Microglia activation as a biomarker for traumatic brain injury

Frontiers in Neurology

Volumn 4 MAR, Issue , 2013, Pages

  Hernandez Ontiveros, Diana G ^a   Tajiri, Naoki ^a   Acosta, Sandra ^a   Giunta, Brian ^a,b   Tan, Jun ^a,b   Borlongan, Cesar V ^a  

^a UNIVERSITY OF SOUTH FLORIDA   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Anti inflammatory therapy; Brain imaging; Head trauma; Inflammatory response; Microglia; Secondary cell death

Indexed keywords

APOCYNIN; BIOLOGICAL MARKER; BRAIN DERIVED NEUROTROPHIC FACTOR; CHEMOKINE RECEPTOR CX3CR1; FRACTALKINE; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 4; INTERLEUKIN 6; INTERLEUKIN 8; LYMPHOTOXIN; MINOCYCLINE; NERVE GROWTH FACTOR; PLACEBO; S NITROSOGLUTATHIONE; TUMOR NECROSIS FACTOR ALPHA;

ARTICLE; CELL ACTIVATION; CELL ACTIVITY; CELL DEATH; CELL FUNCTION; CELL PHAGOCYTOSIS; CELL SURVIVAL; DISEASE COURSE; HUMAN; IMMUNE RESPONSE; MICROGLIA; MOLECULAR DYNAMICS; NEUROPROTECTION; NONHUMAN; PHAGOCYTE; PROTEIN EXPRESSION; TRAUMATIC BRAIN INJURY; TREATMENT RESPONSE;

EID: 84878804076     PISSN: None     EISSN: 16642295     Source Type: Journal    
DOI: 10.3389/fneur.2013.00030     Document Type: Article

References (102)

1. Akhtar, L. N., Qin, H., Muldowney, M. T., Yanagisawa, L. L., Kutsch, O., Clements, J. E., et al. (2010). Suppressor of cytokine signaling 3 inhibits antiviral IFN-beta signaling to enhance HIV-1 replication in macrophages. J. Immunol. 185, 2393-2404.
2. Bagnato, S., Minafra, L., Bravata, V., Boccagni, C., Sant'Angelo, A., Castiglione, A., et al. (2012). Brain-derived neurotrophic factor (Val66Met) polymorphism does not influence recovery from a post-traumatic vegetative state: a blinded retrospective multi-centric study. J. Neurotrauma 29, 2050-2059.
3. Ben Achour, S., and Pascual, O. (2010). Glia: the many ways to modulate synaptic plasticity. Neurochem. Int. 57, 440-445.
4. Bhaskar, K., Konerth, M., Kokiko-Cochran, O. N., Cardona, A., Ransohoff, R. M., and Lamb, B. T. (2010). Regulation of tau pathology by the microglial fractalkine receptor. Neuron 68, 19-31.
5. Bigford, G. E., Alonso, O. F., Dietrich, D., and Keane, R. W. (2009). A novel protein complex in membrane rafts linking the NR2B glutamate receptor and autophagy is disrupted following traumatic brain injury. J. Neurotrauma 26, 703-720.
6. Bogdanova, Y., and Verfaellie, M. (2012). Cognitive sequelae of blast-induced traumatic brain injury: recovery and rehabilitation. Neuropsychol. Rev. 22, 4-20.
7. Borlongan, C. V. (2011). Bone marrow stem cell mobilization in stroke: a "bonehead" may be good after all! Leukemia 25, 1674-1686.
8. Borlongan, C. V., Glover, L. E., Tajiri, N., Kaneko, Y., and Freeman, T. B. (2011). The great migration of bone marrow-derived stem cells toward the ischemic brain: therapeutic implications for stroke and other neurological disorders. Prog. Neurobiol. 95, 213-228.
