Improving peripheral nerve regeneration: From molecular mechanisms to potential therapeutic targets

Experimental Neurology

Volumn 261, Issue , 2014, Pages 826-835

  Chan, K Ming ^a   Gordon, Tessa ^a,b   Zochodne, Douglas W ^c   Power, Hollie A ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c UNIVERSITY OF CALGARY   (Canada)

Author keywords

Animal studies; Molecular mechanisms; Nerve regeneration; Peripheral nerve injury; Therapeutics

Indexed keywords

ACETYLCYSTEINE; CYCLIC AMP; CYCLIC AMP DEPENDENT PROTEIN KINASE; ERYTHROPOIETIN; FASUDIL; GELDANAMYCIN; IBUPROFEN; LEVACECARNINE; MITOGEN ACTIVATED PROTEIN KINASE; N ACETYLGALACTOSAMINE 4 SULFATASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; RAS PROTEIN; RHO FACTOR; ROLIPRAM; TACROLIMUS; TESTOSTERONE; IMMUNOLOGIC FACTOR;

ANEMIA; AUTOIMMUNE DISEASE; CELL SURVIVAL; DRUG MECHANISM; DRUG TARGETING; GRAFT REJECTION; HUMAN; MOLECULAR BIOLOGY; NERVE CELL; NERVE CELL LESION; NERVE FIBER GROWTH; NERVE REGENERATION; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; PERIPHERAL NERVE INJURY; REINNERVATION; REVIEW; SCIATIC NERVE INJURY; SIGNAL TRANSDUCTION; UPREGULATION; ANIMAL; DISEASE MODEL; DRUG EFFECTS; GENETICS; METABOLISM; PERIPHERAL NERVOUS SYSTEM DISEASES; PHYSIOLOGY;

ANIMALS; CYCLIC AMP; DISEASE MODELS, ANIMAL; HUMANS; IMMUNOLOGIC FACTORS; NERVE REGENERATION; PERIPHERAL NERVOUS SYSTEM DISEASES; PHOSPHATIDYLINOSITOL 3-KINASES; RAS PROTEINS; SIGNAL TRANSDUCTION;

EID: 84908256860     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2014.09.006     Document Type: Review

References (125)

1. Aglah C., Gordon T., Posse de Chaves E.I. cAMP promotes neurite outgrowth and extension through protein kinase A but independently of Erk activation in cultured rat motoneurons. Neuropharmacology 2008, 55:8-17.
2. Al Majed A.A., Neumann C.M., Brushart T.M., Gordon T. Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J. Neurosci. 2000, 20:2602-2608.
3. Arthur-Farraj P.J., Latouche M., Wilton D.K., Quintes S., Chabrol E., Banerjee A., Woodhoo A., Jenkins B., Rahman M., Turmaine M., Wicher G.K., Mitter R., Greensmith L., Behrens A., Raivich G., Mirsky R., Jessen K.R. c-Jun reprograms Schwann cells of injured nerves to generate a repair cell essential for regeneration. Neuron 2012, 75:633-647.
4. Avellino A.M., Dailey A.T., Harlan J.M., Sharar S.R., Winn R.K., McNutt L.D., Kliot M. Blocking of up-regulated ICAM-1 does not prevent macrophage infiltration during Wallerian degeneration of peripheral nerve. Exp. Neurol. 2004, 187:430-444.
5. Azizi S., Mohammadi R., Amini K., Fallah R. Effects of topically administered FK506 on sciatic nerve regeneration and reinnervation after vein graft repair of short nerve gaps. Neurosurg. Focus. 2012, 32:E5.
6. Barhwal K., Hota S.K., Prasad D., Singh S.B., Ilavazhagan G. Hypoxia-induced deactivation of NGF-mediated ERK1/2 signaling in hippocampal cells: neuroprotection by acetyl-l-carnitine. J. Neurosci. Res. 2008, 86:2705-2721.
