The Therapeutic Profile of Rolipram, PDE Target and Mechanism of Action as a Neuroprotectant following Spinal Cord Injury

PLoS ONE

Volumn 7, Issue 9, 2012, Pages

  Schaal, Sandra Marie ^a,b   Garg, Maneesh Sen ^a   Ghosh, Mousumi ^a   Lovera, Lilie ^a   Lopez, Michael ^a   Patel, Monal ^a   Louro, Jack ^a   Patel, Samik ^a   Tuesta, Luis ^a   Chan, Wai Man ^a   da Pearse, Damienniel ^a,b  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF MIAMI   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MONOCYTE CHEMOTACTIC PROTEIN 1; PHOSPHODIESTERASE IV; ROLIPRAM;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL INFILTRATION; CELL PROTECTION; CELL SURVIVAL; CONTROLLED STUDY; CYTOKINE PRODUCTION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; MYELINATION; NEUROPROTECTION; NONHUMAN; OLIGODENDROGLIA; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RAT; SPINAL CORD INJURY; STEREOLOGY; TISSUE PREPARATION;

ANIMALS; AXONS; CELL SURVIVAL; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 4; CYTOKINES; FEMALE; MOTOR ACTIVITY; NEUROGLIA; NEURONS; NEUROPROTECTIVE AGENTS; OLIGODENDROGLIA; PHAGOCYTES; PHOSPHODIESTERASE 4 INHIBITORS; PHOSPHORIC DIESTER HYDROLASES; PHOSPHORYLATION; RATS; ROLIPRAM; SPINAL CORD INJURIES; TIME FACTORS;

RATTUS;

EID: 84866533938     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0043634     Document Type: Article

References (130)

1. Hulsebosch CE, (2002) Recent advances in pathophysiology and treatment of spinal cord injury. Adv Physiol Educ 26: 238-255.
2. Beattie MS, (2004) Inflammation and apoptosis: linked therapeutic targets in spinal cord injury. Trends Mol Med 10: 580-583.
3. Keane RW, Davis AR, Dietrich WD, (2006) Inflammatory and apoptotic signaling after spinal cord injury. J Neurotrauma 23: 335-344.
4. Sipski ML, Pearse DD, (2006) Methylprednisolone and other confounders to spinal cord injury clinical trials. Nat Clin Pract Neurol 2: 402-403.
5. Hall ED, Braughler JM, McCall JM, (1992) Antioxidant effects in brain and spinal cord injury. J Neurotrauma 9 Suppl 1: S165-172.
6. Takami T, Oudega M, Bates ML, Wood PM, Kleitman N, et al. (2002) Schwann cell but not olfactory ensheathing glia transplants improve hindlimb locomotor performance in the moderately contused adult rat thoracic spinal cord. J Neurosci 22: 6670-6681.
7. Bradbury EJ, King VR, Simmons LJ, Priestley JV, McMahon SB, (1998) NT-3, but not BDNF, prevents atrophy and death of axotomized spinal cord projection neurons. Eur J Neurosci 10: 3058-3068.
8. Pearse DD, Chatzipanteli K, Marcillo AE, Bunge MB, Dietrich WD, (2003) Comparison of iNOS inhibition by antisense and pharmacological inhibitors after spinal cord injury. J Neuropathol Exp Neurol 62: 1096-1107.
9. Lo TP Jr, Cho KS, Garg MS, Lynch MP, Marcillo AE, et al. (2009) Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats. J Comp Neurol 514: 433-448.
10. Pearse DD, Marcillo AE, Oudega M, Lynch MP, Wood PM, et al. (2004) Transplantation of Schwann cells and olfactory ensheathing glia after spinal cord injury: does pretreatment with methylprednisolone and interleukin-10 enhance recovery? J Neurotrauma 21: 1223-1239.
11. Schaal SM, Kitay BM, Cho KS, Lo TP Jr, Barakat DJ, et al. (2007) Schwann cell transplantation improves reticulospinal axon growth and forelimb strength after severe cervical spinal cord contusion. Cell Transplant 16: 207-228.