9. Bruce-Keller, A. J., Barger, S. W., Moss, N. I., Pham, J. T., Keller, J. N., and Nath, A. (2001). Pro-inflammatory and pro-oxidant properties of the HIV protein Tat in a microglial cell line: attenuation by 17 beta-estradiol. J. Neurochem. 78, 1315-1324.
10. Cao, T., Thomas, T. C., Ziebell, J. M., Pauly, J. R., and Lifshitz, J. (2012). Morphological and genetic activation of microglia after diffuse traumatic brain injury in the rat. Neuroscience. 225, 65-75.
11. Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., et al. (2006). Control of microglial neurotoxicity by the fractalkine receptor. Nat. Neurosci. 9, 917-924.
12. Casha, S., Zygun, D., McGowan, M. D., Bains, I., Yong, V. W., and Hurlbert, R. J. (2012). Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain 135, 1224-1236.
13. Cekic, M., Johnson, S. J., Bhatt, V. H., and Stein, D. G. (2012). Progesterone treatment alters neurotrophin/proneurotrophin balance and receptor expression in rats with traumatic brain injury. Restor. Neurol. Neurosci. 30, 115-126.
14. Chen, T. L. W., Chao, X., Zhang, L., Qu, Y., Huo, J., and Fei, Z. (2011). Salvianolic acid B attenuates brain damage and inflammation after traumatic brain injury in mice. Brain Res. Bull. 84, 163-168.
15. Choi, B. Y., Jang, B. G., Kim, J. H., Lee, B. E., Sohn, M., Song, H. K., et al. (2012). Prevention of traumatic brain injury-induced neuronal death by inhibition of NADPH oxidase activation. Brain Res. 1481, 49-58.
16. Cipriani, R., Villa, P., Chece, G., Lauro, C., Paladini, A., Micotti, E., et al. (2011). CX3CL1 is neuroprotective in permanent focal cerebral ischemia in rodents. J. Neurosci. 31, 16327-16335.
17. Clark, R. S., Bayir, H., Chu, C. T., Alber, S. M., Kochanek, P. M., and Watkins, S. C. (2008). Autophagy is increased in mice after traumatic brain injury and is detectable in human brain after trauma and critical illness. Autophagy 4, 88-90.
18. Colak, T., Cine, N., Bamac, B., Kurtas, O., Ozbek, A., Bicer, U., et al. (2012). Microarray-based gene expression analysis of an animal model for closed head injury. Injury 43, 1264-1270.
19. Combs, C. K., Karlo, J. C., Kao, S. C., and Landreth, G. E. (2001). Beta-amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J. Neurosci. 21, 1179-1188.
20. Coronado, V. G., Xu, L., Basavaraju, S. V., McGuire, L. C., Wald, M. M., Faul, M. D., et al. (2011). Surveillance for traumatic brain injury-related deaths - United States, 1997-2007. MMWR Surveill. Summ. 60, 1-32.
21. Corrigan, J. D., Selassie, A. W., and Orman, J. A. (2010). The epidemiology of traumatic brain injury. J. Head Trauma Rehabil. 25, 72-80.
22. d'Avila, J. C., Lam, T. I., Bingham, D., Shi, J., Won, S. J., Kauppinen, T. M., et al. (2012). Microglial activation induced by brain trauma is suppressed by post-injury treatment with a PARP inhibitor. J. Neuroinflammation 9, 31.
23. Duckworth, J. L., Grimes, J., and Ling, G. S. (2012). Pathophysiology of battlefield associated traumatic brain injury. Pathophysiology. doi:10.1016/j.pathophys.2012.03.001
24. Festoff, B. W., Ameenuddin, S., Arnold, P. M., Wong, A., Santacruz, K. S., and Citron, B. A. (2006). Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease expression early after spinal cord injury. J. Neurochem. 97, 1314-1326.
25. Fiala, M., Lin, J., Ringman, J., Kermani-Arab, V., Tsao, G., Patel, A., et al. (2005). Ineffective phagocytosis of amyloid-beta by macrophages of Alzheimer's disease patients. J. Alzheimers Dis. 7, 255-262. discussion.
