Targeting gaseous molecules to protect against cerebral ischaemic injury: Mechanisms and prospects

Clinical and Experimental Pharmacology and Physiology

Volumn 39, Issue 6, 2012, Pages 566-576

  Zhou, Jun ^a   Wu, Peng Fei ^a   Wang, Fang ^a,b,c   Chen, Jian Guo ^a,b,c  

^a HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^b HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^c BEIJING UNIVERSITY OF POSTS AND TELECOMMUNICATIONS   (China)

Author keywords

Carbon monoxide; Cerebral ischaemia; Gaseous molecule; Hydrogen; Hydrogen sulphide; Nitric oxide

Indexed keywords

CARBON MONOXIDE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; HEME; HEME OXYGENASE 1; HEME OXYGENASE 2; HYDROGEN; HYDROGEN SULFIDE; NEURONAL NITRIC OXIDE SYNTHASE; NITRIC OXIDE;

APOPTOSIS; BRAIN DAMAGE; BRAIN ISCHEMIA; CELL PROTECTION; GAS; HUMAN; NONHUMAN; PATHOPHYSIOLOGY; REVIEW; SYNTHESIS;

ANIMALS; BRAIN ISCHEMIA; CARBON MONOXIDE; CYTOPROTECTION; DRUG DELIVERY SYSTEMS; GASES; HUMANS; HYDROGEN; HYDROGEN SULFIDE; NEUROPROTECTIVE AGENTS; NITRIC OXIDE;

EID: 84861685248     PISSN: 03051870     EISSN: 14401681     Source Type: Journal    
DOI: 10.1111/j.1440-1681.2011.05654.x     Document Type: Review

References (115)