7. Bendszus M., Stoll G. Caught in the act: in vivo mapping of macrophage infiltration in nerve injury by magnetic resonance imaging. J. Neurosci. 2003, 23:10892-10896.
8. Bertrand J., Winton M.J., Rodriguez-Hernandez N., Campenot R.B., McKerracher L. Application of Rho antagonist to neuronal cell bodies promotes neurite growth in compartmented cultures and regeneration of retinal ganglion cell axons in the optic nerve of adult rats. J. Neurosci. 2005, 25:1113-1121.
9. Boyd J.G., Gordon T. Neurotrophic factors and their receptors in axonal regeneration and functional recovery after peripheral nerve injury. Mol. Neurobiol. 2003, 27:277-324.
10. Brushart T.M. Preferential reinnervation of motor nerves by regenerating motor axons. J. Neurosci. 1988, 8:1026-1031.
11. Brushart T.M., Aspalter M., Griffin J.W., Redett R., Hameed H., Zhou C., Wright M., Vyas A., Hoke A. Schwann cell phenotype is regulated by axon modality and central-peripheral location, and persists in vitro. Exp. Neurol. 2013, 247:272-281.
12. Bucci M., Roviezzo F., Cicala C., Sessa W.C., Cirino G. Geldanamycin, an inhibitor of heat shock protein 90 (Hsp90) mediated signal transduction has anti-inflammatory effects and interacts with glucocorticoid receptor in vivo. Br. J. Pharmacol. 2000, 131:13-16.
13. Bunge R.P. Expanding roles for the Schwann cell: ensheathment, myelination, trophism and regeneration. Curr. Opin. Neurobiol. 1993, 3:805-809.
14. Bungner O.V. Ueber die Regeneration und Degenerations-vorgange an Nerven nach Verletzunger. Beitr. Pathol. Anat. 1891, 10:321-393.
15. Cai D., Qiu J., Cao Z., McAtee M., Bregman B.S., Filbin M.T. Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate. J. Neurosci. 2001, 21:4731-4739.
16. Carroll S.L., Miller M.L., Frohnert P.W., Kim S.S., Corbett J.A. Expression of neuregulins and their putative receptors, ErbB2 and ErbB3, is induced during Wallerian degeneration. J. Neurosci. 1997, 17:1642-1659.
17. Chen Y.Y., McDonald D., Cheng C., Magnowski B., Durand J., Zochodne D.W. Axon and Schwann cell partnership during nerve regrowth. J. Neuropathol. Exp. Neurol. 2005, 64:613-622.
18. Cheng L., Khan M., Mudge A.W. Calcitonin gene-related peptide promotes Schwann cell proliferation. J. Cell Biol. 1995, 129:789-796.
19. Cheng C., Webber C.A., Wang J., Xu Y., Martinez J.A., Liu W.Q., McDonald D., Guo G.F., Nguyen M.D., Zochodne D.W. Activated RHOA and peripheral axon regeneration. Exp. Neurol. 2008, 212:358-369.
20. Christie K.J., Zochodne D. Peripheral axon regrowth: new molecular approaches. Neuroscience (Oxford) 2013, 240:310-324.
21. Christie K.J., Webber C.A., Martinez J.A., Singh B., Zochodne D.W. PTEN inhibition to facilitate intrinsic regenerative outgrowth of adult peripheral axons. J. Neurosci. 2010, 30:9306-9315.
22. De Grandis D., Minardi C. Acetyl-l-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. Drugs R D 2002, 3:223-231.
23. Dudek H., Datta S.R., Franke T.F., Birnbaum M.J., Yao R., Cooper G.M., Segal R.A., Kaplan D.R., Greenberg M.E. Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 1997, 275:661-665.
24. Elfar J.C., Jacobson J.A., Puzas J.E., Rosier R.N., Zuscik M.J. Erythropoietin accelerates functional recovery after peripheral nerve injury. J. Bone Joint Surg. Am. 2008, 90:1644-1653.
