Diffuse axonal injury in brain trauma: Insights from alterations in neurofilaments

Frontiers in Cellular Neuroscience

Volumn 8, Issue DEC, 2014, Pages

  Siedler, Declan G ^a,b   Chuah, Meng Inn ^a,b   Kirkcaldie, Matthew T K ^a,b   Vickers, James C ^a,b   King, Anna E ^a,b  

^a Wicking Dementia Research and Education Centre   (Australia)

^b UNIVERSITY OF TASMANIA   (Australia)

Author keywords

Biomarkers; Diffuse axonal injury; Diffuse brain trauma; Neurofilament; Neurofilament compaction; NFL; Traumatic axonal injury; Traumatic brain injury

Indexed keywords

ALPHA INTERNEXIN; CALCIUM; CYCLIN DEPENDENT KINASE; CYCLIN DEPENDENT KINASE 5; CYTOCHROME C; GLIAL FIBRILLARY ACIDIC PROTEIN; MYELIN ASSOCIATED GLYCOPROTEIN; NEUROFILAMENT PROTEIN; NEURON SPECIFIC ENOLASE; PROTEIN S100B;

CALCIUM TRANSPORT; CYTOSKELETON; DIFFUSE AXONAL INJURY; HUMAN; MICROTUBULE; MITOCHONDRION; NERVE FIBER TRANSECTION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN GLYCOSYLATION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; REVIEW; TRAUMATIC BRAIN INJURY;

EID: 84919416241     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2014.00429     Document Type: Review

References (139)

1. Adams, J. H., Doyle, D., Ford, I., Gennarelli, T. A., Graham, D. I., and Mclellan, D. R. (1989). Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology 15, 49-59. doi: 10.1111/j.1365-2559.1989.tb03040.x
2. Anderson, K. J., Scheff, S. W., Miller, K. M., Roberts, K. N., Gilmer, L. K., Yang, C., et al. (2008). The phosphorylated axonal form of the neurofilament subunit NF-H (pNF-H) as a blood biomarker of traumatic brain injury. J. Neurotrauma 25, 1079-1085. doi: 10.1089/neu.2007.0488
3. Barkhoudarian, G., Hovda, D. A., and Giza, C. C. (2011). The molecular pathophysiology of concussive brain injury.Clin. Sports Med. 30, 33-48. doi: 10.1016/j.csm.2010.09.001
4. Bazarian, J. J., Zhong, J., Blyth, B., Zhu, T., Kavcic, V., and Peterson, D. (2007). Diffusion tensor imaging detects clinically important axonal damage after mild traumatic brain injury: a pilot study. J. Neurotrauma 24, 1447-1459. doi: 10.1089/neu.2007.0241
5. Berridge, M. J., Bootman, M. D., and Roderick, H. L. (2003). Calcium signalling: dynamics, homeostasis and remodelling. Nat. Rev. Mol. Cell Biol. 4, 517-529. doi: 10.1038/nrm1155
6. Blennow, K., Hardy, J., and Zetterberg, H. (2012). The neuropathology and neurobiology of traumatic brain injury.Neuron 76, 886-899. doi: 10.1016/j.neuron.2012.11.021
7. Blumbergs, P. C., Scott, G., Manavis, J., Wainwright, H., Simpson, D. A., and Mclean, A. J. (1994). Staining of amyloid precursor protein to study axonal damage in mild head injury. Lancet 344, 1055-1056. doi: 10.1016/s0140-6736(94)91712-4
8. Bossy-Wetzel, E., and Green, D. R. (1999). Caspases induce cytochrome c release from mitochondria by activating cytosolic factors. J. Biol. Chem. 274, 17484-17490. doi: 10.1074/jbc.274.25.17484
9. Bradke, F., Fawcett, J. W., and Spira, M. E. (2012). Assembly of a new growth cone after axotomy: the precursor to axon regeneration. Nat. Rev. Neurosci. 13, 183-193. doi: 10.1038/nrn3176
10. Browne, K. D., Chen, X. H., Meaney, D. F., and Smith, D. H. (2011). Mild traumatic brain injury and diffuse axonal injury in swine. J. Neurotrauma 28, 1747-1755. doi: 10.1089/neu.2011.1913
11. Buki, A., Farkas, O., Doczi, T., and Povlishock, J. T. (2003). Preinjury administration of the calpain inhibitor MDL-28170 attenuates traumatically induced axonal injury. J. Neurotrauma 20, 261-268. doi: 10.1089/089771503321532842
12. Buki, A., Okonkwo, D. O., Wang, K. K., and Povlishock, J. T. (2000). Cytochrome c release and caspase activation in traumatic axonal injury. J. Neurosci. 20, 2825-2834.
