Effect of PACAP in central and peripheral nerve injuries

International Journal of Molecular Sciences

Volumn 13, Issue 7, 2012, Pages 8430-8448

  Tamas, Andrea ^a   Reglodi, Dora ^a   Farkas, Orsolya ^a   Kovesdi, Erzsebet ^a   Pal, Jozsef ^a   Povlishock, John T ^b   Schwarcz, Attila ^a   Czeiter, Endre ^a   Szanto, Zalan ^c   Doczi, Tamas ^a   Buki, Andras ^a   Bukovics, Peter ^a  

^a UNIVERSITY OF PÉCS   (Hungary)

^b VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^c UNIVERSITY OF PÉCS   (Hungary)

Author keywords

Endogenous; Injury; Neuroprotection; Pituitary adenylate cyclase activating polypeptide; Trauma

Indexed keywords

AMYLOID PRECURSOR PROTEIN; CALCIUM ION; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE 27; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE RECEPTOR 1; VASOACTIVE INTESTINAL POLYPEPTIDE RECEPTOR 1; VASOACTIVE INTESTINAL POLYPEPTIDE RECEPTOR 2; NEUROPROTECTIVE AGENT;

AUTONOMIC GANGLION; CALCIUM TRANSPORT; CYTOKINE RELEASE; DIFFUSE AXONAL INJURY; DRUG EFFICACY; FACIAL NERVE INJURY; GENE EXPRESSION; HEAD INJURY; HUMAN; MEDIAL LONGITUDINAL BUNDLE; MESENCHYMAL STEM CELL; NERVE COMPRESSION; NERVE FIBER TRANSECTION; NERVE REGENERATION; NERVE TRANSECTION; NEUROPROTECTION; NONHUMAN; OPTIC NERVE INJURY; PERIPHERAL NERVE INJURY; PYRAMIDAL TRACT; REVIEW; SPINAL CORD INJURY; SPINAL GANGLION; SYMPATHECTOMY; TRAUMATIC BRAIN INJURY; UPREGULATION; ANIMAL; BRAIN INJURIES; METABOLISM; PATHOPHYSIOLOGY; PERIPHERAL NERVE INJURIES; PHYSIOLOGY; SPINAL CORD INJURIES;

ANIMALS; BRAIN INJURIES; HUMANS; NERVE REGENERATION; NEUROPROTECTIVE AGENTS; PERIPHERAL NERVE INJURIES; PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE; SPINAL CORD INJURIES;

EID: 84864352714     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms13078430     Document Type: Review

References (109)

1. Miyata, A.; Jiang, L.; Dahl, R.D.; Kitada, C.; Kubo, K.; Fujino, M.; Minamino, N.; Arimura, A. Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38). Biochem. Biophys. Res. Commun. 1990, 170, 643-648.
2. Sherwood, N.M.; Krueckl, S.L.; McRory, J.E. The origin and function of the pituitary adenylate cyclase-activating polypeptide (PACAP)/glucagon superfamily. Endocr. Rev. 2000, 21, 619-670.
3. Vaudry, D.; Falluel-Morel, A.; Bourgault, S.; Basille, M.; Burel, D.; Wurtz, O.; Fournier, A.; Chow, B.K.; Hashimoto, H.; Galas, L.; Vaudry, H. Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery. Pharmacol. Rev. 2009, 61, 283-357.
4. Arimura, A.; Somogyvari-Vigh, A.; Weill, C.; Fiore, R.C.; Tatsuno, I.; Bay, V.; Brenneman, D.E. PACAP. functions as a neurotrophic factor. Ann. N. Y. Acad. Sci. 1994, 739, 228-243.
5. Somogyvari-Vigh, A.; Reglodi, D. Pituitary adenylate cyclase activating polypeptide: A potential neuroprotective peptide. Curr. Pharm. Des. 2004, 10, 2861-2889.
6. Botia, B.; Basille, M.; Allais, A.; Raoult, E.; Falluel-Morel, A.; Galas, L.; Jolivel, V.; Wurtz, O.; Komuro, H.; Fournier, A.; et al. Neurotrophic effects of PACAP in the cerebellar cortex. Peptides 2007, 28, 1746-1752.
