Role of Inflammation in Secondary Injury Progression after Traumatic Brain Injury and Spinal Cord Injury
Abstract
Trauma to the brain or spinal cord is a type of injury that triggers a cascade of secondary pathophysiological events after the primary mechanical trauma. Neuroinflammation is indeed of foremost importance, acting both as a mediator for tissue repair and an instigator for progressive neurodegeneration. Activated microglia and astrocytes, peripherally derived immune cells infiltrating that site, mediate a complex interaction involving cytokines, oxidative stress, mitochondrial dysfunction, and neurovascular disruption. This early inflammatory signaling helps remove debris and support neuronal regeneration in traumatic brain injury (TBI) and spinal cord injury (SCI). However, when this particular inflammation becomes chronic, it leads to glial damage with aberrant synaptic connections and irreversible harm to neural network circuitry. Mediators, including IL-1β, TNF-α, and the NLRP3 inflammasome, have been identified as promising therapeutic targets; cutting-edge therapies, ranging from small-molecule inhibitors to mitochondrial stabilizers to cell-based interventions, have shown efficacy in preclinical models. Nonetheless, the translation to the clinic has been hindered through shortcomings in classical animal models, failure to integrate biomarker application, and an inability to account for the heterogeneity of human central nervous system (CNS) injury. To bridge this gap, temporally targeted immunomodulation, precision diagnostics, and systems-level approaches will need to align with the molecular pathology involved in disease intervention. Understanding this dual property within post-traumatic inflammation presents an important frontier to develop truly efficacious neuroprotective therapies.
[1] Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M, et al. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2018; 130(4):1080-1097.
[2] GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(1):56-87.
[3] Burke JF, Stulc JL, Skolarus LE, Sears ED, Zahuranec DB, Morgenstern LB. Traumatic brain injury may be an independent risk factor for stroke. Neurology. 2013;81(1):33-9.
[4] Liao CC, Chou YC, Yeh CC, Hu CJ, Chiu WT, Chen TL. Stroke risk and outcomes in patients with traumatic brain injury: 2 nationwide studies. Mayo Clin Proc. 2014;89(2):163-72
[5] Jafari S, Etminan M, Aminzadeh F, Samii A. Head injury and risk of Parkinson disease: a systematic review and meta-analysis. Mov Disord. 2013;28(9):1222-9.
[6] Gardner RC, Burke JF, Nettiksimmons J, Goldman S, Tanner CM, Yaffe K. Traumatic brain injury in later life increases risk for Parkinson disease. Ann Neurol. 2015 ;77(6):987-95.
[7] Crane PK, Gibbons LE, Dams-O'Connor K, Trittschuh E, Leverenz JB, Keene CD, et al. Association of Traumatic Brain Injury With Late-Life Neurodegenerative Conditions and Neuropathologic Findings. JAMA Neurol. 2016;73(9):1062-9.
[8] Walsh S, Donnan J, Fortin Y, Sikora L, Morrissey A, Collins K, et al. A systematic review of the risks factors associated with the onset and natural progression of epilepsy. Neurotoxicology. 2017;61:64-77.
[9] Hay J, Johnson VE, Smith DH, Stewart W. Chronic Traumatic Encephalopathy: The Neuropathological Legacy of Traumatic Brain Injury. Annu Rev Pathol. 2016;11:21-45.
[10] Stern RA, Daneshvar DH, Baugh CM, Seichepine DR, Montenigro PH, Riley DO, et al. Clinical presentation of chronic traumatic encephalopathy. Neurology. 2013;81(13):1122-9.
[11] Guskiewicz KM, Marshall SW, Bailes J, McCrea M, Cantu RC, Randolph C, et al. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery. 2005;57(4):719-26
[12] Mez J, Daneshvar DH, Kiernan PT, Abdolmohammadi B, Alvarez VE, Huber BR, et al. Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football. JAMA. 2017;318(4):360-370.
[13] Donnelly DJ, Popovich PG. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp Neurol. 2008;209(2):378-88.
[14] Duan HQ, Wu QL, Yao X, Fan BY, Shi HY, Zhao CX, et al., Nafamostat mesilate attenuates inflammation and apoptosis and promotes locomotor recovery after spinal cord injury. CNS Neurosci Ther. 2018;24(5):429-438.
[15] Allan SM, Tyrrell PJ, Rothwell NJ. Interleukin-1 and neuronal injury. Nat Rev Immunol. 2005;5(8):629-40.
[16] Burda JE, Bernstein AM, Sofroniew MV. Astrocyte roles in traumatic brain injury. Exp Neurol. 2016;275 Pt 3(0 3):305-315.
[17] Erta M, Quintana A, Hidalgo J. Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci. 2012;8(9):1254-66.
[18] Shlosberg D, Benifla M, Kaufer D, Friedman A. Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury. Nat Rev Neurol. 2010;6(7):393-403.
[19] Takano T, He W, Han X, Wang F, Xu Q, Wang X, et al. Rapid manifestation of reactive astrogliosis in acute hippocampal brain slices. Glia. 2014;62(1):78-95.
[20] Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci. 2009;29(43):13435-44.
[21] Deyts C, Thinakaran G, Parent AT. APP Receptor? To Be or Not To Be. Trends Pharmacol Sci. 2016;37(5):390-411.
[22] Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A, et al., Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017;16(12):987-1048.
[23] GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(5):459-480.
[24] Frost RB, Farrer TJ, Primosch M, Hedges DW. Prevalence of traumatic brain injury in the general adult population: a meta-analysis. Neuroepidemiology. 2013;40(3):154-9.
[25] McKinlay A, Grace RC, Horwood LJ, Fergusson DM, Ridder EM, MacFarlane MR. Prevalence of traumatic brain injury among children, adolescents and young adults: prospective evidence from a birth cohort. Brain Inj. 2008;22(2):175-81.
