Neuroprotective Mechanisms of Melatonin in Hemorrhagic Stroke

Cellular and Molecular Neurobiology

Volumn 37, Issue 7, 2017, Pages 1173-1185

  Wu, Hai Jian ^a   Wu, Cheng ^a   Niu, Huan Jiang ^a   Wang, Kun ^a   Mo, Lian Jie ^a   Shao, An Wen ^b   Dixon, Brandon J ^c   Zhang, Jian Min ^b   Yang, Shu Xu ^a   Wang, Yi Rong ^a  

^a ZHEJIANG UNIVERSITY   (China)

^b ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE   (China)

^c LOMA LINDA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Apoptosis; Hemorrhagic stroke; Inflammation; Melatonin; Neuroprotection; Oxidative stress

Indexed keywords

MELATONIN; NEUROPROTECTIVE AGENT;

BRAIN HEMORRHAGE; CENTRAL NERVOUS SYSTEM DISEASE; DRUG MECHANISM; HUMAN; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; REVIEW; SUBARACHNOID HEMORRHAGE; ANIMAL; CEREBROVASCULAR ACCIDENT; DRUG EFFECT; METABOLISM; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; CEREBRAL HEMORRHAGE; HUMANS; MELATONIN; NEUROPROTECTIVE AGENTS; SIGNAL TRANSDUCTION; STROKE;

EID: 85010960720     PISSN: 02724340     EISSN: 15736830     Source Type: Journal    
DOI: 10.1007/s10571-017-0461-9     Document Type: Review

References (118)

1. Acuna-Castroviejo D, Escames G, Venegas C, Diaz-Casado ME, Lima-Cabello E, Lopez LC, Rosales-Corral S, Tan DX, Reiter RJ (2014) Extrapineal melatonin: sources, regulation, and potential functions. Cell Mol Life Sci 71(16):2997–3025. doi:10.1007/s00018-014-1579-2
2. Adeoye O, Broderick JP (2010) Advances in the management of intracerebral hemorrhage. Nat Rev Neurol 6(11):593–601. doi:10.1038/nrneurol.2010.146
3. Albayrak S, Zhao Q, Siesjo BK, Smith ML (1997) Effect of transient focal ischemia on blood-brain barrier permeability in the rat: correlation to cell injury. Acta Neuropathol 94(2):158–163
4. Ali T, Badshah H, Kim TH, Kim MO (2015) Melatonin attenuates D-galactose-induced memory impairment, neuroinflammation and neurodegeneration via RAGE/NF-kB/JNK signaling pathway in aging mouse model. J Pineal Res 58(1):71–85. doi:10.1111/jpi.12194
5. Aydin MV, Caner H, Sen O, Ozen O, Atalay B, Cekinmez M, Altinors N (2005) Effect of melatonin on cerebral vasospasm following experimental subarachnoid hemorrhage. Neurol Res 27(1):77–82. doi:10.1179/016164105X18331
6. Ayer RE, Sugawara T, Chen W, Tong W, Zhang JH (2008) Melatonin decreases mortality following severe subarachnoid hemorrhage. J Pineal Res 44(2):197–204. doi:10.1111/j.1600-079X.2007.00508.x
7. Ayer A, Hwang BY, Appelboom G, Connolly ES Jr (2012) Clinical trials for neuroprotective therapies in intracerebral hemorrhage: a new roadmap from bench to bedside. Transl Stroke Res 3(4):409–417. doi:10.1007/s12975-012-0207-4
8. Bandyopadhyay D, Biswas K, Bandyopadhyay U, Reiter RJ, Banerjee RK (2000) Melatonin protects against stress-induced gastric lesions by scavenging the hydroxyl radical. J Pineal Res 29(3):143–151
9. Belayev L, Busto R, Zhao W, Ginsberg MD (1996) Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats. Brain Res 739(1–2):88–96
10. Benchenane K, Berezowski V, Fernandez-Monreal M, Brillault J, Valable S, Dehouck MP, Cecchelli R, Vivien D, Touzani O, Ali C (2005) Oxygen glucose deprivation switches the transport of tPA across the blood-brain barrier from an LRP-dependent to an increased LRP-independent process. Stroke 36(5):1065–1070. doi:10.1161/01.STR.0000163050.39122.4f