7. Ravni, A.; Bourgault, S.; Lebon, A.; Chan, P.; Galas, L.; Fournier, A.; Vaudry, H.; Gonzalez, B.; Eiden, L.E.; Vaudry, D. The neurotrophic effects of PACAP in PC12 cells: Control by multiple transduction pathways. J. Neurochem. 2006, 98, 321-329.
8. Dejda, A.; Sokołowska, P.; Nowak, J.Z. Neuroprotective potential of three neuropeptides PACAP, VIP and PHI. Pharmacol. Rep. 2005, 57, 307-320.
9. Dejda, A.; Jolivel, V.; Bourgault, S.; Seaborn, T.; Fournier, A.; Vaudry, H.; Vaudry, D. Inhibitory effect of PACAP on caspase activity in neuronal apoptosis: A better understanding towards therapeutic applications in neurodegenerative diseases. J. Mol. Neurosci. 2008, 36, 26-37.
10. Brenneman, D.E. Neuroprotection: A comparative view of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Peptides 2007, 28, 1720-1726.
11. Ohtaki, H.; Nakamachi, T.; Dohi, K.; Shioda, S. Role of PACAP in ischemic neural death. J. Mol. Neurosci. 2008, 36, 16-25.
12. Bourgault, S.; Vaudry, D.; Dejda, A.; Doan, N.D.; Vaudry, H.; Fournier, A. Pituitary adenylate cyclase-activating polypeptide: Focus on structure-activity relationships of a neuroprotective peptide. Curr. Med. Chem. 2009, 16, 4462-4480.
13. Bourgault, S.; Chatenet, D.; Wurtz, O.; Doan, N.D.; Leprince, J.; Vaudry, H.; Fournier, A.; Vaudry, D. Strategies to convert PACAP from a hypophysiotropic neurohormone into a neuroprotective drug. Curr. Pharm. Des. 2011, 17, 1002-1024.
14. Atlasz, T.; Szabadfi, K.; Kiss, P.; Racz, B.; Gallyas, F.; Tamas, A.; Gaal, V.; Marton, Z.; Gabriel, R.; Reglodi, D. Pituitary adenylate cyclase activating polypeptide in the retina: Focus on the retinoprotective effects. Ann. N. Y. Acad. Sci. 2010, 1200, 128-139.
15. Nakamachi, T.; Farkas, J.; Watanabe, J.; Ohtaki, H.; Dohi, K.; Arata, S.; Shioda, S. Role of PACAP in neural stem/progenitor cell and astrocyte-From neural development to neural repair. Curr. Pharm. Des. 2011, 17, 973-984.
16. Reglodi, D.; Kiss, P.; Lubics, A.; Tamas, A. Review on the protective effects of PACAP in models of neurodegenerative diseases in vitro and in vivo. Curr. Pharm. Des. 2011, 17, 962-972.
17. Dietrich, W.D.; Alonso, O.; Busto, R.; Finklestein, S.P. Posttreatment with intravenous basic fibroblast growth factor reduces histopathological damage following fluid-percussion brain injury in rats. J. Neurotrauma 1996, 13, 309-316.
18. Kawamata, T.; Dietrich, W.D.; Schallert, T.; Gotts, J.E.; Cocke, R.R.; Benowitz, L.I.; Finklestein, S.P. Intracisternal basic fibroblast growth factor enhances functional recovery and up-regulates the expression of a molecular marker of neuronal sprouting following focal cerebral infarction. Proc. Natl. Acad. Sci. USA 1997, 94, 8179-8184.
19. Truettner, J.; Schmidt-Kastner, R.; Busto, R.; Alonso, O.F.; Loor, J.Y.; Dietrich, W.D.; Ginsberg, M.D. Expression of brain-derived neurotrophic factor, nerve growth factor, and heat shock protein HSP70 following fluid percussion brain injury in rats. J. Neurotrauma 1999, 16, 471-486.
20. Leker, R.R.; Shohami, E. Cerebral ischemia and trauma-different etiologies yet similar mechanisms: Neuroprotective opportunities. Brain Res. Rev. 2002, 39, 55-73.
21. Povlishock, J.T. Traumatically induced axonal injury: Pathogenesis and pathobiological implications. Brain Pathol. 1992, 2, 1-12.