[26] Whiteneck GG, Cuthbert JP, Corrigan JD, Bogner JA. Prevalence of Self-Reported Lifetime History of Traumatic Brain Injury and Associated Disability: A Statewide Population-Based Survey. J Head Trauma Rehabil. 2016;31(1):E55-62.
[27] Zaloshnja E, Miller T, Langlois JA, Selassie AW. Prevalence of long-term disability from traumatic brain injury in the civilian population of the United States, 2005. J Head Trauma Rehabil. 2008;23(6):394-400.
[28] World Health Organization. Neurological disorders: public health challenges. World Health Organization; 2006.
[29] Kumar A, Alvarez-Croda DM, Stoica BA, Faden AI, Loane DJ. Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury. J Neurotrauma. 2016;33(19):1732-1750.
[30] Soriano Sánchez JA, Soriano Solís S, Romero Rangel JAI. Role of the Checklist in Neurosurgery, a Realistic Perspective to "The Need for Surgical Safety Checklists in Neurosurgery Now and in the Future - a Systematic Review". World Neurosurg. 2020;134:121-122.
[31] Henry RJ, Ritzel RM, Barrett JP, Doran SJ, Jiao Y, Leach JB, et al., Microglial depletion with CSF1R inhibitor during chronic phase of experimental traumatic brain injury reduces neurodegeneration and neurological deficits. J Neurosci. 2020;40(14):2960-2974.
[32] Johnson VE, Stewart W, Smith DH. Traumatic brain injury and amyloid-β pathology: a link to Alzheimer's disease? Nat Rev Neurosci. 2010;11(5):361-70.
[33] Tomkins O, Friedman O, Ivens S, Reiffurth C, Major S, Dreier JP, et al., Blood–brain barrier disruption results in delayed functional and structural alterations in the rat neocortex. Neurobiol Dis. 2007;25(2):367-77.
[34] Cacheaux LP, Ivens S, David Y, Lakhter AJ, Bar-Klein G, Shapira M, et al. Transcriptome profiling reveals TGF-beta signaling involvement in epileptogenesis. J Neurosci. 2009;29(28):8927-35.
[35] Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008;57(2):178-201.
[36] Ruttan L, Martin K, Liu A, Colella B, Green RE. Long-term cognitive outcome in moderate to severe traumatic brain injury: a meta-analysis examining timed and untimed tests at 1 and 4.5 or more years after injury. Arch Phys Med Rehabil. 2008;89(12 Suppl):S69-76.
[37] Annegers JF, Hauser WA, Coan SP, Rocca WA. A population-based study of seizures after traumatic brain injuries. N Engl J Med. 1998;338(1):20-4.
[38] Herman ST. Epilepsy after brain insult: targeting epileptogenesis. Neurology. 2002;59(9 Suppl 5):S21-6.
[39] Annegers JF, Coan SP. The risks of epilepsy after traumatic brain injury. Seizure. 2000;9(7):453-7.
[40] Korn A, Golan H, Melamed I, Pascual-Marqui R, Friedman A. Focal cortical dysfunction and blood-brain barrier disruption in patients with Postconcussion syndrome. J Clin Neurophysiol. 2005;22(1):1-9.
[41] Pavlovsky L, Seiffert E, Heinemann U, Korn A, Golan H, Friedman A. Persistent BBB disruption may underlie alpha interferon-induced seizures. J Neurol. 2005;252(1):42-6.
[42] Wang HC, Chang WN, Chang HW, Ho JT, Yang TM, Lin WC, et al. Factors predictive of outcome in posttraumatic seizures. J Trauma. 2008;64(4):883-8.
[43] Ivens S, Kaufer D, Flores LP, Bechmann I, Zumsteg D, Tomkins O, et al. TGF-β receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis. Brain. 2007. 130(2): 535-547.
[44] David Y, Cacheaux LP, Ivens S, Lapilover E, Heinemann U, Kaufer D, et al. Astrocytic dysfunction in epileptogenesis: consequence of altered potassium and glutamate homeostasis? J Neurosci. 2009;29(34):10588-99.
[45] Weber JT, AI Maas. Neurotrauma: new insights into pathology and treatment. Vol. 161. 2007: Elsevier.
[46] Heinemann U, Gabriel S, Jauch R, Schulze K, Kivi A, Eilers A, et al. Alterations of glial cell function in temporal lobe epilepsy. Epilepsia. 2000;41 Suppl 6:S185-9.
[47] Jabs R, Seifert G, Steinhäuser C. Astrocytic function and its alteration in the epileptic brain. Epilepsia. 2008;49 Suppl 2:3-12.
[48] Seifert G, Schilling K, Steinhäuser C. Astrocyte dysfunction in neurological disorders: a molecular perspective. Nat Rev Neurosci. 2006;7(3):194-206.
[49] Seiffert E, Dreier JP, Ivens S, Bechmann I, Tomkins O, Heinemann U, et al., Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J Neurosci. 2004;24(36):7829-36.
[50] Tian GF, Azmi H, Takano T, Xu Q, Peng W, Lin J, et al. An astrocytic basis of epilepsy. Nat Med. 2005;11(9):973-81.
[51] Filosa A, Paixão S, Honsek SD, Carmona MA, Becker L, Feddersen B, et al. Neuron-glia communication via EphA4/ephrin-A3 modulates LTP through glial glutamate transport. Nat Neurosci. 2009;12(10):1285-92.
[52] Henneberger C, Papouin T, Oliet SH, Rusakov DA. Long-term potentiation depends on release of D-serine from astrocytes. Nature. 2010;463(7278):232-6.
[53] Wetherington J, Serrano G, Dingledine R. Astrocytes in the epileptic brain. Neuron. 2008;58(2):168-78.
