Concussion leads to widespread axonal sodium channel loss and disruption of the node of Ranvier (original ) (raw )
Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, McLellan DR (1989) Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology 15:49–59. https://doi.org/10.1111/j.1365-2559.1989.tb03040.x Article CAS PubMed Google Scholar
Adams JH, Graham DI, Gennarelli TA, Maxwell WL (1991) Diffuse axonal injury in non-missile head injury. J Neurol Neurosurg Psychiatry 54:481–483. https://doi.org/10.1136/jnnp.54.6.481 Article CAS PubMed PubMed Central Google Scholar
Amor V, Feinberg K, Eshed-Eisenbach Y, Vainshtein A, Frechter S, Grumet M et al (2014) Long-term maintenance of Na+ channels at nodes of Ranvier depends on glial contact mediated by gliomedin and NrCAM. J Neurosci 34:5089–5098. https://doi.org/10.1523/JNEUROSCI.4752-13.2014 Article CAS PubMed PubMed Central Google Scholar
Amor V, Zhang C, Vainshtein A, Zhang A, Zollinger DR, Eshed-Eisenbach Y et al (2017) The paranodal cytoskeleton clusters Na(+) channels at nodes of Ranvier. Elife. https://doi.org/10.7554/eLife.21392 Article PubMed PubMed Central Google Scholar
Arancibia-Carcamo IL, Ford MC, Cossell L, Ishida K, Tohyama K, Attwell D (2017) Node of Ranvier length as a potential regulator of myelinated axon conduction speed. Elife. https://doi.org/10.7554/eLife.23329 Article PubMed PubMed Central Google Scholar
Armstrong RC, Mierzwa AJ, Marion CM, Sullivan GM (2016) White matter involvement after TBI: clues to axon and myelin repair capacity. Exp Neurol 275(Pt 3):328–333. https://doi.org/10.1016/j.expneurol.2015.02.011 Article CAS PubMed Google Scholar
Bazarian JJ, Zhong J, Blyth B, Zhu T, Kavcic V, Peterson D (2007) Diffusion tensor imaging detects clinically important axonal damage after mild traumatic brain injury: a pilot study. J Neurotrauma 24:1447–1459. https://doi.org/10.1089/neu.2007.0241 Article PubMed Google Scholar
Bean BP (2007) The action potential in mammalian central neurons. Nat Rev Neurosci 8:451–465. https://doi.org/10.1038/nrn2148 Article CAS PubMed Google Scholar
Blumbergs PC, Scott G, Manavis J, Wainwright H, Simpson DA, McLean AJ (1994) Staining of amyloid precursor protein to study axonal damage in mild head injury. Lancet 344:1055–1056. https://doi.org/10.1016/s0140-6736(94)91712-4 Article CAS PubMed Google Scholar
Broglio SP, Lapointe A, O’Connor KL, McCrea M (2017) Head impact density: a model to explain the elusive concussion threshold. J Neurotrauma 34:2675–2683. https://doi.org/10.1089/neu.2016.4767 Article PubMed PubMed Central Google Scholar
Browne KD, Chen XH, Meaney DF, Smith DH (2011) Mild traumatic brain injury and diffuse axonal injury in swine. J Neurotrauma 28:1747–1755. https://doi.org/10.1089/neu.2011.1913 Article PubMed PubMed Central Google Scholar
Catterall WA (2017) Forty years of sodium channels: structure, function, pharmacology, and epilepsy. Neurochem Res 42:2495–2504. https://doi.org/10.1007/s11064-017-2314-9 Article CAS PubMed PubMed Central Google Scholar
Chen L, Huang J, Zhao P, Persson AK, Dib-Hajj FB, Cheng X et al (2018) Conditional knockout of NaV1.6 in adult mice ameliorates neuropathic pain. Sci Rep 8:3845. https://doi.org/10.1038/s41598-018-22216-w Article CAS PubMed PubMed Central Google Scholar
Cicchetti DV (1994) Guidelines, criteria, and rules of thumb for evaluating normed and standardized assessment instruments in psychology. Psychol Assess 6:284–290. https://doi.org/10.1037/1040-3590.6.4.284 Article Google Scholar
Cicchetti DV (2001) The precision of reliability and validity estimates re-visited: distinguishing between clinical and statistical significance of sample size requirements. J Clin Exp Neuropsychol 23:695–700. https://doi.org/10.1076/jcen.23.5.695.1249 Article CAS PubMed Google Scholar
