Nuclear Factor-kappaB Activation in Axons and Schwann Cells in Experimental Sciatic Nerve Injury and Its Role in Modulating Axon Regeneration: Studies with Etanercept

Overview

Journal J Neuropathol Exp Neurol

Publisher Oxford University Press

Specialties Neurology
Pathology

Date 2009 May 22

PMID 19458540

Citations 17

Authors

Darrell Smith

Christopher Tweed

Paul Fernyhough

Gordon W Glazner

Affiliations

Soon will be listed here.

Abstract

Early inflammatory events may inhibit functional recovery after injury in both the peripheral and central nervous systems. We investigated the role of the inflammatory tumor necrosis factor/nuclear factor-kappaB (NF-kappaB) axis on events subsequent to sciatic nerve crush injury in adult rats. Electrophoretic mobility shift assays revealed that within 6 hours after crush, NF-kappaB DNA-binding activity increased significantly in a 1-cm section around the crush site. By immunofluorescence staining, there was increased nuclear localization of the NF-kappaB subunits p50 but not p65 or c-Rel in Schwann cells but no obvious inflammatory cell infiltration. In rats injected subcutaneously with etanercept, a tumor necrosis factor receptor chimera that binds free cytokine, the injury-induced rise in NF-kappaB DNA-binding activity was inhibited, and nuclear localization of p50 in Schwann cells was lowered after the injury. Axonal growth 3 days after nerve crush assessed with immunofluorescence for GAP43 demonstrated that the regeneration distance of leading axons from the site of nerve crush was greater in etanercept-treated animals than in saline-treated controls. These data indicate that tumor necrosis factor mediates rapid activation of injury-induced NF-kappaB DNA binding in Schwann cells and that these events are associated with inhibition of postinjury axonal sprouting.

Citing Articles

Limited Nerve Regeneration across Acellular Nerve Allografts (ANAs) Coincides with Changes in Blood Vessel Morphology and the Development of a Pro-Inflammatory Microenvironment.

Acevedo Cintron J, Hunter D, Schellhardt L, Pan D, Mackinnon S, Wood M Int J Mol Sci. 2024; 25(12).

PMID: 38928119 PMC: 11204013. DOI: 10.3390/ijms25126413.

The involvement of Neuregulin-1 in the process of facial nerve injury repair through the utilization of dental pulp stem cells.

Yao L, Xu W, Liu L, Xu X, Xi H, Xue B BMC Oral Health. 2024; 24(1):238.

PMID: 38355448 PMC: 10868091. DOI: 10.1186/s12903-024-03953-z.

Gene correlation network analysis to identify regulatory factors in sciatic nerve injury.

Li L, Du X, Ling H, Li Y, Wu X, Jin A J Orthop Surg Res. 2021; 16(1):622.

PMID: 34663380 PMC: 8522103. DOI: 10.1186/s13018-021-02756-0.

Neuroprotective Effect of Wurmb by Suppressing TRPV1 Following Sciatic Nerve Crush Injury in a Rat.

Kang M, Lee G, Choi G, Yoon H, Hyun K Nutrients. 2020; 12(9).

PMID: 32867278 PMC: 7551127. DOI: 10.3390/nu12092618.

Interaction between Schwann cells and other cells during repair of peripheral nerve injury.

Qu W, Zhu Z, Liu J, Song D, Tian H, Chen B Neural Regen Res. 2020; 16(1):93-98.

PMID: 32788452 PMC: 7818858. DOI: 10.4103/1673-5374.286956.

References

Shubayev V, Myers R . Upregulation and interaction of TNFalpha and gelatinases A and B in painful peripheral nerve injury. Brain Res. 2000; 855(1):83-9. DOI: 10.1016/s0006-8993(99)02321-5. View

Rogers J, Mastroeni D, Leonard B, Joyce J, Grover A . Neuroinflammation in Alzheimer's disease and Parkinson's disease: are microglia pathogenic in either disorder?. Int Rev Neurobiol. 2007; 82:235-46. DOI: 10.1016/S0074-7742(07)82012-5. View

Hang C, Chen G, Shi J, Zhang X, Li J . Cortical expression of nuclear factor kappaB after human brain contusion. Brain Res. 2006; 1109(1):14-21. DOI: 10.1016/j.brainres.2006.06.045. View

George A, Buehl A, Sommer C . Wallerian degeneration after crush injury of rat sciatic nerve increases endo- and epineurial tumor necrosis factor-alpha protein. Neurosci Lett. 2004; 372(3):215-9. DOI: 10.1016/j.neulet.2004.09.075. View