22. Maxwell, W.L.; Povlishock, J.T.; Graham, D.L. A mechanistic analysis of nondisruptive axonal injury: A review. J. Neurotrauma 1997, 14, 419-440.
23. Buki, A.; Okonkwo, D.O.; Wang, K.K.; Povlishock, J.T. Cytochrome c release and caspase activation in traumatic axonal injury. J. Neurosci. 2000, 20, 2825-2834.
24. Bramlett, H.M.; Dietrich, W.D. Pathophysiology of cerebral ischemia and brain trauma: Similarities and differences. J. Cereb. Blood Flow Metab. 2004, 24, 133-150.
25. Uchida, D.; Arimura, A.; Somogyvari-Vigh, A.; Shioda, S.; Banks, W.A. Prevention of ischemia-induced death of hippocampal neurons by pituitary adenylate cyclase activating polypeptide. Brain Res. 1996, 736, 280-286.
26. Reglodi, D.; Somogyvari-Vigh, A.; Vigh, S.; Kozicz, T.; Arimura, A. Delayed systemic administration of PACAP38 is neuroprotective in transient middle cerebral artery occlusion in the rat. Stroke 2000, 31, 1411-1417.
27. Reglodi, D.; Tamas, A.; Somogyvari-Vigh, A.; Szanto, Z.; Kertes, E.; Lenard, L.; Arimura, A.; Lengvari, I. Effects of pretreatment with PACAP on the infarct size and functional outcome in rat permanent focal cerebral ischemia. Peptides 2002, 23, 2227-2234.
28. Tamas, A.; Reglodi, D.; Szanto, Z.; Borsiczky, B.; Nemeth, J.; Lengvari, I. Comparative neuroprotective effects of preischemic PACAP and VIP administration in permanent occlusion of the middle cerebral artery in rats. Neuroendocrinol. Lett. 2002, 23, 249-254.
29. Waschek, J.A. Multiple action of pituitary adenyly cyclase activating peptide in nervous system development and regeneration. Dev. Neurosci. 2002, 24, 14-23.
30. Rink, A.; Fung, K.M.; Trojanowski, J.Q.; Lee, V.M.; Neugebauer, E.; McIntosh, T.K. Evidence of apoptotic cell death after experimental traumatic brain injury in the rat. Am. J. Pathol. 1995, 147, 1575-1583.
31. Skoglosa, Y.; Takei, N.; Lindholm, D. Distribution of pituitary adenylate cyclase activating polypeptide mRNA in the developing rat brain. Mol. Brain Res. 1999, 65, 1-13.
32. Watanabe, J.; Nakamachi, T.; Matsuno, R.; Hayashi, D.; Nakamura, M.; Kikuyama, S.; Nakajo, S.; Shioda, S. Localization, characterization and function of pituitary adenylate cyclase-activating polypeptide during brain development. Peptides 2007, 28, 1713-1719.
33. Skoglosa, Y.; Lewen, A.; Takei, N.; Hillered, L.; Lindholm, D. Regulation of pituitary adenylate cyclase activating polypeptide and its receptor type 1 after traumatic brain injury: Comparison with brain-derived neurotrophic factor and the induction of neuronal cell death. Neuroscience 1999, 90, 235-247.
34. Van Landeghem, F.K.; Weiss, T.; Oehmichen, M.; von Deimling, A. Cellular localization of pituitary adenylate cyclase-activating peptide (PACAP) following traumatic brain injury in humans. Acta Neuropathol. 2007, 113, 683-693.
35. Jaworski, D.M. Expression of pituitary adenylate cyclase-activating polypeptide (PACAP) and the PACAP-selective receptor in cultured rat astrocytes, human brain tumors, and in response to acute intracranial injury. Cell Tissue Res. 2000, 300, 219-230.
36. Ma, W.; Bisby, M.A. Ultrastructural localization of increased neuropeptide immunoreactivity in the axons and cells of the gracile nucleus following chronic constriction injury of the sciatic nerve. Neuroscience 1999, 93, 335-348.
37. Dun, N.J.; Miyazaki, T.; Tang, H.; Dun, E.C. Pituitary adenylate cyclase activating polypeptide immunoreactivity in the rat spinal cord and medulla: Implication of sensory and autonomic functions. Neuroscience 1996, 73, 677-686.