25. Evans-Jones G., Kay S.P., Weindling A.M., Cranny G., Ward A., Bradshaw A., Hernon C. Congenital brachial palsy: incidence, causes, and outcome in the United Kingdom and Republic of Ireland. Arch. Dis. Child. Fetal Neonatal Ed. 2003, 88:F185-F189.
26. Fansa H., Keilhoff G., Altmann S., Plogmeier K., Wolf G., Schneider W. The effect of the immunosuppressant FK 506 on peripheral nerve regeneration following nerve grafting. J. Hand Surg. (Br.) 1999, 24:38-42.
27. Fischer D., Petkova V., Thanos S., Benowitz L.I. Switching mature retinal ganglion cells to a robust growth state in vivo: gene expression and synergy with RhoA inactivation. J. Neurosci. 2004, 24:8726-8740.
28. Fu S.Y., Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged axotomy. J. Neurosci. 1995, 15:3876-3885.
29. Fu S.Y., Gordon T. Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation. J. Neurosci. 1995, 15:3886-3895.
30. Fu S.Y., Gordon T. The cellular and molecular basis of peripheral nerve regeneration. Mol. Neurobiol. 1997, 14:67-116.
31. Fu Q., Hue J., Li S. Nonsteroidal anti-inflammatory drugs promote axon regeneration via RhoA inhibition. J. Neurosci. 2007, 27:4154-4164.
32. Fujioka T., Fujioka A., Duman R.S. Activation of cAMP signaling facilitates the morphological maturation of newborn neurons in adult hippocampus. J. Neurosci. 2004, 24:319-328.
33. Gao Y., Deng K., Hou J., Bryson J.B., Barco A., Nikulina E., Spencer T., Mellado W., Kandel E.R., Filbin M.T. Activated CREB is sufficient to overcome inhibitors in myelin and promote spinal axon regeneration in vivo. Neuron 2004, 44:609-621.
34. Gaudet A.D., Popovich P.G., Ramer M.S. Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury. J. Neuroinflammation 2011, 8:110. (13 pages).
35. Gold B.G., Zhong Y.P. FK506 requires stimulation of the extracellular signal-regulated kinase 1/2 and the steroid receptor chaperone protein p23 for neurite elongation. Neurosignals 2004, 13:122-129.
36. Gordon T. Neurotrophic factor expression in denervated motor and sensory Schwann cells: relevance to specificity of peripheral nerve regeneration. Exp. Neurol. 2014, 254:99-108.
37. Govek E.E., Newey S.E., Van A.L. The role of the Rho GTPases in neuronal development. Genes Dev. 2005, 19:1-49.
38. Groves M.L., McKeon R., Werner E., Nagarsheth M., Meador W., English A.W. Axon regeneration in peripheral nerves is enhanced by proteoglycan degradation. Exp. Neurol. 2005, 195:278-292.
39. Gutmann E., Guttmann L., Medawar P.B., Young J.Z. The rate of regeneration of nerve. J. Exp. Biol. 1942, 19:14-44.
40. Hall S.M. The biology of chronically denervated Schwann cells. Ann. N. Y. Acad. Sci. 1999, 883:215-233.
41. Hamel M.G., Ajmo J.M., Leonardo C.C., Zuo F., Sandy J.D., Gottschall P.E. Multimodal signaling by the ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) promotes neurite extension. Exp. Neurol. 2008, 210:428-440.
42. Hannila S.S., Filbin M.T. The role of cyclic AMP signaling in promoting axonal regeneration after spinal cord injury. Exp. Neurol. 2008, 209:321-332.
43. Hanson M.G., Shen S., Wiemelt A.P., McMorris F.A., Barres B.A. Cyclic AMP elevation is sufficient to promote the survival of spinal motor neurons in vitro. J. Neurosci. 1998, 18:7361-7371.