12. Sutherland EW, Rall TW, (1960) Formation of adenosine-3,5-phosphate (cyclic adenylate) and its relation to the action of several neurohormones or hormones. Acta Endocrinol Suppl (Copenh) (Suppl 50) pp. 171-174.
13. Francis SH, Corbin JD, (1999) Cyclic nucleotide-dependent protein kinases: intracellular receptors for cAMP and cGMP action. Crit Rev Clin Lab Sci 36: 275-328.
14. Troadec JD, Marien M, Mourlevat S, Debeir T, Ruberg M, et al. (2002) Activation of the mitogen-activated protein kinase (ERK(1/2)) signaling pathway by cyclic AMP potentiates the neuroprotective effect of the neurotransmitter noradrenaline on dopaminergic neurons. Mol Pharmacol 62: 1043-1052.
15. Meyer-Franke A, Kaplan MR, Pfrieger FW, Barres BA, (1995) Characterization of the signaling interactions that promote the survival and growth of developing retinal ganglion cells in culture. Neuron 15: 805-819.
16. Prasad KN, Hsie AW, (1971) Morphologic differentiation of mouse neuroblastoma cells induced in vitro by dibutyryl adenosine 3′:5′-cyclic monophosphate. Nat New Biol 233: 141-142.
17. Ming GL, Song HJ, Berninger B, Holt CE, Tessier-Lavigne M, et al. (1997) cAMP-dependent growth cone guidance by netrin-1. Neuron 19: 1225-1235.
18. Rodger J, Goto H, Cui Q, Chen PB, Harvey AR, (2005) cAMP regulates axon outgrowth and guidance during optic nerve regeneration in goldfish. Mol Cell Neurosci 30: 452-464.
19. Pearse DD, Pereira FC, Marcillo AE, Bates ML, Berrocal YA, et al. (2004) cAMP and Schwann cells promote axonal growth and functional recovery after spinal cord injury. Nat Med 10: 610-616.
20. Atkins CM, Oliva AA Jr, Alonso OF, Pearse DD, Bramlett HM, et al. (2007) Modulation of the cAMP signaling pathway after traumatic brain injury. Exp Neurol 208: 145-158.
21. Beavo JA, (1995) Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol Rev 75: 725-748.
22. Souness JE, Rao S, (1997) Proposal for pharmacologically distinct conformers of PDE4 cyclic AMP phosphodiesterases. Cell Signal 9: 227-236.
23. Burnouf C, Pruniaux MP, (2002) Recent advances in PDE4 inhibitors as immunoregulators and anti-inflammatory drugs. Curr Pharm Des 8: 1255-1296.
24. Houslay MD, Schafer P, Zhang KY, (2005) Keynote review: phosphodiesterase-4 as a therapeutic target. Drug Discov Today 10: 1503-1519.
25. Lugnier C, (2006) Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents. Pharmacol Ther 109: 366-398.
26. Iona S, Cuomo M, Bushnik T, Naro F, Sette C, et al. (1998) Characterization of the rolipram-sensitive, cyclic AMP-specific phosphodiesterases: identification and differential expression of immunologically distinct forms in the rat brain. Mol Pharmacol 53: 23-32.
27. Verghese MW, McConnell RT, Lenhard JM, Hamacher L, Jin SL, (1995) Regulation of distinct cyclic AMP-specific phosphodiesterase (phosphodiesterase type 4) isozymes in human monocytic cells. Mol Pharmacol 47: 1164-1171.
28. Wachtel H, (1983) Neurotropic effects of the optical isomers of the selective adenosine cyclic 3′,5′-monophosphate phosphodiesterase inhibitor rolipram in rats in-vivo. J Pharm Pharmacol 35: 440-444.
29. Torphy TJ, Undem BJ, (1991) Phosphodiesterase inhibitors: new opportunities for the treatment of asthma. Thorax 46: 512-523.