38. Pettersson, L.M.; Heine, T.; Verge, V.M.; Sundler, F.; Danielsen, N. PACAP mRNA is expressed in rat spinal cord neurons. J. Comp. Neurol. 2004, 471, 85-96.
39. Kim, W.K.; Kan, Y.; Ganea, D.; Hart, R.P.; Gozes, I.; Jonakait, G.M. Vasoactive intestinal peptide and pituitary adenylyl cyclase-activating polypeptide inhibit tumor necrosis factor-alpha production in injured spinal cord and in activated microglia via a cAMP-dependent pathway. J. Neurosci. 2000, 20, 3622-3630.
40. Tsuchikawa, D.; Nakamachi, T.; Tsuchida, M.; Wada, Y.; Hori, M.; Farkas, J.; Yoshikawa, A.; Kagami, N.; Imai, N.; Shintani, N.; et al. Neuroprotective effect of endogenous pituitary adenylate cyclase-activating polypeptide on spinal cord injury. J. Mol. Neurosi. 2012, doi:10.1007/s12031-012-9817-2.
41. Zhang, Q.; Shi, T.J.; Ji, R.R.; Zhang, Y.Z.; Sundler, F.; Hannibal, J.; Fahrenkrug, J.; Hokfelt, T. Expression of pituitary adenylate cyclase-activating polypeptide in dorsal root ganglia following axotomy: Time course and coexistence. Brain Res. 1995, 705, 149-158.
42. Zhang, Y.Z.; Hannibal, J.; Zhao, Q.; Moller, K.; Danielsen, N.; Fahrenkrug, J.; Sundler, F. Pituitary adenylate cyclase activating peptide expression in the rat dorsal root ganglia: Up-regulation after peripheral nerve injury. Neuroscience 1996, 74, 1099-1110.
43. Jongsma Wallin, H.; Danielsen, N.; Johnston, J.M.; Gratto, K.A.; Karchewski, L.A.; Verge, V.M. Exogenous NT-3 and NGF differentially modulate PACAP expression in adult sensory neurons, suggesting distinct roles in injury and inflammation. Eur. J. Neurosci. 2001, 14, 267-282.
44. Pettersson, L.M.; Dahlin, L.B.; Danielsen, N. Changes in expression of PACAP in rat sensory neurons in response to sciatic nerve compression. Eur. J. Neurosci. 2004, 20, 1838-1848.
45. Dickinson, T.; Mitchell, R.; Robberecht, P.; Fleetwood-Walker, S.M. The role of VIP/PACAP receptor subtypes in spinal somatosensory processing in rats with an experimental peripheral mononeuropathy. Neuropharmacology 1999, 38, 167-180.
46. Moller, K.; Reimer, M.; Ekblad, E.; Hannibal, J.; Fahrenkrug, J.; Kanje, M.; Sundler, F. The effects of axotomy and preganglionic denervation on the expression of pituitary adenylate cyclase activating peptide (PACAP), galanin and PACAP type 1 receptors in the rat superior cervical ganglion. Brain Res. 1997, 775, 166-182.
47. Klimaschewski, L.; Hauser, C.; Heym, C. PACAP immunoreactivity in the rat superior cervical ganglion in comparison to VIP. Neuroreport 1996, 7, 2797-2801.
48. Zhou, X.; Rodriguez, W.I.; Casillas, R.A.; Ma, V.; Tam, J.; Hu, Z.; Lelievre, V.; Chao, A.; Waschek, J.A. Axotomy-induced changes in pituitary adenylate cyclase activating polypeptide (PACAP) and PACAP receptor gene expression in the adult rat facial motor nucleus. J. Neurosci. Res. 1999, 57, 953-961.
49. Armstrong, B.D.; Abad, C.; Chhith, S.; Cheung-Lau, G.; Hajji, O.E.; Nobuta, H.; Waschek, J.A. Impaired nerve regeneration and enhanced neuroinflammatory response in mice lacking pituitary adenylyl cyclase activating peptide. Neuroscience 2008, 151, 63-73.