1. Wagner SR, Lanier WL. Metabolism of glucose, glycogen, and high-energy phosphates during complete cerebral ischaemia. A comparison of normoglycemic, chronically hyperglycemic diabetic, and acutely hyperglycemic nondiabetic rats. Anesthesiology 1994; 81: 1516-26.
2. Miller JR, Myers RE. Neuropathology of systemic circulatory arrest in adult monkeys. Neurology 1972; 22: 888-904.
3. Badruddin A, Taqi MA, Abraham MG, Dani D, Zaidat OO. Neurocritical care of a reperfused brain. Curr. Neurol. Neurosci. Rep. 2011; 11: 104-10.
4. Love S. Oxidative stress in brain ischaemia. Brain Pathol. 1999; 9: 119-31.
5. Harukuni I, Bhardwaj A. Mechanisms of brain injury after global cerebral ischaemia. Neurol.Clin. 2006; 24: 1-21.
6. Sutherland BA, Papadakis M, Chen RL, Buchan AM. Cerebral blood flow alteration in neuroprotection following cerebral ischaemia. J. Physiol. 2011; 589: 4105-14.
7. Kidwell CS, Alger JR, Saver JL. Beyond mismatch: Evolving paradigms in imaging the ischaemic penumbra with multimodal magnetic resonance imaging. Stroke 2003; 34: 2729-35.
8. Kinoshita Y, Ueyama T, Senba E, Terada T, Nakai K, Itakura T. Expression of c-fos, heat shock protein 70, neurotrophins, and cyclooxygenase-2 mRNA in response to focal cerebral ischaemia/reperfusion in rats and their modification by magnesium sulfate. J. Neurotrauma 2001; 18: 435-45.
9. Madden KP. Effect of gamma-aminobutyric acid modulation on neuronal ischaemia in rabbits. Stroke 1994; 25: 2271-74.
10. Slemmer JE, Shacka JJ, Sweeney MI, Weber JT. Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging. Curr. Med. Chem. 2008; 15: 404-14.
11. Lees KR, Zivin JA, Ashwood T et al. NXY-059 for acute ischaemic stroke. N. Engl. J. Med. 2006; 354: 588-600.
12. Lisboa RC, Jovanovic BD, Alberts MJ. Analysis of the safety and efficacy of intra-arterial thrombolytic therapy in ischaemic stroke. Stroke 2002; 33: 2866-71.
13. Bang OY, Lee JS, Lee PH, Lee G. Autologous mesenchymal stem cell transplantation in stroke patients. Ann. Neurol. 2005; 57: 874-882.
14. Nakatomi H, Kuriu T, Okabe S et al. Regeneration of hippocampal pyramidal neurons after ischaemic brain injury by recruitment of endogenous neural progenitors. Cell 2002; 110: 429-41.
15. Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat. Rev. Drug Discov. 2011; 10: 209-19.
16. Ganta S, Deshpande D, Korde A, Amiji M. A review of multifunctional nanoemulsion systems to overcome oral and CNS drug delivery barriers. Mol. Membr. Biol. 2010; 27: 260-73.
17. Christl SU, Murgatroyd PR, Gibson GR, Cummings JH. Production, metabolism, and excretion of hydrogen in the large intestine. Gastroenterology 1992; 102: 1269-77.
18. Hammer HF. Colonic hydrogen absorption: Quantification of its effect on hydrogen accumulation caused by bacterial fermentation of carbohydrates. Gut 1993; 34: 818-22.
19. Kajimura M, Fukuda R, Bateman RM, Yamamoto T, Suematsu M. Interactions of multiple gas-transducing systems: Hallmarks and uncertainties of CO, NO, and H2S gas biology. Antioxid. Redox Signal. 2010; 13: 157-92.
20. Wang R. The gasotransmitter role of hydrogen sulfide. Antioxid. Redox Signal. 2003; 5: 493-501.
21. Taqatqeh F, Mergia E, Neitz A, Eysel UT, Koesling D, Mittmann T. More than a retrograde messenger: Nitric oxide needs two cGMP pathways to induce hippocampal long-term potentiation. J. Neurosci. 2009; 29: 9344-50.
22. Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: Structure, function and inhibition. Biochem. J. 2001; 357: 593-615.
23. Knowles RG, Moncada S. Nitric oxide synthases in mammals. Biochem. J. 1994; 298: 249-58.
24. Murphy S, Simmons ML, Agullo L et al. Synthesis of nitric oxide in CNS glial cells. Trends Neurosci. 1993; 16: 323-28.
25. Olivenza R, Moro MA, Lizasoain I et al. Chronic stress induces the expression of inducible nitric oxide synthase in rat brain cortex. J. Neurochem. 2000; 74: 785-91.
