Differential cellular FGF-2 upregulation in the rat facial nucleus following axotomy, functional electrical stimulation and corticosterone: a possible therapeutic target to Bell’s palsy^[*]

Abstract

Background The etiology of Bell’s palsy can vary but anterograde axonal degeneration may delay spontaneous functional recovery leading the necessity of therapeutic interventions. Corticotherapy and/or complementary rehabilitation interventions have been employed. Thus the natural history of the disease reports to a neurotrophic resistance of adult facial motoneurons leading a favorable evolution however the related molecular mechanisms that might be therapeutically addressed in the resistant cases are not known. Fibroblast growth factor-2 (FGF-2) pathway signaling is a potential candidate for therapeutic development because its role on wound repair and autocrine/paracrine trophic mechanisms in the lesioned nervous system.

Methods Adult rats received unilateral facial nerve crush, transection with amputation of nerve branches, or sham operation. Other group of unlesioned rats received a daily functional electrical stimulation in the levator labii superioris muscle (1 mA, 30 Hz, square wave) or systemic corticosterone (10 mgkg^-1). Animals were sacrificed seven days later.

Results Crush and transection lesions promoted no changes in the number of neurons but increased the neurofilament in the neuronal neuropil of axotomized facial nuclei. Axotomy also elevated the number of GFAP astrocytes (143% after crush; 277% after transection) and nuclear FGF-2 (57% after transection) in astrocytes (confirmed by two-color immunoperoxidase) in the ipsilateral facial nucleus. Image analysis reveled that a seven days functional electrical stimulation or corticosterone led to elevations of FGF-2 in the cytoplasm of neurons and in the nucleus of reactive astrocytes, respectively, without astrocytic reaction.

Conclusion FGF-2 may exert paracrine/autocrine trophic actions in the facial nucleus and may be relevant as a therapeutic target to Bell’s palsy.

^*This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

• References

• 1 Bodenez C, Bernat I, Willer JC, Barre P, Lamas G, Tankere F. Facial nerve decompression for idiopathic Bell’s palsy: report of 13 cases and literature review. J Laryngol Otol 2010; 124: 272-278 10.1017/S0022215109991265 19796438
• 2 Hazin R, Azizzadeh B, Bhatti MT. Medical and surgical management of facial nerve palsy. Curr Opin Ophthalmol 2009; 20: 440-450 10.1097/ICU.0b013e3283313cbf 19696671
• 3 Browning GG. Bell’s palsy: a review of three systematic reviews of steroid and anti-viral therapy. Clin Otolaryngol 2010; 35: 56-58 10.1111/j.1749-4486.2010.02084.x 20447166
• 4 Grothe C, Wewetzer K. Fibroblast growth factor and its implications for developing and regenerating neurons. Int J Dev Biol 1996; 40: 403-410 8735955
• 5 Chadi G, Fuxe K. Analysis of trophic responses in lesioned brain: focus on basic fibroblast growth factor mechanisms. Braz J Med Biol Res 1998; 31: 231-241 10.1590/S0100-879X1998000200007 9686146
• 6 Fuxe K, Tinner B, Zoli M, Pettersson RF, Baird A, Biagini G, Chadi G, Agnati LF. Computer-assisted mapping of basic fibroblast growth factor immunoreactive nerve cell populations in the rat brain. J Chem Neuroanat 1996; 11: 13-35 10.1016/0891-0618(96)00119-6 8841886
• 7 Humpel C, Lippoldt A, Chadi G, Ganten D, Olson L, Fuxe K. Fast and widespread increase of basic fibroblast growth factor messenger RNA and protein in the forebrain after kainate-induced seizures. Neuroscience 1993; 57: 913-922 10.1016/0306-4522(93)90037-G 8309552