50. Larsen, J.O.; Hannibal, J.; Knudsen, S.M.; Fahrenkrug, J. Expression of pituitary adenylate cyclase-activating polypeptide (PACAP) in the mesencephalic trigeminal nucleus of the rat after transsection of the masseteric nerve. Brain Res. Mol. Brain Res. 1997, 46, 109-117.
51. Buki, A.; Povlishock, J.T. All roads lead to disconnection?-Traumatic axonal injury revisited. Acta Neurochir. Wien 2006, 148, 181-193.
52. Buki, A.; Kovesdi, E.; Pal, J.; Czeiter, E. Clinical and Model Research of Neurotrauma. In Neuroproteomics; Ottens, A.K., Wang, K.K., Eds.; Humana Press: New York, NY, USA, 2009; pp. 41-57.
53. Foda, M.A.; Marmarou, A. A new model of diffuse brain injury in rats. Part II: Morphological characterization. J. Neurosurg. 1994, 80, 301-313.
54. Marmarou, A.; Foda, M.A.; van den Brink, W.; Campbell, J.; Kita, H.; Demetriadou, K. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J. Neurosurg. 1994, 80, 291-300.
55. Gentleman, S.M.; Nash, M.J.; Sweeting, C.J.; Graham, D.I.; Roberts, G.W. Beta-amyloid precursor protein (beta APP) as a marker for axonal injury after head injury. Neurosci. Lett. 1993, 160, 139-144.
56. Stone, J.R.; Singleton, R.H.; Povlishock, J.T. Antibodies to the C-terminus of the beta-amyloid precursor protein (APP): A site specific marker for the detection of traumatic axonal injury. Brain Res. 2000, 871, 288-302.
57. Lee, V.M.; Carden, M.J.; Schlaepfer, W.W.; Trojanowski, J.Q. Monoclonal antibodies distinguish several differentially phosphorylated states of the two largest rat neurofilament subunits (NF-H and NF-M) and demonstrate their existence in the normal nervous system of adult rats. J. Neurosci. 1987, 7, 3474-3488.
58. Povlishock, J.T.; Marmarou, A.; McIntosh, T.; Trojanowski, J.Q.; Moroi, J. Impact acceleration injury in the rat: Evidence for focal axolemmal change and related neurofilament sidearm alteration. J. Neuropathol. Exp. Neurol. 1997, 56, 347-359.
59. Okonkwo, D.O.; Pettus, E.H.; Moroi, J.; Povlishock, J.T. Alteration of the neurofilament sidearm and its relation to neurofilament compaction occurring with traumatic axonal injury. Brain Res. 1998, 784, 1-6.
60. Farkas, O.; Tamas, A.; Zsombok, A.; Reglodi, D.; Pal, J.; Buki, A.; Lengvari, I.; Povlishock, J.T.; Doczi, T. Effects of pituitary adenylate cyclase activating polypeptide in a rat model of traumatic brain injury. Regul. Pept. 2004, 123, 69-75.
61. Tamas, A.; Zsombok, A.; Farkas, O.; Reglodi, D.; Pal, J.; Buki, A.; Lengvari, I.; Povlishock, J.T.; Doczi, T. Postinjury administration of pituitary adenylate cyclase activating polypeptide (PACAP) attenuates traumatically induced axonal injury in rats. J. Neurotrauma 2006, 23, 686-695.
62. Kovesdi, E.; Tamas, A.; Reglodi, D.; Bukovics, P.; Toth, G.; Doczi, T.; Hernadi, I.; Buki, A. Behavioral aspects of posttraumatic administration of PACAP using a rat model of impact acceleration head injury. J. Mol. Neurosci. 2007, 33, 330 (abstract).
63. Dixon, C.E.; Lyeth, B.G.; Povlishock, J.T.; Findling, R.L.; Hamm, R.J.; Marmarou, A.; Young, H.F.; Hayes, R.L. A fluid percussion model of experimental brain injury in the rat. J. Neurosurg. 1987, 67, 110-119.
64. McIntosh, T.K.; Noble, L.; Andrews, B.; Faden, A.I. Traumatic brain injury in the rat: Characterization of a midline fluid-percussion model. Cent. Nerv. Syst. Trauma 1987, 4, 119-134.