44. Hart A.M., Wiberg M., Youle M., Terenghi G. Systemic acetyl-l-carnitine eliminates sensory neuronal loss after peripheral axotomy: a new clinical approach in the management of peripheral nerve trauma. Exp. Brain Res. 2002, 145:182-189.
45. Hart A.M., Terenghi G., Kellerth J.O., Wiberg M. Sensory neuroprotection, mitochondrial preservation, and therapeutic potential of N-acetyl-cysteine after nerve injury. Neuroscience 2004, 125:91-101.
46. Hart A.M., Wilson A.D., Montovani C., Smith C., Johnson M., Terenghi G., Youle M. Acetyl-l-carnitine: a pathogenesis based treatment for HIV-associated antiretroviral toxic neuropathy. AIDS 2004, 18:1549-1560.
47. Hershman D.L., Unger J.M., Crew K.D., Minasian L.M., Awad D., Moinpour C.M., Hansen L., Lew D.L., Greenlee H., Fehrenbacher L., Wade J.L., Wong S.F., Hortobagyi G.N., Meyskens F.L., Albain K.S. Randomized double-blind placebo-controlled trial of acetyl-l-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy. J. Clin. Oncol. 2013, 31:2627-2633.
48. Hetman M., Kanning K., Cavanaugh J.E., Xia Z. Neuroprotection by brain-derived neurotrophic factor is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase. J. Biol. Chem. 1999, 274:22569-22580.
49. Hiraga A., Kuwabara S., Doya H., Kanai K., Fujitani M., Taniguchi J., Arai K., Mori M., Hattori T., Yamashita T. Rho-kinase inhibition enhances axonal regeneration after peripheral nerve injury. J. Peripher. Nerv. Syst. 2006, 11:217-224.
50. Hoke A. Mechanisms of disease: what factors limit the success of peripheral nerve regeneration in humans?. Nat. Clin. Pract. Neurol. 2006, 2:448-454.
51. Hoke A., Keswani S.C. Neuroprotection in the PNS: erythropoietin and immunophilin ligands. Ann. N. Y. Acad. Sci. 2005, 1053:491-501.
52. Hoke A., Redett R., Hameed H., Jari R., Zhou C., Li Z.B., Griffin J.W., Brushart T.M. Schwann cells express motor and sensory phenotypes that regulate axon regeneration. J. Neurosci. 2006, 26:9646-9655.
53. Igarashi M., Li W.W., Sudo Y., Fishman M.C. Ligand-induced growth cone collapse: amplification and blockade by variant GAP-43 peptides. J. Neurosci. 1995, 15:5660-5667.
54. Jander S., Pohl J., Gillen C., Stoll G. Differential expression of interleukin-10 mRNA in Wallerian degeneration and immune-mediated inflammation of the rat peripheral nervous system. J. Neurosci. Res. 1996, 43:254-259.
55. Jin E., Sano M. Neurite outgrowth of NG108-15 cells induced by heat shock protein 90 inhibitors. Cell Biochem. Funct. 2008, 26:825-832.
56. Jones K.J., Kinderman N.B., Oblinger M.M. Alterations in glial fibrillary acidic protein (GFAP) mRNA levels in the hamster facial motor nucleus: effects of axotomy and testosterone. Neurochem. Res. 1997, 22:1359-1366.
57. Kaplan D.R., Miller F.D. Neurotrophin signal transduction in the nervous system. Curr. Opin. Neurobiol. 2000, 10:381-391.
58. Karsidag S., Akcal A., Sahin S., Karsidag S., Kabukcuoglu F., Ugurlu K. Neurophysiological and morphological responses to treatment with acetyl-l-carnitine in a sciatic nerve injury model: preliminary data. J. Hand Surg. (Br.) 2012, 37:529-536.
59. Klesse L.J., Meyers K.A., Marshall C.J., Parada L.F. Nerve growth factor induces survival and differentiation through two distinct signaling cascades in PC12 cells. Oncogene 1999, 18:2055-2068.