13. Buki, A., and Povlishock, J. T. (2006). All roads lead to disconnection?-Traumatic axonal injury revisited. Acta Neurochir. (Wien) 148, 181-193; discussion 193-184. doi: 10.1007/s00701-005-0674-4
14. Campbell, M. J., and Morrison, J. H. (1989). Monoclonal antibody to neurofilament protein (SMI-32) labels a subpopulation of pyramidal neurons in the human and monkey neocortex. J. Comp. Neurol. 282, 191-205. doi: 10.1002/cne.902820204
15. Capano, C. P., Pernas-Alonso, R., and Di Porzio, U. (2001). Neurofilament homeostasis and motoneurone degeneration. Bioessays 23, 24-33. doi: 10.1002/1521-1878(200101)23:1<24::aid-bies1004>3.0.co;2-h
16. Carter, J. (1998). Neurofilament (NF) assembly; divergent characteristics of human and rodent NF-L subunits. J. Biol. Chem. 273, 5101-5108. doi: 10.1074/jbc.273.9.5101
17. Chang, R., Kwak, Y., and Gebremichael, Y. (2009). Structural properties of neurofilament sidearms: sequence-based modelling of neurofilament architecture. J. Mol. Biol. 391, 648-660. doi: 10.1016/j.jmb.2009.06.045
18. Chen, X. H., Meaney, D. F., Xu, B. N., Nonaka, M., Mcintosh, T. K., Wolf, J. A., et al. (1999). Evolution of neurofilament subtype accumulation in axons following diffuse brain injury in the pig. J. Neuropathol. Exp. Neurol.58, 588-596. doi: 10.1097/00005072-199906000-00003
19. Chen, J., Nakata, T., Zhang, Z., and Hirokawa, N. (2000). The C-terminal tail domain of neurofilament protein-H (NF-H) forms the crossbridges and regulates neurofilament bundle formation. J. Cell Sci. 113(Pt. 21), 3861-3869.
20. Chung, R. S., Staal, J. A., Mccormack, G. H., Dickson, T. C., Cozens, M. A., Chuckowree, J. A., et al. (2005). Mild axonal stretch injury in vitro induces a progressive series of neurofilament alterations ultimately leading to delayed axotomy. J. Neurotrauma 22, 1081-1091. doi: 10.1089/neu.2005.22.1081
21. Creed, J. A., Dileonardi, A. M., Fox, D. P., Tessler, A. R., and Raghupathi, R. (2011). Concussive brain trauma in the mouse results in acute cognitive deficits and sustained impairment of axonal function. J. Neurotrauma 28, 547-563. doi: 10.1089/neu.2010.1729
22. Czeiter, E., Buki, A., Bukovics, P., Farkas, O., Pal, J., Kovesdi, E., et al. (2009). Calpain inhibition reduces axolemmal leakage in traumatic axonal injury. Molecules 14, 5115-5123. doi: 10.3390/molecules14125115
23. Dale, J. M., and Garcia, M. L. (2012). Neurofilament phosphorylation during development and disease: which came first, the phosphorylation or the accumulation? J. Amino Acids 2012:382107. doi: 10.1155/2012/382107
24. Dash, P. K., Mach, S. A., and Moore, A. N. (2002). The role of extracellular signal-regulated kinase in cognitive and motor deficits following experimental traumatic brain injury. Neuroscience 114, 755-767. doi: 10.1016/s0306-4522(02)00277-4
25. Dashiell, S. M., Tanner, S. L., Pant, H. C., and Quarles, R. H. (2002). Myelin-associated glycoprotein modulates expression and phosphorylation of neuronal cytoskeletal elements and their associated kinases. J. Neurochem. 81, 1263-1272. doi: 10.1046/j.1471-4159.2002.00927.x
26. de Waegh, S. M., Lee, V. M., and Brady, S. T. (1992). Local modulation of neurofilament phosphorylation, axonal caliber and slow axonal transport by myelinating Schwann cells. Cell 68, 451-463. doi: 10.1016/0092-8674(92)90183-d
27. Dickson, T. C., Chuckowree, J. A., Chuah, M. I., West, A. K., and Vickers, J. C. (2005). alpha-Internexin immunoreactivity reflects variable neuronal vulnerability in Alzheimer's disease and supports the role of the beta-amyloid plaques in inducing neuronal injury. Neurobiol. Dis. 18, 286-295. doi: 10.1016/j.nbd.2004.10.001
28. DiLeonardi, A. M., Huh, J. W., and Raghupathi, R. (2009). Impaired axonal transport and neurofilament compaction occur in separate populations of injured axons following diffuse brain injury in the immature rat. Brain Res. 1263, 174-182. doi: 10.1016/j.brainres.2009.01.021
29. Dileonardi, A. M., Huh, J. W., and Raghupathi, R. (2012). Differential effects of FK506 on structural and functional axonal deficits after diffuse brain injury in the immature rat. J. Neuropathol. Exp. Neurol. 71, 959-972. doi: 10.1097/nen.0b013e31826f5876
30. Dong, D. L., Xu, Z. S., Chevrier, M. R., Cotter, R. J., Cleveland, D. W., and Hart, G. W. (1993). Glycosylation of mammalian neurofilaments. Localization of multiple O-linked N-acetylglucosamine moieties on neurofilament polypeptides L and M. J. Biol. Chem. 268, 16679-16687.