• 8 Matsuyama A, Iwata H, Okumura N, Yoshida S, Imaizumi K, Lee Y, Shiraishi S, Shiosaka S. Localization of basic fibroblast growth factor-like immunoreactivity in the rat brain. Brain Res 1992; 587: 49-65 10.1016/0006-8993(92)91427-G 1525649
• 9 Chadi G, Moller A, Rosen L, Janson AM, Agnati LA, Goldstein M, Ogren SO, Pettersson RF, Fuxe K. Protective actions of human recombinant basic fibroblast growth factor on MPTP-lesioned nigrostriatal dopamine neurons after intraventricular infusion. Exp Brain Res 1993; 97: 145-158 10.1007/BF00228825 7907549
• 10 Walicke PA. Basic and acidic fibroblast growth factors have trophic effects on neurons from multiple CNS regions. J Neurosci 1988; 8: 2618-2627 3249247
• 11 Chadi G, Cao Y, Pettersson RF, Fuxe K. Temporal and spatial increase of astroglial basic fibroblast growth factor synthesis after 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine neurons. Neuroscience 1994; 61: 891-910 10.1016/0306-4522(94)90411-1 7838386
• 12 Logan A, Frautschy SA, Gonzalez AM, Baird A. A time course for the focal elevation of synthesis of basic fibroblast growth factor and one of its high-affinity receptors (flg) following a localized cortical brain injury. J Neurosci 1992; 12: 3828-3837 1403086
• 13 Finklestein SP, Apostolides PJ, Caday CG, Prosser J, Philips MF, Klagsbrun M. Increased basic fibroblast growth factor (bFGF) immunoreactivity at the site of focal brain wounds. Brain Res 1988; 460: 253-259 10.1016/0006-8993(88)90370-8 3224261
• 14 Gomez-Pinilla F, Lee JW, Cotman CW. Basic FGF in adult rat brain: cellular distribution and response to entorhinal lesion and fimbria-fornix transection. J Neuroscience 1992; 12: 345-355
• 15 de Oliveira GP, Duobles T, Castelucci P, Chadi G. Differential regulation of FGF-2 in neurons and reactive astrocytes of axotomized rat hypoglossal nucleus. A possible therapeutic target for neuroprotection in peripheral nerve pathology. Act Hist 2010; 112: 604-17 10.1016/j.acthis.2009.06.008
• 16 Fior-Chadi DR, Varella TC, Maximino JR, Chadi G. Aortic coarctation hypertension induces fibroblast growth factor-2 immunoreactivity in the stimulated nucleus tractus solitarii. J Mol Hist 2007; 38: 285-294 10.1007/s10735-007-9101-x
• 17 Gomide V, Chadi G. Glial bFGF and S100 immunoreactivities increase in ascending dopamine pathways following striatal 6-OHDA-induced partial lesion of the nigrostriatal system: a sterological analysis. Int J Neurosci 2005; 115: 537-555 10.1080/00207450590521064 15809219
• 18 Levy Bde F, Cunha Jdo C, Chadi G. Cellular analysis of S100Beta and fibroblast growth factor-2 in the dorsal root ganglia and sciatic nerve of rodents. focus on paracrine actions of activated satellite cells after axotomy. Int J Neurosci 2007; 117: 1481-1503 10.1080/15569520701502716 17729158
• 19 Chadi G, Rosen L, Cintra A, Tinner B, Zoli M, Pettersson RF, Fuxe K. Corticosterone increases FGF-2 (bFGF) immunoreactivity in the substantia nigra of the rat. Neuroreport 1993; 4: 783-786 10.1097/00001756-199306000-00047 8347826
• 20 Miles JD. Empirical evaluation of a neuromuscular model for functional electrical stimulation of the lower limb. PhD dissertation U. Southern Calif 2001;
• 21 Pilyavskii AI, Maisky VA, Kalezic I, Ljubisavljevic M, Kostyukov AI, Windhorst U, Johansson H. c-fos Expression and NADPH-d reactivity in spinal neurons after fatiguing stimulation of hindlimb muscles in the rat. Brain Res 2001; 923: 91-102 10.1016/S0006-8993(01)03049-9 11743976