60. Kokkalis Z.T., Soucacos P.N., Terzis J.K. Effect of acetyl-l-carnitine on axonal sprouting following donor nerve injury distal to an end-to-side neurorrhaphy model. J. Reconstr. Microsurg. 2009, 25:483-495.
61. Kostopoulos V.K., Davis C.L., Terzis J.K. Effects of acetylo-l-carnitine in end-to-side neurorrhaphy: a pilot study. Microsurgery 2009, 29:456-463.
62. Krekoski C.A., Neubauer D., Zuo J., Muir D. Axonal regeneration into acellular nerve grafts is enhanced by degradation of chondroitin sulfate proteoglycan. J. Neurosci. 2001, 21:6206-6213.
63. Kujawa K.A., Kinderman N.B., Jones K.J. Testosterone-induced acceleration of recovery from facial paralysis following crush axotomy of the facial nerve in male hamsters. Exp. Neurol. 1989, 105:80-85.
64. Lehmann M., Fournier A., Selles-Navarro I., Dergham P., Sebok A., Leclerc N., Tigyi G., McKerracher L. Inactivation of Rho signaling pathway promotes CNS axon regeneration. J. Neurosci. 1999, 19:7537-7547.
65. Lykissas M.G., Sakellariou E., Vekris M.D., Kontogeorgakos V.A., Batistatou A.K., Mitsionis G.I., Beris A.E. Axonal regeneration stimulated by erythropoietin: an experimental study in rats. J. Neurosci. Methods 2007, 164:107-115.
66. Madura T., Kubo T., Tanag M., Matsuda K., Tomita K., Yano K., Hosokawa K. The Rho-associated kinase inhibitor fasudil hydrochloride enhances neural regeneration after axotomy in the peripheral nervous system. Plast. Reconstr. Surg. 2007, 119:526-535.
67. Madura T., Tomita K., Terenghi G. Ibuprofen improves functional outcome after axotomy and immediate repair in the peripheral nervous system. J. Plast. Reconstr. Aesthet. Surg. 2011, 64:1641-1646.
68. Manaenko A., Fathali N., Chen H., Suzuki H., Williams S., Zhang J.H., Tang J. Heat shock protein 70 upregulation by geldanamycin reduces brain injury in a mouse model of intracerebral hemorrhage. Neurochem. Int. 2010, 57:844-850.
69. Marenzi G., Assanelli E., Marana I., Lauri G., Campodonico J., Grazi M., De M.M., Galli S., Fabbiocchi F., Montorsi P., Veglia F., Bartorelli A.L. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N. Engl. J. Med. 2006, 354:2773-2782.
70. Mazzoni I.E., Said F.A., Aloyz R., Miller F.D., Kaplan D. Ras regulates sympathetic neuron survival by suppressing the p53-mediated cell death pathway. J. Neurosci. 1999, 19:9716-9727.
71. Mesulam M.M., Brushart T.M. Transganglionic and anterograde transport of horseradish peroxidase across dorsal root ganglia: a tetramethylbenzidine method for tracing central sensory connections of muscles and peripheral nerves. Neuroscience 1979, 4:1107-1117.
72. Mi R., Chen W., Hoke A. Pleiotrophin is a neurotrophic factor for spinal motor neurons. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:4664-4669.
73. Mohammadi R., Hirsaee M.A., Amini K. Improvement of functional recovery of transected peripheral nerve by means of artery grafts filled with diclofenac. Int. J. Surg. 2013, 11:259-264.
74. Moschou M., Kosmidis E.K., Kaloyianni M., Geronikaki A., Dabarakis N., Theophilidis G. In vitro assessment of the neurotoxic and neuroprotective effects of N-acetyl-l-cysteine (NAC) on the rat sciatic nerve fibers. Toxicol. In Vitro 2008, 22:267-274.
75. Neckers L., Workman P. Hsp90 molecular chaperone inhibitors: are we there yet?. Clin. Cancer Res. 2012, 18:64-76.
76. Neumann S., Bradke F., Tessier-Lavigne M., Basbaum A.I. Regeneration of sensory axons within the injured spinal cord induced by intraganglionic cAMP elevation. Neuron 2002, 34:885-893.