30. Francischi JN, Yokoro CM, Poole S, Tafuri WL, Cunha FQ, et al. (2000) Anti-inflammatory and analgesic effects of the phosphodiesterase 4 inhibitor rolipram in a rat model of arthritis. Eur J Pharmacol 399: 243-249.
31. DeMarch Z, Giampa C, Patassini S, Martorana A, Bernardi G, et al. (2007) Beneficial effects of rolipram in a quinolinic acid model of striatal excitotoxicity. Neurobiol Dis 25: 266-273.
32. Sommer N, Martin R, McFarland HF, Quigley L, Cannella B, et al. (1997) Therapeutic potential of phosphodiesterase type 4 inhibition in chronic autoimmune demyelinating disease. J Neuroimmunol 79: 54-61.
33. Gong B, Vitolo OV, Trinchese F, Liu S, Shelanski M, et al. (2004) Persistent improvement in synaptic and cognitive functions in an Alzheimer mouse model after rolipram treatment. J Clin Invest 114: 1624-1634.
34. Navarro J, Punzon C, Jimenez JL, Fernandez-Cruz E, Pizarro A, et al. (1998) Inhibition of phosphodiesterase type IV suppresses human immunodeficiency virus type 1 replication and cytokine production in primary T cells: involvement of NF-kappaB and NFAT. J Virol 72: 4712-4720.
35. Jin SL, Conti M, (2002) Induction of the cyclic nucleotide phosphodiesterase PDE4B is essential for LPS-activated TNF-alpha responses. Proc Natl Acad Sci U S A 99: 7628-7633.
36. Thrivikraman KV, Huot RL, Plotsky PM, (2002) Jugular vein catheterization for repeated blood sampling in the unrestrained conscious rat. Brain Res Brain Res Protoc 10: 84-94.
37. Gruner JA, (1992) A monitored contusion model of spinal cord injury in the rat. J Neurotrauma 9: 123-126; discussion 126-128.
38. Pearse DD, Bushell G, Leah JD, (2001) Jun, Fos and Krox in the thalamus after C-fiber stimulation: coincident-input-dependent expression, expression across somatotopic boundaries, and nucleolar translocation. Neuroscience 107: 143-159.
39. Pearse DD, Lo TP Jr, Cho KS, Lynch MP, Garg MS, et al. (2005) Histopathological and behavioral characterization of a novel cervical spinal cord displacement contusion injury in the rat. J Neurotrauma 22: 680-702.
40. Xu XM, Guenard V, Kleitman N, Bunge MB, (1995) Axonal regeneration into Schwann cell-seeded guidance channels grafted into transected adult rat spinal cord. J Comp Neurol 351: 145-160.
41. Barakat DJ, Gaglani SM, Neravetla SR, Sanchez AR, Andrade CM, et al. (2005) Survival, integration, and axon growth support of glia transplanted into the chronically contused spinal cord. Cell Transplant 14: 225-240.
42. Damoiseaux JG, Dopp EA, Calame W, Chao D, MacPherson GG, et al. (1994) Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1. Immunology 83: 140-147.
43. Bhat RV, Axt KJ, Fosnaugh JS, Smith KJ, Johnson KA, et al. (1996) Expression of the APC tumor suppressor protein in oligodendroglia. Glia 17: 169-174.
44. Ye Y, Conti M, Houslay MD, Farooqui SM, Chen M, et al. (1997) Noradrenergic activity differentially regulates the expression of rolipram-sensitive, high-affinity cyclic AMP phosphodiesterase (PDE4) in rat brain. J Neurochem 69: 2397-2404.
45. Farooqui SM, Zhang K, Makhay M, Jackson K, Farooqui SQ, et al. (2000) Noradrenergic lesions differentially alter the expression of two subtypes of low Km cAMP-sensitive phosphodiesterase type 4 (PDE4A and PDE4B) in rat brain. Brain Res 867: 52-61.
46. Farooqui SM, Al-Bagdadi F, Houslay MD, Bolger GB, Stout R, et al. (2001) Surgically induced cryptorchidism-related degenerative changes in spermatogonia are associated with loss of cyclic adenosine monophosphate-dependent phosphodiesterases type 4 in abdominal testes of rats. Biol Reprod 64: 1583-1589.
