Effect of methylene blue on the genomic response to reperfusion injury induced by cardiac arrest and cardiopulmonary resuscitation in porcine brain.

Publisher: BioMed Central Country of Publication: England NLM ID: 101319628 Publication Model: Electronic Cited Medium: Internet ISSN: 1755-8794 (Electronic) Linking ISSN: 17558794 NLM ISO Abbreviation: BMC Med Genomics Subsets: MEDLINE

Original Publication: London : BioMed Central

Cardiopulmonary Resuscitation*; Brain/*metabolism ; Gene Expression/*drug effects ; Heart Arrest/*complications ; Methylene Blue/*therapeutic use ; Neuroprotective Agents/*therapeutic use ; Reperfusion Injury/*genetics; Animals ; Apoptosis ; Cluster Analysis ; Female ; Gene Expression Profiling ; Genomics ; Guanylate Cyclase/genetics ; Guanylate Cyclase/metabolism ; Male ; Neurogenesis ; Receptors, Cytoplasmic and Nuclear/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism ; Reperfusion Injury/drug therapy ; Reperfusion Injury/etiology ; Soluble Guanylyl Cyclase ; Swine ; Time Factors

Background: Cerebral ischemia/reperfusion injury is a common secondary effect of cardiac arrest which is largely responsible for postresuscitative mortality. Therefore development of therapies which restore and protect the brain function after cardiac arrest is essential. Methylene blue (MB) has been experimentally proven neuroprotective in a porcine model of global ischemia-reperfusion in experimental cardiac arrest. However, no comprehensive analyses have been conducted at gene expression level.
Methods: Pigs underwent either untreated cardiac arrest (CA) or CA with subsequent cardiopulmonary resuscitation (CPR) accompanied with an infusion of saline or an infusion of saline with MB. Genome-wide transcriptional profiling using the Affymetrix porcine microarray was performed to 1) gain understanding of delayed neuronal death initiation in porcine brain during ischemia and after 30, 60 and 180 min following reperfusion, and 2) identify the mechanisms behind the neuroprotective effect of MB after ischemic injury (at 30, 60 and 180 min).
Results: Our results show that restoration of spontaneous circulation (ROSC) induces major transcriptional changes related to stress response, inflammation, apoptosis and even cytoprotection. In contrast, the untreated ischemic and anoxic insult affected only few genes mainly involved in intra-/extracellular ionic balance. Furthermore, our data show that the neuroprotective role of MB is diverse and fulfilled by regulation of the expression of soluble guanylate cyclase and biological processes accountable for inhibition of apoptosis, modulation of stress response, neurogenesis and neuroprotection.
Conclusions: Our results support that MB could be a valuable intervention and should be investigated as a therapeutic agent against neural damage associated with I/R injury induced by cardiac arrest.

