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Shirley R, Ord EN, Work LM. Oxidative Stress and the Use of Antioxidants in Stroke. Antioxidants (Basel). 2014;3(3):472-501doi: 10.3390/antiox3030472.
Shirley, R., Ord, E. N., & Work, L. M. (2014). Oxidative Stress and the Use of Antioxidants in Stroke. Antioxidants (Basel, Switzerland), 3(3), 472-501. https://doi.org/10.3390/antiox3030472
Shirley, Rachel, et al. "Oxidative Stress and the Use of Antioxidants in Stroke." Antioxidants (Basel, Switzerland) vol. 3,3 (2014): 472-501. doi: https://doi.org/10.3390/antiox3030472
Shirley R, Ord EN, Work LM. Oxidative Stress and the Use of Antioxidants in Stroke. Antioxidants (Basel). 2014 Jul 03;3(3):472-501. doi: 10.3390/antiox3030472. PMID: 26785066; PMCID: PMC4665418.
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Antioxidants (Basel). 2014 Jul 03;3(3):472-501. doi: 10.3390/antiox3030472.

Oxidative Stress and the Use of Antioxidants in Stroke.

Antioxidants (Basel, Switzerland)

Rachel Shirley, Emily N J Ord, Lorraine M Work

Affiliations

  1. Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, BHF GCRC, 126 University Place, Glasgow G12 8TA, UK. [email protected].
  2. Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, BHF GCRC, 126 University Place, Glasgow G12 8TA, UK. [email protected].
  3. Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, BHF GCRC, 126 University Place, Glasgow G12 8TA, UK. [email protected].

PMID: 26785066 PMCID: PMC4665418 DOI: 10.3390/antiox3030472

Abstract

Transient or permanent interruption of cerebral blood flow by occlusion of a cerebral artery gives rise to an ischaemic stroke leading to irreversible damage or dysfunction to the cells within the affected tissue along with permanent or reversible neurological deficit. Extensive research has identified excitotoxicity, oxidative stress, inflammation and cell death as key contributory pathways underlying lesion progression. The cornerstone of treatment for acute ischaemic stroke remains reperfusion therapy with recombinant tissue plasminogen activator (rt-PA). The downstream sequelae of events resulting from spontaneous or pharmacological reperfusion lead to an imbalance in the production of harmful reactive oxygen species (ROS) over endogenous anti-oxidant protection strategies. As such, anti-oxidant therapy has long been investigated as a means to reduce the extent of injury resulting from ischaemic stroke with varying degrees of success. Here we discuss the production and source of these ROS and the various strategies employed to modulate levels. These strategies broadly attempt to inhibit ROS production or increase scavenging or degradation of ROS. While early clinical studies have failed to translate success from bench to bedside, the combination of anti-oxidants with existing thrombolytics or novel neuroprotectants may represent an avenue worthy of clinical investigation. Clearly, there is a pressing need to identify new therapeutic alternatives for the vast majority of patients who are not eligible to receive rt-PA for this debilitating and devastating disease.