[54] Tomkins O, Shelef I, Kaizerman I, Eliushin A, Afawi Z, Misk A, et al. Blood–brain barrier disruption in post-traumatic epilepsy. J Neurol Neurosurg Psychiatry. 2008;79(7):774-7.
[55] Oby E, Janigro D. The blood-brain barrier and epilepsy. Epilepsia. 2006;47(11):1761-74.
[56] Fabene PF, Navarro Mora G, Martinello M, Rossi B, Merigo F, Ottoboni L, et al. A role for leukocyte-endothelial adhesion mechanisms in epilepsy. Nat Med. 2008;14(12):1377-83.
[57] Ivens S, Gabriel S, Greenberg G, Friedman A, Shelef I. Blood-brain barrier breakdown as a novel mechanism underlying cerebral hyperperfusion syndrome. J Neurol. 2010;257(4):615-20.
[58] Marchi N, Angelov L, Masaryk T, Fazio V, Granata T, Hernandez N, et al. Seizure‐promoting effect of blood–brain barrier disruption. Epilepsia. 2007. 48(4): 732-742.
[59] Noble LJ, Wrathall JR. Distribution and time course of protein extravasation in the rat spinal cord after contusive injury. Brain Res. 1989;482(1):57-66.
[60] Whetstone WD, Hsu JY, Eisenberg M, Werb Z, Noble-Haeusslein LJ. Blood-spinal cord barrier after spinal cord injury: relation to revascularization and wound healing. J Neurosci Res. 2003;74(2):227-39.
[61] Popovich PG, Horner PJ, Mullin BB, Stokes BT. A quantitative spatial analysis of the blood-spinal cord barrier. I. Permeability changes after experimental spinal contusion injury. Exp Neurol. 1996;142(2):258-75.
[62] Schnell L, Fearn S, Schwab ME, Perry VH, Anthony DC. Cytokine-induced acute inflammation in the brain and spinal cord. J Neuropathol Exp Neurol. 1999;58(3):245-54.
[63] Armao D, Kornfeld M, Estrada EY, Grossetete M, Rosenberg GA. Neutral proteases and disruption of the blood-brain barrier in rat. Brain Res. 1997;767(2):259-64.
[64] Butt AM. Effect of inflammatory agents on electrical resistance across the blood-brain barrier in pial microvessels of anaesthetized rats. Brain Res. 1995;696(1-2):145-50.
[65] Carlson SL, Parrish ME, Springer JE, Doty K, Dossett L. Acute inflammatory response in spinal cord following impact injury. Exp Neurol. 1998;151(1):77-88.
[66] Ellis W. Pulsed subcutaneous electrical stimulation in spinal cord injury: preliminary results. Bioelectromagnetics. 1987;8(2):159-64.
[67] Nag S, P Picard, D Stewart. Increased immunolocalization of nitric oxide synthases during blood-brain barrier breakdown and cerebral edema. in Brain Edema XI: Proceedings of the 11th International Symposium, Newcastle-upon-Tyne, United Kingdom, June 6–10, 1999. 2000. Springer.
[68] Sarker MH, Easton AS, Fraser PA. Regulation of cerebral microvascular permeability by histamine in the anaesthetized rat. J Physiol. 1998;507 ( Pt 3)(Pt 3):909-18.
[69] Unterberg A, Wahl M, Baethmann A. Effects of free radicals on permeability and vasomotor response of cerebral vessels. Acta Neuropathol. 1988;76(3):238-44.
[70] Mautes AE, Weinzierl MR, Donovan F, Noble LJ. Vascular events after spinal cord injury: contribution to secondary pathogenesis. Phys Ther. 2000;80(7):673-87.
[71] Woodcock T, Morganti-Kossmann MC. The role of markers of inflammation in traumatic brain injury. Front Neurol. 2013;4:18.
[72] Ricart PA, Andres TM, Apazidis A, Errico TJ, Trobisch PD. Validity of Cobb angle measurements using digitally photographed radiographs. Spine J. 2011;11(10):942-6.
[73] Smith DH, Johnson VE, Stewart W. Chronic neuropathologies of single and repetitive TBI: substrates of dementia? Nat Rev Neurol. 2013;9(4):211-21.
[74] Northington FJ, Chavez-Valdez R, Martin LJ. Neuronal cell death in neonatal hypoxia-ischemia. Ann Neurol. 2011;69(5):743-58.
[75] Silver J, Miller JH. Regeneration beyond the glial scar. Nat Rev Neurosci. 2004;5(2):146-56.
[76] O'Callaghan JP. Measurement of glial fibrillary acidic protein. Curr Protoc Toxicol. 2002 May;Chapter 12:Unit12.8.
[77] van Geel WJ, de Reus HP, Nijzing H, Verbeek MM, Vos PE, Lamers KJ. Measurement of glial fibrillary acidic protein in blood: an analytical method. Clin Chim Acta. 2002;326(1-2):151-4.
[78] Pelinka LE, Kroepfl A, Leixnering M, Buchinger W, Raabe A, Redl H. GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome. J Neurotrauma. 2004;21(11):1553-61.
[79] Pelinka LE, Kroepfl A, Schmidhammer R, Krenn M, Buchinger W, Redl H, et al. Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma. J Trauma. 2004;57(5):1006-12.
[80] Nylén K, Ost M, Csajbok LZ, Nilsson I, Blennow K, Nellgård B, et al. Increased serum-GFAP in patients with severe traumatic brain injury is related to outcome. J Neurol Sci. 2006;240(1-2):85-91.
[81] Vos PE, Jacobs B, Andriessen TM, Lamers KJ, Borm GF, Beems T, et al. GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort study. Neurology. 2010. 75(20): 1786-93.
[82] Papa L, Lewis LM, Falk JL, Zhang Z, Silvestri S, Giordano P, et al. Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention. Ann Emerg Med. 2012;59(6):471-83.