Brain Res Mol Brain Res. 2002 Dec;108(1-2):81-93. (PMID: 12480181)
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2445-50. (PMID: 10051662)
Mol Cancer Ther. 2008 Jan;7(1):233-41. (PMID: 18187809)
Brain Res. 2009 Feb 3;1252:1-14. (PMID: 19071098)
Science. 1997 Jan 3;275(5296):90-4. (PMID: 8974401)
J Cell Biol. 2000 Jun 26;149(7):1443-54. (PMID: 10871284)
Am J Physiol Heart Circ Physiol. 2003 Aug;285(2):H669-78. (PMID: 12676772)
EMBO J. 2006 Apr 19;25(8):1590-602. (PMID: 16601685)
J Cereb Blood Flow Metab. 2003 Jul;23(7):773-9. (PMID: 12843781)
Cell. 1999 Jul 9;98(1):81-90. (PMID: 10412983)
Neuron. 2007 Dec 6;56(5):823-37. (PMID: 18054859)
J Cell Sci. 2004 Mar 1;117(Pt 7):1139-50. (PMID: 14970262)
FASEB J. 2005 Nov;19(13):1905-7. (PMID: 16162853)
Am J Cardiol. 2004 Jan 15;93(2):131-5. (PMID: 14715335)
Ann Emerg Med. 2008 Sep;52(3):244-52. (PMID: 18374452)
Science. 1998 Jan 30;279(5351):696-700. (PMID: 9445473)
Am J Physiol. 1991 Nov;261(5 Pt 2):R1286-93. (PMID: 1951777)
Eur J Clin Pharmacol. 2000 Jun;56(3):247-50. (PMID: 10952480)
J Biol Chem. 1996 Nov 1;271(44):27205-8. (PMID: 8910287)
Crit Care Med. 2006 Nov;34(11):2806-13. (PMID: 16957637)
Eur J Neurosci. 2002 Jun;15(12):1937-52. (PMID: 12099900)
EMBO J. 2003 Nov 17;22(22):6089-100. (PMID: 14609955)
Neurosci Biobehav Rev. 2007;31(5):728-51. (PMID: 17445892)
Nat Genet. 2003 Nov;35(3):270-6. (PMID: 14578885)
J Biol Chem. 2007 Dec 21;282(51):37124-33. (PMID: 17940279)
Neurochem Res. 2009 Jun;34(6):1167-82. (PMID: 19115107)
Brain Res Mol Brain Res. 2000 May 31;78(1-2):131-7. (PMID: 10891592)
Biochem Biophys Res Commun. 2003 Nov 21;311(3):577-82. (PMID: 14623309)
Basic Life Sci. 1988;49:895-8. (PMID: 2855011)
Nat Rev Mol Cell Biol. 2006 Jan;7(1):54-62. (PMID: 16493413)
Cell Cycle. 2008 May 1;7(9):1146-50. (PMID: 18418049)
J Neurosci Res. 2004 Sep 15;77(6):843-57. (PMID: 15334602)
Oncogene. 2007 Apr 19;26(18):2595-605. (PMID: 17086213)
Brain Res. 2002 Jul 5;943(1):56-67. (PMID: 12088839)
J Biol Chem. 2001 Aug 17;276(33):31340-8. (PMID: 11418592)
Restor Neurol Neurosci. 2006;24(1):17-23. (PMID: 16518024)
Lab Anim Sci. 1990 May;40(3):293-8. (PMID: 2162986)
Gastroenterology. 2003 Jul;125(1):70-9. (PMID: 12851872)
Curr Biol. 2006 Sep 19;16(18):1850-6. (PMID: 16979564)
Comp Med. 2004 Feb;54(1):36-43. (PMID: 15027616)
Crit Care Med. 2002 Apr;30(4 Suppl):S140-4. (PMID: 11940789)
Biochem Pharmacol. 1993 Jan 26;45(2):367-74. (PMID: 7679577)
Circulation. 2005 Dec 13;112(24 Suppl):IV1-203. (PMID: 16314375)
J Cell Biol. 2002 Feb 4;156(3):495-509. (PMID: 11815631)
Nat Neurosci. 2007 Feb;10(2):177-85. (PMID: 17220882)
Stroke. 1997 Oct;28(10):2039-44. (PMID: 9341716)
Neuroscience. 1997 Sep;80(2):501-9. (PMID: 9284352)
Cancer Metastasis Rev. 1998 Mar;17(1):7-23. (PMID: 9544420)
Resuscitation. 2006 Apr;69(1):15-22. (PMID: 16488070)
Can J Physiol Pharmacol. 1981 Feb;59(2):150-6. (PMID: 6112057)
J Mol Biol. 2002 May 17;318(5):1351-65. (PMID: 12083523)
Nat Cell Biol. 2004 Aug;6(8):749-55. (PMID: 15258591)
Brain Res. 2002 Aug 9;946(1):139-47. (PMID: 12133603)
J Pharmacol Exp Ther. 1990 Sep;254(3):872-6. (PMID: 2168487)
J Neurosci. 1997 Sep 1;17(17):6678-84. (PMID: 9254680)
Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18183-8. (PMID: 16330768)