31. Elder, G. A., Friedrich, V. L. Jr., Kang, C., Bosco, P., Gourov, A., Tu, P. H., et al. (1998). Requirement of heavy neurofilament subunit in the development of axons with large calibers. J. Cell Biol. 143, 195-205. doi: 10.1083/jcb.143.1.195
32. Farkas, O., Lifshitz, J., and Povlishock, J. T. (2006). Mechanoporation induced by diffuse traumatic brain injury: an irreversible or reversible response to injury? J. Neurosci. 26, 3130-3140. doi: 10.1523/jneurosci.5119-05.2006
33. Fletcher, D. A., and Mullins, R. D. (2010). Cell mechanics and the cytoskeleton. Nature 463, 485-492. doi: 10.1038/nature08908
34. Fliegner, K. H., Kaplan, M. P., Wood, T. L., Pintar, J. E., and Liem, R. K. (1994). Expression of genes for the neuronal intermediate filament protein alpha-internexin coincides with the onset of neuronal differentiation in the developing rat nervous system. J. Comp. Neurol. 342, 161-173. doi: 10.1002/cne.903420202
35. Fournier, A. J., Rajbhandari, L., Shrestha, S., Venkatesan, A., and Ramesh, K. T. (2014). In vitro and in situ visualization of cytoskeletal deformation under load: traumatic axonal injury. FASEB J. doi: 10.1096/fj.14-251942. [Epub ahead of print].
36. Gaiottino, J., Norgren, N., Dobson, R., Topping, J., Nissim, A., Malaspina, A., et al. (2013). Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. PLoS One 8:e75091. doi: 10.1371/journal.pone.0075091
37. Gatson, J. W., Barillas, J., Hynan, L. S., Diaz-Arrastia, R., Wolf, S. E., and Minei, J. P. (2014). Detection of neurofilament-H in serum as a diagnostic tool to predict injury severity in patients who have suffered mild traumatic brain injury. J. Neurosurg. 121, 1232-1238. doi: 10.3171/2014.7.JNS132474
38. Gitler, D., and Spira, M. E. (1998). Real time imaging of calcium-induced localized proteolytic activity after axotomy and its relation to growth cone formation. Neuron 20, 1123-1135. doi: 10.1016/s0896-6273(00)80494-8
39. Greer, J. E., Hånell, A., McGinn, M. J., and Povlishock, J. T. (2013). Mild traumatic brain injury in the mouse induces axotomy primarily within the axon initial segment. Acta Neuropathol. 126, 59-74. doi: 10.1007/s00401-013-1119-4
40. Gupta, R. K., and Przekwas, A. (2013). Mathematical models of blast-induced TBI: current status, challenges and prospects. Front. Neurol. 4:59. doi: 10.3389/fneur.2013.00059
41. Gyorgy, A., Ling, G., Wingo, D., Walker, J., Tong, L., Parks, S., et al. (2011). Time-dependent changes in serum biomarker levels after blast traumatic brain injury. J. Neurotrauma 28, 1121-1126. doi: 10.1089/neu.2010.1561
42. Hayakawa, K., Okazaki, R., Ishii, K., Ueno, T., Izawa, N., Tanaka, Y., et al. (2012). Phosphorylated neurofilament subunit NF-H as a biomarker for evaluating the severity of spinal cord injury patients, a pilot study. Spinal Cord 50, 493-496. doi: 10.1038/sc.2011.184
43. He, X. S., Xiang, Z., Zhou, F., Fu, L. A., and Shuang, W. (2004). Calcium overloading in traumatic axonal injury by lateral head rotation: a morphological evidence in rat model. J. Clin. Neurosci. 11, 402-407. doi: 10.1016/j.jocn.2004.01.001
44. Hirokawa, N., and Takeda, S. (1998). Gene targeting studies begin to reveal the function of neurofilament proteins.J. Cell Biol. 143, 1-4. doi: 10.1083/jcb.143.1.1
45. Hollis, E. R. 2nd, Jamshidi, P., Low, K., Blesch, A., and Tuszynski, M. H. (2009). Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation. Proc. Natl. Acad. Sci. U S A 106, 7215-7220. doi: 10.1073/pnas.0810624106
46. Hosie, K. A., King, A. E., Blizzard, C. A., Vickers, J. C., and Dickson, T. C. (2012). Chronic excitotoxin-induced axon degeneration in a compartmented neuronal culture model. ASN Neuro 4:e00076. doi: 10.1042/an20110031
47. Hou, P. F., Liu, Z. H., Li, N., Cheng, W. J., and Guo, S. W. (2014). Knockdown of STIM1 improves neuronal survival after traumatic neuronal injury through regulating mGluR1-dependent Ca signaling in mouse cortical neurons. Cell. Mol. Neurobiol. doi: 10.1007/s10571-014-0123-0. [Epub ahead of print].