[83] Czeiter E, Mondello S, Kovacs N, Sandor J, Gabrielli A, Schmid K, et al. Brain injury biomarkers may improve the predictive power of the IMPACT outcome calculator. J Neurotrauma. 2012;29(9):1770-8.
[84] Mondello S, Robicsek SA, Gabrielli A, Brophy GM, Papa L, Tepas J, et al. αII-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients. J Neurotrauma. 2010;27(7):1203-13.
[85] Drewes G, Ebneth A, Mandelkow EM. MAPs, MARKs and microtubule dynamics. Trends Biochem Sci. 1998;23(8):307-11.
[86] Kitagawa K, Matsumoto M, Niinobe M, Mikoshiba K, Hata R, Ueda H, et al. Microtubule-associated protein 2 as a sensitive marker for cerebral ischemic damage—immunohistochemical investigation of dendritic damage. Neuroscience. 1989;31(2):401-11.
[87] Posmantur RM, Kampfl A, Taft WC, Bhattacharjee M, Dixon CE, Bao J, et al. Diminished microtubule-associated protein 2 (MAP2) immunoreactivity following cortical impact brain injury. J Neurotrauma. 1996;13(3):125-37.
[88] Park D, Joo SS, Lee HJ, Choi KC, Kim SU, Kim YB. Microtubule-associated protein 2, an early blood marker of ischemic brain injury. J Neurosci Res. 2012;90(2):461-7.
[89] Mondello S, Gabrielli A, Catani S, D'Ippolito M, Jeromin A, Ciaramella A, et al. Increased levels of serum MAP-2 at 6-months correlate with improved outcome in survivors of severe traumatic brain injury. Brain Inj. 2012;26(13-14):1629-35.
[90] Adamczak S, Dale G, de Rivero Vaccari JP, Bullock MR, Dietrich WD, Keane RW. Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome: clinical article. J Neurosurg. 2012;117(6):1119-25.
[91] Lammertse D, Dungan D, Dreisbach J, Falci S, Flanders A, Marino R, et al. Neuroimaging in traumatic spinal cord injury: an evidence-based review for clinical practice and research: report of the National Institute on Disability and Rehabilitation Research Spinal Cord Injury Measures Meeting. J Spinal Cord Med. 2007. 30(3): 205-214.
[92] Skouen JS, Brisby H, Otani K, Olmarker K, Rosengren L, Rydevik B. Protein markers in cerebrospinal fluid in experimental nerve root injury. A study of slow-onset chronic compression effects or the biochemical effects of nucleus pulposus on sacral nerve roots. Spine (Phila Pa 1976). 1999;24(21):2195-200.
[93] Nagy G, Dzsinich C, Selmeci L, Sepa G, Dzsinich M, Kékesi V, et al. Biochemical alterations in cerebrospinal fluid during thoracoabdominal aortic cross-clamping in dogs. Ann Vasc Surg. 2002;16(4):436-41.
[94] Cao F, Yang XF, Liu WG, Hu WW, Li G, Zheng XJ, et al. Elevation of neuron-specific enolase and S-100β protein level in experimental acute spinal cord injury. J Clin Neurosci. 2008;15(5):541-4.
[95] Ma J, Novikov LN, Karlsson K, Kellerth JO, Wiberg M. Plexus avulsion and spinal cord injury increase the serum concentration of S-100 protein: an experimental study in rats. Scand J Plast Reconstr Surg Hand Surg. 2001;35(4):355-9.
[96] Loy DN, Sroufe AE, Pelt JL, Burke DA, Cao QL, Talbott JF, et al. Serum biomarkers for experimental acute spinal cord injury: rapid elevation of neuron-specific enolase and S-100β. Neurosurgery. 2005;56(2):391-7.
[97] van Dongen EP, Ter Beek HT, Boezeman EH, Schepens MA, Langemeijer HJ, Aarts LP. Normal serum concentrations of S-100 protein and changes in cerebrospinal fluid concentrations of S-100 protein during and after thoracoabdominal aortic aneurysm surgery: is S-100 protein a biochemical marker of clinical value in detecting spinal cord ischemia? J Vasc Surg. 1998;27(2):344-6.
[98] van Dongen EP, ter Beek HT, Schepens MA, Morshuis WJ, Haas FJ, de Boer A, et al. The relationship between evoked potentials and measurements of S-100 protein in cerebrospinal fluid during and after thoracoabdominal aortic aneurysm surgery. J Vasc Surg. 1999. 30(2): 293-300.
[99] Kunihara T, Shiiya N, Yasuda K. Changes in S100beta protein levels in cerebrospinal fluid after thoracoabdominal aortic operations. J Thorac Cardiovasc Surg. 2001;122(5):1019-20.
[100] Winnerkvist A, Anderson RE, Hansson LO, Rosengren L, Estrera AE, Huynh TT, et al. Multilevel somatosensory evoked potentials and cerebrospinal proteins: indicators of spinal cord injury in thoracoabdominal aortic aneurysm surgery. Eur J Cardiothorac Surg. 2007;31(4):637-42.
[101] Marquardt G, Setzer M, Seifert V. Protein S-100b for individual prediction of functional outcome in spinal epidural empyema. Spine (Phila Pa 1976). 2004;29(1):59-62.
[102] Brisby H, Olmarker K, Rosengren L, Cederlund CG, Rydevik B. Markers of nerve tissue injury in the cerebrospinal fluid in patients with lumbar disc herniation and sciatica. Spine (Phila Pa 1976). 1999;24(8):742-6.
[103] Marquardt G, Setzer M, Seifert V. Protein S-100b as serum marker for prediction of functional outcome in metastatic spinal cord compression. Acta Neurochir (Wien). 2004;146(5):449-52.