• 22 Blum EK, Haun C, Ryan JE. A musculo-skeletal model of rat ankle motion and its experimental test on rat. J Biomech 2007; 40: 891-899 10.1016/j.jbiomech.2006.03.003 16750538
• 23 Gomide VC, Silveira GA, Chadi G. Transient and widespread astroglial activation in the brain after a striatal 6-OHDA-induced partial lesion of the nigrostriatal system. Int J Neurosci 2005; 115: 99-117 10.1080/00207450490512696 15768855
• 24 Rodrigues RW, Gomide VC, Chadi G. Astroglial and microglial activation in the wistar rat ventral tegmental area after a single striatal injection of 6-hydroxydopamine. Int J Neurosci 2004; 114: 197-216 10.1080/00207450490249338 14702208
• 25 Paxinos G, Watson C. The rat brain: in stereotaxic coordinates. Harcourt Brace Jovanovich; San Diego: 1986
• 26 Gonzalez AM, Buscaglia M, Ong M, Baird A. Distribution of basic fibroblast growth factor in the 18-day rat fetus: localization in the basement membranes of diverse tissues. J Cell Biol 1990; 110: 753-765 10.1083/jcb.110.3.753 2116039 1689733
• 27 Chadi G, Andrade MS, Leme RJ, Gomide VC. Experimental models of partial lesion of rat spinal cord to investigate neurodegeneration, glial activation, and behavior impairments. Int J Neurosci 2001; 111: 137-165 10.3109/00207450108994227 11912671
• 28 Gomide VC, Chadi G. The trophic factors S-100beta and basic fibroblast growth factor are increased in the forebrain reactive astrocytes of adult callosotomized rat. Brain Res 1999; 835: 162-174 10.1016/S0006-8993(99)01557-7 10415371
• 29 Silva TP, Silveira GA, Fior-Chadi DR, Chadi G. Effects of ethanol consumption on vasopressin and neuropeptide Y immunoreactivity and mRNA expression in peripheral and central areas related to cardiovascular regulation. Alcohol 2004; 32: 213-222 10.1016/j.alcohol.2004.02.003 15282115
• 30 Gomide VC, Chadi G. Prenatal ethanol enhances rotational behavior to apomorphine in the 24-month-old rat offspring with small striatal lesion. Neurotoxicol and Teratol 2004; 26: 417-427 10.1016/j.ntt.2003.12.006
• 31 Chadi G, Maximino JR, de Oliveira GP. The importance of molecular histology to study glial influence on neurodegenerative disorders. Focus on recent developed single cell laser microdissection. J Mol Hist 2009; 40: 241-250 10.1007/s10735-009-9235-0
• 32 Chadi G, Silva C, Maximino JR, Fuxe K, da Silva GO. Adrenalectomy counteracts the local modulation of astroglial fibroblast growth factor system without interfering with the pattern of 6-OHDA-induced dopamine degeneration in regions of the ventral midbrain. Brain Res 2008; 1190: 23-38 10.1016/j.brainres.2007.11.024 18086466
• 33 Chadi G, Gomide VC. FGF-2 and S100beta immunoreactivities increase in reactive astrocytes, but not in microglia, in ascending dopamine pathways following a striatal 6-OHDA-induced partial lesion of the nigrostriatal system. Cell Biol Int 2004; 28: 849-861 10.1016/j.cellbi.2004.08.005 15566955
• 34 Hollander M, Wolfe DA. Non-parametric Statistical Methods. Wiley; New York: 1973
• 35 Aldskogius H, Barron KD, Regal R. Axon reaction in dorsal motor vagal and hypoglossal neurons of the adult rat. Light microscopy and RNA-cytochemistry. J Comp Neurol 1980; 193: 165-177 10.1002/cne.901930111 6159377
• 36 Lieberman AR. The axon reaction: a review of the principal features of perikaryal responses to axon injury. Int Rev Neurobiol 1971; 14: 49-124 full_text 4948651
• 37 Freeman MD, Nystrom A, Centeno C. Chronic whiplash and central sensitization; an evaluation of the role of a myofascial trigger points in pain modulation. J Brachial Plex Peripher Nerve Inj 2009; 4: 2 10.1186/1749-7221-4-2 2680858 19389231