Cullen DK, Harris JP, Browne KD, Wolf JA, Duda JE, Meaney DF et al (2016) A porcine model of traumatic brain injury via head rotational acceleration. Methods Mol Biol 1462:289–324. https://doi.org/10.1007/978-1-4939-3816-2_17 Article CAS PubMed PubMed Central Google Scholar
Duma SM, Manoogian SJ, Bussone WR, Brolinson PG, Goforth MW, Donnenwerth JJ et al (2005) Analysis of real-time head accelerations in collegiate football players. Clin J Sport Med 15:3–8. https://doi.org/10.1097/00042752-200501000-00002 Article PubMed Google Scholar
Eshed-Eisenbach Y, Peles E (2013) The making of a node: a co-production of neurons and glia. Curr Opin Neurobiol 23:1049–1056. https://doi.org/10.1016/j.conb.2013.06.003 Article CAS PubMed Google Scholar
Felmingham KL, Baguley IJ, Green AM (2004) Effects of diffuse axonal injury on speed of information processing following severe traumatic brain injury. Neuropsychology 18:564–571. https://doi.org/10.1037/0894-4105.18.3.564 Article PubMed Google Scholar
Ford MC, Alexandrova O, Cossell L, Stange-Marten A, Sinclair J, Kopp-Scheinpflug C et al (2015) Tuning of Ranvier node and internode properties in myelinated axons to adjust action potential timing. Nat Commun 6:8073. https://doi.org/10.1038/ncomms9073 Article CAS PubMed Google Scholar
Frechede B, McIntosh AS (2009) Numerical reconstruction of real-life concussive football impacts. Med Sci Sports Exerc 41:390–398. https://doi.org/10.1249/MSS.0b013e318186b1c5 Article PubMed Google Scholar
Freeman SA, Desmazieres A, Fricker D, Lubetzki C, Sol-Foulon N (2016) Mechanisms of sodium channel clustering and its influence on axonal impulse conduction. Cell Mol Life Sci 73:723–735. https://doi.org/10.1007/s00018-015-2081-1 Article CAS PubMed Google Scholar
Gasser A, Ho TS, Cheng X, Chang KJ, Waxman SG, Rasband MN et al (2012) An ankyrinG-binding motif is necessary and sufficient for targeting Nav1.6 sodium channels to axon initial segments and nodes of Ranvier. J Neurosci 32:7232–7243. https://doi.org/10.1523/JNEUROSCI.5434-11.2012 Article CAS PubMed PubMed Central Google Scholar
Graham DI, Gentleman SM, Lynch A, Roberts GW (1995) Distribution of beta-amyloid protein in the brain following severe head injury. Neuropathol Appl Neurobiol 21:27–34. https://doi.org/10.1111/j.1365-2990.1995.tb01025.x Article CAS PubMed Google Scholar
Iwata A, Stys PK, Wolf JA, Chen XH, Taylor AG, Meaney DF et al (2004) Traumatic axonal injury induces proteolytic cleavage of the voltage-gated sodium channels modulated by tetrodotoxin and protease inhibitors. J Neurosci 24:4605–4613. https://doi.org/10.1523/JNEUROSCI.0515-03.2004 Article CAS PubMed PubMed Central Google Scholar
Jenkins SM, Bennett V (2002) Developing nodes of Ranvier are defined by ankyrin-G clustering and are independent of paranodal axoglial adhesion. Proc Natl Acad Sci USA 99:2303–2308. https://doi.org/10.1073/pnas.042601799 Article CAS PubMed PubMed Central Google Scholar
Jette N, Coderre E, Nikolaeva MA, Enright PD, Iwata A, Smith DH et al (2006) Spatiotemporal distribution of spectrin breakdown products induced by anoxia in adult rat optic nerve in vitro. J Cereb Blood Flow Metab 26:777–786. https://doi.org/10.1038/sj.jcbfm.9600226 Article CAS PubMed Google Scholar
Johnson VE, Meaney DF, Cullen DK, Smith DH (2015) Animal models of traumatic brain injury. Handb Clin Neurol 127:115–128. https://doi.org/10.1016/B978-0-444-52892-6.00008-8 Article PubMed PubMed Central Google Scholar
Johnson VE, Stewart W, Arena JD, Smith DH (2017) Traumatic brain injury as a trigger of neurodegeneration. Adv Neurobiol 15:383–400. https://doi.org/10.1007/978-3-319-57193-5_15 Article PubMed Google Scholar