Keywords: anti-oxidant; oxidative stress; stroke

References

  1. Neuroscience. 1999 Jan;88(1):185-91 - PubMed
  2. Annu Rev Pharmacol Toxicol. 1999;39:67-101 - PubMed
  3. J Cereb Blood Flow Metab. 1999 Jul;19(7):778-87 - PubMed
  4. J Neurochem. 1999 Oct;73(4):1549-56 - PubMed
  5. Stroke. 1999 Dec;30(12):2752-8 - PubMed
  6. J Biol Chem. 2000 Mar 17;275(11):8226-32 - PubMed
  7. J Cereb Blood Flow Metab. 2000 Mar;20(3):452-7 - PubMed
  8. J Neurochem. 2000 Apr;74(4):1636-45 - PubMed
  9. J Neurosci. 2000 Apr 15;20(8):2817-24 - PubMed
  10. Stroke. 2000 Aug;31(8):1965-72; discussion 1972-3 - PubMed
  11. Stroke. 2000 Oct;31(10):2287-94 - PubMed
  12. Stroke. 2000 Nov;31(11):2543-51 - PubMed
  13. Life Sci. 2000 Sep 29;67(19):2387-92 - PubMed
  14. J Cereb Blood Flow Metab. 2000 Nov;20(11):1529-36 - PubMed
  15. J Biol Chem. 2001 Apr 13;276(15):12035-40 - PubMed
  16. Stroke. 2001 Jan;32(1):190-8 - PubMed
  17. Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H1241-8 - PubMed
  18. J Biol Chem. 2001 Jun 29;276(26):23681-8 - PubMed
  19. Brain Res. 2001 Aug 3;909(1-2):46-50 - PubMed
  20. Stroke. 2001 Aug;32(8):1906-11 - PubMed
  21. J Cereb Blood Flow Metab. 2001 Sep;21(9):1105-14 - PubMed
  22. Stroke. 2001 Sep;32(9):2149-54 - PubMed
  23. J Neurochem. 2001 Sep;78(6):1389-99 - PubMed
  24. Br J Pharmacol. 2002 Jan;135(1):103-12 - PubMed
  25. Am J Ther. 1995 Aug;2(8):553-560 - PubMed
  26. Cochrane Database Syst Rev. 2002;(1):CD001924 - PubMed
  27. Am J Physiol Heart Circ Physiol. 2002 Apr;282(4):H1485-94 - PubMed
  28. Neurology. 2002 Mar 26;58(6):945-52 - PubMed
  29. J Cereb Blood Flow Metab. 2002 Apr;22(4):393-403 - PubMed
  30. J Cereb Blood Flow Metab. 2002 May;22(5):520-5 - PubMed
  31. Ann N Y Acad Sci. 2002 Apr;959:263-74 - PubMed
  32. Drug Resist Updat. 2001 Aug;4(4):253-67 - PubMed
  33. Neurosci Res. 2002 May;43(1):75-9 - PubMed
  34. Lancet. 2002 Jul 6;360(9326):23-33 - PubMed
  35. J Cereb Blood Flow Metab. 2002 Jul;22(7):798-809 - PubMed
  36. J Cereb Blood Flow Metab. 2002 Jul;22(7):861-8 - PubMed
  37. J Neurosci. 2002 Aug 1;22(15):6480-90 - PubMed
  38. FASEB J. 2002 Dec;16(14):1997-9 - PubMed
  39. Brain Res Mol Brain Res. 2002 Dec 30;109(1-2):34-44 - PubMed
  40. Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3497-500 - PubMed
  41. Cerebrovasc Dis. 2003;15(3):222-9 - PubMed
  42. Stroke. 2003 Sep;34(9):2228-33 - PubMed
  43. Am J Physiol. 1992 Nov;263(5 Pt 2):H1356-62 - PubMed
  44. Trends Biochem Sci. 2003 Sep;28(9):502-8 - PubMed
  45. Free Radic Biol Med. 2003 Dec 15;35(12):1619-31 - PubMed
  46. Front Biosci. 2004 Jan 01;9:777-85 - PubMed
  47. J Bone Miner Res. 2004 Apr;19(4):642-51 - PubMed
  48. Yakugaku Zasshi. 2004 Mar;124(3):99-111 - PubMed
  49. Stroke. 2004 Jun;35(6):1449-53 - PubMed
  50. J Cereb Blood Flow Metab. 2004 Mar;24(3):343-9 - PubMed
  51. Neuroreport. 2004 Mar 1;15(3):413-6 - PubMed