• 38 Smith CB, Crane AM, Kadekaro M, Agranoff BW, Sokoloff L. Stimulation of protein synthesis and glucose utilization in the hypoglossal nucleus induced by axotomy. J Neurosci 1984; 4: 2489-2496 6491719
• 39 Yamada KM, Spooner BS, Wessells NK. Axon growth: roles of microfilaments and microtubules. Proc Natl Acad Sci USA 1970; 66: 1206-1212 10.1073/pnas.66.4.1206 335807 5273449
• 40 Fargo KN, Foecking EM, Jones KJ, Sengelaub DR. Neuroprotective actions of androgens on motoneurons. Front neuroendocrinol 2009; 30: 130-141 10.1016/j.yfrne.2009.04.005 2726741 19393684
• 41 Rosson GD, Williams EH, Dellon AL. Motor nerve regeneration across a conduit. Microsurgery 2009; 29: 107-114 10.1002/micr.20580 18942644
• 42 Tetzlaff W, Alexander SW, Miller FD, Bisby MA. Response of facial and rubrospinal neurons to axotomy: changes in mRNA expression for cytoskeletal proteins and GAP-43. J Neurosci 1991; 11: 2528-2544 1831228
• 43 Tetzlaff W, Bisby MA, Kreutzberg GW. Changes in cytoskeletal proteins in the rat facial nucleus following axotomy. J Neurosci 1988; 8: 3181-3189 3139845
• 44 Bisby MA, Tetzlaff W. Changes in cytoskeletal protein synthesis following axon injury and during axon regeneration. Mol Neurobiol 1992; 6: 107-123 10.1007/BF02780547 1476674
• 45 Dallo JG, Reichert BV, Valladao Junior JB, Silva C, Luca BA, Levy Bde F, Chadi G. Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair. Act Cir Bras 2007; 22: 485-494
• 46 Mader K, Andermahr J, Angelov DN, Neiss WF. Dual mode of signalling of the axotomy reaction: retrograde electric stimulation or block of retrograde transport differently mimic the reaction of motoneurons to nerve transection in the rat brainstem. J Neurotrauma 2004; 21: 956-968 10.1089/0897715041526113 15307907
• 47 Casamenti F, Prosperi C, Scali C, Giovannelli L, Colivicchi MA, Faussone-Pellegrini MS, Pepeu G. Interleukin-1beta activates forebrain glial cells and increases nitric oxide production and cortical glutamate and GABA release in vivo: implications for Alzheimer’s disease. Neuroscience 1999; 91: 831-842 10.1016/S0306-4522(98)00680-0 10391466
• 48 Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Act Neuropathol 2010; 119: 7-35 10.1007/s00401-009-0619-8
• 49 Paixao S, Klein R. Neuron-astrocyte communication and synaptic plasticity. Curr Opin Neurobiol 2010; 20: 466-73 10.1016/j.conb.2010.04.008 20471242
• 50 Davies AM, Larmet Y, Wright E, Vogel KS. Coordination of trophic interactions by separate developmental programs in sensory neurons and their target fields. J Cell Sci Suppl 1991; 15: 111-116 1824102
• 51 Groves MJ, Christopherson T, Giometto B, Scaravilli F. Axotomy-induced apoptosis in adult rat primary sensory neurons. J Neurocytol 1997; 26: 615-624 10.1023/A:1018541726460 9352447
• 52 Kuno M. Motoneuronal cell death and neurotrophic factors. Clin Neurol 1993; 33: 1275-1277
• 53 Meyer M, Matsuoka I, Wetmore C, Olson L, Thoenen H. Enhanced synthesis of brain-derived neurotrophic factor in the lesioned peripheral nerve: different mechanisms are responsible for the regulation of BDNF and NGF mRNA. J Cell Biol 1992; 119: 45-54 10.1083/jcb.119.1.45 2289627 1527172
• 54 Heumann R, Korsching S, Bandtlow C, Thoenen H. Changes of nerve growth factor synthesis in nonneuronal cells in response to sciatic nerve transection. J Cell Biol 1987; 104: 1623-1631 10.1083/jcb.104.6.1623 2114490 3034917