77. Noble J., Munro C.A., Prasad V.S., Midha R. Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries. J. Trauma 1998, 45:116-122.
78. Olmarker K., Stromberg J., Blomquist J., Zachrisson P., Nannmark U., Nordborg C., Rydevik B. Chondroitinase ABC (pharmaceutical grade) for chemonucleolysis. Functional and structural evaluation after local application on intraspinal nerve structures and blood vessels. Spine 1996, 21:1952-1956.
79. Pearse D.D., Pereira F.C., Marcillo A.E., Bates M.L., Berrocal Y.A., Filbin M.T., Bartlett-Bunge M. cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nat. Med. 2002, 10:610-616.
80. Poduslo J.F., Walikonis R.S., Domec M.C., Berg C.T., Holtz-Heppelmann C.J. The second messenger, cyclic AMP, is not sufficient for myelin gene induction in the peripheral nervous system. J. Neurochem. 1995, 65:149-159.
81. Read D.E., Gorman A.M. Involvement of Akt in neurite outgrowth. Cell. Mol. Life Sci. 2009, 66:2975-2984.
82. Reid A.J., Shawcross S.G., Hamilton A.E., Wiberg M., Terenghi G. N-acetylcysteine alters apoptotic gene expression in axotomised primary sensory afferent subpopulations. Neurosci. Res. 2009, 65:148-155.
83. Rustemeyer J., van de Wal R., Keipert C., Dicke U. Administration of low-dose FK 506 accelerates histomorphometric regeneration and functional outcomes after allograft nerve repair in a rat model. J. Craniomaxillofac. Surg. 2010, 38:134-140.
84. Sharma N., Coughlin L., Porter R.G., Tanzer L., Wurster R.D., Marzo S.J., Jones K.J., Foecking E.M. Effects of electrical stimulation and gonadal steroids on rat facial nerve regenerative properties. Restor. Neurol. Neurosci. 2009, 27:633-644.
85. Shim S., Ming G.L. Roles of channels and receptors in the growth cone during PNS axonal regeneration. Exp. Neurol. 2010, 223:38-44.
86. Sima A.A., Calvani M., Mehra M., Amato A. Acetyl-l-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. Diabetes Care 2005, 28:89-94.
87. Singh A.K., Szczech L., Tang K.L., Barnhart H., Sapp S., Wolfson M., Reddan D. Correction of anemia with epoetin alfa in chronic kidney disease. N. Engl. J. Med. 2006, 355:2085-2098.
88. Siren A.L., Fasshauer T., Bartels C., Ehrenreich H. Therapeutic potential of erythropoietin and its structural or functional variants in the nervous system. Neurotherapeutics 2009, 6:108-127.
89. Song H.J., Ming G.L., Poo M.M. cAMP-induced switching in turning direction of nerve growth cones. Nature 1997, 388:275-279.
90. Starzl T.E., Todo S., Fung J., Demetris A.J., Venkataramman R., Jain A. FK 506 for liver, kidney, and pancreas transplantation. Lancet 1989, 2:1000-1004.
91. Stewart H.J., Eccleston P.A., Jessen K.R., Mirsky R. Interaction between cAMP elevation, identified growth factors, and serum components in regulating Schwann cell growth. J. Neurosci. Res. 1991, 30:346-352.
92. Stoll G., Jander S., Myers R.R. Degeneration and regeneration of the peripheral nervous system: from Augustus Waller's observations to neuroinflammation. J. Peripher. Nerv. Syst. 2002, 7:13-27.
93. Strittmatter S.M., Igarashi M., Fishman M.C. GAP-43 amino terminal peptides modulate growth cone morphology and neurite outgrowth. J. Neurosci. 1994, 14:5503-5513.