48. Huh, J. W., Laurer, H. L., Raghupathi, R., Helfaer, M. A., and Saatman, K. E. (2002). Rapid loss and partial recovery of neurofilament immunostaining following focal brain injury in mice. Exp. Neurol. 175, 198-208. doi: 10.1006/exnr.2002.7880
49. Ilvesmäki, T., Luoto, T. M., Hakulinen, U., Brander, A., Ryymin, P., Eskola, H., et al. (2014). Acute mild traumatic brain injury is not associated with white matter change on diffusion tensor imaging. Brain 137, 1876-1882. doi: 10.1093/brain/awu095
50. Jacomy, H., Zhu, Q., Couillard-Després, S., Beaulieu, J. M., and Julien, J.-P. (1999). Disruption of type IV intermediate filament network in mice lacking the neurofilament medium and heavy subunits. J. Neurochem. 73, 972-984. doi: 10.1046/j.1471-4159.1999.0730972.x
51. Jaffe, H., Veeranna, Shetty, K. T., and Pant, H. C. (1998). Characterization of the phosphorylation sites of human high molecular weight neurofilament protein by electrospray ionization tandem mass spectrometry and database searching. Biochemistry 37, 3931-3940. doi: 10.1021/bi972518u
52. Johnson, V. E., Stewart, W., and Smith, D. H. (2013). Axonal pathology in traumatic brain injury. Exp. Neurol. 246, 35-43. doi: 10.1016/j.expneurol.2012.01.013
53. Kallakuri, S., Li, Y., Zhou, R., Bandaru, S., Zakaria, N., Zhang, L., et al. (2012). Impaired axoplasmic transport is the dominant injury induced by an impact acceleration injury device: an analysis of traumatic axonal injury in pyramidal tract and corpus callosum of rats. Brain Res. 1452, 29-38. doi: 10.1016/j.brainres.2012.02.065
54. Kamber, D., Erez, H., and Spira, M. E. (2009). Local calcium-dependent mechanisms determine whether a cut axonal end assembles a retarded endbulb or competent growth cone. Exp. Neurol. 219, 112-125. doi: 10.1016/j.expneurol.2009.05.004
55. Kaplan, M. P., Chin, S. S., Fliegner, K. H., and Liem, R. K. (1990). Alpha-internexin, a novel neuronal intermediate filament protein, precedes the low molecular weight neurofilament protein (NF-L) in the developing rat brain. J. Neurosci. 10, 2735-2748.
56. Karr, J. E., Areshenkoff, C. N., and Garcia-Barrera, M. A. (2014). The neuropsychological outcomes of concussion: a systematic review of meta-analyses on the cognitive sequelae of mild traumatic brain injury. Neuropsychology 28, 321-336. doi: 10.1037/neu0000037
57. Kelley, B. J., Farkas, O., Lifshitz, J., and Povlishock, J. T. (2006). Traumatic axonal injury in the perisomatic domain triggers ultrarapid secondary axotomy and Wallerian degeneration. Exp. Neurol. 198, 350-360. doi: 10.1016/j.expneurol.2005.12.017
58. Kilinc, D., Gallo, G., and Barbee, K. A. (2009). Mechanical membrane injury induces axonal beading through localized activation of calpain. Exp. Neurol. 219, 553-561. doi: 10.1016/j.expneurol.2009.07.014
59. King, A. E., Dickson, T. C., Blizzard, C. A., Foster, S. S., Chung, R. S., West, A. K., et al. (2007). Excitotoxicity mediated by non-NMDA receptors causes distal axonopathy in long-term cultured spinal motor neurons. Eur. J. Neurosci. 26, 2151-2159. doi: 10.1111/j.1460-9568.2007.05845.x
60. King, A. E., Southam, K. A., Dittman, J., and Vickers, J. C. (2013). Excitotoxin-induced caspase-3 activation and microtubule disintegration in axons is inhibited by taxol. Acta Neuropathol. Commun. 1:59. doi: 10.1186/2051-5960-1-59
61. Kirkcaldie, M. T., Dickson, T. C., King, C. E., Grasby, D., Riederer, B. M., and Vickers, J. C. (2002). Neurofilament triplet proteins are restricted to a subset of neurons in the rat netocortex. J. Chem. Neuroanat. 24, 163-171. doi: 10.1016/s0891-0618(02)00043-1
62. Knoferle, J., Koch, J. C., Ostendorf, T., Michel, U., Planchamp, V., Vutova, P., et al. (2010). Mechanisms of acute axonal degeneration in the optic nerve in vivo. Proc. Natl. Acad. Sci. U S A 107, 6064-6069. doi: 10.1073/pnas.0909794107
63. Lariviere, R. C., and Julien, J. P. (2004). Functions of intermediate filaments in neuronal development and disease.J. Neurobiol. 58, 131-148. doi: 10.1002/neu.10270