  52. J Biol Chem. 2004 Aug 13;279(33):34250-5 - PubMed
  53. J Biol Chem. 2004 Sep 3;279(36):37575-87 - PubMed
  54. J Exp Biol. 2004 Aug;207(Pt 18):3221-31 - PubMed
  55. Cell. 2004 Sep 17;118(6):665-6 - PubMed
  56. Nat Med. 2004 Dec;10(12):1379-83 - PubMed
  57. Neurobiol Dis. 2004 Dec;17(3):491-9 - PubMed
  58. Ann Neurol. 2005 Apr;57(4):571-5 - PubMed
  59. Free Radic Biol Med. 2005 Jun 1;38(11):1433-44 - PubMed
  60. Stroke. 1992 Jun;23(6):894-9 - PubMed
  61. Invest Ophthalmol Vis Sci. 2005 Jul;46(7):2487-94 - PubMed
  62. FASEB J. 2005 Jul;19(9):1088-95 - PubMed
  63. Brain Res. 2005 Aug 9;1052(2):202-11 - PubMed
  64. Neurochem Int. 2005 Nov;47(6):442-8 - PubMed
  65. Free Radic Biol Med. 2005 Aug 15;39(4):429-43 - PubMed
  66. Curr Opin Pharmacol. 2006 Feb;6(1):53-60 - PubMed
  67. Ann Neurol. 2006 Mar;59(3):467-77 - PubMed
  68. J Cereb Blood Flow Metab. 2006 Dec;26(12):1465-78 - PubMed
  69. Intern Med. 2006;45(5):253-7 - PubMed
  70. Eur J Neurosci. 2006 Apr;23(7):1757-65 - PubMed
  71. Stroke. 2006 Aug;37(8):2189-90 - PubMed
  72. Stroke. 2006 Oct;37(10):2644-7 - PubMed
  73. Annu Rev Pharmacol Toxicol. 2007;47:629-56 - PubMed
  74. Stroke. 2006 Dec;37(12):2970-8 - PubMed
  75. Biochem Soc Trans. 2006 Dec;34(Pt 6):1366-9 - PubMed
  76. Neurosci Lett. 2007 Jan 3;411(1):32-6 - PubMed
  77. Clin Sci (Lond). 2007 Jan;112(1):1-25 - PubMed
  78. Stroke. 2007 Feb;38(2):388-94 - PubMed
  79. J Neurosci. 2007 Jan 31;27(5):1129-38 - PubMed
  80. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3597-602 - PubMed
  81. Stroke. 2007 May;38(5):1515-8 - PubMed
  82. Nat Med. 2007 Jun;13(6):688-94 - PubMed
  83. Biochem J. 2007 Aug 15;406(1):105-14 - PubMed
  84. J Clin Invest. 2007 Jul;117(7):1961-7 - PubMed
  85. J Neurosci. 2007 Aug 1;27(31):8309-13 - PubMed
  86. N Engl J Med. 2007 Aug 9;357(6):562-71 - PubMed
  87. J Int Med Res. 2007 Jul-Aug;35(4):517-22 - PubMed
  88. Arch Intern Med. 2007 Aug 13-27;167(15):1610-8 - PubMed
  89. Trends Neurosci. 2007 Sep;30(9):433-9 - PubMed
  90. Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3356-65 - PubMed
  91. Am J Physiol Cell Physiol. 2008 Feb;294(2):C460-6 - PubMed
  92. Am J Clin Nutr. 2008 Jan;87(1):64-9 - PubMed
  93. Apoptosis. 2008 Mar;13(3):377-82 - PubMed
  94. Stroke. 2008 Apr;39(4):1121-6 - PubMed
  95. Stroke. 2008 Jun;39(6):1869-74 - PubMed
  96. J Neurosci Res. 2008 Aug 15;86(11):2524-34 - PubMed
  97. J Cereb Blood Flow Metab. 2008 Oct;28(10):1707-21 - PubMed
  98. Brain Dev. 2009 Apr;31(4):307-17 - PubMed
  99. Stroke. 2009 Mar;40(3):e50-2 - PubMed
  100. Neuroscience. 2009 Feb 6;158(3):1007-20 - PubMed
  101. N Engl J Med. 2008 Sep 25;359(13):1317-29 - PubMed
  102. Pediatr Int. 2008 Aug;50(4):481-8 - PubMed
  103. JAMA. 2008 Nov 12;300(18):2123-33 - PubMed
  104. J Biol Chem. 2009 Jan 23;284(4):2176-86 - PubMed