[104] Guéz M, Hildingsson C, Rosengren L, Karlsson K, Toolanen G. Nervous tissue damage markers in cerebrospinal fluid after cervical spine injuries and whiplash trauma. J Neurotrauma. 2003;20(9):853-8.
[105] Kwon BK, Stammers AM, Belanger LM, Bernardo A, Chan D, Bishop CM, et al. Cerebrospinal fluid inflammatory cytokines and biomarkers of injury severity in acute human spinal cord injury. J Neurotrauma. 2010;27(4):669-82.
[2] GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(1):56-87.
[3] Burke JF, Stulc JL, Skolarus LE, Sears ED, Zahuranec DB, Morgenstern LB. Traumatic brain injury may be an independent risk factor for stroke. Neurology. 2013;81(1):33-9.
[4] Liao CC, Chou YC, Yeh CC, Hu CJ, Chiu WT, Chen TL. Stroke risk and outcomes in patients with traumatic brain injury: 2 nationwide studies. Mayo Clin Proc. 2014;89(2):163-72
[5] Jafari S, Etminan M, Aminzadeh F, Samii A. Head injury and risk of Parkinson disease: a systematic review and meta-analysis. Mov Disord. 2013;28(9):1222-9.
[6] Gardner RC, Burke JF, Nettiksimmons J, Goldman S, Tanner CM, Yaffe K. Traumatic brain injury in later life increases risk for Parkinson disease. Ann Neurol. 2015 ;77(6):987-95.
[7] Crane PK, Gibbons LE, Dams-O'Connor K, Trittschuh E, Leverenz JB, Keene CD, et al. Association of Traumatic Brain Injury With Late-Life Neurodegenerative Conditions and Neuropathologic Findings. JAMA Neurol. 2016;73(9):1062-9.
[8] Walsh S, Donnan J, Fortin Y, Sikora L, Morrissey A, Collins K, et al. A systematic review of the risks factors associated with the onset and natural progression of epilepsy. Neurotoxicology. 2017;61:64-77.
[9] Hay J, Johnson VE, Smith DH, Stewart W. Chronic Traumatic Encephalopathy: The Neuropathological Legacy of Traumatic Brain Injury. Annu Rev Pathol. 2016;11:21-45.
[10] Stern RA, Daneshvar DH, Baugh CM, Seichepine DR, Montenigro PH, Riley DO, et al. Clinical presentation of chronic traumatic encephalopathy. Neurology. 2013;81(13):1122-9.
[11] Guskiewicz KM, Marshall SW, Bailes J, McCrea M, Cantu RC, Randolph C, et al. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery. 2005;57(4):719-26
[12] Mez J, Daneshvar DH, Kiernan PT, Abdolmohammadi B, Alvarez VE, Huber BR, et al. Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football. JAMA. 2017;318(4):360-370.
[13] Donnelly DJ, Popovich PG. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp Neurol. 2008;209(2):378-88.
[14] Duan HQ, Wu QL, Yao X, Fan BY, Shi HY, Zhao CX, et al., Nafamostat mesilate attenuates inflammation and apoptosis and promotes locomotor recovery after spinal cord injury. CNS Neurosci Ther. 2018;24(5):429-438.
[15] Allan SM, Tyrrell PJ, Rothwell NJ. Interleukin-1 and neuronal injury. Nat Rev Immunol. 2005;5(8):629-40.
[16] Burda JE, Bernstein AM, Sofroniew MV. Astrocyte roles in traumatic brain injury. Exp Neurol. 2016;275 Pt 3(0 3):305-315.
[17] Erta M, Quintana A, Hidalgo J. Interleukin-6, a major cytokine in the central nervous system. Int J Biol Sci. 2012;8(9):1254-66.
[18] Shlosberg D, Benifla M, Kaufer D, Friedman A. Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury. Nat Rev Neurol. 2010;6(7):393-403.
[19] Takano T, He W, Han X, Wang F, Xu Q, Wang X, et al. Rapid manifestation of reactive astrogliosis in acute hippocampal brain slices. Glia. 2014;62(1):78-95.
[20] Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci. 2009;29(43):13435-44.
[21] Deyts C, Thinakaran G, Parent AT. APP Receptor? To Be or Not To Be. Trends Pharmacol Sci. 2016;37(5):390-411.
[22] Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A, et al., Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol. 2017;16(12):987-1048.
[23] GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(5):459-480.
[24] Frost RB, Farrer TJ, Primosch M, Hedges DW. Prevalence of traumatic brain injury in the general adult population: a meta-analysis. Neuroepidemiology. 2013;40(3):154-9.
[25] McKinlay A, Grace RC, Horwood LJ, Fergusson DM, Ridder EM, MacFarlane MR. Prevalence of traumatic brain injury among children, adolescents and young adults: prospective evidence from a birth cohort. Brain Inj. 2008;22(2):175-81.
[26] Whiteneck GG, Cuthbert JP, Corrigan JD, Bogner JA. Prevalence of Self-Reported Lifetime History of Traumatic Brain Injury and Associated Disability: A Statewide Population-Based Survey. J Head Trauma Rehabil. 2016;31(1):E55-62.
[27] Zaloshnja E, Miller T, Langlois JA, Selassie AW. Prevalence of long-term disability from traumatic brain injury in the civilian population of the United States, 2005. J Head Trauma Rehabil. 2008;23(6):394-400.
[28] World Health Organization. Neurological disorders: public health challenges. World Health Organization; 2006.
[29] Kumar A, Alvarez-Croda DM, Stoica BA, Faden AI, Loane DJ. Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury. J Neurotrauma. 2016;33(19):1732-1750.
[30] Soriano Sánchez JA, Soriano Solís S, Romero Rangel JAI. Role of the Checklist in Neurosurgery, a Realistic Perspective to "The Need for Surgical Safety Checklists in Neurosurgery Now and in the Future - a Systematic Review". World Neurosurg. 2020;134:121-122.