26. Galea E, Feinstein DL, Reis DJ. Induction of calcium-independent nitric oxide synthase activity in primary rat glial cultures. Proc. Natl Acad. Sci. USA 1992; 89: 10945-49.
27. Kolesnikov YA, Pan YX, Babey AM, Jain S, Wilson R, Pasternak GW. Functionally differentiating two neuronal nitric oxide synthase isoforms through antisense mapping: Evidence for opposing NO actions on morphine analgesia and tolerance. Proc. Natl Acad. Sci. USA 1997; 94: 8220-25.
28. Iadecola C. Bright and dark sides of nitric oxide in ischaemic brain injury. Trends Neurosci. 1997; 20: 132-39.
29. Robert G. Keynes, John Garthwaite. Nitric oxide and its role in ischaemic brain injury. Curr. Mol. Med. 2004; 4: 179-91.
30. Petegnief V, Font-Nieves M, Martin ME, Salinas M, Planas AM. Nitric oxide mediates NMDA-induced persistent inhibition of protein synthesis through dephosphorylation of eukaryotic initiation factor 4E-binding protein 1 and eukaryotic initiation factor 4G proteolysis. Biochem. J. 2008; 411: 667-77.
31. Iadecola C, Kahles T, Gallo EF, Anrather J. Neurovascular protection by ischaemic tolerance: Role of nitric oxide. J. Physiol. 2011; 589: 4137-45.
32. Zhang F, Xu S, Iadecola C. Time dependence of effect of nitric oxide synthase inhibition on cerebral ischaemic damage. J. Cereb. Blood Flow Metab. 1995; 15: 595-601.
33. Strosznajder J, Chalimoniuk M. Biphasic enhancement of nitric oxide synthase activity and cGMP level following brain ischaemia in gerbils. Acta Neurobiol. Exp. 1996; 56: 71-81.
34. Chen YR, Chen CL, Liu X, He G, Zweier JL. Involvement of phospholipid, biomembrane integrity, and NO peroxidase activity in the NO catabolism by cytochrome c oxidase. Arch. Biochem. Biophys. 2005; 439: 200-10.
35. Foley LM, Hitchens TK, Melick JA, Bayir H, Ho C, Kochanek PM. Effect of inducible nitric oxide synthase on cerebral blood flow after experimental traumatic brain injury in mice. J. Neurotrauma 2008; 25: 299-10.
36. Batteur-Parmentier S, Margaill I, Plotkine M. Modulation by nitric oxide of cerebral neutrophil accumulation after transient focal ischaemia in rats. J. Cereb. Blood Flow Metab. 2000; 20: 812-19.
37. Sommer C, Gass P, Kiessling M. Selective c-JUN expression in CA1 neurons of the gerbil hippocampus during and after acquisition of an ischemia-tolerant state. Brain Pathol. 1995; 5: 135-44.
38. Yamada T, Kawahara K, Kosugi T, Tanaka M. Nitric oxide produced during sublethal ischaemia is crucial for the preconditioning-induced down-regulation of glutamate transporter GLT-1 in neuron/astrocyte co-cultures. Neurochem. Res. 2006; 31: 49-56.
39. Willmot M, Gray L, Gibson C, Murphy S, Bath PM. A systematic review of nitric oxide donors and L-arginine in experimental stroke; effects on infarct size and cerebral blood flow. Nitric Oxide 2005; 12: 141-9.
40. Pansiot J, Loron G, Olivier P et al. Neuroprotective effect of inhaled nitric oxide on excitotoxic-induced brain damage in neonatal rat. PLoS ONE 2010; 5: e10916.
41. Huang Z, Huang PL, Panahian N, Dalkara T, Fishman MC, Moskowitz MA. Effects of cerebral ischaemia in mice deficient in neuronal nitric oxide synthase. Science 1994; 265: 1883-5.
42. Zhao X, Haensel C, Araki E, Ross ME, Iadecola C. Gene-dosing effect and persistence of reduction in ischaemic brain injury in mice lacking inducible nitric oxide synthase. Brain Res. 2000; 872: 215-8.
43. Sims NR, Anderson MF. Mitochondrial contributions to tissue damage in stroke. Neurochem. Int. 2002; 40: 511-26.
44. Huang Z, Huang PL, Ma J et al. Enlarged infarcts in endothelial nitric oxide synthase knockout mice are attenuated by nitro-l-arginine. J. Cereb. Blood Flow Metab. 1996; 16: 981-7.
45. Zhang F, Iadecola C. Reduction of focal cerebral ischaemic damage by delayed treatment with nitric oxide donors. J. Cereb. Blood Flow Metab. 1994; 14: 574-80.
46. Bath PM. The effect of nitric oxide-donating vasodilators on monocyte chemotaxis and intracellular cGMP concentrations in vitro. Eur. J. Clin. Pharmacol. 1993; 45: 53-8.