26. Forstreuter, F., Lucius, R., and Mentlein, R. (2002). Vascular endothelial growth factor induces chemotaxis and proliferation of microglial cells. J. Neuroimmunol. 132, 93-98.
27. Frei, K., Siepl, C., Groscurth, P., Bodmer, S., Schwerdel, C., and Fontana, A. (1987). Antigen presentation and tumor cytotoxicity by interferon-gamma-treated microglial cells. Eur. J. Immunol. 17, 1271-1278.
28. Frugier, T., Morganti-Kossmann, M. C., O'Reilly, D., and McLean, C. A. (2010). In situ detection of inflammatory mediators in post mortem human brain tissue after traumatic injury. J. Neurotrauma 27, 497-507.
29. Giunta, B., Obregon, D., Velisetty, R., Sanberg, P. R., Borlongan, C. V., and Tan, J. (2012). The immunology of traumatic brain injury: a prime target for Alzheimer's disease prevention. J. Neuroinflammation 9, 185.
30. Goeller, J., Wardlaw, A., Treichler, D., O'Bruba, J., and Weiss, G. (2012). Investigation of cavitation as a possible damage mechanism in blast-induced traumatic brain injury. J. Neurotrauma 29, 1970-1981.
31. Gordon, S., and Taylor, P. R. (2005). Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5, 953-964.
32. Hamada, Y., Ikata, T., Katoh, S., Katoh, K., Niwa, M., Tsutsumishita, Y., et al. (1996). Effects of exogenous transforming growth factor-beta 1 on spinal cord injury in rats. Neurosci. Lett. 203, 97-100.
33. Hanisch, U. K. (2002). Microglia as a source and target of cytokines. Glia 40, 140-155.
34. Hanisch, U. K., and Kettenmann, H. (2007). Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10, 1387-1394.
35. Helmy, A., Antoniades, C. A., Guilfoyle, M. R., Carpenter, K. L., and Hutchinson, P. J. (2012). Principal component analysis of the cytokine and chemokine response to human traumatic brain injury. PLoS ONE 7:e39677. doi:10.1371/journal.pone.0039677
36. Heneka, M. T., Feinstein, D. L., Galea, E., Gleichmann, M., Wullner, U., and Klockgether, T. (1999). Peroxisome proliferator-activated receptor gamma agonists protect cerebellar granule cells from cytokine-induced apoptotic cell death by inhibition of inducible nitric oxide synthase. J. Neuroimmunol. 100, 156-168.
37. Heppner, F. L., Prinz, M., and Aguzzi, A. (2001). Pathogenesis of prion diseases: possible implications of microglial cells. Prog. Brain Res. 132, 737-750.
38. Jacobowitz, D. M., Cole, J. T., McDaniel, D. P., Pollard, H. B., and Watson, W. D. (2012). Microglia activation along the corticospinal tract following traumatic brain injury in the rat: a neuroanatomical study. Brain Res. 1465, 80-89.
39. Jeon, H., Kim, J. H., Lee, W. H., Lee, M. S., and Suk, K. (2012). Plasminogen activator inhibitor type 1 regulates microglial motility and phagocytic activity. J. Neuroinflammation 9, 149.
40. Jin, X., Ishii, H., Bai, Z., Itokazu, T., and Yamashita, T. (2012). Temporal changes in cell marker expression and cellular infiltration in a controlled cortical impact model in adult male C57BL/6 mice. PLoS ONE 7:e41892. doi:10.1371/journal.pone.0041892
41. Kapadia, R., Yi, J. H., and Vemuganti, R. (2008). Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists. Front. Biosci. 13, 1813-1826.
42. Khan, M., Im, Y. B., Shunmugavel, A., Gilg, A. G., Dhindsa, R. K., Singh, A. K., et al. (2009). Administration of S-nitrosoglutathione after traumatic brain injury protects the neurovascular unit and reduces secondary injury in a rat model of controlled cortical impact. J. Neuroinflammation 6, 32.