[31] Henry RJ, Ritzel RM, Barrett JP, Doran SJ, Jiao Y, Leach JB, et al., Microglial depletion with CSF1R inhibitor during chronic phase of experimental traumatic brain injury reduces neurodegeneration and neurological deficits. J Neurosci. 2020;40(14):2960-2974.
[32] Johnson VE, Stewart W, Smith DH. Traumatic brain injury and amyloid-β pathology: a link to Alzheimer's disease? Nat Rev Neurosci. 2010;11(5):361-70.
[33] Tomkins O, Friedman O, Ivens S, Reiffurth C, Major S, Dreier JP, et al., Blood–brain barrier disruption results in delayed functional and structural alterations in the rat neocortex. Neurobiol Dis. 2007;25(2):367-77.
[34] Cacheaux LP, Ivens S, David Y, Lakhter AJ, Bar-Klein G, Shapira M, et al. Transcriptome profiling reveals TGF-beta signaling involvement in epileptogenesis. J Neurosci. 2009;29(28):8927-35.
[35] Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008;57(2):178-201.
[36] Ruttan L, Martin K, Liu A, Colella B, Green RE. Long-term cognitive outcome in moderate to severe traumatic brain injury: a meta-analysis examining timed and untimed tests at 1 and 4.5 or more years after injury. Arch Phys Med Rehabil. 2008;89(12 Suppl):S69-76.
[37] Annegers JF, Hauser WA, Coan SP, Rocca WA. A population-based study of seizures after traumatic brain injuries. N Engl J Med. 1998;338(1):20-4.
[38] Herman ST. Epilepsy after brain insult: targeting epileptogenesis. Neurology. 2002;59(9 Suppl 5):S21-6.
[39] Annegers JF, Coan SP. The risks of epilepsy after traumatic brain injury. Seizure. 2000;9(7):453-7.
[40] Korn A, Golan H, Melamed I, Pascual-Marqui R, Friedman A. Focal cortical dysfunction and blood-brain barrier disruption in patients with Postconcussion syndrome. J Clin Neurophysiol. 2005;22(1):1-9.
[41] Pavlovsky L, Seiffert E, Heinemann U, Korn A, Golan H, Friedman A. Persistent BBB disruption may underlie alpha interferon-induced seizures. J Neurol. 2005;252(1):42-6.
[42] Wang HC, Chang WN, Chang HW, Ho JT, Yang TM, Lin WC, et al. Factors predictive of outcome in posttraumatic seizures. J Trauma. 2008;64(4):883-8.
[43] Ivens S, Kaufer D, Flores LP, Bechmann I, Zumsteg D, Tomkins O, et al. TGF-β receptor-mediated albumin uptake into astrocytes is involved in neocortical epileptogenesis. Brain. 2007. 130(2): 535-547.
[44] David Y, Cacheaux LP, Ivens S, Lapilover E, Heinemann U, Kaufer D, et al. Astrocytic dysfunction in epileptogenesis: consequence of altered potassium and glutamate homeostasis? J Neurosci. 2009;29(34):10588-99.
[45] Weber JT, AI Maas. Neurotrauma: new insights into pathology and treatment. Vol. 161. 2007: Elsevier.
[46] Heinemann U, Gabriel S, Jauch R, Schulze K, Kivi A, Eilers A, et al. Alterations of glial cell function in temporal lobe epilepsy. Epilepsia. 2000;41 Suppl 6:S185-9.
[47] Jabs R, Seifert G, Steinhäuser C. Astrocytic function and its alteration in the epileptic brain. Epilepsia. 2008;49 Suppl 2:3-12.
[48] Seifert G, Schilling K, Steinhäuser C. Astrocyte dysfunction in neurological disorders: a molecular perspective. Nat Rev Neurosci. 2006;7(3):194-206.
[49] Seiffert E, Dreier JP, Ivens S, Bechmann I, Tomkins O, Heinemann U, et al., Lasting blood-brain barrier disruption induces epileptic focus in the rat somatosensory cortex. J Neurosci. 2004;24(36):7829-36.
[50] Tian GF, Azmi H, Takano T, Xu Q, Peng W, Lin J, et al. An astrocytic basis of epilepsy. Nat Med. 2005;11(9):973-81.
[51] Filosa A, Paixão S, Honsek SD, Carmona MA, Becker L, Feddersen B, et al. Neuron-glia communication via EphA4/ephrin-A3 modulates LTP through glial glutamate transport. Nat Neurosci. 2009;12(10):1285-92.
[52] Henneberger C, Papouin T, Oliet SH, Rusakov DA. Long-term potentiation depends on release of D-serine from astrocytes. Nature. 2010;463(7278):232-6.
[53] Wetherington J, Serrano G, Dingledine R. Astrocytes in the epileptic brain. Neuron. 2008;58(2):168-78.
[54] Tomkins O, Shelef I, Kaizerman I, Eliushin A, Afawi Z, Misk A, et al. Blood–brain barrier disruption in post-traumatic epilepsy. J Neurol Neurosurg Psychiatry. 2008;79(7):774-7.
[55] Oby E, Janigro D. The blood-brain barrier and epilepsy. Epilepsia. 2006;47(11):1761-74.
[56] Fabene PF, Navarro Mora G, Martinello M, Rossi B, Merigo F, Ottoboni L, et al. A role for leukocyte-endothelial adhesion mechanisms in epilepsy. Nat Med. 2008;14(12):1377-83.
[57] Ivens S, Gabriel S, Greenberg G, Friedman A, Shelef I. Blood-brain barrier breakdown as a novel mechanism underlying cerebral hyperperfusion syndrome. J Neurol. 2010;257(4):615-20.