65. Kovesdi, E.; Tamas, A.; Reglodi, D.; Farkas, O.; Pal, J.; Toth, G.; Bukovics, P.; Doczi, T.; Buki, A. Posttraumatic administration of pituitary adenylate cyclase activating polypeptide in central fluid percussion injury in rats. Neurotox. Res. 2008, 13, 71-78.
66. Povlishock, J.T.; Stone, J.R. Traumatic Axonal Injury. In Head Trauma:Basic, Preclinical and Clinical Directions; Miller, L.P., Hayes, R.L., Eds.; Wiley: New York, NY, USA, 2001.
67. Suehiro, E.; Singleton, R.H.; Stone, J.R.; Povlishock, J.T. The immunophilin ligand FK506 attenuates the axonal damage associated with rapid rewarming following posttraumatic hypothermia. Exp. Neurol. 2001, 172, 199-210.
68. Chen, W.H.; Tzeng, S.F. Pituitary adenylate cyclase-activating polypeptide prevents cell death in the spinal cord with traumatic injury. Neurosci. Lett. 2005, 384, 117-121.
69. Fang, K.M.; Chen, J.K.; Hung, S.C.; Chen, M.C.; Wu, Y.T.; Wu, T.J.; Lin, H.I.; Chen, C.H.; Cheng, H.; Yang, C.S.; Tzeng, S.F. Effects of combinatorial treatment with pituitary adenylate cyclase activating peptide and human mesenchymal stem cells on spinal cord tissue repair. PLoS One 2010, 5, doi:10.1371/journal.pone.0015299.
70. Kimura, H.; Kawatani, M.; Ito, E.; Ishikawa, K. PACAP facilitate the nerve regeneration factors in the facial nerve injury. Regul. Pept. 2004, 123, 135-138.
71. Seki, T.; Itoh, H.; Nakamachi, T.; Shioda, S. Suppression of ganglion cell death by PACAP following optic nerve transection in the rat. J. Mol. Neurosci. 2008, 36, 57-60.
72. Mulder, H.; Jongsma, H.; Zhang, Y.; Gebre-Medhin, S.; Sundler, F.; Danielsen, N. Pituitary adenylate cyclase-activating polypeptide and islet amyloid polypeptide in primary sensory neurons: Functional implications from plasticity in expression on nerve injury and inflammation. Mol. Neurobiol. 1999, 19, 229-253.
73. Aldskogius, H.; Arvidsson, J.; Grant, G. The reaction of primary sensory neurons to peripheral nerve injury with particular emphasis on transganglionic changes. Brain Res. 1985, 357, 27-46.
74. Moller, K.; Zhang, Y.Z.; Hakanson, R.; Luts, A.; Sjolund, B.; Uddman, R.; Sundler, F. Pituitary adenylate cyclase activating peptide is a sensory neuropeptide: Immunocytochemical and immunochemical evidence. Neuroscience 1993, 57, 725-732.
75. Mulder, H.; Uddman, R.; Moller, K.; Zhang, Y.Z.; Ekblad, E.; Alumets, J.; Sundler, F. Pituitary adenylate cyclase activating polypeptide expression in sensory neurons. Neuroscience 1994, 63, 307-312.
76. Dun, E.C.; Huang, R.L.; Dun, S.L.; Dun, N.J. Pituitary adenylate cyclase activating polypeptide-immunoreactivity in human spinal cord and dorsal root ganglia. Brain Res. 1996, 721, 233-237.
77. Jongsma, H.; Danielsen, N.; Sundler, F.; Kanje, M. Alterations of PACAP and PACAP receptor binding in sensory neurons following peripheral axotomy. Soc. Neurosci. Abstr. 1998, 24, 2049.
78. Mulder, H.; Uddman, R.; Moller, K.; Elsas, T.; Ekblad, E.; Alumets, J.; Sundler, F. Pituitary adenylate cyclase activating polypeptide is expressed in autonomic neurons. Regul. Pept. 1995, 59, 121-128.
79. Sundler, F.; Ekblad, E.; Hannibal, J.; Moller, K.; Zhang, Y.Z.; Mulder, H.; Elsas, T.; Grunditz, T.; Danielsen, N.; Fahrenkrug, J.; Uddman, R. Pituitary adenylate cyclase-activating peptide in sensory and autonomic ganglia: Localization and regulation. Ann. N. Y. Acad. Sci. 1996, 805, 410-426; discussion 427-428.