64. Lee, S., Pant, H. C., and Shea, T. B. (2014). Divergent and convergent roles for kinases and phosphatases in neurofilament dynamics. J. Cell Sci. 127, 4064-4077. doi: 10.1242/jcs.153346
65. Lee, M. K., Xu, Z., Wong, P. C., and Cleveland, D. W. (1993). Neurofilaments are obligate heteropolymers in vivo. J. Cell Biol. 122, 1337-1350. doi: 10.1083/jcb.122.6.1337
66. Li, J., Li, X. Y., Feng, D. F., and Pan, D. C. (2010). Biomarkers associated with diffuse traumatic axonal injury: exploring pathogenesis, early diagnosis and prognosis. J. Trauma 69, 1610-1618. doi: 10.1097/TA.0b013e3181f5a9ed
67. Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I., and Schrieber, S. L. (1991). Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell 66, 807-815. doi: 10.1016/0092-8674(91)90124-h
68. Liu, Q., Xie, F., Siedlak, S. L., Nunomura, A., Honda, K., Moreira, P. I., et al. (2004). Neurofilament proteins in neurodegenerative diseases. Cell. Mol. Life Sci. 61, 3057-3075. doi: 10.1007/s00018-004-4268-8
69. Liu, S., Yin, F., Zhang, J., and Qian, Y. (2014). The role of calpains in traumatic brain injury. Brain Inj. 28, 133-137. doi: 10.3109/02699052.2013.860479
70. Ma, M. (2013). Role of calpains in the injury-induced dysfunction and degeneration of the mammalian axon.Neurobiol. Dis. 60, 61-79. doi: 10.1016/j.nbd.2013.08.010
71. Ma, M., Shofer, F. S., and Neumar, R. W. (2012). Calpastatin overexpression protects axonal transport in an in vivo model of traumatic axonal injury. J. Neurotrauma 29, 2555-2563. doi: 10.1089/neu.2012.2473
72. Maas, A. I., Stocchetti, N., and Bullock, R. (2008). Moderate and severe traumatic brain injury in adults. Lancet Neurol. 7, 728-741. doi: 10.1016/s1474-4422(08)70164-9
73. Marmarou, C. R., and Povlishock, J. T. (2006). Administration of the immunophilin ligand FK506 differentially attenuates neurofilament compaction and impaired axonal transport in injured axons following diffuse traumatic brain injury. Exp. Neurol. 197, 353-362. doi: 10.1016/j.expneurol.2005.10.003
74. Matsukawa, H., Shinoda, M., Fujii, M., Takahashi, O., Yamamoto, D., Murakata, A., et al. (2011). Genu of corpus callosum as a prognostic factor in diffuse axonal injury. J. Neurosurg. 115, 1019-1024. doi: 10.3171/2011.6.JNS11513
75. McKee, A. C., Daneshvar, D. H., Alvarez, V. E., and Stein, T. D. (2014). The neuropathology of sport. Acta Neuropathol. 127, 29-51. doi: 10.1007/s00401-013-1230-6
76. Meythaler, J. M., Peduzzi, J. D., Eleftheriou, E., and Novack, T. A. (2001). Current concepts: diffuse axonal injury-associated traumatic brain injury. Arch. Phys. Med. Rehabil. 82, 1461-1471. doi: 10.1053/apmr.2001.25137
77. Millecamps, S., Gowing, G., Corti, O., Mallet, J., and Julien, J. P. (2007). Conditional NF-L transgene expression in mice for in vivo analysis of turnover and transport rate of neurofilaments. J. Neurosci. 27, 4947-4956. doi: 10.1523/jneurosci.5299-06.2007
78. Monsma, P. C., Li, Y., Fenn, J. D., Jung, P., and Brown, A. (2014). Local regulation of neurofilament transport by myelinating cells. J. Neurosci. 34, 2979-2988. doi: 10.1523/JNEUROSCI.4502-13.2014
79. Mori, T., Wang, X., Jung, J. C., Sumii, T., Singhal, A. B., Fini, M. E., et al. (2002). Mitogen-activated protein kinase inhibition in traumatic brain injury: in vitro and in vivo effects. J. Cereb. Blood Flow Metab. 22, 444-452. doi: 10.1097/00004647-200204000-00008
80. Nakamura, Y., Hashimoto, R., Kashiwagi, Y., Aimoto, S., Fukusho, E., Matsumoto, N., et al. (2000). Major phosphorylation site (Ser55) of neurofilament L by cyclic AMP-dependent protein kinase in rat primary neuronal culture. J. Neurochem. 74, 949-959. doi: 10.1046/j.1471-4159.2000.0740949.x
81. Neary, J. T. (2005). Protein kinase signaling cascades in CNS trauma. IUBMB Life 57, 711-718. doi: 10.1080/15216540500319143
82. Neselius, S., Brisby, H., Granholm, F., Zetterberg, H., and Blennow, K. (2014). Monitoring concussion in a knocked-out boxer by CSF biomarker analysis. Knee Surg. Sports Traumatol. Arthrosc. doi: 10.1007/s00167-014-3066-6. [Epub ahead of print].