47. Berrocal YA, Pearse DD, Andrade CM, Hechtman JF, Puentes R, et al. (2007) Increased spinal c-Fos expression with noxious and non-noxious peripheral stimulation after severe spinal contusion. Neurosci Lett 413: 58-62.
48. Abercrombie M, (1946) Estimation of nuclear population from microtome sections. Anat Rec 94: 239-247.
49. Leskovar A, Moriarty LJ, Turek JJ, Schoenlein IA, Borgens RB, (2000) The macrophage in acute neural injury: changes in cell numbers over time and levels of cytokine production in mammalian central and peripheral nervous systems. J Exp Biol 203: 1783-1795.
50. West NR, Collins GH, (1989) Cellular changes during repair of a cryogenic spinal cord injury in the rat: an electron microscopic study. J Neuropathol Exp Neurol 48: 94-108.
51. Basso DM, Beattie MS, Bresnahan JC, (1995) A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 12: 1-21.
52. Pearse DD, Sanchez AR, Pereira FC, Andrade CM, Puzis R, et al. (2007) Transplantation of Schwann cells and/or olfactory ensheathing glia into the contused spinal cord: Survival, migration, axon association, and functional recovery. Glia 55: 976-1000.
53. Larson JL, Pino MV, Geiger LE, Simeone CR, (1996) The toxicity of repeated exposures to rolipram, a type IV phosphodiesterase inhibitor, in rats. Pharmacol Toxicol 78: 44-49.
54. Nikulina E, Tidwell JL, Dai HN, Bregman BS, Filbin MT, (2004) The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery. Proc Natl Acad Sci U S A 101: 8786-8790.
55. Walsh KA, Weant KA, Cook AM, (2010) Potential benefits of high-dose methylprednisolone in acute spinal cord injuries. Orthopedics 33: 249-252.
56. Geisler FH, Dorsey FC, Coleman WP, (1991) Recovery of motor function after spinal-cord injury-a randomized, placebo-controlled trial with GM-1 ganglioside. N Engl J Med 324: 1829-1838.
57. Tator CH, Fehlings MG, (1999) Review of clinical trials of neuroprotection in acute spinal cord injury. Neurosurg Focus 6: e8.
58. Beaumont E, Whitaker CM, Burke DA, Hetman M, Onifer SM, (2009) Effects of rolipram on adult rat oligodendrocytes and functional recovery after contusive cervical spinal cord injury. Neuroscience 163: 985-990.
59. Bethea JR, Dietrich WD, (2002) Targeting the host inflammatory response in traumatic spinal cord injury. Curr Opin Neurol 15: 355-360.
60. Genain CP, Roberts T, Davis RL, Nguyen MH, Uccelli A, et al. (1995) Prevention of autoimmune demyelination in non-human primates by a cAMP-specific phosphodiesterase inhibitor. Proc Natl Acad Sci U S A 92: 3601-3605.
61. Heaslip RJ, Evans DY, (1995) Emetic, central nervous system, and pulmonary activities of rolipram in the dog. Eur J Pharmacol 286: 281-290.
62. Kajana S, Goshgarian HG, (2009) Systemic administration of rolipram increases medullary and spinal cAMP and activates a latent respiratory motor pathway after high cervical spinal cord injury. J Spinal Cord Med 32: 175-182.
63. Laliberte F, Liu S, Gorseth E, Bobechko B, Bartlett A, et al. (2002) In vitro PKA phosphorylation-mediated human PDE4A4 activation. FEBS Lett 512: 205-208.
64. Whitaker CM, Beaumont E, Wells MJ, Magnuson DS, Hetman M, et al. (2008) Rolipram attenuates acute oligodendrocyte death in the adult rat ventrolateral funiculus following contusive cervical spinal cord injury. Neurosci Lett 438: 200-204.