80. Uddman, R.; Tajti, J.; Moller, S.; Sundler, F.; Edvinsson, L. Neuronal messengers and peptide receptors in the human sphenopalatine and otic ganglia. Brain Res. 1999, 826, 193-199.
81. May, V.; Braas, K.M. Pituitary adenylate cyclase activating polypeptide (PACAP) regulation of sympathetic neuron neuropeptide Y and cathecolamine expression. J. Neurochem. 1995, 65, 978-987.
82. Rohlmann, A.; Laskawi, R.; Hofer, A.; Dermietzel, R.; Wolff, J.R. Astrocytes as rapid sensors of peripheral axotomy in the facial nucleus of rats. Neuroreport 1994, 5, 409-412.
83. Armstrong, B.D.; Hu, Z.; Abad, C.; Yamamoto, M.; Rodriguez, W.I.; Cheng, J.; Tam, J.; Gomariz, R.P.; Patterson, P.H.; Waschek, J.A. Lymphocyte regulation of neuropeptide gene expression after neuronal injury. J. Neurosci. Res. 2003, 74, 240-247.
84. Suarez, V.; Guntinas-Lichius, O.; Streppel, M.; Ingorokva, S.; Grosheva, M.; Neiss, W.F.; Angelov, D.N.; Klimaschewski, L. The axotomy-induced neuropeptides galanin and pituitary adenylate cyclase-activating peptide promote axonal sprouting of primary afferent and cranial motor neurones. Eur. J. Neurosci. 2006, 24, 1555-1564.
85. Murray, C.J.; Lopez, A.D. Global mortality, disability, and the contribution of risk factors: Global burden of disease study. Lancet 1997, 349, 1436-1442.
86. Langlois, J.A.; Rutland-Brown, W.; Wald, M.M. The epidemiology and impact of traumatic brain injury: A brief overview. J. Head Trauma Rehabil. 2006, 21, 375-378.
87. Narayan, R.K.; Michel, M.E.; Ansell, B.; Baethmann, A.; Biegon, A.; Bracken, M.B.; Bullock, M.R.; Choi, S.C.; Clifton, G.L.; Contant, C.F.; et al. Clinical trials in head injury. J. Neurotrauma 2002, 19, 503-557.
88. Saatman, K.E.; Duhaime, A.C.; Bullock, R.; Maas, A.I.; Valadka, A.; Manley, G.T. Classification of traumatic brain injury for targeted therapies. J. Neurotrauma 2008, 25, 719-738.
89. Ghajar, J.E. The future of traumatic brain injury. Mt. Sinai J. Med. 2009, 76, 190-193.
90. Canonico, P.L.; Copani, A.; D'Agata, V.; Musco, S.; Petralia, S.; Travali, S.; Stivala, F.; Cavallaro, S. Activation of pituitary adenylate cyclase-activating polypeptide receptors prevents apoptotic cell death in cultured cerebellar granule cells. Ann. N. Y. Acad. Sci. 1996, 805, 470-472.
91. Tanaka, J.; Koshimura, K.; Murakami, Y.; Sohmiya, M.; Yanaihara, N.; Kato, Y. Neuronal protection from apoptosis by pituitary adenylate cyclase-activating polypeptide. Regul. Pept. 1997, 72, 1-8.
92. Shioda, S.; Ozawa, H.; Dohi, K.; Mizushima, H.; Matsumoto, K.; Nakajo, S.; Takaki, A.; Zhou, C.J.; Nakai, Y.; Arimura, A. PACAP protects hippocampal neurons against apoptosis: Involvement of JNK/SAPK signaling pathway. Ann. N. Y. Acad. Sci. 1998, 865, 111-117.
93. Racz, B.; Gasz, B.; Borsiczky, B.; Gallyas, F., Jr.; Tamas, A.; Jozsa, R.; Lubics, A.; Kiss, P.; Roth, E.; Ferencz, A.; et al. Protective effects of pituitary adenylate cyclase activating polypeptide in endothelial cells against oxidative stress-induced apoptosis. Gen. Comp. Endocrinol. 2007, 153, 115-123.