11. Beslow LA, Smith SE, Vossough A, Licht DJ, Kasner SE, Favilla CG, Halperin AR, Gordon DM, Jones CI, Cucchiara AJ, Ichord RN (2011) Hemorrhagic transformation of childhood arterial ischemic stroke. Stroke 42(4):941–946. doi:10.1161/STROKEAHA.110.604199
12. Bolitho SJ, Naismith SL, Rajaratnam SM, Grunstein RR, Hodges JR, Terpening Z, Rogers N, Lewis SJ (2014) Disturbances in melatonin secretion and circadian sleep-wake regulation in Parkinson disease. Sleep Med 15(3):342–347. doi:10.1016/j.sleep.2013.10.016
13. Caner B, Hou J, Altay O, Fujii M, Zhang JH (2012) Transition of research focus from vasospasm to early brain injury after subarachnoid hemorrhage. J Neurochem 123(Suppl 2):12–21. doi:10.1111/j.1471-4159.2012.07939.x
14. Cardinali DP, Srinivasan V, Brzezinski A, Brown GM (2012) Melatonin and its analogs in insomnia and depression. J Pineal Res 52(4):365–375. doi:10.1111/j.1600-079X.2011.00962.x
15. Carloni S, Favrais G, Saliba E, Albertini MC, Chalon S, Longini M, Gressens P, Buonocore G, Balduini W (2016) Melatonin modulates neonatal brain inflammation through endoplasmic reticulum stress, autophagy, and miR-34a/silent information regulator 1 pathway. J Pineal Res 61(3):370–380. doi:10.1111/jpi.12354
16. Cervantes M, Morali G, Letechipia-Vallejo G (2008) Melatonin and ischemia-reperfusion injury of the brain. J Pineal Res 45(1):1–7. doi:10.1111/j.1600-079X.2007.00551.x
17. Chahbouni M, Escames G, Venegas C, Sevilla B, Garcia JA, Lopez LC, Munoz-Hoyos A, Molina-Carballo A, Acuna-Castroviejo D (2010) Melatonin treatment normalizes plasma pro-inflammatory cytokines and nitrosative/oxidative stress in patients suffering from Duchenne muscular dystrophy. J Pineal Res 48(3):282–289. doi:10.1111/j.1600-079X.2010.00752.x
18. Chakraborty J, Nthenge-Ngumbau DN, Rajamma U, Mohanakumar KP (2014) Melatonin protects against behavioural dysfunctions and dendritic spine damage in 3-nitropropionic acid-induced rat model of Huntington’s disease. Behav Brain Res 264:91–104. doi:10.1016/j.bbr.2014.01.048
19. Chen HY, Chen TY, Lee MY, Chen ST, Hsu YS, Kuo YL, Chang GL, Wu TS, Lee EJ (2006a) Melatonin decreases neurovascular oxidative/nitrosative damage and protects against early increases in the blood-brain barrier permeability after transient focal cerebral ischemia in mice. J Pineal Res 41(2):175–182. doi:10.1111/j.1600-079X.2006.00351.x
20. Chen TY, Lee MY, Chen HY, Kuo YL, Lin SC, Wu TS, Lee EJ (2006b) Melatonin attenuates the postischemic increase in blood-brain barrier permeability and decreases hemorrhagic transformation of tissue-plasminogen activator therapy following ischemic stroke in mice. J Pineal Res 40(3):242–250. doi:10.1111/j.1600-079X.2005.00307.x
21. Chen J, Chen G, Li J, Qian C, Mo H, Gu C, Yan F, Yan W, Wang L (2014a) Melatonin attenuates inflammatory response-induced brain edema in early brain injury following a subarachnoid hemorrhage: a possible role for the regulation of pro-inflammatory cytokines. J Pineal Res 57(3):340–347. doi:10.1111/jpi.12173
22. Chen J, Wang L, Wu C, Hu Q, Gu C, Yan F, Li J, Yan W, Chen G (2014b) Melatonin-enhanced autophagy protects against neural apoptosis via a mitochondrial pathway in early brain injury following a subarachnoid hemorrhage. J Pineal Res 56(1):12–19. doi:10.1111/jpi.12086
23. Chen S, Feng H, Sherchan P, Klebe D, Zhao G, Sun X, Zhang J, Tang J, Zhang JH (2014c) Controversies and evolving new mechanisms in subarachnoid hemorrhage. Prog Neurobiol 115:64–91. doi:10.1016/j.pneurobio.2013.09.002