43. Khan, M., Sakakima, H., Dhammu, T. S., Shunmugavel, A., Im, Y. B., Gilg, A. G., et al. (2011). S-nitrosoglutathione reduces oxidative injury and promotes mechanisms of neurorepair following traumatic brain injury in rats. J. Neuroinflammation 8, 78.
44. Kohman, R. A. (2012). Aging microglia: relevance to cognition and neural plasticity. Methods Mol. Biol. 934, 193-218.
45. Krueger, F., Pardini, M., Huey, E. D., Raymont, V., Solomon, J., Lipsky, R. H., et al. (2011). The role of the Met66 brain-derived neurotrophic factor allele in the recovery of executive functioning after combat-related traumatic brain injury. J. Neurosci. 31, 598-606.
46. Lai, Y., Hickey, R. W., Chen, Y., Bayir, H., Sullivan, M. L., Chu, C. T., et al. (2008). Autophagy is increased after traumatic brain injury in mice and is partially inhibited by the antioxidant gamma-glutamylcysteinyl ethyl ester. J. Cereb. Blood Flow Metab. 28, 540-550.
47. Landis, S. C., Amara, S. G., Asadullah, K., Austin, C. P., Blumenstein, R., Bradley, E. W., et al. (2012). A call for transparent reporting to optimize the predictive value of preclinical research. Nature 490, 187-191.
48. Lee, C. H., Hyun, S. J., Yoon, C. Y., Lim, J. Y., Jahng, T. A., and Kim, K. J. (2012). Neuroprotective effects of sacral epidural neuromodulation following spinal cord injury: an experimental study in rats. J. Korean Neurosurg. Soc. 52, 509-512.
49. Li, G. Z., Zhang, Y., Zhao, J. B., Wu, G. J., Su, X. F., and Hang, C. H. (2011). Expression of myeloid differentiation primary response protein 88 (Myd88) in the cerebral cortex after experimental traumatic brain injury in rats. Brain Res. 1396, 96-104.
50. Liu, C. L., Chen, S., Dietrich, D., and Hu, B. R. (2008). Changes in autophagy after traumatic brain injury. J. Cereb. Blood Flow Metab. 28, 674-683.
51. Lo, E. H. (2008). A new penumbra: transitioning from injury into repair after stroke. Nat. Med. 14, 497-500.
52. Loov, C., Hillered, L., Ebendal, T., and Erlandsson, A. (2012). Engulfing astrocytes protect neurons from contact-induced apoptosis following injury. PLoS ONE 7:e33090. doi:10.1371/journal.pone.0033090
53. Luo, C. L., Li, B. X., Li, Q. Q., Chen, X. P., Sun, Y. X., Bao, H. J., et al. (2011). Autophagy is involved in traumatic brain injury-induced cell death and contributes to functional outcome deficits in mice. Neuroscience 184, 54-63.
54. Ma, H., Yu, B., Kong, L., Zhang, Y., and Shi, Y. (2012). Neural stem cells over-expressing brain-derived neurotrophic factor (BDNF) stimulate synaptic protein expression and promote functional recovery following transplantation in rat model of traumatic brain injury. Neurochem. Res. 37, 69-83.
55. Mannix, R. C., and Whalen, M. J. (2012). Traumatic brain injury, microglia, and beta amyloid. Int. J. Alzheimers Dis. 2012, 608732.
56. Mizuno, T., Kawanokuchi, J., Numata, K., and Suzumura, A. (2003). Production and neuroprotective functions of fractalkine in the central nervous system. Brain Res. 979, 65-70.
57. Mosher, K. I., Andres, R. H., Fukuhara, T., Bieri, G., Hasegawa-Moriyama, M., He, Y., et al. (2012). Neural progenitor cells regulate microglia functions and activity. Nat. Neurosci. 15, 1485-1487.