94. Racz, B.; Gasz, B.; Gallyas, F., Jr.; Kiss, P.; Tamas, A.; Szanto, Z.; Lubics, A.; Lengvari, I.; Toth, G.; Hegyi, O.; et al. PKA-Bad-14-3-3 and Akt-Bad-14-3-3 signaling pathways are involved in the protective effects of PACAP against ischemia/reperfusion-induced cardiomyocyte apoptosis. Regul. Pept. 2008, 145, 105-115.
95. Seaborn, T.; Masmoudi-Kouli, O.; Fournier, A.; Vaudry, H.; Vaudry, D. Protective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) against apoptosis. Curr. Pharm. Des. 2011, 17, 204-214.
96. Povlishock, J.T.; Katz, D.I. Update of neuropathology and neurological recovery after traumatic brain injury. J. Head Trauma Rehabil. 2005, 20, 76-94.
97. Hirsch, T.; Susin, S.A.; Marzo, I.; Marchetti, P.; Zamzami, N.; Kroemer, G. Mitochondrial permeability transition in apoptosis and necrosis. Cell Biol. Toxicol. 1998, 14, 141-145.
98. Susin, S.A.; Zamzami, N.; Kroemerm, G. Mitochondria as regulators of apoptosis: Doubt no more. Biochim. Biophys. Acta 1998, 1366, 151-165.
99. Susin, S.A.; Lorenzo, H.K.; Zamzami, N.; Marzo, I.; Snow, B.E.; Brothers, G.M.; Mangion, J.; Jacotot, E.; Costantini, P.; Loeffler, M.; et al. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 1999, 397, 441-446.
100. Yakovlev, A.G.; Faden, A.I. Mechanisms of neural cell death: Implications for development of neuroprotective treatment strategies. NeuroRx 2004, 1, 5-16.
101. Tabuchi, A.; Funaji, K.; Nakatsubo, J.; Fukuchi, M.; Tsuchiya, T.; Tsuda, M. Inactivation of aconitase during the apoptosis of mouse cerebellar granule neurons induced by a deprivation of membrane depolarization. J. Neurosci. Res. 2003, 71, 504-515.
102. Racz, B.; Horvath, G.; Reglodi, D.; Gasz, B.; Kiss, P.; Gallyas, F., Jr.; Sumegi, B.; Toth, G.; Nemeth, A.; Lubics, A.; et al. PACAP ameliorates oxidative stress in the chicken inner ear: An in vitro study. Regul. Pept. 2010, 160, 91-98.
103. Delgado, M.; Jonakait, G.M.; Ganea, D. Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit chemokine production in activated microglia. Glia 2002, 39, 148-161.
104. Delgado, M.; Abad, C.; Martinez, C.; Juarranz, M.G.; Leceta, J.; Ganea, D.; Gomariz, R.P. PACAP in immunity and inflammation. Ann. N. Y. Acad. Sci. 2003, 992, 141-157.
105. Ganea, D.; Delgado, M. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as modulators of both innate and adaptive immunity. Crit. Rev. Oral Biol. Med. 2002, 13, 229-237.
106. Delgado, M.; Pozo, D.; Martinez, C.; Leceta, J.; Calvo, J.R.; Ganea, D.; Gomariz, R.P. Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit endotoxin-induced TNF-alpha production by macrophages: In vitro and in vivo studies. J. Immunol. 1999, 162, 2358-2367.
107. Buki, A.; Okonkwo, D.O.; Povlishock, J.T. Postinjury cyclosporin A administration limits axonal damage and disconnection in traumatic brain injury. J. Neurotrauma 1999, 16, 511-521.
108. Okonkwo, D.O.; Melon, D.E.; Pellicane, A.J.; Mutlu, L.K.; Rubin, D.G.; Stone, J.R.; Helm, G.A. Dose-response of cyclosporin A in attenuating traumatic axonal injury in rat. Neuroreport 2003, 14, 463-466.
109. Fukui, S.; Signoretti, S.; Dunbar, J.G.; Marmarou, A. The effect of cyclosporin A on brain edema formation following experimental cortical contusion. Acta Neurochir. Suppl. 2003, 86, 301-303.