24. Chen J, Qian C, Duan H, Cao S, Yu X, Li J, Gu C, Yan F, Wang L, Chen G (2015a) Melatonin attenuates neurogenic pulmonary edema via the regulation of inflammation and apoptosis after subarachnoid hemorrhage in rats. J Pineal Res 59(4):469–477. doi:10.1111/jpi.12278
25. Chen S, Wu H, Tang J, Zhang J, Zhang JH (2015b) Neurovascular events after subarachnoid hemorrhage: focusing on subcellular organelles. Acta Neurochir Suppl 120:39–46. doi:10.1007/978-3-319-04981-6_7
26. Chung SY, Han SH (2003) Melatonin attenuates kainic acid-induced hippocampal neurodegeneration and oxidative stress through microglial inhibition. J Pineal Res 34(2):95–102
27. Cuzzocrea S, Costantino G, Gitto E, Mazzon E, Fulia F, Serraino I, Cordaro S, Barberi I, De Sarro A, Caputi AP (2000) Protective effects of melatonin in ischemic brain injury. J Pineal Res 29(4):217–227
28. Dijkhuizen RM, Asahi M, Wu O, Rosen BR, Lo EH (2002) Rapid breakdown of microvascular barriers and subsequent hemorrhagic transformation after delayed recombinant tissue plasminogen activator treatment in a rat embolic stroke model. Stroke 33(8):2100–2104
29. Ding K, Wang H, Xu J, Li T, Zhang L, Ding Y, Zhu L, He J, Zhou M (2014) Melatonin stimulates antioxidant enzymes and reduces oxidative stress in experimental traumatic brain injury: the Nrf2-ARE signaling pathway as a potential mechanism. Free Radic Biol Med 73:1–11. doi:10.1016/j.freeradbiomed.2014.04.031
30. Dong Y, Fan C, Hu W, Jiang S, Ma Z, Yan X, Deng C, Di S, Xin Z, Wu G, Yang Y, Reiter RJ, Liang G (2016) Melatonin attenuated early brain injury induced by subarachnoid hemorrhage via regulating NLRP3 inflammasome and apoptosis signaling. J Pineal Res 60(3):253–262. doi:10.1111/jpi.12300
31. Ersahin M, Toklu HZ, Cetinel S, Yuksel M, Yegen BC, Sener G (2009) Melatonin reduces experimental subarachnoid hemorrhage-induced oxidative brain damage and neurological symptoms. J Pineal Res 46(3):324–332. doi:10.1111/j.1600-079X.2009.00664.x
32. Fang Q, Chen G, Zhu W, Dong W, Wang Z (2009) Influence of melatonin on cerebrovascular proinflammatory mediators expression and oxidative stress following subarachnoid hemorrhage in rabbits. Mediators Inflamm 2009:426346. doi:10.1155/2009/426346
33. Fischer TW, Kleszczynski K, Hardkop LH, Kruse N, Zillikens D (2013) Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR-induced depletion, and protects against the formation of DNA damage (8-hydroxy-2′-deoxyguanosine) in ex vivo human skin. J Pineal Res 54(3):303–312. doi:10.1111/jpi.12018
34. Fujii M, Yan J, Rolland WB, Soejima Y, Caner B, Zhang JH (2013) Early brain injury, an evolving frontier in subarachnoid hemorrhage research. Transl Stroke Res 4(4):432–446. doi:10.1007/s12975-013-0257-2
35. Galano A, Tan DX, Reiter RJ (2013) On the free radical scavenging activities of melatonin’s metabolites. AFMK and AMK. J Pineal Res 54(3):245–257. doi:10.1111/jpi.12010
36. Gehrman PR, Connor DJ, Martin JL, Shochat T, Corey-Bloom J, Ancoli-Israel S (2009) Melatonin fails to improve sleep or agitation in double-blind randomized placebo-controlled trial of institutionalized patients with Alzheimer disease. Am J Geriatr Psychiatry 17(2):166–169. doi:10.1097/JGP.0b013e318187de18