58. Mosser, D. M. (2003). The many faces of macrophage activation. J. Leukoc. Biol. 73, 209-212.
59. Murphy, R. A., Singer, R. H., Saide, J. D., Pantazis, N. J., Blanchard, M. H., Byron, K. S., et al. (1977). Synthesis and secretion of a high molecular weight form of nerve growth factor by skeletal muscle cells in culture. Proc. Natl. Acad. Sci. U.S.A. 74, 4496-4500.
60. Nagamoto-Combs, K., and Combs, C. K. (2010). Microglial phenotype is regulated by activity of the transcription factor, NFAT (nuclear factor of activated T cells). J. Neurosci. 30, 9641-9646.
61. Nagamoto-Combs, K., McNeal, D. W., Morecraft, R. J., and Combs, C. K. (2007). Prolonged microgliosis in the rhesus monkey central nervous system after traumatic brain injury. J. Neurotrauma 24, 1719-1742.
62. Nagamoto-Combs, K., Morecraft, R. J., Darling, W. G., and Combs, C. K. (2010). Long-term gliosis and molecular changes in the cervical spinal cord of the rhesus monkey after traumatic brain injury. J. Neurotrauma 27, 565-585.
63. Namas, R., Ghuma, A., Hermus, L., Zamora, R., Okonkwo, D. O., Billiar, T. R., et al. (2009). The acute inflammatory response in trauma/hemorrhage and traumatic brain injury: current state and emerging prospects. Libyan J. Med. 4, 97-103.
64. Noda, M., Doi, Y., Liang, J., Kawanokuchi, J., Sonobe, Y., Takeuchi, H., et al. (2011). Fractalkine attenuates excito-neurotoxicity via microglial clearance of damaged neurons and antioxidant enzyme heme oxygenase-1 expression. J. Biol. Chem. 286, 2308-2319.
65. Pabon, M. M., Bachstetter, A. D., Hudson, C. E., Gemma, C., and Bickford, P. C. (2011). CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson's disease. J. Neuroinflammation 8, 9.
66. Pál, G., Vincze, C., Renner, E., Wappler, E. A., Nagy, Z., Lovas, G., et al. (2012). Time course, distribution and cell types of induction of transforming growth factor betas following middle cerebral artery occlusion in the rat brain. PLoS ONE 7:e46731. doi:10.1371/journal.pone.0046731
67. Panek, R. B., and Benveniste, E. N. (1995). Class II MHC gene expression in microglia. Regulation by the cytokines IFN-gamma, TNF-alpha, and TGF-beta. J. Immunol. 154, 2846-2854.
68. Qin, H., Wilson, C. A., Lee, S. J., and Benveniste, E. N. (2006). IFN-beta-induced SOCS-1 negatively regulates CD40 gene expression in macrophages and microglia. FASEB J. 20, 985-987.
69. Ramlackhansingh, A. F., Brooks, D. J., Greenwood, R. J., Bose, S. K., Turkheimer, F. E., Kinnunen, K. M., et al. (2011). Inflammation after trauma: microglial activation and traumatic brain injury. Ann. Neurol. 70, 374-383.
70. Rancan, M., Bye, N., Otto, V. I., Trentz, O., Kossmann, T., Frentzel, S., et al. (2004). The chemokine fractalkine in patients with severe traumatic brain injury and a mouse model of closed head injury. J. Cereb. Blood Flow Metab. 24, 1110-1118.
71. Rostami, E., Krueger, F., Zoubak, S., Dal Monte, O., Raymont, V., Pardini, M., et al. (2011). BDNF polymorphism predicts general intelligence after penetrating traumatic brain injury. PLoS ONE 6:e27389. doi:10.1371/journal.pone.0027389
72. Sawada, M., Suzumura, A., Yamamoto, H., and Marunouchi, T. (1990). Activation and proliferation of the isolated microglia by colony stimulating factor-1 and possible involvement of protein kinase C. Brain Res. 509, 119-124.
73. Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., et al. (2012). Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74, 691-705.
74. Schober, M. E., Block, B., Requena, D. F., Hale, M. A., and Lane, R. H. (2012). Developmental traumatic brain injury decreased brain derived neurotrophic factor expression late after injury. Metab. Brain Dis. 27, 167-173.
75. Shi, W., Nie, D., Jin, G., Chen, W., Xia, L., Wu, X., et al. (2012). BDNF blended chitosan scaffolds for human umbilical cord MSC transplants in traumatic brain injury therapy. Biomaterials 33, 3119-3126.
76. Shojo, H., Kaneko, Y., Mabuchi, T., Kibayashi, K., Adachi, N., and Borlongan, C. V. (2010). Genetic and histologic evidence implicates role of inflammation in traumatic brain injury-induced apoptosis in the rat cerebral cortex following moderate fluid percussion injury. Neuroscience 171, 1273-1282.
77. Smith, D. H., Chen, X. H., Pierce, J. E., Wolf, J. A., Trojanowski, J. Q., Graham, D. I., et al. (1997). Progressive atrophy and neuron death for one year following brain trauma in the rat. J. Neurotrauma 14, 715-727.
78. Stammers, A. T., Liu, J., and Kwon, B. K. (2012). Expression of inflammatory cytokines following acute spinal cord injury in a rodent model. J. Neurosci. Res. 90, 782-790.
79. Streit, W. J., Hurley, S. D., McGraw, T. S., and Semple-Rowland, S. L. (2000). Comparative evaluation of cytokine profiles and reactive gliosis supports a critical role for interleukin-6 in neuron-glia signaling during regeneration. J. Neurosci. Res. 61, 10-20.
80. Suh, H. S., Zhao, M. L., Choi, N., Belbin, T. J., Brosnan, C. F., and Lee, S. C. (2009). TLR3 and TLR4 are innate antiviral immune receptors in human microglia: role of IRF3 in modulating antiviral and inflammatory response in the CNS. Virology 392, 246-259.
81. Suzumura, A., Mezitis, S. G., Gonatas, N. K., and Silberberg, D. H. (1987). MHC antigen expression on bulk isolated macrophage-microglia from newborn mouse brain: induction of Ia antigen expression by gamma-interferon. J. Neuroimmunol. 15, 263-278.
82. Suzumura, A., Sawada, M., Yamamoto, H., and Marunouchi, T. (1990). Effects of colony stimulating factors on isolated microglia in vitro. J. Neuroimmunol. 30, 111-120.
83. Tamashiro, T. T., Dalgard, C. L., and Byrnes, K. R. (2012). Primary microglia isolation from mixed glial cell cultures of neonatal rat brain tissue. J. Vis. Exp. 66, e3814. doi:10.3791/3814
84. Teng, Y. D., Choi, H., Onario, R. C., Zhu, S., Desilets, F. C., Lan, S., et al. (2004). Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury. Proc. Natl. Acad. Sci. U.S.A. 101, 3071-3076.
85. Thiel, A., Radlinska, B. A., Paquette, C., Sidel, M., Soucy, J. P., Schirrmacher, R., et al. (2010). The temporal dynamics of poststroke neuroinflammation: a longitudinal diffusion tensor imaging-guided PET study with 11C-PK11195 in acute subcortical stroke. J. Nucl. Med. 51, 1404-1412.
86. Tisdall, M. M., and Smith, M. (2006). Cerebral microdialysis: research technique or clinical tool. Br. J. Anaesth. 97, 18-25.
87. Town, T., Nikolic, V., and Tan, J. (2005). The microglial "activation" continuum: from innate to adaptive responses. J. Neuroinflammation 2, 24.
88. Tsai, M. C., Chen, W. J., Tsai, M. S., Ching, C. H., and Chuang, J. I. (2011). Melatonin attenuates brain contusion-induced oxidative insult, inactivation of signal transducers and activators of transcription 1, and upregulation of suppressor of cytokine signaling-3 in rats. J. Pineal Res. 51, 233-245.