47. Welch G, Loscalzo J. Nitric oxide and the cardiovascular system. J. Card. Surg. 1994; 9: 361-71.
48. Pluta RM, Rak R, Wink DA et al. Effects of nitric oxide on reactive oxygen species production and infarction size after brain reperfusion injury. Neurosurgery 2001; 48: 884-92.
49. Lipton SA, Rayudu PV, Choi YB, Sucher NJ, Chen HS. Redox modulation of the NMDA receptor by NO-related species. Prog. Brain Res. 1998; 118: 73-82.
50. Sadoshima S, Nagao T, Okada Y, Fujii K, Ibayashi S, Fujishima M. l-Arginine ameliorates recirculation and metabolic derangement in brain ischaemia in hypertensive rats. Brain Res. 1997; 744: 246-52.
51. Fredduzzi S, Mariucci G, Tantucci M, Del Soldato P, Ambrosini MV. Nitro-aspirin (NCX4016) reduces brain damage induced by focal cerebral ischaemia in the rat. Neurosci. Lett. 2001; 302: 121-4.
52. Zhang R, Zhang L, Zhang Z et al. A nitric oxide donor induces neurogenesis and reduces functional deficits after stroke in rats. Ann. Neurol. 2001; 50: 602-11.
53. Morikawa E, Moskowitz MA, Huang Z, Yoshida T, Irikura K, Dalkara T. l-Arginine infusion promotes nitric oxide-dependent vasodilation, increases regional cerebral blood flow, and reduces infarction volume in the rat. Stroke 1994; 25: 429-35.
54. Salom JB, Orti M, Centeno JM, Torregrosa G, Alborch E. Reduction of infarct size by the NO donors sodium nitroprusside and spermine/NO after transient focal cerebral ischaemia in rats. Brain Res. 2000; 865: 149-56.
55. Butterworth RJ, Cluckie A, Jackson SH, Buxton-Thomas M, Bath PM. Pathophysiological assessment of nitric oxide (given as sodium nitroprusside) in acute ischaemic stroke. Cerebrovasc. Dis. 1998; 8: 158-65.
56. Molloy J, Martin JF, Baskerville PA, Fraser SC, Markus HS. S-Nitrosoglutathione reduces the rate of embolization in humans. Circulation 1998; 98: 1372-75.
57. Kaposzta Z, Baskerville PA, Madge D, Fraser S, Martin JF, Markus HS. l-Arginine and S-nitrosoglutathione reduce embolization in humans. Circulation 2001; 103: 2371-75.
58. Dore S. Decreased activity of the antioxidant heme oxygenase enzyme: Implications in ischaemia and in Alzheimer's disease. Free Radic. Biol. Med. 2002; 32: 1276-82.
59. Maines MD. The heme oxygenase system: A regulator of second messenger gases. Annu. Rev. Pharmacol. Toxicol. 1997; 37: 517-54.
60. Verma A, Hirsch DJ, Glatt CE, Ronnett GV, Snyder SH. Carbon monoxide: A putative neural messenger. Science 1993; 259: 381-84.
61. Zakhary R, Poss KD, Jaffrey SR, Ferris CD, Tonegawa S, Snyder SH. Targeted gene deletion of heme oxygenase 2 reveals neural role for carbon monoxide. Proc. Natl Acad. Sci. USA 1997; 94: 14848-53.
62. Zakhary R, Gaine SP, Dinerman JL, Ruat M, Flavahan NA, Snyder SH. Heme oxygenase 2: Endothelial and neuronal localization and role in endothelium-dependent relaxation. Proc. Natl Acad. Sci. USA 1996; 93: 795-98.
63. Leffler CW, Parfenova H, Jaggar JH, Wang R. Carbon monoxide and hydrogen sulfide: Gaseous messengers in cerebrovascular circulation. J. Appl. Physiol. 2006; 100: 1065-76.
64. Dore S, Sampei K, Goto S et al. Heme oxygenase-2 is neuroprotective in cerebral ischaemia. Mol. Med. 1999; 5: 656-63.
65. Dore S, Takahashi M, Ferris CD et al. Bilirubin, formed by activation of heme oxygenase-2, protects neurons against oxidative stress injury. Proc. Natl Acad. Sci. USA 1999; 96: 2445-50.
66. Namiranian K, Koehler RC, Sapirstein A, Doré S. Stroke outcomes in mice lacking the genes for neuronal heme oxygenase-2 and nitric oxide synthase. Curr. Neurovasc. Res. 2005; 2: 23-7.
67. Gueron G, De Siervi A, Ferrando M et al. Critical role of endogenous heme oxygenase 1 as a tuner of the invasive potential of prostate cancer cells. Mol. Cancer Res. 2009; 7: 1745-55.
68. Beschorner R, Adjodah D, Schwab JM et al. Long-term expression of heme oxygenase-1 (HO-1, HSP-32) following focal cerebral infarctions and traumatic brain injury in humans. Acta Neuropathol. 2000; 100: 377-84.