37. Gursoy-Ozdemir Y, Can A, Dalkara T (2004) Reperfusion-induced oxidative/nitrative injury to neurovascular unit after focal cerebral ischemia. Stroke 35(6):1449–1453. doi:10.1161/01.STR.0000126044.83777.f4
38. Han HS, Suk K (2005) The function and integrity of the neurovascular unit rests upon the integration of the vascular and inflammatory cell systems. Curr Neurovasc Res 2(5):409–423
39. Hartman RE, Rojas HA, Lekic T, Ayer R, Lee S, Jadhav V, Titova E, Tang J, Zhang JH (2008) Long-term effects of melatonin after intracerebral hemorrhage in rats. Acta Neurochir Suppl 105:99–100
40. Hayter CL, Bishop GM, Robinson SR (2004) Pharmacological but not physiological concentrations of melatonin reduce iron-induced neuronal death in rat cerebral cortex. Neurosci Lett 362(3):182–184. doi:10.1016/j.neulet.2004.02.024
41. Huang ZG, Xue D, Preston E, Karbalai H, Buchan AM (1999) Biphasic opening of the blood-brain barrier following transient focal ischemia: effects of hypothermia. Can J Neurol Sci 26(4):298–304
42. Hung YC, Chen TY, Lee EJ, Chen WL, Huang SY, Lee WT, Lee MY, Chen HY, Wu TS (2008) Melatonin decreases matrix metalloproteinase-9 activation and expression and attenuates reperfusion-induced hemorrhage following transient focal cerebral ischemia in rats. J Pineal Res 45(4):459–467. doi:10.1111/j.1600-079X.2008.00617.x
43. Ikram MA, Wieberdink RG, Koudstaal PJ (2012) International epidemiology of intracerebral hemorrhage. Curr Atheroscler Rep 14(4):300–306. doi:10.1007/s11883-012-0252-1
44. Jickling GC, Liu D, Stamova B, Ander BP, Zhan X, Lu A, Sharp FR (2014) Hemorrhagic transformation after ischemic stroke in animals and humans. J Cereb Blood Flow Metab 34(2):185–199. doi:10.1038/jcbfm.2013.203
45. Jimenez-Jorge S, Guerrero JM, Jimenez-Caliani AJ, Naranjo MC, Lardone PJ, Carrillo-Vico A, Osuna C, Molinero P (2007) Evidence for melatonin synthesis in the rat brain during development. J Pineal Res 42(3):240–246. doi:10.1111/j.1600-079X.2006.00411.x
46. Jou MJ, Peng TI, Yu PZ, Jou SB, Reiter RJ, Chen JY, Wu HY, Chen CC, Hsu LF (2007) Melatonin protects against common deletion of mitochondrial DNA-augmented mitochondrial oxidative stress and apoptosis. J Pineal Res 43(4):389–403. doi:10.1111/j.1600-079X.2007.00490.x
47. Kapadia A, Schweizer TA, Spears J, Cusimano M, Macdonald RL (2014) Nonaneurysmal perimesencephalic subarachnoid hemorrhage: diagnosis, pathophysiology, clinical characteristics, and long-term outcome. World Neurosurg 82(6):1131–1143. doi:10.1016/j.wneu.2014.07.006
48. Keep RF, Hua Y, Xi G (2012) Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol 11(8):720–731. doi:10.1016/S1474-4422(12)70104-7
49. Kleszczynski K, Zillikens D, Fischer TW (2016) Melatonin enhances mitochondrial ATP synthesis, reduces reactive oxygen species formation, and mediates translocation of the nuclear erythroid 2-related factor 2 resulting in activation of phase-2 antioxidant enzymes (gamma-GCS, HO-1, NQO1) in ultraviolet radiation-treated normal human epidermal keratinocytes (NHEK). J Pineal Res 61(2):187–197. doi:10.1111/jpi.12338
50. Kotler M, Rodriguez C, Sainz RM, Antolin I, Menendez-Pelaez A (1998) Melatonin increases gene expression for antioxidant enzymes in rat brain cortex. J Pineal Res 24(2):83–89
51. Lees KR, Bluhmki E, von Kummer R, Brott TG, Toni D, Grotta JC, Albers GW, Kaste M, Marler JR, Hamilton SA, Tilley BC, Davis SM, Donnan GA, Hacke W, Ecass AN, Group Er-PS, Allen K, Mau J, Meier D, del Zoppo G, De Silva DA, Butcher KS, Parsons MW, Barber PA, Levi C, Bladin C, Byrnes G (2010) Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet 375(9727):1695–1703. doi:10.1016/S0140-6736(10)60491-6