65. Koopmans GC, Deumens R, Buss A, Geoghegan L, Myint AM, et al. (2009) Acute rolipram/thalidomide treatment improves tissue sparing and locomotion after experimental spinal cord injury. Exp Neurol 216: 490-498.
66. Iannotti CA, Clark M, Horn KP, van Rooijen N, Silver J, et al. (2011) A combination immunomodulatory treatment promotes neuroprotection and locomotor recovery after contusion SCI. Exp Neurol 230: 3-15.
67. Bretzner F, Plemel JR, Liu J, Richter M, Roskams AJ, et al. (2010) Combination of olfactory ensheathing cells with local versus systemic cAMP treatment after a cervical rubrospinal tract injury. J Neurosci Res 88: 2833-2846.
68. Dai H, MacArthur L, McAtee M, Hockenbury N, Tidwell JL, et al. (2009) Activity-based therapies to promote forelimb use after a cervical spinal cord injury. J Neurotrauma 26: 1719-1732.
69. Yang L, Calingasan NY, Lorenzo BJ, Beal MF, (2008) Attenuation of MPTP neurotoxicity by rolipram, a specific inhibitor of phosphodiesterase IV. Exp Neurol 211: 311-314.
70. Horrobin DF, (1977) Interactions between prostaglandins and calcium: the importance of bell-shaped dose-response curves. Prostaglandins 14: 667-677.
71. Barnette MS, Grous M, Cieslinski LB, Burman M, Christensen SB, et al. (1995) Inhibitors of phosphodiesterase IV (PDE IV) increase acid secretion in rabbit isolated gastric glands: correlation between function and interaction with a high-affinity rolipram binding site. J Pharmacol Exp Ther 273: 1396-1402.
72. Barnette MS, Manning CD, Cieslinski LB, Burman M, Christensen SB, et al. (1995) The ability of phosphodiesterase IV inhibitors to suppress superoxide production in guinea pig eosinophils is correlated with inhibition of phosphodiesterase IV catalytic activity. J Pharmacol Exp Ther 273: 674-679.
73. Duplantier AJ, Biggers MS, Chambers RJ, Cheng JB, Cooper K, et al. (1996) Biarylcarboxylic acids and-amides: inhibition of phosphodiesterase type IV versus [3H]rolipram binding activity and their relationship to emetic behavior in the ferret. J Med Chem 39: 120-125.
74. Harris AL, Connell MJ, Ferguson EW, Wallace AM, Gordon RJ, et al. (1989) Role of low Km cyclic AMP phosphodiesterase inhibition in tracheal relaxation and bronchodilation in the guinea pig. J Pharmacol Exp Ther 251: 199-206.
75. Houslay MD, (2001) PDE4 cAMP-specific phosphodiesterases. Prog Nucleic Acid Res Mol Biol 69: 249-315.
76. Saldou N, Obernolte R, Huber A, Baecker PA, Wilhelm R, et al. (1998) Comparison of recombinant human PDE4 isoforms: interaction with substrate and inhibitors. Cell Signal 10: 427-440.
77. Zhang HT, Zhao Y, Huang Y, Deng C, Hopper AT, et al. (2006) Antidepressant-like effects of PDE4 inhibitors mediated by the high-affinity rolipram binding state (HARBS) of the phosphodiesterase-4 enzyme (PDE4) in rats. Psychopharmacology (Berl) 186: 209-217.
78. Aspiotis R, Deschenes D, Dube D, Girard Y, Huang Z, et al. (2010) The discovery and synthesis of highly potent subtype selective phosphodiesterase 4D inhibitors. Bioorg Med Chem Lett 20: 5502-5505.
79. Belmadani A, Kumar S, Schipma M, Collins MA, Neafsey EJ, (2004) Inhibition of amyloid-beta-induced neurotoxicity and apoptosis by moderate ethanol preconditioning. Neuroreport 15: 2093-2096.