  105. Cardiovasc Ther. 2008 Winter;26(4):247-52 - PubMed
  106. Expert Opin Pharmacother. 2009 Feb;10(2):323-31 - PubMed
  107. J Neural Transm (Vienna). 2009 Apr;116(4):395-404 - PubMed
  108. Stroke. 2009 Jun;40(6):2244-50 - PubMed
  109. Stroke. 1991 Oct;22(10):1276-83 - PubMed
  110. Brain Res. 2009 May 13;1270:1-9 - PubMed
  111. J Cereb Blood Flow Metab. 2009 Jul;29(7):1262-72 - PubMed
  112. Stroke. 2009 Jul;40(7):e497 - PubMed
  113. Brain Res. 2009 Aug 25;1286:215-20 - PubMed
  114. Free Radic Biol Med. 2009 Oct 1;47(7):941-52 - PubMed
  115. Neuromolecular Med. 2010 Jun;12(2):193-204 - PubMed
  116. Hypertension. 2009 Aug;54(2):322-8 - PubMed
  117. Curr Neuropharmacol. 2009 Mar;7(1):65-74 - PubMed
  118. Br J Clin Pharmacol. 2009 Nov;68(5):662-8 - PubMed
  119. Nitric Oxide. 2010 Sep 15;23(2):75-93 - PubMed
  120. Expert Opin Pharmacother. 2010 Jul;11(10):1753-63 - PubMed
  121. J Cereb Blood Flow Metab. 2010 Nov;30(11):1874-82 - PubMed
  122. Physiol Rev. 1991 Jul;71(3):813-47 - PubMed
  123. Neurobiol Dis. 2010 Oct;40(1):185-92 - PubMed
  124. Transl Stroke Res. 2010 Jan 26;1(1):40-7 - PubMed
  125. PLoS Biol. 2010 Jun 29;8(6):e1000412 - PubMed
  126. Mol Immunol. 2010 Aug;47(13):2170-5 - PubMed
  127. Ann N Y Acad Sci. 2010 Jul;1201:96-103 - PubMed
  128. J Cereb Blood Flow Metab. 2011 Mar;31(3):868-80 - PubMed
  129. PLoS Biol. 2010 Sep 21;8(9):null - PubMed
  130. BMJ. 2010 Nov 04;341:c5702 - PubMed
  131. Nat Rev Immunol. 2010 Dec;10(12):826-37 - PubMed
  132. Exp Neurol. 2011 Jan;227(1):224-31 - PubMed
  133. J Neuroinflammation. 2010 Dec 06;7:88 - PubMed
  134. Brain Res. 2011 Feb 4;1372:92-102 - PubMed
  135. Thromb Haemost. 2011 Apr;105(4):579-85 - PubMed
  136. Neurobiol Dis. 2011 Jun;42(3):341-8 - PubMed
  137. PLoS One. 2011 Mar 01;6(3):e17514 - PubMed
  138. BMC Neurol. 2011 Mar 30;11:39 - PubMed
  139. Stroke. 2011 Jun;42(6):1665-72 - PubMed
  140. Stroke. 2011 Jul;42(7):1952-5 - PubMed
  141. Neuroscientist. 2011 Aug;17(4):389-406 - PubMed
  142. Neuropharmacology. 2011 Dec;61(8):1193-201 - PubMed
  143. Stroke. 2011 Dec;42(12):3574-9 - PubMed
  144. CNS Neurosci Ther. 2011 Dec;17(6):590-8 - PubMed
  145. PLoS One. 2011;6(12):e28393 - PubMed
  146. Circ Res. 2012 Mar 2;110(5):727-38 - PubMed
  147. Brain Res. 2012 Feb 3;1436:168-77 - PubMed
  148. J Cereb Blood Flow Metab. 2012 Apr;32(4):585-97 - PubMed
  149. J Neurosci. 2012 Feb 29;32(9):3235-44 - PubMed
  150. J Appl Physiol (1985). 2012 Jun;112(12):2068-76 - PubMed
  151. J Neurosci. 2012 May 9;32(19):6642-50 - PubMed
  152. Cell Mol Life Sci. 2012 Jul;69(14):2345-63 - PubMed
  153. Exp Transl Stroke Med. 2012 May 24;4(1):11 - PubMed
  154. Stroke. 2012 Nov;43(11):3078-84 - PubMed
  155. J Cardiovasc Pharmacol. 2012 Dec;60(6):538-43 - PubMed
  156. Mol Neurobiol. 2013 Feb;47(1):9-23 - PubMed
  157. Sci Rep. 2012;2:896 - PubMed
  158. Lancet. 2012 Dec 15;380(9859):2095-128 - PubMed