94. Suhs K.W., Hein K., Sattler M.B., Gorlitz A., Ciupka C., Scholz K., Kasmann-Kellner B., Papanagiotou P., Schaffler N., Restemeyer C., Bittersohl D., Hassenstein A., Seitz B., Reith W., Fassbender K., Hilgers R., Heesen C., Bahr M., Diem R. A randomized, double-blind, phase 2 study of erythropoietin in optic neuritis. Ann. Neurol. 2012, 72:199-210.
95. Sulaiman O.A., Gordon T. Effects of short- and long-term Schwann cell denervation on peripheral nerve regeneration, myelination, and size. GLIA 2000, 32:234-246.
96. Sulaiman O.A., Voda J., Gold B.G., Gordon T. FK506 increases peripheral nerve regeneration after chronic axotomy but not after chronic Schwann cell denervation. Exp. Neurol. 2002, 175:127-137.
97. Sun H.H., Saheb-Al-Zamani M., Yan Y., Hunter D.A., Mackinnon S.E., Johnson P.J. Geldanamycin accelerated peripheral nerve regeneration in comparison to FK-506 in vivo. Neuroscience 2012, 223:114-123.
98. Sunderland S. Rate of regeneration in human peripheral nerves. Arch. Neurol. Psychiatry 1947, 58:1-6.
99. Suzuki Y., Shibuya M., Satoh S., Sugimoto Y., Takakura K. A postmarketing surveillance study of fasudil treatment after aneurysmal subarachnoid hemorrhage. Surg. Neurol. 2007, 68:126-131.
100. Taglialatela G., Angelucci L., Ramacci M.T., Werrbach-Perez K., Jackson G.R., Perez-Polo J.R. Stimulation of nerve growth factor receptors in PC12 by acetyl-l-carnitine. Biochem. Pharmacol. 1992, 44:577-585.
101. Tanaka H., Ono K., Shibasaki H., Isa T., Ikenaka K. Conduction properties of identified neural pathways in the central nervous system of mice in vivo. Neurosci. Res. 2004, 49:113-122.
102. Terzis J.K., Konofaos P. Low-dose FK506 after contralateral C7 transfer to the musculocutaneous nerve using two different tubes: a study in rats. Ann. Plast. Surg. 2010, 64:622-631.
103. Tetzlaff W., Bisby M.A., Kreutzberg G.W. Changes in cytoskeletal proteins in the rat facial nucleus following axotomy. J. Neurosci. 1988, 8:3181-3189.
104. Tetzlaff J., Tanzer L., Jones K.J. Exogenous androgen treatment delays the stress response following hamster facial nerve injury. J. Neuroendocrinol. 2007, 19:383-389.
105. Thoenen H., Sendtner M. Neurotrophins: from enthusiastic expectations through sobering experiences to rational therapeutic approaches. Nat. Neurosci. 2002, (5 Suppl.):1046-1050.
106. Toth C.C., Willis D., Twiss J.L., Walsh S., Martinez J.A., Liu W.Q., Midha R., Zochodne D.W. Locally synthesized calcitonin gene-related peptide has a critical role in peripheral nerve regeneration. J. Neuropathol. Exp. Neurol. 2009, 68:326-337.
107. Udina E., Ladak A., Furey M., Brushart T., Tyreman N., Gordon T. Rolipram-induced elevation of cAMP or chondroitinase ABC breakdown of inhibitory proteoglycans in the extracellular matrix promotes peripheral nerve regeneration. Exp. Neurol. 2010, 223:143-152.
108. Vanhaesebroeck B., Alessi D.R. The PI3K-PDK1 connection: more than just a road to PKB. Biochem. J. 2000, 346(Pt 3):561-576.
109. Vicari R.M., Chaitman B., Keefe D., Smith W.B., Chrysant S.G., Tonkon M.J., Bittar N., Weiss R.J., Morales-Ballejo H., Thadani U. Efficacy and safety of fasudil in patients with stable angina: a double-blind, placebo-controlled, phase 2 trial. J. Am. Coll. Cardiol. 2005, 46:1803-1811.