80. Belmadani A, Neafsey EJ, Collins MA, (2003) Human immunodeficiency virus type 1 gp120 and ethanol coexposure in rat organotypic brain slice cultures: Curtailment of gp120-induced neurotoxicity and neurotoxic mediators by moderate but not high ethanol concentrations. J Neurovirol 9: 45-54.
81. Wang Q, Sun AY, Simonyi A, Kalogeris TJ, Miller DK, et al. (2007) Ethanol preconditioning protects against ischemia/reperfusion-induced brain damage: role of NADPH oxidase-derived ROS. Free Radic Biol Med 43: 1048-1060.
82. Wang F, Wang Y, Geng X, Asmaro K, Peng C, et al. (2012) Neuroprotective effect of acute ethanol administration in a rat with transient cerebral ischemia. Stroke 43: 205-210.
83. Kelly DF, Lee SM, Pinanong PA, Hovda DA, (1997) Paradoxical effects of acute ethanolism in experimental brain injury. J Neurosurg 86: 876-882.
84. Altura BM, Gebrewold A, (1996) alpha-Tocopherol attenuates alcohol-induced cerebral vascular damage in rats: possible role of oxidants in alcohol brain pathology and stroke. Neurosci Lett 220: 207-210.
85. Davis KM, Wu JY, (2001) Role of glutamatergic and GABAergic systems in alcoholism. J Biomed Sci 8: 7-19.
86. Sivaswamy S, Neafsey EJ, Collins MA, (2010) Neuroprotective preconditioning of rat brain cultures with ethanol: potential transduction by PKC isoforms and focal adhesion kinase upstream of increases in effector heat shock proteins. Eur J Neurosci 32: 1800-1812.
87. Piriyawat P, Labiche LA, Burgin WS, Aronowski JA, Grotta JC, (2003) Pilot dose-escalation study of caffeine plus ethanol (caffeinol) in acute ischemic stroke. Stroke 34: 1242-1245.
88. Strong R, Grotta JC, Aronowski J, (2000) Combination of low dose ethanol and caffeine protects brain from damage produced by focal ischemia in rats. Neuropharmacology 39: 515-522.
89. Aronowski J, Strong R, Shirzadi A, Grotta JC, (2003) Ethanol plus caffeine (caffeinol) for treatment of ischemic stroke: preclinical experience. Stroke 34: 1246-1251.
90. Block F, Tondar A, Schmidt W, Schwarz M, (1997) Delayed treatment with rolipram protects against neuronal damage following global ischemia in rats. Neuroreport 8: 3829-3832.
91. Block F, Bozdag I, Nolden-Koch M, (2001) Inflammation contributes to the postponed ischemic neuronal damage following treatment with a glutamate antagonist in rats. Neurosci Lett 298: 103-106.
92. Block F, Schmidt W, Nolden-Koch M, Schwarz M, (2001) Rolipram reduces excitotoxic neuronal damage. Neuroreport 12: 1507-1511.
93. Block F, Loos M, Frohn C, Schwarz M, (2004) Association between inflammation and nigral neuronal damage following striatal excitotoxic lesion. Brain Res 998: 29-35.
94. Crowe MJ, Bresnahan JC, Shuman SL, Masters JN, Beattie MS, (1997) Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys. Nat Med 3: 73-76.
95. Liu XZ, Xu XM, Hu R, Du C, Zhang SX, et al. (1997) Neuronal and glial apoptosis after traumatic spinal cord injury. J Neurosci 17: 5395-5406.
96. Griffiths IR, McCulloch MC, (1983) Nerve fibres in spinal cord impact injuries. Part 1. Changes in the myelin sheath during the initial 5 weeks. J Neurol Sci 58: 335-349.
97. Rabchevsky AG, Patel SP, Springer JE, (2011) Pharmacological interventions for spinal cord injury: where do we stand? How might we step forward? Pharmacol Ther 132: 15-29.
98. Mu X, Azbill RD, Springer JE, (2000) Riluzole and methylprednisolone combined treatment improves functional recovery in traumatic spinal cord injury. J Neurotrauma 17: 773-780.