• 55 Thoenen H. The changing scene of neurotrophic factors. Trends Neurosci 1991; 14: 165-170 10.1016/0166-2236(91)90097-E 1713715
• 56 Heumann R, Lindholm D, Bandtlow C, Meyer M, Radeke MJ, Misko TP, Shooter E, Thoenen H. Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration, and regeneration: role of macrophages. Proc Natl Acad Sci USA 1987; 84: 8735-8739 10.1073/pnas.84.23.8735 299621 2825206
• 57 Frim DM, Uhler TA, Short MP, Ezzedine ZD, Klagsbrun M, Breakefield XO, Isacson O. Effects of biologically delivered NGF, BDNF and bFGF on striatal excitotoxic lesions. Neuroreport 1993; 4: 367-370 10.1097/00001756-199304000-00006 8098961
• 58 Koketsu N, Berlove DJ, Moskowitz MA, Kowall NW, Caday CG, Finklestein SP. Pretreatment with intraventricular basic fibroblast growth factor decreases infarct size following focal cerebral ischemia in rats. Ann Neurol 1994; 35: 451-457 10.1002/ana.410350413 8154872
• 59 Nozaki K, Finklestein SP, Beal MF. Basic fibroblast growth factor protects against hypoxia-ischemia and NMDA neurotoxicity in neonatal rats. J Cereb Blood Flow Metab 1993; 13: 221-228 8436614
• 60 do Carmo CunhaJ, de Freitas AzevedoLevy B, de Luca BA, de Andrade MS, Gomide VC, Chadi G. Responses of reactive astrocytes containing S100beta protein and fibroblast growth factor-2 in the border and in the adjacent preserved tissue after a contusion injury of the spinal cord in rats: implications for wound repair and neuroregeneration. Wound Repair Regen 2007; 15: 134-146 10.1111/j.1524-475X.2006.00194.x 17244329
• 61 Emmett CJ, Aswani SP, Stewart GR, Fairchild D, Johnson RM. Dose-response comparison of recombinant human nerve growth factor and recombinant human basic fibroblast growth factor in the fimbria fornix model of acute cholinergic degeneration. Brain Res 1995; 673: 199-207 10.1016/0006-8993(94)01414-D 7606433
• 62 Grothe C, Zachmann K, Unsicker K. Basic FGF-like immunoreactivity in the developing and adult rat brainstem. J Comp Neurol 1991; 305: 328-336 10.1002/cne.903050213 2026791
• 63 Grothe C, Unsicker K. Basic fibroblast growth factor in the hypoglossal system: specific retrograde transport, trophic, and lesion-related responses. J Neurosci Res 1992; 32: 317-328 10.1002/jnr.490320304 1279188
• 64 Ferguson IA, Johnson EM. Fibroblast growth factor receptor-bearing neurons in the CNS: identification by receptor-mediated retrograde transport. J Comp Neurol 1991; 313: 693-706 10.1002/cne.903130412 1664437
• 65 Park TH, Mytilineou C. Protection from 1-methyl-4-phenylpyridinium (MPP+) toxicity and stimulation of regrowth of MPP(+)-damaged dopaminergic fibers by treatment of mesencephalic cultures with EGF and basic FGF. Brain Res 1992; 599: 83-97 10.1016/0006-8993(92)90855-4 1362921
• 66 Otto D, Unsicker K. Basic FGF reverses chemical and morphological deficits in the nigrostriatal system of MPTP-treated mice. J Neurosci 1990; 10: 1912-1921 1972393
• 67 Andrade MS, Mendonca LM, Chadi G. Treadmill running protects spinal cord contusion from secondary degeneration. Brain Res 2010; 1346: 266-78 10.1016/j.brainres.2010.05.070 20513364
• 68 Cintra A, Bhatnagar M, Chadi G, Tinner B, Lindberg J, Gustafsson JA, Agnati LF, Fuxe K. Glial and neuronal glucocorticoid receptor immunoreactive cell populations in developing, adult, and aging brain. Ann N Y Acad Sci 1994; 746: 42-61 discussion 61-43 10.1111/j.1749-6632.1994.tb39210.x 7825905
• 69 Covenas R, DeLeon M, Chadi G, Cintra A, Gustafsson JA, Narvaez JA, Fuxe K. Adrenalectomy increases the number of substance P and somatostatin immunoreactive nerve cells in the rat lumbar dorsal root ganglia. Brain Res 1994; 640: 352-356 10.1016/0006-8993(94)91893-7 7516260