Gardiner N, Fernyhough P, Tomlinson D, Mayer U, von der Mark H, Streuli C . Alpha7 integrin mediates neurite outgrowth of distinct populations of adult sensory neurons. Mol Cell Neurosci. 2005; 28(2):229-40. DOI: 10.1016/j.mcn.2004.08.017. View

Huang T, Sayers N, Fernyhough P, Verkhratsky A . Diabetes-induced alterations in calcium homeostasis in sensory neurones of streptozotocin-diabetic rats are restricted to lumbar ganglia and are prevented by neurotrophin-3. Diabetologia. 2002; 45(4):560-70. DOI: 10.1007/s00125-002-0785-x. View

Delcroix J, Averill S, Fernandes K, Tomlinson D, Priestley J, Fernyhough P . Axonal transport of activating transcription factor-2 is modulated by nerve growth factor in nociceptive neurons. J Neurosci. 1999; 19(18):RC24. PMC: 6782468. View

Rojo L, Fernandez J, Maccioni A, Jimenez J, Maccioni R . Neuroinflammation: implications for the pathogenesis and molecular diagnosis of Alzheimer's disease. Arch Med Res. 2007; 39(1):1-16. DOI: 10.1016/j.arcmed.2007.10.001. View

Delcroix J, Tomlinson D, Fernyhough P . Diabetes and axotomy-induced deficits in retrograde axonal transport of nerve growth factor correlate with decreased levels of p75LNTR protein in lumbar dorsal root ganglia. Brain Res Mol Brain Res. 1998; 51(1-2):82-90. DOI: 10.1016/s0169-328x(97)00215-5. View

10.

Fernyhough P, Smith D, Schapansky J, Van der Ploeg R, Gardiner N, Tweed C . Activation of nuclear factor-kappaB via endogenous tumor necrosis factor alpha regulates survival of axotomized adult sensory neurons. J Neurosci. 2005; 25(7):1682-90. PMC: 6725919. DOI: 10.1523/JNEUROSCI.3127-04.2005. View

11.

Wood J . Regulation of NF-kappa B activity in rat dorsal root ganglia and PC12 cells by tumour necrosis factor and nerve growth factor. Neurosci Lett. 1995; 192(1):41-4. DOI: 10.1016/0304-3940(95)11603-t. View

12.

Murwani R, Armati P . Peripheral nerve fibroblasts as a source of IL-6, TNFalpha and IL-1 and their modulation by IFNgamma. J Neurol Sci. 1999; 161(2):99-109. DOI: 10.1016/s0022-510x(98)00271-8. View

13.

Meunier A, Latremoliere A, Dominguez E, Mauborgne A, Philippe S, Hamon M . Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat. Mol Ther. 2007; 15(4):687-97. DOI: 10.1038/sj.mt.6300107. View

14.

Politi C, Del Turco D, Sie J, Golinski P, Tegeder I, Deller T . Accumulation of phosphorylated I kappaB alpha and activated IKK in nodes of Ranvier. Neuropathol Appl Neurobiol. 2007; 34(3):357-65. DOI: 10.1111/j.1365-2990.2007.00901.x. View

15.

Song X, Zhou F, Zhong J, Wu L, Zhou X . Knockout of p75(NTR) impairs re-myelination of injured sciatic nerve in mice. J Neurochem. 2005; 96(3):833-42. DOI: 10.1111/j.1471-4159.2005.03564.x. View

16.

Subang M, Richardson P . Influence of injury and cytokines on synthesis of monocyte chemoattractant protein-1 mRNA in peripheral nervous tissue. Eur J Neurosci. 2001; 13(3):521-8. DOI: 10.1046/j.1460-9568.2001.01425.x. View

17.

Shamash S, Reichert F, Rotshenker S . The cytokine network of Wallerian degeneration: tumor necrosis factor-alpha, interleukin-1alpha, and interleukin-1beta. J Neurosci. 2002; 22(8):3052-60. PMC: 6757534. DOI: 20026249. View

18.

Tracey D, Klareskog L, Sasso E, Salfeld J, Tak P . Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2007; 117(2):244-79. DOI: 10.1016/j.pharmthera.2007.10.001. View

19.

Pollock G, Pennypacker K, Memet S, Israel A, Saporta S . Activation of NF-kappaB in the mouse spinal cord following sciatic nerve transection. Exp Brain Res. 2005; 165(4):470-7. DOI: 10.1007/s00221-005-2318-6. View

20.

Makwana M, Raivich G . Molecular mechanisms in successful peripheral regeneration. FEBS J. 2005; 272(11):2628-38. DOI: 10.1111/j.1742-4658.2005.04699.x. View