69. Aztatzi-Santillan E, Nares-Lopez FE, Marquez-Valadez B, Aguilera P, Chanez-Cardenas ME. The protective role of heme oxygenase-1 in cerebral ischaemia. Cent. Nerv. Syst. Agents Med. Chem. 2010; 10: 310-6.
70. Fu R, Zhao ZQ, Zhao HY, Zhao JS, Zhu XL. Expression of heme oxygenase-1 protein and messenger RNA in permanent cerebral ischaemia in rats. Neurol. Res. 2006; 28: 38-45.
71. Panahian N, Yoshiura M, Maines MD. Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice. J. Neurochem. 1999; 72: 1187-203.
72. Zeynalov E, Dore S. Low doses of carbon monoxide protect against experimental focal brain ischaemia. Neurotox. Res. 2009; 15: 133-7.
73. Imuta N, Hori O, Kitao Y et al. Hypoxia-mediated induction of heme oxygenase type I and carbon monoxide release from astrocytes protects nearby cerebral neurons from hypoxia-mediated apoptosis. Antioxid. Redox Signal. 2007; 9: 543-52.
74. Reiffenstein RJ, Hulbert WC, Roth SH. Toxicology of hydrogen sulfide. Annu. Rev. Pharmacol. Toxicol. 1992; 32: 109-134.
75. Li L, Moore PK. Putative biological roles of hydrogen sulfide in health and disease: A breath of not so fresh air? Trends Pharmacol. Sci. 2008; 29: 84-90.
76. 2S be the third endogenous gaseous transmitter? FASEB J. 2002; 16: 1792-98.
77. Abe K, Kimura H. The possible role of hydrogen sulfide as an endogenous neuromodulator. J. Neurosci. 1996; 16: 1066-71.
78. 2S): The third gas of interest for pharmacologists. Pharmacol. Rep. 2007; 59: 4-24.
79. Shibuya N, Tanaka M, Yoshida M et al. 3-Mercaptopyruvate sulfurtransferase produces hydrogen sulfide and bound sulfane sulfur in the brain. Antioxid. Redox Signal. 2009; 11: 703-14.
80. Qingyou Z, Junbao D, Weijin Z, Hui Y, Chaoshu T, Chunyu Z. Impact of hydrogen sulfide on carbon monoxide/heme oxygenase pathway in the pathogenesis of hypoxic pulmonary hypertension. Biochem. Biophys. Res. Commun. 2004; 317: 30-7.
81. Mok YY, Atan MS, Yoke Ping C et al. Role of hydrogen sulphide in haemorrhagic shock in the rat: Protective effect of inhibitors of hydrogen sulphide biosynthesis. Br. J. Pharmacol. 2004; 143: 881-98.
82. Qu K, Chen CP, Halliwell B, Moore PK, Wong PT. Hydrogen sulfide is a mediator of cerebral ischaemic damage. Stroke 2006; 37: 889-93.
83. 2S generated by heart in rat and its effects on cardiac function. Biochem. Biophys. Res. Commun. 2004; 313: 362-8.
84. Sivarajah A, McDonald MC, Thiemermann C. The production of hydrogen sulfide limits myocardial ischaemia and reperfusion injury and contributes to the cardioprotective effects of preconditioning with endotoxin, but not ischaemia in the rat. Shock 2006; 26: 154-61.
85. Tay AS, Hu LF, Lu M, Wong PT, Bian JS. Hydrogen sulfide protects neurons against hypoxic injury via stimulation of ATP-sensitive potassium channel/protein kinase C/extracellular signal-regulated kinase/heat shock protein 90 pathway. Neuroscience 2010; 167: 277-86.
86. Hu LF, Lu M, Wong PT, Bian JS. Hydrogen sulfide: Neurophysiology and neuropathology. Antioxid. Redox Signal. 2011; 15: 405-19.
87. Hu LF, Lu M, Wu ZY, Wong PT, Bian JS. Hydrogen sulfide inhibits rotenone-induced apoptosis via preservaton of mitochondrial function. Mol. Pharmacol. 2009; 75: 27-34.
88. Coyle JT, Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science 1993; 262: 689-95.
89. Kimura Y, Kimura H. Hydrogen sulfide protects neurons from oxidative stress. FASEB J. 2004; 18: 1165-7.
90. Lu M, Hu LF, Hu G, Bian JS. Hydrogen sulfide protects astrocytes against H(2)O(2)-induced neural injury via enhancing glutamate uptake. Free Radic. Biol. Med. 2008; 45: 1705-13.
91. Hu LF, Wong PT, Moore PK, Bian JS. Hydrogen sulfide attenuates lipopolysaccharide-induced inflammation by inhibitiong of p38 mitogen-activated protein kinase in microglia. J. Neurochem. 2007; 100: 1121-28.
92. Li Z, Wang Y, Xie Y, Yang Z, Zhang T. Protective effects of exogenous hydrogen sulfide on neurons of hippocampus in a rat model of brain ischaemia. Neurochem. Res. 2011; 36: 1840-49.