52. Leibowitz A, Volkov A, Voloshin K, Shemesh C, Barshack I, Grossman E (2016) Melatonin prevents kidney injury in a high salt diet-induced hypertension model by decreasing oxidative stress. J Pineal Res 60(1):48–54. doi:10.1111/jpi.12287
53. Lekic T, Hartman R, Rojas H, Manaenko A, Chen W, Ayer R, Tang J, Zhang JH (2010) Protective effect of melatonin upon neuropathology, striatal function, and memory ability after intracerebral hemorrhage in rats. J Neurotrauma 27(3):627–637. doi:10.1089/neu.2009.1163
54. Li ZQ, Liang GB, Xue YX, Liu YH (2009) Effects of combination treatment of dexamethasone and melatonin on brain injury in intracerebral hemorrhage model in rats. Brain Res 1264:98–103. doi:10.1016/j.brainres.2009.01.055
55. Li H, Wang Y, Feng D, Liu Y, Xu M, Gao A, Tian F, Zhang L, Cui Y, Wang Z, Chen G (2014) Alterations in the time course of expression of the Nox family in the brain in a rat experimental cerebral ischemia and reperfusion model: effects of melatonin. J Pineal Res 57(1):110–119. doi:10.1111/jpi.12148
56. Lin AM, Ho LT (2000) Melatonin suppresses iron-induced neurodegeneration in rat brain. Free Radic Biol Med 28(6):904–911
57. Liu YJ, Zhuang J, Zhu HY, Shen YX, Tan ZL, Zhou JN (2007) Cultured rat cortical astrocytes synthesize melatonin: absence of a diurnal rhythm. J Pineal Res 43(3):232–238. doi:10.1111/j.1600-079X.2007.00466.x
58. Liu YJ, Meng FT, Wang LL, Zhang LF, Cheng XP, Zhou JN (2012) Apolipoprotein E influences melatonin biosynthesis by regulating NAT and MAOA expression in C6 cells. J Pineal Res 52(4):397–402. doi:10.1111/j.1600-079X.2011.00954.x
59. Macchi MM, Bruce JN (2004) Human pineal physiology and functional significance of melatonin. Front Neuroendocrinol 25(3–4):177–195. doi:10.1016/j.yfrne.2004.08.001
60. Macdonald RL (2014) Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol 10(1):44–58. doi:10.1038/nrneurol.2013.246
61. Maharaj DS, Maharaj H, Daya S, Glass BD (2006) Melatonin and 6-hydroxymelatonin protect against iron-induced neurotoxicity. J Neurochem 96(1):78–81. doi:10.1111/j.1471-4159.2005.03532.x
62. Martin M, Macias M, Escames G, Reiter RJ, Agapito MT, Ortiz GG, Acuna-Castroviejo D (2000) Melatonin-induced increased activity of the respiratory chain complexes I and IV can prevent mitochondrial damage induced by ruthenium red in vivo. J Pineal Res 28(4):242–248
63. Martinez-Cruz F, Espinar A, Pozo D, Osuna C, Guerrero JM (2002) Melatonin prevents focal rat cerebellum injury as assessed by induction of heat shock protein (HO-1) following subarachnoid injections of lysed blood. Neurosci Lett 331(3):208–210
64. Medeiros CA, Carvalhedo de Bruin PF, Lopes LA, Magalhaes MC, de Lourdes Seabra M, de Bruin VM (2007) Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson’s disease. A randomized, double blind, placebo-controlled study. J Neurol 254(4):459–464. doi:10.1007/s00415-006-0390-x
65. Mesenge C, Margaill I, Verrecchia C, Allix M, Boulu RG, Plotkine M (1998) Protective effect of melatonin in a model of traumatic brain injury in mice. J Pineal Res 25(1):41–46
66. Mukherjee D, Ghosh AK, Dutta M, Mitra E, Mallick S, Saha B, Reiter RJ, Bandyopadhyay D (2015) Mechanisms of isoproterenol-induced cardiac mitochondrial damage: protective actions of melatonin. J Pineal Res 58(3):275–290. doi:10.1111/jpi.12213