110. Webber C., Zochodne D. The nerve regenerative microenvironment: early behavior and partnership of axons and Schwann cells. Exp. Neurol. 2010, 223:51-59.
111. Webber C.A., Xu Y., Vanneste K.J., Martinez J.A., Verge V.M., Zochodne D.W. Guiding adult mammalian sensory axons during regeneration. J. Neuropathol. Exp. Neurol. 2008, 67:212-222.
112. Welin D., Novikova L.N., Wiberg M., Kellerth J.O., Novikov L.N. Effects of N-acetyl-cysteine on the survival and regeneration of sural sensory neurons in adult rats. Brain Res. 2009, 1287:58-66.
113. Wilson A.D., Hart A., Brannstrom T., Wiberg M., Terenghi G. Delayed acetyl-l-carnitine administration and its effect on sensory neuronal rescue after peripheral nerve injury. J. Plast. Reconstr. Aesthet. Surg. 2007, 60:114-118.
114. Wilson A.D., Hart A., Wiberg M., Terenghi G. Acetyl-l-carnitine increases nerve regeneration and target organ reinnervation - a morphological study. J. Plast. Reconstr. Aesthet. Surg. 2009, 63:1186-1195.
115. Wilson A.D., Hart A., Wiberg M., Terenghi G. Acetyl-l-carnitine increases nerve regeneration and target organ reinnervation - a morphological study. J. Plast. Reconstr. Aesthet. Surg. 2010, 63:1186-1195.
116. Witzel C., Rohde C., Brushart T.M. Pathway sampling by regenerating peripheral axons. J. Comp. Neurol. 2005, 485:183-190.
117. Wu K.Y., Hengst U., Cox L.J., Macosko E.Z., Jeromin A., Urquhart E.R., Jaffrey S.R. Local translation of RhoA regulates growth cone collapse. Nature 2005, 436:1020-1024.
118. Xing B., Li H., Wang H., Mukhopadhyay D., Fisher D., Gilpin C.J., Li S. RhoA-inhibiting NSAIDs promote axonal myelination after spinal cord injury. Exp. Neurol. 2011, 231:247-260.
119. Yan C.Y., Greene L.A. Prevention of PC12 cell death by N-acetylcysteine requires activation of the Ras pathway. J. Neurosci. 1998, 18:4042-4049.
120. Yan Y., Sun H.H., Hunter D.A., Mackinnon S.E., Johnson P.J. Efficacy of short-term FK506 administration on accelerating nerve regeneration. Neurorehabil. Neural Repair 2012, 26:570-580.
121. Ydens E., Cauwels A., Asselbergh B., Goethals S., Peeraer L., Lornet G., Almeida-Souza L., Van Ginderachter J.A., Timmerman V., Janssens S. Acute injury in the peripheral nervous system triggers an alternative macrophage response. J. Neuroinflammation 2012, 9:176. (17 pages).
122. You S., Petrov T., Chung P.H., Gordon T. The expression of the low affinity nerve growth factor receptor in long-term denervated Schwann cells. GLIA 1997, 20:87-100.
123. Youle M., Osio M. A double-blind, parallel-group, placebo-controlled, multicentre study of acetyl l-carnitine in the symptomatic treatment of antiretroviral toxic neuropathy in patients with HIV-1 infection. HIV Med. 2007, 8:241-250.
124. Zhang C.G., Welin D., Novikov L., Kellerth J.O., Wiberg M., Hart A.M. Motorneuron protection by N-acetyl-cysteine after ventral root avulsion and ventral rhizotomy. Br. J. Plast. Surg. 2005, 58:765-773.
125. Zuo J., Neubauer D., Graham J., Krekoski C.A., Ferguson T.A., Muir D. Regeneration of axons after nerve transection repair is enhanced by degradation of chondroitin sulfate proteoglycan. Exp. Neurol. 2002, 176:221-228.