  159. Lancet. 2012 Dec 15;380(9859):2197-223 - PubMed
  160. Circ Res. 2013 Feb 15;112(4):651-63 - PubMed
  161. Br J Pharmacol. 2013 Jun;169(3):604-18 - PubMed
  162. Stroke. 2013 May;44(5):1418-25 - PubMed
  163. Stroke. 2013 Jun;44(6):1754-60 - PubMed
  164. Free Radic Biol Med. 2014 Jan;66:20-3 - PubMed
  165. J Cereb Blood Flow Metab. 2013 Aug;33(8):1215-24 - PubMed
  166. Nat Med. 2013 Jun;19(6):753-9 - PubMed
  167. Curr Med Res Opin. 2013 Sep;29(9):1105-14 - PubMed
  168. ScientificWorldJournal. 2013 Jun 17;2013:175280 - PubMed
  169. Brain Res. 2013 Sep 19;1531:17-24 - PubMed
  170. Exp Neurol. 2013 Nov;249:33-8 - PubMed
  171. J Hypertens. 2014 Mar;32(3):555-64 - PubMed
  172. Transl Stroke Res. 2011 Sep;2(3):399-403 - PubMed
  173. Antioxid Redox Signal. 2015 Aug 10;23(5):406-27 - PubMed
  174. Acta Physiol Scand Suppl. 1986;548:87-99 - PubMed
  175. J Appl Physiol (1985). 1985 Jun;58(6):1929-41 - PubMed
  176. J Neurochem. 1985 Jan;44(1):143-8 - PubMed
  177. J Biol Chem. 1973 Jul 10;248(13):4793-6 - PubMed
  178. Gastroenterology. 1981 Jul;81(1):22-9 - PubMed
  179. Brain Pathol. 1994 Jan;4(1):49-57 - PubMed
  180. Neuropharmacology. 1994 Nov;33(11):1447-52 - PubMed
  181. Sheng Li Ke Xue Jin Zhan. 1995 Jan;26(1):50-2 - PubMed
  182. J Biol Chem. 1995 Jan 20;270(3):1230-7 - PubMed
  183. Eur J Biochem. 1994 Aug 1;223(3):1019-26 - PubMed
  184. Brain Res. 1994 May 9;645(1-2):157-63 - PubMed
  185. J Pharmacol Exp Ther. 1994 Mar;268(3):1597-604 - PubMed
  186. Stroke. 1996 Jan;27(1):76-81 - PubMed
  187. J Clin Invest. 1996 Jan 15;97(2):493-500 - PubMed
  188. Stroke. 1996 Sep;27(9):1453-8 - PubMed
  189. Exp Neurol. 1996 Oct;141(2):330-6 - PubMed
  190. J Neurosci. 1996 Nov 1;16(21):6795-806 - PubMed
  191. Neuropharmacology. 1996 Jun;35(6):689-93 - PubMed
  192. J Pharmacol Exp Ther. 1996 Nov;279(2):748-58 - PubMed
  193. J Pharmacol Exp Ther. 1996 Nov;279(2):759-66 - PubMed
  194. J Neurochem. 1997 Feb;68(2):710-4 - PubMed
  195. Brain Res. 1997 Jan 16;745(1-2):210-21 - PubMed
  196. J Neurochem. 1997 Jul;69(1):232-45 - PubMed
  197. Pharmacol Rev. 1997 Jun;49(2):143-55 - PubMed
  198. Br J Pharmacol. 1997 Nov;122(6):1251-6 - PubMed
  199. Stroke. 1997 Dec;28(12):2338-46 - PubMed
  200. Acta Neurochir Suppl. 1997;70:62-4 - PubMed
  201. Nature. 1998 Jan 1;391(6662):43-50 - PubMed
  202. Stroke. 1998 Jan;29(1):12-7 - PubMed
  203. J Cereb Blood Flow Metab. 1998 Feb;18(2):196-205 - PubMed
  204. Brain Res Mol Brain Res. 1998 Jan;53(1-2):333-8 - PubMed
  205. J Biol Chem. 1998 Apr 17;273(16):9357-60 - PubMed
  206. Cerebrovasc Dis. 1998 May-Jun;8(3):172-81 - PubMed
  207. Cell Mol Neurobiol. 1998 Dec;18(6):667-82 - PubMed
  208. Brain Res. 1999 Jan 23;816(2):471-9 - PubMed
  209. Stroke. 1999 Feb;30(2):441-8; discussion 449 - PubMed

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