Mol Cell Biol. 1997 Jun;17(6):3459-67. (PMID: 9154845)
Crit Care Med. 2008 Mar;36(3):842-7. (PMID: 18431271)
Stroke. 2003 Aug;34(8):1987-93. (PMID: 12843358)
Brain Res. 2006 Sep 19;1110(1):193-200. (PMID: 16870162)
J Neurosci. 1998 Nov 15;18(22):9312-25. (PMID: 9801370)
Prog Brain Res. 1985;63:197-210. (PMID: 3835579)
Cell. 2006 Dec 1;127(5):929-40. (PMID: 17129780)
J Mol Endocrinol. 2008 Nov;41(5):251-61. (PMID: 18768664)
J Chemother. 2002 Oct;14(5):431-43. (PMID: 12462423)
J Biol Chem. 1998 Aug 7;273(32):20511-6. (PMID: 9685407)
Genes Cells. 2003 Feb;8(2):189-202. (PMID: 12581160)
Biochim Biophys Acta. 2008 Feb;1783(2):169-76. (PMID: 18155172)
Ann Neurol. 2001 Jul;50(1):93-103. (PMID: 11456315)
Novartis Found Symp. 2007;288:230-242; discussion 242-5, 276-81. (PMID: 18494262)
Resuscitation. 2007 Oct;75(1):88-97. (PMID: 17482336)
Exp Cell Res. 2007 Nov 1;313(18):3914-23. (PMID: 17643427)
J Biol Chem. 2007 Jul 6;282(27):19884-93. (PMID: 17439943)
Cell Death Differ. 2004 Apr;11(4):403-15. (PMID: 14752508)
Resuscitation. 2008 Dec;79(3):350-79. (PMID: 18963350)
Mol Biol Cell. 2005 Oct;16(10):4648-59. (PMID: 16093351)
J Biol Chem. 2007 Dec 28;282(52):37429-35. (PMID: 17938176)
Science. 2003 Feb 28;299(5611):1394-7. (PMID: 12610305)
Ann N Y Acad Sci. 2007 Dec;1122:231-44. (PMID: 18077576)
BMC Genomics. 2004 May 23;5(1):32. (PMID: 15154973)
J Cereb Blood Flow Metab. 2005 Mar;25(3):338-47. (PMID: 15660102)
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21. (PMID: 11309499)
Stroke. 2002 Aug;33(8):2115-22. (PMID: 12154274)
Mol Med. 2007 Jul-Aug;13(7-8):380-7. (PMID: 17622314)
Nature. 1994 Jul 21;370(6486):216-8. (PMID: 8028668)
J Neurosci. 2005 Apr 6;25(14):3628-37. (PMID: 15814794)
Resuscitation. 2005 Dec;67 Suppl 1:S39-86. (PMID: 16321716)
Stroke. 2008 Dec;39(12):3389-96. (PMID: 18845796)
J Neurosci. 2008 Jan 16;28(3):681-95. (PMID: 18199768)
Surgery. 2005 Jul;138(1):93-9. (PMID: 16003322)
Acta Neuropathol. 1986;71(1-2):88-93. (PMID: 3776478)
Biol Psychiatry. 1986 Aug;21(10):915-20. (PMID: 3091097)
Mol Microbiol. 2002 Jul;45(1):145-53. (PMID: 12100555)
J Neurosci. 2005 Apr 27;25(17):4406-19. (PMID: 15858067)
J Cell Sci. 2000 Jun;113 ( Pt 11):1871-82. (PMID: 10806098)
Neurosci Lett. 2008 Oct 10;443(3):155-9. (PMID: 18680785)
FASEB J. 2001 Jan;15(1):134-144. (PMID: 11149901)
Resuscitation. 1995 Aug;30(1):23-7. (PMID: 7481099)
FEBS Lett. 2004 Apr 9;563(1-3):155-60. (PMID: 15063741)
Eur J Neurosci. 2007 Aug;26(3):624-32. (PMID: 17634068)
J Cereb Blood Flow Metab. 2004 Feb;24(2):212-23. (PMID: 14747748)
Neuropeptides. 2008 Oct-Dec;42(5-6):653-61. (PMID: 18644622)
J Neurosci. 2001 Jun 1;21(11):3839-48. (PMID: 11356872)
J Biol Chem. 2000 Dec 15;275(50):39631-9. (PMID: 11035026)
Eur J Clin Pharmacol. 1996;50(4):249-52. (PMID: 8803513)
Physiol Rev. 1999 Oct;79(4):1431-568. (PMID: 10508238)
J Neurosci. 2008 Nov 26;28(48):12788-97. (PMID: 19036971)

0 (Neuroprotective Agents)
0 (Receptors, Cytoplasmic and Nuclear)
EC 4.6.1.2 (Guanylate Cyclase)
EC 4.6.1.2 (Soluble Guanylyl Cyclase)
T42P99266K (Methylene Blue)

Date Created: 20100703 Date Completed: 20100908 Latest Revision: 20240322

20240322

PMC2904268

10.1186/1755-8794-3-27

20594294