• 70 Silva C, Fuxe K, Chadi G. Involvement of astroglial fibroblast growth factor-2 and microglia in the nigral 6-OHDA parkinsonism and a possible role of glucocorticoid hormone on the glial mediated local trophism and wound repair. J Neural Transm Suppl 2009; 185-202 20411778
• 71 Follesa P, Wrathall JR, Mocchetti I. Increased basic fibroblast growth factor mRNA following contusive spinal cord injury. Brain Res Mol Brain Res 1994; 22: 1-8 10.1016/0169-328X(94)90026-4 8015371
• 72 Cuevas P, Carceller F, Gimenez-Gallego G. Acidic fibroblast growth factor prevents death of spinal cord motoneurons in newborn rats after nerve section. Neurol Res 1995; 17: 396-399 8584134
• 73 Vejsada R, Sagot Y, Kato AC. BDNF-mediated rescue of axotomized motor neurones decreases with increasing dose. Neuroreport 1994; 5: 1889-1892 10.1097/00001756-199410000-00012 7841370
• 74 Yan Q, Matheson C, Lopez OT, Miller JA. The biological responses of axotomized adult motoneurons to brain-derived neurotrophic factor. J Neurosci 1994; 14: 5281-5291 8083736
• 75 Sendtner M, Kreutzberg GW, Thoenen H. Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy. Nature 1990; 345: 440-441 10.1038/345440a0 2342575
• 76 Yan Q, Matheson C, Lopez OT. In vivo neurotrophic effects of GDNF on neonatal and adult facial motor neurons. Nature 1995; 373: 341-344 10.1038/373341a0 7830768
• 77 Sagot Y, Tan SA, Hammang JP, Aebischer P, Kato AC. GDNF slows loss of motoneurons but not axonal degeneration or premature death of pmn/pmn mice. J Neurosci 1996; 16: 2335-2341 8601813
• 78 Salinas RA, Alvarez G, Ferreira J. Corticosteroids for Bell’s palsy (idiopathic facial paralysis). Cochrane Database Syst Rev (Online) 2010;
• 79 Milani P, Mondelli M, Ginanneschi F, Mazzocchio R, Rossi A. Progesterone - new therapy in mild carpal tunnel syndrome? Study design of a randomized clinical trial for local therapy. J Brachial Plex Peripher Nerve Inj 2010; 5: 11 10.1186/1749-7221-5-11 2873263 20420674
• 80 Chao HM, Sakai RR, Ma LY, McEwen BS. Adrenal steroid regulation of neurotrophic factor expression in the rat hippocampus. Endocrinology 1998; 139: 3112-3118 10.1210/en.139.7.3112 9645683
• 81 Laping NJ, Nichols NR, Day JR, Finch CE. Corticosterone differentially regulates the bilateral response of astrocyte mRNAs in the hippocampus to entorhinal cortex lesions in male rats. Brain Res Mol Brain Res 1991; 10: 291-297 10.1016/0169-328X(91)90087-E 1717807
• 82 Pollock JD, Krempin M, Rudy B. Differential effects of NGF, FGF, EGF, cAMP, and dexamethasone on neurite outgrowth and sodium channel expression in PC12 cells. J Neurosci 1990; 10: 2626-2637 2167354
• 83 Barbany G, Persson H. Adrenalectomy attenuates kainic acid-elicited increases of messenger RNAs for neurotrophins and their receptors in the rat brain. Neuroscience 1993; 54: 909-922 10.1016/0306-4522(93)90584-3 8341424
• 84 Chao HM, McEwen BS. Glucocorticoids and the expression of mRNAs for neurotrophins, their receptors and GAP-43 in the rat hippocampus. Brain Res Mol Brain Res 1994; 26: 271-276 10.1016/0169-328X(94)90099-X 7854057
• 85 Riva MA, Fumagalli F, Blom JM, Donati E, Racagni G. Adrenalectomy reduces FGF-1 and FGF-2 gene expression in specific rat brain regions and differently affects their induction by seizures. Brain Res Mol Brain Res 1995; 34: 190-196 10.1016/0169-328X(95)00157-N 8750822