83. Nixon, R. A. (1998). The slow axonal transport of cytoskeletal proteins. Curr. Opin. Cell Biol. 10, 87-92. doi: 10.1016/s0955-0674(98)80090-2
84. Nixon, R. A., Paskevich, P. A., Sihag, R. K., and Thayer, C. Y. (1994). Phosphorylation on carboxyl terminus domains of neurofilament proteins in retinal ganglion cell neurons in vivo: influences on regional neurofilament accumulation, interneurofilament spacing and axon caliber. J. Cell Biol. 126, 1031-1046. doi: 10.1083/jcb.126.4.1031
85. Nixon, R. A., and Yuan, A. E. (2011). Cytoskeleton of the Nervous System. New York: Springer.
86. Okonkwo, D. O., Pettus, E. H., Moroi, J., and Povlishock, J. (1998). Alteration of the neurofilament sidearm and its relation to neurofilament compaction ocurring with traumatic axonal injury. Brain Res. 784, 1-6. doi: 10.1016/s0006-8993(97)01075-5
87. Okonkwo, D. O., and Povlishock, J. T. (1999). An intrathecal bolus of cyclosporin A before injury preserves mitochondrial integrity and attenuates axonal disruption in traumatic brain injury. J. Cereb. Blood Flow Metab.19, 443-451. doi: 10.1097/00004647-199904000-00010
88. Paulussen, M., Jacobs, S., Van Der Gucht, E., Hof, P. R., and Arckens, L. (2011). Cytoarchitecture of the mouse neocortex revealed by the low-molecular-weight neurofilament protein subunit. Brain Struct. Funct. 216, 183-199. doi: 10.1007/s00429-011-0311-3
89. Paxinos, G., Watson, C. R., Carrive, P., Kirkcaldie, M. T., and Ashwell, K. W. S. (2009). Chemoarchitectonic Atlas of the Rat Brain. San Diego: Academic Press.
90. Peng, T. I., and Jou, M. J. (2010). Oxidative stress caused by mitochondrial calcium overload. Ann. N Y Acad. Sci.1201, 183-188. doi: 10.1111/j.1749-6632.2010.05634.x
91. Perrot, R., Berges, R., Bocquet, A., and Eyer, J. (2008). Review of the multiple aspects of neurofilament functions and their possible contribution to neurodegeneration. Mol. Neurobiol. 38, 27-65. doi: 10.1007/s12035-008-8033-0
92. Petzold, A. (2005). Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss. J. Neurol. Sci. 233, 183-198. doi: 10.1016/j.jns.2005.03.015
93. Povlishock, J. T., and Christman, C. W. (1995). The pathobiology of traumatically induced axonal injury in animals and humans: a review of current thoughts. J. Neurotrauma 12, 555-564. doi: 10.1089/neu.1995.12.555
94. Povlishock, J. T., Marmarou, A., McIntosh, T., Trojanowski, J. Q., and Moroi, J. (1997). Impact acceleration injury in the rat: evidence for focal axolemmal change and related neurofilament sidearm alteration. J. Neuropathol. Exp. Neurol. 56, 347-359. doi: 10.1097/00005072-199704000-00003
95. Prahlad, V., Helfand, B. T., Langford, G. M., Vale, R. D., and Goldman, R. D. (2000). Fast transport of neurofilament protein along microtubules in squid axoplasm. J. Cell Sci. 113(Pt. 22), 3939-3946.
96. Prins, M., Greco, T., Alexander, D., and Giza, C. C. (2013). The pathophysiology of traumatic brain injury at a glance. Dis. Model. Mech. 6, 1307-1315. doi: 10.1242/dmm.011585
97. Rao, M. V., Engle, L. J., Mohan, P. S., Yuan, A., Qiu, D., Cataldo, A., et al. (2002). Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density. J. Cell Sci.159, 279-290. doi: 10.1083/jcb.200205062
98. Roots, B. I. (1983). Neurofilament accumulation induced in synapses by leupeptin. Science 221, 971-972. doi: 10.1126/science.6192501
99. Roskoski, R. Jr. (2012). ERK1/2 MAP kinases: structure, function and regulation. Pharmacol. Res. 66, 105-143. doi: 10.1016/j.phrs.2012.04.005
100. Roy, S., Coffee, P., Smith, G., Liem, R. K., Brady, S. T., and Black, M. M. (2000). Neurofilaments are transported rapidly but intermittently in axons: implications for slow axonal transport. J. Neurosci. 20, 6849-6861.
101. Saatman, K. E., Abai, B., Grosvenor, A., Vorwerk, C. K., Smith, D. H., and Meaney, D. F. (2003). Traumatic axonal injury results in biphasic calpain activation and retrograde transport impairment in mice. J. Cereb. Blood Flow Metab. 23, 34-42. doi: 10.1097/00004647-200301000-00004
102. Saatman, K. E., Creed, J., and Raghupathi, R. (2010). Calpain as a therapeutic target in traumatic brain injury.Neurotherapeutics 7, 31-42. doi: 10.1016/j.nurt.2009.11.002
103. Saatman, K. E., Serbest, G., and Burkhardt, M. F. (2009). Axonal Damage due to Traumatic Brain Injury. New York: Springer Publishing.
104. Schumacher, P. A., Eubanks, J. H., and Fehlings, M. G. (1999). Increased calpain I-mediated proteolysis and preferential loss of dephosphorylated NF200, following traumatic spinal cord injury. Neuroscience 91, 733-744. doi: 10.1016/s0306-4522(98)00552-1
105. Sengul, G., Watson, C. R., Tanaka, I., and Paxinos, G. (2013). Atlas of the Spinal Cord: Mouse, Rat, Rhesus, Marmoset, and Human. San Diego: Academic Press.