Johnson VE, Stewart JE, Begbie FD, Trojanowski JQ, Smith DH, Stewart W (2013) Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain 136:28–42. https://doi.org/10.1093/brain/aws322 Article PubMed PubMed Central Google Scholar
Johnson VE, Stewart W, Smith DH (2013) Axonal pathology in traumatic brain injury. Exp Neurol 246:35–43. https://doi.org/10.1016/j.expneurol.2012.01.013 Article CAS PubMed Google Scholar
Johnson VE, Stewart W, Weber MT, Cullen DK, Siman R, Smith DH (2016) SNTF immunostaining reveals previously undetected axonal pathology in traumatic brain injury. Acta Neuropathol 131:115–135. https://doi.org/10.1007/s00401-015-1506-0 Article CAS PubMed Google Scholar
Johnson VE, Weber MT, Xiao R, Cullen DK, Meaney DF, Stewart W et al (2018) Mechanical disruption of the blood–brain barrier following experimental concussion. Acta Neuropathol 135:711–726. https://doi.org/10.1007/s00401-018-1824-0 Article CAS PubMed PubMed Central Google Scholar
Kourtidou P, McCauley SR, Bigler ED, Traipe E, Wu TC, Chu ZD et al (2013) Centrum semiovale and corpus callosum integrity in relation to information processing speed in patients with severe traumatic brain injury. J Head Trauma Rehabil 28:433–441. https://doi.org/10.1097/HTR.0b013e3182585d06 Article PubMed Google Scholar
Labasque M, Devaux JJ, Leveque C, Faivre-Sarrailh C (2011) Fibronectin type III-like domains of neurofascin-186 protein mediate gliomedin binding and its clustering at the developing nodes of Ranvier. J Biol Chem 286:42426–42434. https://doi.org/10.1074/jbc.M111.266353 Article CAS PubMed PubMed Central Google Scholar
Leclercq PD, McKenzie JE, Graham DI, Gentleman SM (2001) Axonal injury is accentuated in the caudal corpus callosum of head-injured patients. J Neurotrauma 18:1–9. https://doi.org/10.1089/089771501750055721 Article CAS PubMed Google Scholar
Liu CH, Rasband MN (2019) Axonal spectrins: nanoscale organization, functional domains and spectrinopathies. Front Cell Neurosci 13:234. https://doi.org/10.3389/fncel.2019.00234 Article CAS PubMed PubMed Central Google Scholar
Maas AIR, Menon DK, Adelson PD, Andelic N, Bell MJ, Belli A et al (2017) Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. Lancet Neurol 16:987–1048. https://doi.org/10.1016/S1474-4422(17)30371-X Article PubMed Google Scholar
Marion CM, Radomski KL, Cramer NP, Galdzicki Z, Armstrong RC (2018) Experimental traumatic brain injury identifies distinct early and late phase axonal conduction deficits of white matter pathophysiology, and reveals intervening recovery. J Neurosci 38:8723–8736. https://doi.org/10.1523/JNEUROSCI.0819-18.2018 Article CAS PubMed PubMed Central Google Scholar
Mayer AR, Ling J, Mannell MV, Gasparovic C, Phillips JP, Doezema D et al (2010) A prospective diffusion tensor imaging study in mild traumatic brain injury. Neurology 74:643–650. https://doi.org/10.1212/WNL.0b013e3181d0ccdd Article CAS PubMed PubMed Central Google Scholar
Meaney DF, Smith DH (2011) Biomechanics of concussion. Clin Sports Med 30(19–31):vii. https://doi.org/10.1016/j.csm.2010.08.009 Article Google Scholar
Nelson LD, Temkin NR, Dikmen S, Barber J, Giacino JT, Yuh E et al (2019) Recovery after mild traumatic brain injury in patients presenting to US level I trauma centers: a transforming research and clinical knowledge in traumatic brain injury (TRACK-TBI) study. JAMA Neurol 76:1049–1059. https://doi.org/10.1001/jamaneurol.2019.1313 Article PubMed PubMed Central Google Scholar
Ozen I, Arkan S, Clausen F, Ruscher K, Marklund N (2022) Diffuse traumatic injury in the mouse disrupts axon-myelin integrity in the cerebellum. J Neurotrauma 39:411–422. https://doi.org/10.1089/neu.2021.0321 Article PubMed Google Scholar