89. Tyor, W. R., Avgeropoulos, N., Ohlandt, G., and Hogan, E. L. (2002). Treatment of spinal cord impact injury in the rat with transforming growth factor-beta. J. Neurol. Sci. 200, 33-41.
90. Urrea, C., Castellanos, D. A., Sagen, J., Tsoulfas, P., Bramlett, H. M., and Dietrich, W. D. (2007). Widespread cellular proliferation and focal neurogenesis after traumatic brain injury in the rat. Restor. Neurol. Neurosci. 25, 65-76.
91. Venkatesan, C., Chrzaszcz, M., Choi, N., and Wainwright, M. S. (2010). Chronic upregulation of activated microglia immunoreactive for galectin-3/Mac-2 and nerve growth factor following diffuse axonal injury. J. Neuroinflammation 7, 32.
92. Venters, H. D., Dantzer, R., and Kelley, K. W. (2000). A new concept in neurodegeneration: TNFalpha is a silencer of survival signals. Trends Neurosci. 23, 175-180.
93. Voss, E. V., Skuljec, J., Gudi, V., Skripuletz, T., Pul, R., Trebst, C., et al. (2012). Characterisation of microglia during de- and remyelination: can they create a repair promoting environment? Neurobiol. Dis. 45, 519-528.
94. Walker, D. G., Kim, S. U., and McGeer, P. L. (1995). Complement and cytokine gene expression in cultured microglial derived from postmortem human brains. J. Neurosci. Res. 40, 478-493.
95. Williams, K., Bar-Or, A., Ulvestad, E., Olivier, A., Antel, J. P., and Yong, V. W. (1992). Biology of adult human microglia in culture: comparisons with peripheral blood monocytes and astrocytes. J. Neuropathol. Exp. Neurol. 51, 538-549.
96. Wu, J. C., Chen, K. Y., Yu, Y. W., Huang, S. W., Shih, H. M., Chiu, W. T., et al. (2012). Location and level of Etk expression in neurons are associated with varied severity of traumatic brain injury. PLoS ONE 7:e39226. doi:10.1371/journal.pone.0039226
97. Yu, I., Inaji, M., Maeda, J., Okauchi, T., Nariai, T., Ohno, K., et al. (2010). Glial cell-mediated deterioration and repair of the nervous system after traumatic brain injury in a rat model as assessed by positron emission tomography. J. Neurotrauma 27, 1463-1475.
98. Yune, T. Y., Lee, J. Y., Jung, G. Y., Kim, S. J., Jiang, M. H., Kim, Y. C., et al. (2007). Minocycline alleviates death of oligodendrocytes by inhibiting pro-nerve growth factor production in microglia after spinal cord injury. J. Neurosci. 27, 7751-7761.
99. Zhang, Q. G., Laird, M. D., Han, D., Nguyen, K., Scott, E., Dong, Y., et al. (2012). Critical role of NADPH oxidase in neuronal oxidative damage and microglia activation following traumatic brain injury. PLoS ONE 7:e34504. doi:10.1371/journal.pone.0034504
100. Zhang, Y. B., Li, S. X., Chen, X. P., Yang, L., Zhang, Y. G., Liu, R., et al. (2008). Autophagy is activated and might protect neurons from degeneration after traumatic brain injury. Neurosci. Bull. 24, 143-149.
101. Ziebell, J. M., Bye, N., Semple, B. D., Kossmann, T., and Morganti-Kossmann, M. C. (2011). Attenuated neurological deficit, cell death and lesion volume in Fas-mutant mice is associated with altered neuroinflammation following traumatic brain injury. Brain Res. 1414, 94-105.
102. Zujovic, V., Benavides, J., Vige, X., Carter, C., and Taupin, V. (2000). Fractalkine modulates TNF-alpha secretion and neurotoxicity induced by microglial activation. Glia 29, 305-315.