99. Schwartz G, Fehlings MG, (2001) Evaluation of the neuroprotective effects of sodium channel blockers after spinal cord injury: improved behavioral and neuroanatomical recovery with riluzole. J Neurosurg 94: 245-256.
100. Teng YD, Choi H, Onario RC, Zhu S, Desilets FC, 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.
101. Pinzon A, Marcillo A, Quintana A, Stamler S, Bunge MB, et al. (2008) A re-assessment of minocycline as a neuroprotective agent in a rat spinal cord contusion model. Brain Res 1243: 146-151.
102. Casha S, Zygun D, McGowan MD, Bains I, Yong VW, et al. (2012) Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain 135: 1224-1236.
103. Gorio A, Gokmen N, Erbayraktar S, Yilmaz O, Madaschi L, et al. (2002) Recombinant human erythropoietin counteracts secondary injury and markedly enhances neurological recovery from experimental spinal cord trauma. Proc Natl Acad Sci U S A 99: 9450-9455.
104. Kontogeorgakos VA, Voulgaris S, Korompilias AV, Vekris M, Polyzoidis KS, et al. (2009) The efficacy of erythropoietin on acute spinal cord injury. An experimental study on a rat model. Arch Orthop Trauma Surg 129: 189-194.
105. Mann C, Lee JH, Liu J, Stammers AM, Sohn HM, et al. (2008) Delayed treatment of spinal cord injury with erythropoietin or darbepoetin-a lack of neuroprotective efficacy in a contusion model of cord injury. Exp Neurol 211: 34-40.
106. Pinzon A, Marcillo A, Pabon D, Bramlett HM, Bunge MB, et al. (2008) A re-assessment of erythropoietin as a neuroprotective agent following rat spinal cord compression or contusion injury. Exp Neurol 213: 129-136.
107. Guizar-Sahagun G, Rodriguez-Balderas CA, Franco-Bourland RE, Martinez-Cruz A, Grijalva I, et al. (2009) Lack of neuroprotection with pharmacological pretreatment in a paradigm for anticipated spinal cord lesions. Spinal Cord 47: 156-160.
108. Ghosh M, Garcia-Castillo D, Aguirre V, Golshani R, Atkins CM, et al. (2012) Proinflammatory cytokine regulation of cyclic AMP-phosphodiesterase 4 signaling in microglia in vitro and following CNS injury. Glia doi: 10.1002/glia.22401.
109. MacKenzie SJ, Houslay MD, (2000) Action of rolipram on specific PDE4 cAMP phosphodiesterase isoforms and on the phosphorylation of cAMP-response-element-binding protein (CREB) and p38 mitogen-activated protein (MAP) kinase in U937 monocytic cells. Biochem J 347: 571-578.
110. Barber R, Baillie GS, Bergmann R, Shepherd MC, Sepper R, et al. (2004) Differential expression of PDE4 cAMP phosphodiesterase isoforms in inflammatory cells of smokers with COPD, smokers without COPD, and nonsmokers. Am J Physiol Lung Cell Mol Physiol 287: L332-343.
111. Shepherd MC, Baillie GS, Stirling DI, Houslay MD, (2004) Remodelling of the PDE4 cAMP phosphodiesterase isoform profile upon monocyte-macrophage differentiation of human U937 cells. Br J Pharmacol 142: 339-351.
112. Beard MB, Huston E, Campbell L, Gall I, McPhee I, et al. (2002) In addition to the SH3 binding region, multiple regions within the N-terminal noncatalytic portion of the cAMP-specific phosphodiesterase, PDE4A5, contribute to its intracellular targeting. Cell Signal 14: 453-465.
113. Huston E, Beard M, McCallum F, Pyne NJ, Vandenabeele P, et al. (2000) The cAMP-specific phosphodiesterase PDE4A5 is cleaved downstream of its SH3 interaction domain by caspase-3. Consequences for altered intracellular distribution. J Biol Chem 275: 28063-28074.
114. D'Sa C, Tolbert LM, Conti M, Duman RS, (2002) Regulation of cAMP-specific phosphodiesterases type 4B and 4D (PDE4) splice variants by cAMP signaling in primary cortical neurons. J Neurochem 81: 745-757.