[58] Marchi N, Angelov L, Masaryk T, Fazio V, Granata T, Hernandez N, et al. Seizure‐promoting effect of blood–brain barrier disruption. Epilepsia. 2007. 48(4): 732-742.
[59] Noble LJ, Wrathall JR. Distribution and time course of protein extravasation in the rat spinal cord after contusive injury. Brain Res. 1989;482(1):57-66.
[60] Whetstone WD, Hsu JY, Eisenberg M, Werb Z, Noble-Haeusslein LJ. Blood-spinal cord barrier after spinal cord injury: relation to revascularization and wound healing. J Neurosci Res. 2003;74(2):227-39.
[61] Popovich PG, Horner PJ, Mullin BB, Stokes BT. A quantitative spatial analysis of the blood-spinal cord barrier. I. Permeability changes after experimental spinal contusion injury. Exp Neurol. 1996;142(2):258-75.
[62] Schnell L, Fearn S, Schwab ME, Perry VH, Anthony DC. Cytokine-induced acute inflammation in the brain and spinal cord. J Neuropathol Exp Neurol. 1999;58(3):245-54.
[63] Armao D, Kornfeld M, Estrada EY, Grossetete M, Rosenberg GA. Neutral proteases and disruption of the blood-brain barrier in rat. Brain Res. 1997;767(2):259-64.
[64] Butt AM. Effect of inflammatory agents on electrical resistance across the blood-brain barrier in pial microvessels of anaesthetized rats. Brain Res. 1995;696(1-2):145-50.
[65] Carlson SL, Parrish ME, Springer JE, Doty K, Dossett L. Acute inflammatory response in spinal cord following impact injury. Exp Neurol. 1998;151(1):77-88.
[66] Ellis W. Pulsed subcutaneous electrical stimulation in spinal cord injury: preliminary results. Bioelectromagnetics. 1987;8(2):159-64.
[67] Nag S, P Picard, D Stewart. Increased immunolocalization of nitric oxide synthases during blood-brain barrier breakdown and cerebral edema. in Brain Edema XI: Proceedings of the 11th International Symposium, Newcastle-upon-Tyne, United Kingdom, June 6–10, 1999. 2000. Springer.
[68] Sarker MH, Easton AS, Fraser PA. Regulation of cerebral microvascular permeability by histamine in the anaesthetized rat. J Physiol. 1998;507 ( Pt 3)(Pt 3):909-18.
[69] Unterberg A, Wahl M, Baethmann A. Effects of free radicals on permeability and vasomotor response of cerebral vessels. Acta Neuropathol. 1988;76(3):238-44.
[70] Mautes AE, Weinzierl MR, Donovan F, Noble LJ. Vascular events after spinal cord injury: contribution to secondary pathogenesis. Phys Ther. 2000;80(7):673-87.
[71] Woodcock T, Morganti-Kossmann MC. The role of markers of inflammation in traumatic brain injury. Front Neurol. 2013;4:18.
[72] Ricart PA, Andres TM, Apazidis A, Errico TJ, Trobisch PD. Validity of Cobb angle measurements using digitally photographed radiographs. Spine J. 2011;11(10):942-6.
[73] Smith DH, Johnson VE, Stewart W. Chronic neuropathologies of single and repetitive TBI: substrates of dementia? Nat Rev Neurol. 2013;9(4):211-21.
[74] Northington FJ, Chavez-Valdez R, Martin LJ. Neuronal cell death in neonatal hypoxia-ischemia. Ann Neurol. 2011;69(5):743-58.
[75] Silver J, Miller JH. Regeneration beyond the glial scar. Nat Rev Neurosci. 2004;5(2):146-56.
[76] O'Callaghan JP. Measurement of glial fibrillary acidic protein. Curr Protoc Toxicol. 2002 May;Chapter 12:Unit12.8.
[77] van Geel WJ, de Reus HP, Nijzing H, Verbeek MM, Vos PE, Lamers KJ. Measurement of glial fibrillary acidic protein in blood: an analytical method. Clin Chim Acta. 2002;326(1-2):151-4.
[78] Pelinka LE, Kroepfl A, Leixnering M, Buchinger W, Raabe A, Redl H. GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome. J Neurotrauma. 2004;21(11):1553-61.
[79] Pelinka LE, Kroepfl A, Schmidhammer R, Krenn M, Buchinger W, Redl H, et al. Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma. J Trauma. 2004;57(5):1006-12.
[80] Nylén K, Ost M, Csajbok LZ, Nilsson I, Blennow K, Nellgård B, et al. Increased serum-GFAP in patients with severe traumatic brain injury is related to outcome. J Neurol Sci. 2006;240(1-2):85-91.
[81] Vos PE, Jacobs B, Andriessen TM, Lamers KJ, Borm GF, Beems T, et al. GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort study. Neurology. 2010. 75(20): 1786-93.
[82] Papa L, Lewis LM, Falk JL, Zhang Z, Silvestri S, Giordano P, et al. Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention. Ann Emerg Med. 2012;59(6):471-83.
[83] Czeiter E, Mondello S, Kovacs N, Sandor J, Gabrielli A, Schmid K, et al. Brain injury biomarkers may improve the predictive power of the IMPACT outcome calculator. J Neurotrauma. 2012;29(9):1770-8.
[84] Mondello S, Robicsek SA, Gabrielli A, Brophy GM, Papa L, Tepas J, et al. αII-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients. J Neurotrauma. 2010;27(7):1203-13.
[85] Drewes G, Ebneth A, Mandelkow EM. MAPs, MARKs and microtubule dynamics. Trends Biochem Sci. 1998;23(8):307-11.
[86] Kitagawa K, Matsumoto M, Niinobe M, Mikoshiba K, Hata R, Ueda H, et al. Microtubule-associated protein 2 as a sensitive marker for cerebral ischemic damage—immunohistochemical investigation of dendritic damage. Neuroscience. 1989;31(2):401-11.