67. Naskar A, Prabhakar V, Singh R, Dutta D, Mohanakumar KP (2015) Melatonin enhances L-DOPA therapeutic effects, helps to reduce its dose, and protects dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice. J Pineal Res 58(3):262–274. doi:10.1111/jpi.12212
68. Negi G, Kumar A, Sharma SS (2011) Melatonin modulates neuroinflammation and oxidative stress in experimental diabetic neuropathy: effects on NF-kB and Nrf2 cascades. J Pineal Res 50(2):124–131. doi:10.1111/j.1600-079X.2010.00821.x
69. Okatani Y, Wakatsuki A, Reiter RJ (2002a) Melatonin protects hepatic mitochondrial respiratory chain activity in senescence-accelerated mice. J Pineal Res 32(3):143–148
70. Okatani Y, Wakatsuki A, Reiter RJ, Miyahara Y (2002b) Hepatic mitochondrial dysfunction in senescence-accelerated mice: correction by long-term, orally administered physiological levels of melatonin. J Pineal Res 33(3):127–133
71. Pandi-Perumal SR, Srinivasan V, Maestroni GJ, Cardinali DP, Poeggeler B, Hardeland R (2006) Melatonin: nature’s most versatile biological signal? FEBS J 273(13):2813–2838. doi:10.1111/j.1742-4658.2006.05322.x
72. Pang SF, Li Y, Jiang DH, Chang B, Xie BL (1990) Acute cerebral hemorrhage changes the nocturnal surge of plasma melatonin in humans. J Pineal Res 9(3):193–208
73. Pei Z, Cheung RT (2004) Pretreatment with melatonin exerts anti-inflammatory effects against ischemia/reperfusion injury in a rat middle cerebral artery occlusion stroke model. J Pineal Res 37(2):85–91. doi:10.1111/j.1600-079X.2004.00138.x
74. Poeggeler B, Saarela S, Reiter RJ, Tan DX, Chen LD, Manchester LC, Barlow-Walden LR (1994) Melatonin–a highly potent endogenous radical scavenger and electron donor: new aspects of the oxidation chemistry of this indole accessed in vitro. Ann N Y Acad Sci 738:419–420
75. Qureshi AI, Suri MF, Ostrow PT, Kim SH, Ali Z, Shatla AA, Guterman LR, Hopkins LN (2003) Apoptosis as a form of cell death in intracerebral hemorrhage. Neurosurgery 52(5):1041–1047; discussion 1047–1048
76. Radogna F, Cristofanon S, Paternoster L, D’Alessio M, De Nicola M, Cerella C, Dicato M, Diederich M, Ghibelli L (2008) Melatonin antagonizes the intrinsic pathway of apoptosis via mitochondrial targeting of Bcl-2. J Pineal Res 44(3):316–325. doi:10.1111/j.1600-079X.2007.00532.x
77. Regrigny O, Delagrange P, Scalbert E, Atkinson J, Lartaud-Idjouadiene I (1998) Melatonin improves cerebral circulation security margin in rats. Am J Physiol 275(1 Pt 2):H139–H144
78. Regrigny O, Dupuis F, Atkinson J, Liminana P, Scalbert E, Delagrange P, Chillon JM (2001) Cerebral arteriolar structure and function in pinealectomized rats. Am J Physiol Heart Circ Physiol 281(4):H1476–H1480
79. Reiter RJ, Manchester LC, Tan DX (2010) Neurotoxins: free radical mechanisms and melatonin protection. Curr Neuropharmacol 8(3):194–210. doi:10.2174/157015910792246236
80. Reiter RJ, Tan DX, Rosales-Corral S, Manchester LC (2013) The universal nature, unequal distribution and antioxidant functions of melatonin and its derivatives. Mini Rev Med Chem 13(3):373–384
81. Reiter RJ, Mayo JC, Tan DX, Sainz RM, Alatorre-Jimenez M, Qin L (2016) Melatonin as an antioxidant: under promises but over delivers. J Pineal Res 61(3):253–278. doi:10.1111/jpi.12360