106. Shea, T. B., and Chan, W. K. (2008). Regulation of neurofilament dynamics by phosphorylation. Eur. J. Neurosci.27, 1893-1901. doi: 10.1111/j.1460-9568.2008.06165.x
107. Siman, R., Toraskar, N., Dang, A., McNeil, E., McGarvey, M., Plaum, J., et al. (2009). A panel of neuron-enriched proteins as markers for traumatic brain injury in humans. J. Neurotrauma 26, 1867-1877. doi: 10.1089/neu.2009.0882
108. Skandsen, T., Kvistad, K. A., Solheim, O., Strand, I. H., Folvik, M., and Vik, A. (2010). Prevalence and impact of diffuse axonal injury in patients with moderate and severe head injury: a cohort study of early magnetic resonance imaging findings and 1-year outcome. J. Neurosurg. 113, 556-563. doi: 10.3171/2009.9.jns09626
109. Smith, D. H., Hicks, R., and Povlishock, J. T. (2013). Therapy development for diffuse axonal injury. J. Neurotrauma 30, 307-323. doi: 10.1089/neu.2012.2825
110. Smith, D. H., and Meaney, D. F. (2000). Axonal damage in traumatic brain injury. Neuroscientist 6, 483-495. doi: 10.1177/107385840000600611
111. Smith, D. H., Nonaka, M., Miller, R., Leoni, M., Chen, X. H., Alsop, D., et al. (2000). Immediate coma following inertial brain injury dependent on axonal damage in the brainstem. J. Neurosurg. 93, 315-322. doi: 10.3171/jns.2000.93.2.0315
112. Smith, D. H., Uryu, K., Saatman, K. E., Trojanowski, J. Q., and Mcintosh, T. K. (2003). Protein accumulation in traumatic brain injury. Neuromolecular Med. 4, 59-72. doi: 10.1385/nmm:4:1-2:59
113. Smith, D. H., Wolf, J. A., Lusardi, T. A., Lee, V. M., and Meaney, D. F. (1999). High tolerance and delayed elastic response of cultured axons to dynamic stretch injury. J. Neurosci. 19, 4263-4269.
114. Spain, A., Daumas, S., Lifshitz, J., Rhodes, J., Andrews, P. J., Horsburgh, K., et al. (2010). Mild fluid percussion injury in mice produces evolving selective axonal pathology and cognitive deficits relevant to human brain injury.J. Neurotrauma 27, 1429-1438. doi: 10.1089/neu.2010.1288
115. Staal, J. A., Dickson, T. C., Chung, R. S., and Vickers, J. C. (2007). Cyclosporin-A treatment attenuates delayed cytoskeletal alterations and secondary axotomy following mild axonal stretch injury. Dev. Neurobiol. 67, 1831-1842. doi: 10.1002/dneu.20552
116. Staal, J. A., Dickson, T. C., Gasperini, R., Liu, Y., Foa, L., and Vickers, J. C. (2010). Initial calcium release from intracellular stores followed by calcium dysregulation is linked to secondary axotomy following transient axonal stretch injury. J. Neurochem. 112, 1147-1155. doi: 10.1111/j.1471-4159.2009.06531.x
117. Staal, J. A., and Vickers, J. C. (2011). Selective vulnerability of non-myelinated axons to stretch injury in an in vitro co-culture system. J. Neurotrauma 28, 841-847. doi: 10.1089/neu.2010.1658
118. Stevenson, W., Chang, R., and Gebremichael, Y. (2011). Phosphorylation-mediated conformational changes in the mouse neurofilament architecture: insight from a neurofilament brush model. J. Mol. Biol. 405, 1101-1118. doi: 10.1016/j.jmb.2010.11.022
119. Stirling, D. P., Cummins, K., Wayne Chen, S. R., and Stys, P. (2014). Axoplasmic reticulum Ca(2+) release causes secondary degeneration of spinal axons. Ann. Neurol. 75, 220-229. doi: 10.1002/ana.24099
120. Stone, J. R., Okonkwo, D. O., Dialo, A. O., Rubin, D. G., Mutlu, L. K., Povlishock, J. T., et al. (2004). Impaired axonal transport and altered axolemmal permeability occur in distinct populations of damaged axons following traumatic brain injury. Exp. Neurol. 190, 59-69. doi: 10.1016/j.expneurol.2004.05.022
121. Stone, J. R., Singleton, R. H., and Povlishock, J. T. (2001). Intra-axonal neurofilament compaction does not evoke local axonal swelling in all traumatically injured axons. Exp. Neurol. 172, 320-331. doi: 10.1006/exnr.2001.7818
122. Suehiro, E., and Povlishock, J. T. (2001). Exacerbation of traumatically induced axonal injury by rapid posthypothermic rewarming and attenuation of axonal change by cyclosporin A. J. Neurosurg. 94, 493-498. doi: 10.3171/jns.2001.94.3.0493
123. Tang-Schomer, M. D., Johnson, V. E., Baas, P. W., Stewart, W., and Smith, D. H. (2012). Partial interruption of axonal transport due to microtubule breakage accounts for the formation of periodic varicosities after traumatic axonal injury. Exp. Neurol. 233, 364-372. doi: 10.1016/j.expneurol.2011.10.030
124. Tang-Schomer, M. D., Patel, A. R., Baas, P. W., and Smith, D. H. (2010). Mechanical breaking of microtubules in axons during dynamic stretch injury underlies delayed elasticity, microtubule disassembly and axon degeneration.FASEB J. 24, 1401-1410. doi: 10.1096/fj.09-142844
125. Tisdall, M., and Petzold, A. (2012). Comment on "Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model". Sci. Transl. Med. 4:157le158. doi: 10.1126/scitranslmed.3004403
126. Veeranna, Amin, N. D., Ahn, N. G., Jaffe, H., Winters, C. A., Grant, P., et al. (1998). Mitogen-activated protein kinases (Erk1,2) phosphorylate Lys-Ser-Pro (KSP) repeats in neurofilament proteins NF-H and NF-M. J. Neurosci.18, 4008-4021.