[87] Posmantur RM, Kampfl A, Taft WC, Bhattacharjee M, Dixon CE, Bao J, et al. Diminished microtubule-associated protein 2 (MAP2) immunoreactivity following cortical impact brain injury. J Neurotrauma. 1996;13(3):125-37.
[88] Park D, Joo SS, Lee HJ, Choi KC, Kim SU, Kim YB. Microtubule-associated protein 2, an early blood marker of ischemic brain injury. J Neurosci Res. 2012;90(2):461-7.
[89] Mondello S, Gabrielli A, Catani S, D'Ippolito M, Jeromin A, Ciaramella A, et al. Increased levels of serum MAP-2 at 6-months correlate with improved outcome in survivors of severe traumatic brain injury. Brain Inj. 2012;26(13-14):1629-35.
[90] Adamczak S, Dale G, de Rivero Vaccari JP, Bullock MR, Dietrich WD, Keane RW. Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome: clinical article. J Neurosurg. 2012;117(6):1119-25.
[91] Lammertse D, Dungan D, Dreisbach J, Falci S, Flanders A, Marino R, et al. Neuroimaging in traumatic spinal cord injury: an evidence-based review for clinical practice and research: report of the National Institute on Disability and Rehabilitation Research Spinal Cord Injury Measures Meeting. J Spinal Cord Med. 2007. 30(3): 205-214.
[92] Skouen JS, Brisby H, Otani K, Olmarker K, Rosengren L, Rydevik B. Protein markers in cerebrospinal fluid in experimental nerve root injury. A study of slow-onset chronic compression effects or the biochemical effects of nucleus pulposus on sacral nerve roots. Spine (Phila Pa 1976). 1999;24(21):2195-200.
[93] Nagy G, Dzsinich C, Selmeci L, Sepa G, Dzsinich M, Kékesi V, et al. Biochemical alterations in cerebrospinal fluid during thoracoabdominal aortic cross-clamping in dogs. Ann Vasc Surg. 2002;16(4):436-41.
[94] Cao F, Yang XF, Liu WG, Hu WW, Li G, Zheng XJ, et al. Elevation of neuron-specific enolase and S-100β protein level in experimental acute spinal cord injury. J Clin Neurosci. 2008;15(5):541-4.
[95] Ma J, Novikov LN, Karlsson K, Kellerth JO, Wiberg M. Plexus avulsion and spinal cord injury increase the serum concentration of S-100 protein: an experimental study in rats. Scand J Plast Reconstr Surg Hand Surg. 2001;35(4):355-9.
[96] Loy DN, Sroufe AE, Pelt JL, Burke DA, Cao QL, Talbott JF, et al. Serum biomarkers for experimental acute spinal cord injury: rapid elevation of neuron-specific enolase and S-100β. Neurosurgery. 2005;56(2):391-7.
[97] van Dongen EP, Ter Beek HT, Boezeman EH, Schepens MA, Langemeijer HJ, Aarts LP. Normal serum concentrations of S-100 protein and changes in cerebrospinal fluid concentrations of S-100 protein during and after thoracoabdominal aortic aneurysm surgery: is S-100 protein a biochemical marker of clinical value in detecting spinal cord ischemia? J Vasc Surg. 1998;27(2):344-6.
[98] van Dongen EP, ter Beek HT, Schepens MA, Morshuis WJ, Haas FJ, de Boer A, et al. The relationship between evoked potentials and measurements of S-100 protein in cerebrospinal fluid during and after thoracoabdominal aortic aneurysm surgery. J Vasc Surg. 1999. 30(2): 293-300.
[99] Kunihara T, Shiiya N, Yasuda K. Changes in S100beta protein levels in cerebrospinal fluid after thoracoabdominal aortic operations. J Thorac Cardiovasc Surg. 2001;122(5):1019-20.
[100] Winnerkvist A, Anderson RE, Hansson LO, Rosengren L, Estrera AE, Huynh TT, et al. Multilevel somatosensory evoked potentials and cerebrospinal proteins: indicators of spinal cord injury in thoracoabdominal aortic aneurysm surgery. Eur J Cardiothorac Surg. 2007;31(4):637-42.
[101] Marquardt G, Setzer M, Seifert V. Protein S-100b for individual prediction of functional outcome in spinal epidural empyema. Spine (Phila Pa 1976). 2004;29(1):59-62.
[102] Brisby H, Olmarker K, Rosengren L, Cederlund CG, Rydevik B. Markers of nerve tissue injury in the cerebrospinal fluid in patients with lumbar disc herniation and sciatica. Spine (Phila Pa 1976). 1999;24(8):742-6.
[103] Marquardt G, Setzer M, Seifert V. Protein S-100b as serum marker for prediction of functional outcome in metastatic spinal cord compression. Acta Neurochir (Wien). 2004;146(5):449-52.
[104] Guéz M, Hildingsson C, Rosengren L, Karlsson K, Toolanen G. Nervous tissue damage markers in cerebrospinal fluid after cervical spine injuries and whiplash trauma. J Neurotrauma. 2003;20(9):853-8.
[105] Kwon BK, Stammers AM, Belanger LM, Bernardo A, Chan D, Bishop CM, et al. Cerebrospinal fluid inflammatory cytokines and biomarkers of injury severity in acute human spinal cord injury. J Neurotrauma. 2010;27(4):669-82.
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| Traumatic brain injury (TBI) Spinal cord injury (SCI) Central nervous system (CNS) | ||
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Amirdosara M, Hajiesmaeili M, Hosseininasab S, Zangi M. Role of Inflammation in Secondary Injury Progression after Traumatic Brain Injury and Spinal Cord Injury. Arch Anesth & Crit Care. 2025;.