Palacios EM, Owen JP, Yuh EL, Wang MB, Vassar MJ, Ferguson AR et al (2020) The evolution of white matter microstructural changes after mild traumatic brain injury: a longitudinal DTI and NODDI study. Sci Adv 6:eaaz6892. https://doi.org/10.1126/sciadv.aaz6892 Article CAS PubMed PubMed Central Google Scholar
Pfister BJ, Bonislawski DP, Smith DH, Cohen AS (2006) Stretch-grown axons retain the ability to transmit active electrical signals. FEBS Lett 580:3525–3531. https://doi.org/10.1016/j.febslet.2006.05.030 Article CAS PubMed PubMed Central Google Scholar
Raghavan M, Fee D, Barkhaus PE (2019) Generation and propagation of the action potential. Handb Clin Neurol 160:3–22. https://doi.org/10.1016/B978-0-444-64032-1.00001-1 Article PubMed Google Scholar
Rasband MN, Peles E (2015) The nodes of Ranvier: molecular assembly and maintenance. Cold Spring Harb Perspect Biol 8:a020495. https://doi.org/10.1101/cshperspect.a020495 Article PubMed Google Scholar
Rasband MN, Peles E (2021) Mechanisms of node of Ranvier assembly. Nat Rev Neurosci 22:7–20. https://doi.org/10.1038/s41583-020-00406-8 Article CAS PubMed Google Scholar
Reeves TM, Greer JE, Vanderveer AS, Phillips LL (2010) Proteolysis of submembrane cytoskeletal proteins ankyrin-G and alphaII-spectrin following diffuse brain injury: a role in white matter vulnerability at nodes of Ranvier. Brain Pathol 20:1055–1068. https://doi.org/10.1111/j.1750-3639.2010.00412.x Article CAS PubMed PubMed Central Google Scholar
Reeves TM, Phillips LL, Povlishock JT (2005) Myelinated and unmyelinated axons of the corpus callosum differ in vulnerability and functional recovery following traumatic brain injury. Exp Neurol 196:126–137. https://doi.org/10.1016/j.expneurol.2005.07.014 Article PubMed Google Scholar
von Reyn CR, Mott RE, Siman R, Smith DH, Meaney DF (2012) Mechanisms of calpain mediated proteolysis of voltage gated sodium channel alpha-subunits following in vitro dynamic stretch injury. J Neurochem 121:793–805. https://doi.org/10.1111/j.1471-4159.2012.07735.x Article CAS Google Scholar
von Reyn CR, Spaethling JM, Mesfin MN, Ma M, Neumar RW, Smith DH et al (2009) Calpain mediates proteolysis of the voltage-gated sodium channel alpha-subunit. J Neurosci 29:10350–10356. https://doi.org/10.1523/JNEUROSCI.2339-09.2009 Article CAS Google Scholar
Rios JC, Melendez-Vasquez CV, Einheber S, Lustig M, Grumet M, Hemperly J et al (2000) Contactin-associated protein (Caspr) and contactin form a complex that is targeted to the paranodal junctions during myelination. J Neurosci 20:8354–8364Article CAS Google Scholar
Rios JC, Rubin M, St Martin M, Downey RT, Einheber S, Rosenbluth J et al (2003) Paranodal interactions regulate expression of sodium channel subtypes and provide a diffusion barrier for the node of Ranvier. J Neurosci 23:7001–7011Article CAS Google Scholar
Royeck M, Horstmann MT, Remy S, Reitze M, Yaari Y, Beck H (2008) Role of axonal NaV1.6 sodium channels in action potential initiation of CA1 pyramidal neurons. J Neurophysiol 100:2361–2380. https://doi.org/10.1152/jn.90332.2008 Article CAS PubMed Google Scholar
Rush AM, Wittmack EK, Tyrrell L, Black JA, Dib-Hajj SD, Waxman SG (2006) Differential modulation of sodium channel Na(v)1.6 by two members of the fibroblast growth factor homologous factor 2 subfamily. Eur J Neurosci 23:2551–2562. https://doi.org/10.1111/j.1460-9568.2006.04789.x Article PubMed Google Scholar
Shahim P, Tegner Y, Wilson DH, Randall J, Skillback T, Pazooki D et al (2014) Blood biomarkers for brain injury in concussed professional ice hockey players. JAMA Neurol 71:684–692. https://doi.org/10.1001/jamaneurol.2014.367 Article PubMed Google Scholar