127. Wang, J., Hamm, R. J., and Povlishock, J. T. (2011). Traumatic axonal injury in the optic nerve: evidence for axonal swelling, disconnection, dieback and reorganization. J. Neurotrauma 28, 1185-1198. doi: 10.1089/neu.2011.1756
128. Wolf, J. A., Stys, P. K., Lusardi, T., Meaney, D., and Smith, D. H. (2001). Traumatic axonal injury induces calcium influx modulated by tetrodotoxin-sensitive sodium channels. J. Neurosci. 21, 1923-1930.
129. Wu, Y. J., Tang, Y. F., Xiao, Z. C., Bao, Z. M., and He, B. P. (2008). NG2 cells response to axonal alteration in the spinal cord white matter in mice with genetic disruption of neurofilament light subunit expression. Mol. Neurodegener. 3:18. doi: 10.1186/1750-1326-3-18
130. Xiong, S., Mu, T., Wang, G., and Jiang, X. (2014). Mitochondria-mediated apoptosis in mammals. Protein Cell 5, 737-749. doi: 10.1007/s13238-014-0089-1
131. Yin, X. H., Crawford, T. O., Griffin, J. W., Tu, P. H., Lee, V. M. Y., Li, C. M., et al. (1998). Myelin-associated glycoprotein is a myelin signal that modulates the caliber of myelinated axons. J. Neurosci. 18, 1953-1962.
132. Yokobori, S., Hosein, K., Burks, S., Sharma, I., Gajavelli, S., and Bullock, R. (2013). Biomarkers for the clinical differential diagnosis in traumatic brain injury-a systematic review. CNS Neurosci. Ther. 19, 556-565. doi: 10.1111/cns.12127
133. Yu, C. G., Yezierski, R. P., Joshi, A., Raza, K., Li, Y., and Geddes, J. W. (2010). Involvement of ERK2 in traumatic spinal cord injury. J. Neurochem. 113, 131-142. doi: 10.1111/j.1471-4159.2010.06579.x
134. Yuan, A., Rao, M. V., Sasaki, T., Chen, Y., Kumar, A., Veeranna, et al. (2006). Alpha-internexin is structurally and functionally associated with the neurofilament triplet proteins in the mature CNS. J. Neurosci. 26, 10006-10019. doi: 10.1523/jneurosci.2580-06.2006
135. Yuan, A., Rao, M. V., Veeranna, and Nixon, R. A. (2012). Neurofilaments at a glance. J. Cell Sci. 125(Pt. 14), 3257-3263. doi: 10.1242/jcs.104729
136. Yuan, A., Sasaki, T., Rao, M. V., Kumar, A., Kanumuri, V., Dunlop, D. S., et al. (2009). Neurofilaments form a highly stable stationary cytoskeleton after reaching a critical level in axons. J. Neurosci. 29, 11316-11329. doi: 10.1523/jneurosci.1942-09.2009
137. Zheng, Y. L., Li, B. S., and Veeranna, Pant, H. C. (2003). Phosphorylation of the head domain of neurofilament protein (NF-M): a factor regulating topographic phosphorylation of NF-M tail domain KSP sites in neurons. J. Biol. Chem. 278, 24026-24032. doi: 10.1074/jbc.m303079200
138. Žurek, J., Bartlová, L., and Fedora, M. (2011). Hyperphosphorylated neurofilament NF-H as a predictor of mortality after brain injury in children. Brain Inj. 25, 221-226. doi: 10.3109/02699052.2010.541895
139. Žurek, J., and Fedora, M. (2012). The usefulness of S100B, NSE, GFAP, NF-H, secretagogin and Hsp70 as a predictive biomarker of outcome in children with traumatic brain injury. Acta Neurochir. (Wien) 154, 93-103; discussion 103. doi: 10.1007/s00701-011-1175-2