115. Murdoch H, Mackie S, Collins DM, Hill EV, Bolger GB, et al. (2007) Isoform-selective susceptibility of DISC1/phosphodiesterase-4 complexes to dissociation by elevated intracellular cAMP levels. J Neurosci 27: 9513-9524.
116. MacKenzie SJ, Yarwood SJ, Peden AH, Bolger GB, Vernon RG, et al. (1998) Stimulation of p70S6 kinase via a growth hormone-controlled phosphatidylinositol 3-kinase pathway leads to the activation of a PDE4A cyclic AMP-specific phosphodiesterase in 3T3-F442A preadipocytes. Proc Natl Acad Sci U S A 95: 3549-3554.
117. Houslay MD, Sullivan M, Bolger GB, (1998) The multienzyme PDE4 cyclic adenosine monophosphate-specific phosphodiesterase family: intracellular targeting, regulation, and selective inhibition by compounds exerting anti-inflammatory and antidepressant actions. Adv Pharmacol 44: 225-342.
118. Dastidar SG, Rajagopal D, Ray A, (2007) Therapeutic benefit of PDE4 inhibitors in inflammatory diseases. Curr Opin Investig Drugs 8: 364-372.
119. McTigue DM, Tani M, Krivacic K, Chernosky A, Kelner GS, et al. (1998) Selective chemokine mRNA accumulation in the rat spinal cord after contusion injury. J Neurosci Res 53: 368-376.
120. Lee YL, Shih K, Bao P, Ghirnikar RS, Eng LF, (2000) Cytokine chemokine expression in contused rat spinal cord. Neurochem Int 36: 417-425.
121. Lee SM, Rosen S, Weinstein P, van Rooijen N, Noble-Haeusslein LJ, (2011) Prevention of both neutrophil and monocyte recruitment promotes recovery after spinal cord injury. J Neurotrauma 28: 1893-1907.
122. Bethea JR, Nagashima H, Acosta MC, Briceno C, Gomez F, et al. (1999) Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma 16: 851-863.
123. Lee SI, Jeong SR, Kang YM, Han DH, Jin BK, et al. (2010) Endogenous expression of interleukin-4 regulates macrophage activation and confines cavity formation after traumatic spinal cord injury. J Neurosci Res 88: 2409-2419.
124. Noble LJ, Donovan F, Igarashi T, Goussev S, Werb Z, (2002) Matrix metalloproteinases limit functional recovery after spinal cord injury by modulation of early vascular events. J Neurosci 22: 7526-7535.
125. Yu F, Kamada H, Niizuma K, Endo H, Chan PH, (2008) Induction of mmp-9 expression and endothelial injury by oxidative stress after spinal cord injury. J Neurotrauma 25: 184-195.
126. Bielekova B, Richert N, Howard T, Packer AN, Blevins G, et al. (2009) Treatment with the phosphodiesterase type-4 inhibitor rolipram fails to inhibit blood-brain barrier disruption in multiple sclerosis. Mult Scler 15: 1206-1214.
127. Wang X, Baughman KW, Basso DM, Strittmatter SM, (2006) Delayed Nogo receptor therapy improves recovery from spinal cord contusion. Ann Neurol 60: 540-549.
128. Kajana S, Goshgarian HG, (2008) Administration of phosphodiesterase inhibitors and an adenosine A1 receptor antagonist induces phrenic nerve recovery in high cervical spinal cord injured rats. Exp Neurol 210: 671-680.
129. Hatinen S, Sairanen M, Sirvio J, Jolkkonen J, (2008) Improved sensorimotor function by rolipram following focal cerebral ischemia in rats. Restor Neurol Neurosci 26: 493-499.
130. Downing TL, Wang A, Yan ZQ, Nout Y, Lee AL, et al. (2012) Drug-eluting microfibrous patches for the local delivery of rolipram in spinal cord repair. J Control Release 161: 910-917.