• 86 Riva MA, Fumagalli F, Racagni G. Opposite regulation of basic fibroblast growth factor and nerve growth factor gene expression in rat cortical astrocytes following dexamethasone treatment. J Neurochem 1995; 64: 2526-2533 10.1046/j.1471-4159.1995.64062526.x 7760032
• 87 Smith MA, Makino S, Kvetnansky R, Post RM. Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 1995; 15: 1768-1777 7891134
• 88 Fuxe K, Tinner B, Chadi G, Harfstrand A, Agnati LF. Evidence for a regional distribution of hyaluronic acid in the rat brain using a highly specific hyaluronic acid recognizing protein. Neurosci Lett 1994; 169: 25-30 10.1016/0304-3940(94)90348-4 7519339
• 89 Schultz GS, Wysocki A. Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen 2009; 17: 153-162 10.1111/j.1524-475X.2009.00466.x 19320882
• 90 Cardoso JR, Teixeira EC, Moreira MD, Favero FM, Fontes SV, Bulle de Oliveira AS. Effects of exercises on Bell’s palsy: systematic review of randomized controlled trials. Otol Neurotol 2008; 29: 557-560 10.1097/MAO.0b013e31816c7bf1 18520590
• 91 Finsterer J. Management of peripheral facial nerve palsy. Eur Arch Otorhinolaryngol 2008; 265: 743-752 10.1007/s00405-008-0646-4 2440925 18368417
• 92 Hadlock T, Lindsay R, Edwards C, Smitson C, Weinberg J, Knox C, Heaton JT. The effect of electrical and mechanical stimulation on the regenerating rodent facial nerve. Laryngoscope 2010; 120: 1094-1102 20513023
• 93 Irintchev A, Angelov DN, Guntinas-Lichius O. Regeneration of the facial nerve in comparison to other peripheral nerves : from bench to bedside. Hno 2010; 58: 426-432 10.1007/s00106-010-2100-3 20454881
• 94 Skouras E, Merkel D, Grosheva M, Angelova SK, Schiffer G, Thelen U, Kaidoglou K, Sinis N, Igelmund P, Dunlop SA, Pavlov S, Irintchev A, Angelov DN. Manual stimulation, but not acute electrical stimulation prior to reconstructive surgery, improves functional recovery after facial nerve injury in rats. Restor Neurol Neurosci 2009; 27: 237-251 19531878
• 95 Sinis N, Horn F, Genchev B, Skouras E, Merkel D, Angelova SK, Kaidoglou K, Michael J, Pavlov S, Igelmund P, Schaller HE, Irintchev A, Dunlop SA, Angelov DN. Electrical stimulation of paralyzed vibrissal muscles reduces endplate reinnervation and does not promote motor recovery after facial nerve repair in rats. Ann Anat 2009; 191: 356-370 10.1016/j.aanat.2009.03.004 19481914
• 96 Sapmaz E, Kaygusuz I, Alpay HC, Akpolat N, Keles E, Karlidag T, Orhan I, Yalcin S. Histopathologic and functional effects of facial nerve following electrical stimulation. Eur Arch Otorhinolaryngol 2010; 267: 607-612 10.1007/s00405-009-1107-4 19784664
• 97 Otto RA. Restoration of function in the paralyzed rabbit orbicularis oculi muscle by direct functional electrical stimulation. Laryngoscope 1997; 107: 101-111 10.1097/00005537-199701000-00020 9001273
• 98 Rothstein J, Berlinger NT. Electronic reanimation of facial paralysis–a feasibility study. Otolaryngol Head Neck Surg 1986; 94: 82-85 3081862
• 99 Tobey DN, Sutton D. Contralaterally elicited electrical stimulation of paralyzed facial muscles. Otolaryngology 1978; 86: 812-818
• 100 Hetzler LE, Sharma N, Tanzer L, Wurster RD, Leonetti J, Marzo SJ, Jones KJ, Foecking EM. Accelerating functional recovery after rat facial nerve injury: Effects of gonadal steroids and electrical stimulation. Otolaryngol Head Neck Surg 2008; 139: 62-67 10.1016/j.otohns.2008.02.006 18585563
• 101 Sharma N, Marzo SJ, Jones KJ, Foecking EM. Electrical stimulation and testosterone differentially enhance expression of regeneration-associated genes. Exp Neurol 2010; 223: 183-191 10.1016/j.expneurol.2009.04.031 19427307