93. Minamishima S, Bougaki M, Sips PY et al. Hydrogen sulfide improves survival after cardiac arrest and cardiopulmonary resuscitation via a nitric oxide synthase 3-dependent mechanism in mice. Circulation 2009; 120: 888-96.
94. Ren C, Du A, Li D, Sui J, Mayhan WG, Zhao H. Dynamic change of hydrogen sulfide during global cerebral ischaemia-reperfusion and its effect in rats. Brain Res. 2010; 1345: 197-205.
95. Biermann J, Lagreze WA, Schallner N, Schwer CI, Goebel U. Inhalative preconditioning with hydrogen sulfide attenuated apoptosis after retinal ischaemia/reperfusion injury. Mol. Vis. 2011; 17: 1275-86.
96. Numagami Y, Sato S, Ohnishi ST. Attenuation of rat ischaemic brain damage by aged garlic extracts: A possible protecting mechanism as antioxidants. Neurochem. Int. 1996; 29: 135-43.
97. Saleem S, Ahmad M, Ahmad AS et al. Behavioral and histologic neuroprotection of aqueous garlic extract after reversible focal cerebral ischaemia. J. Med. Food 2006; 9: 537-44.
98. Kimura H, Nagai Y, Umemura K, Kimura Y. Physiological roles of hydrogen sulfide: Synaptic modulation, neuroprotection, and smooth muscle relaxation. Antioxid. Redox Signal. 2005; 7: 795-803.
99. Zheng XF, Sun XJ, Xia ZF. Hydrogen resuscitation, a new cytoprotective approach. Clin. Exp. Pharmacol. Physiol. 2011; 38: 155-63.
100. Hayashida K, Sano M, Ohsawa I et al. Inhalation of hydrogen gas reduces infarct size in the rat model of myocardial ischaemia-reperfusion injury. Biochem. Biophys. Res. Commun. 2008; 373: 30-5.
101. Fukuda K, Asoh S, Ishikawa M, Yamamoto Y, Ohsawa I, Ohta S. Inhalation of hydrogen gas suppresses hepatic injury caused by ischaemia/reperfusion through reducing oxidative stress. Biochem. Biophys. Res. Commun. 2007; 361: 670-4.
102. Ohsawa I, Ishikawa M, Takahashi K et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med. 2007; 13: 688-94.
103. Chen CH, Manaenko A, Zhan Y et al. Hydrogen gas reduced acute hyperglycemia-enhanced hemorrhagic transformation in a focal ischaemia rat model. Neuroscience 2010; 169: 402-14.
104. Cai J, Kang Z, Liu K et al. Neuroprotective effects of hydrogen saline in neonatal hypoxia-ischaemia rat model. Brain Res. 2009; 1256: 129-37.
105. Nagata K, Nakashima-Kamimura N, Mikami T, Ohsawa I, Ohta S. Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology 2009; 34: 501-8.
106. Cai J, Kang Z, Liu WW et al. Hydrogen therapy reduces apoptosis in neonatal hypoxia-ischaemia rat model. Neurosci. Lett. 2008; 441: 167-72.
107. Ji Q, Hui K, Zhang L, Sun X, Li W, Duan M. The effect of hydrogen-rich saline on the brain of rats with transient ischemia. J. Surg. Res. 2011; 168: e95-e01.
108. Muir KW, Tyrrell P, Sattar N, Warburton E. Inflammation and ischaemic stroke. Curr. Opin. Neurol. 2007; 20: 334-42.
109. Allen CL, Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int. J. Stroke 2009; 4: 461-70.
110. Floyd RA, Carney JM. Free radical damage to protein and DNA: Mechanisms involved and relevant observations on brain undergoing oxidative stress. Ann. Neurol. 1992; 32(Suppl.): S22-27.
111. White KA, Marletta MA. Nitric oxide synthase is a cytochrome P-450 type hemoprotein. Biochemistry 1992; 31: 6627-31.
112. Wang J, Lu S, Moenne-Loccoz P, Ortiz de Montellano PR. Interaction of nitric oxide with human heme oxygenase-1. J. Biol. Chem. 2003; 278: 2341-47.
113. Nagasaka Y, Fernandez BO, Garcia-Saura MF et al. Brief periods of nitric oxide inhalation protect against myocardial ischaemia-reperfusion injury. Anesthesiology 2008; 109: 675-82.
114. Liu C, Wu J, Xu K et al. Neuroprotection by baicalein in ischaemic brain injury involves PTEN/AKT pathway. J. Neurochem. 2010; 112: 1500-12.
115. Wu WN, Wu PF, Chen XL et al. Sinomenine protects against ischaemic brain injury: Involvement of co-inhibition of acid-sensing ion channel 1a and L-type calcium channel. Br. J. Pharmacol. 2011; 164: 1445-59.