalloproteinases. Proteomics 6:1192–1199
Lind SE, Smith DB, Janmey PA et al (1986) Role of plasma gelsolin and the vitamin D-binding protein in clearing actin from the circulation. J Clin Invest 78:736–742
Haddad JG, Harper KD, Guoth M et al (1990) Angiopathic consequences of saturating the plasma scavenger system for actin. Proc Natl Acad Sci U S A 87:1381–1385
Lee PS, Sampath K, Karumanchi SA et al (2009) Plasma gelsolin and circulating actin correlate with hemodialysis mortality. J Am Soc Nephrol 20:1140–1148
Lee PS, Patel SR, Christiani DC et al (2008) Plasma gelsolin depletion and circulating actin in sepsis: a pilot study. PLoS One 3:e3712
Lee PS, Drager LR, Stossel TP et al (2006) Relationship of plasma gelsolin levels to outcomes in critically ill surgical patients. Ann Surg 243:399–403
Le HT, Hirko AC, Thinschmidt JS et al (2011) The protective effects of plasma gelsolin on stroke outcome in rats. Exp Transl Stroke Med 3:13
Chou SH, Lee PS, Konigsberg RG et al (2011) Plasma-type gelsolin is decreased in human blood and cerebrospinal fluid after subarachnoid hemorrhage. Stroke 42(12):3624–3627
Xu JF, Liu WG, Dong XQ et al (2011) Change in plasma gelsolin level after traumatic brain injury. J Trauma Acute Care Surg 72:491–496
Wijman CA, Smirnakis SM, Vespa P et al (2012) Research and technology in neurocritical care. Neurocrit Care 16:42–54
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Chou, S.HY., Lo, E.H., Ning, M. (2014). Molecular Biomarkers in Neurocritical Care: The Next Frontier. In: Lo, E., Lok, J., Ning, M., Whalen, M. (eds) Vascular Mechanisms in CNS Trauma. Springer Series in Translational Stroke Research, vol 5. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8690-9_27
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