Sherman DL, Tait S, Melrose S, Johnson R, Zonta B, Court FA et al (2005) Neurofascins are required to establish axonal domains for saltatory conduction. Neuron 48:737–742. https://doi.org/10.1016/j.neuron.2005.10.019 Article CAS PubMed Google Scholar
Siman R, Shahim P, Tegner Y, Blennow K, Zetterberg H, Smith DH (2015) Serum SNTF increases in concussed professional ice hockey players and relates to the severity of postconcussion symptoms. J Neurotrauma 32:1294–1300. https://doi.org/10.1089/neu.2014.3698 Article PubMed PubMed Central Google Scholar
Smith DH, Dolle JP, Ameen-Ali KE, Bretzin A, Cortes E, Crary JF et al (2021) Collaborative neuropathology network characterizing outcomes of TBI (CONNECT-TBI). Acta Neuropathol Commun 9:32. https://doi.org/10.1186/s40478-021-01122-9 Article PubMed PubMed Central Google Scholar
Smith DH, Johnson VE, Trojanowski JQ, Stewart W (2019) Chronic traumatic encephalopathy—confusion and controversies. Nat Rev Neurol 15:179–183. https://doi.org/10.1038/s41582-018-0114-8 Article PubMed PubMed Central Google Scholar
Smith DH, Nonaka M, Miller R, Leoni M, Chen XH, Alsop D et al (2000) Immediate coma following inertial brain injury dependent on axonal damage in the brainstem. J Neurosurg 93:315–322. https://doi.org/10.3171/jns.2000.93.2.0315 Article CAS PubMed Google Scholar
Smith DH, Stewart W (2020) “Concussion” is not a true diagnosis. Nat Rev Neurol 16:457–458. https://doi.org/10.1038/s41582-020-0382-y Article PubMed PubMed Central Google Scholar
Song H, Chen C, Kelley B, Tomasevich A, Lee H, Dolle JP et al (2022) Traumatic brain injury recapitulates developmental changes of axons. Prog Neurobiol 217:102332. https://doi.org/10.1016/j.pneurobio.2022.102332 Article PubMed Google Scholar
Tait S, Gunn-Moore F, Collinson JM, Huang J, Lubetzki C, Pedraza L et al (2000) An oligodendrocyte cell adhesion molecule at the site of assembly of the paranodal axo-glial junction. J Cell Biol 150:657–666. https://doi.org/10.1083/jcb.150.3.657 Article CAS PubMed PubMed Central Google Scholar
Ueda R, Hara H, Hata J, Senoo A (2021) White matter degeneration in diffuse axonal injury and mild traumatic brain injury observed with automatic tractography. Neuroreport 32:936–941. https://doi.org/10.1097/WNR.0000000000001688 Article CAS PubMed Google Scholar
Wolf JA, Johnson BN, Johnson VE, Putt ME, Browne KD, Mietus CJ et al (2017) Concussion induces hippocampal circuitry disruption in swine. J Neurotrauma 34:2303–2314. https://doi.org/10.1089/neu.2016.4848 Article PubMed PubMed Central Google Scholar
Yallampalli R, Wilde EA, Bigler ED, McCauley SR, Hanten G, Troyanskaya M et al (2013) Acute white matter differences in the fornix following mild traumatic brain injury using diffusion tensor imaging. J Neuroimaging 23:224–227. https://doi.org/10.1111/j.1552-6569.2010.00537.x Article PubMed Google Scholar
Yang Y, Lacas-Gervais S, Morest DK, Solimena M, Rasband MN (2004) BetaIV spectrins are essential for membrane stability and the molecular organization of nodes of Ranvier. J Neurosci 24:7230–7240. https://doi.org/10.1523/JNEUROSCI.2125-04.2004 Article CAS PubMed PubMed Central Google Scholar
Yuen TJ, Browne KD, Iwata A, Smith DH (2009) Sodium channelopathy induced by mild axonal trauma worsens outcome after a repeat injury. J Neurosci Res 87:3620–3625. https://doi.org/10.1002/jnr.22161 Article CAS PubMed PubMed Central Google Scholar
Zhou W, Goldin AL (2004) Use-dependent potentiation of the Nav1.6 sodium channel. Biophys J 87:3862–3872. https://doi.org/10.1529/biophysj.104.045963 Article CAS PubMed PubMed Central Google Scholar