82. Rinkel GJ, Algra A (2011) Long-term outcomes of patients with aneurysmal subarachnoid haemorrhage. Lancet Neurol 10(4):349–356. doi:10.1016/S1474-4422(11)70017-5
83. Rodriguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V, Reiter RJ (2004) Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 36(1):1–9
84. Rojas H, Lekic T, Chen W, Jadhav V, Titova E, Martin RD, Tang J, Zhang J (2008) The antioxidant effects of melatonin after intracerebral hemorrhage in rats. Acta Neurochir Suppl 105:19–21
85. Rosales-Corral SA, Acuna-Castroviejo D, Coto-Montes A, Boga JA, Manchester LC, Fuentes-Broto L, Korkmaz A, Ma S, Tan DX, Reiter RJ (2012) Alzheimer’s disease: pathological mechanisms and the beneficial role of melatonin. J Pineal Res 52(2):167–202. doi:10.1111/j.1600-079X.2011.00937.x
86. Samantaray S, Das A, Thakore NP, Matzelle DD, Reiter RJ, Ray SK, Banik NL (2009) Therapeutic potential of melatonin in traumatic central nervous system injury. J Pineal Res 47(2):134–142. doi:10.1111/j.1600-079X.2009.00703.x
87. Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M (2008) Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med 4(5):487–504
88. Sehba FA, Hou J, Pluta RM, Zhang JH (2012) The importance of early brain injury after subarachnoid hemorrhage. Prog Neurobiol 97(1):14–37. doi:10.1016/j.pneurobio.2012.02.003
89. Singhal NK, Srivastava G, Agrawal S, Jain SK, Singh MP (2012) Melatonin as a neuroprotective agent in the rodent models of Parkinson’s disease: is it all set to irrefutable clinical translation? Mol Neurobiol 45(1):186–199. doi:10.1007/s12035-011-8225-x
90. Skaper SD, Ancona B, Facci L, Franceschini D, Giusti P (1998) Melatonin prevents the delayed death of hippocampal neurons induced by enhanced excitatory neurotransmission and the nitridergic pathway. FASEB J 12(9):725–731
91. Tai SH, Chen HY, Lee EJ, Chen TY, Lin HW, Hung YC, Huang SY, Chen YH, Lee WT, Wu TS (2010) Melatonin inhibits postischemic matrix metalloproteinase-9 (MMP-9) activation via dual modulation of plasminogen/plasmin system and endogenous MMP inhibitor in mice subjected to transient focal cerebral ischemia. J Pineal Res 49(4):332–341. doi:10.1111/j.1600-079X.2010.00797.x
92. Tan DX, Chen LD, Poeggeler BL, Manchester LC, Reiter RJ (1993a) Melatonin: a potent, endogenous hydroxyl radical scavenger. Endocr J 1(4):57–60. doi:10.1111/j.1749-6632.1994.tb21831.x
93. Tan DX, Poeggeler B, Reiter RJ, Chen LD, Chen S, Manchester LC, Barlow-Walden LR (1993b) The pineal hormone melatonin inhibits DNA-adduct formation induced by the chemical carcinogen safrole in vivo. Cancer Lett 70(1–2):65–71
94. Tan DX, Manchester LC, Hardeland R, Lopez-Burillo S, Mayo JC, Sainz RM, Reiter RJ (2003) Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. J Pineal Res 34(1):75–78
95. Tang J, Liu J, Zhou C, Ostanin D, Grisham MB, Neil Granger D, Zhang JH (2005) Role of NADPH oxidase in the brain injury of intracerebral hemorrhage. J Neurochem 94(5):1342–1350. doi:10.1111/j.1471-4159.2005.03292.x
96. Terruso V, D’Amelio M, Di Benedetto N, Lupo I, Saia V, Famoso G, Mazzola MA, Aridon P, Sarno C, Ragonese P, Savettieri G (2009) Frequency and determinants for hemorrhagic transformation of cerebral infarction. Neuroepidemiology 33(3):261–265. doi:10.1159/000229781
97. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (1995) Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333(24):1581–1587. doi:10.1056/NEJM199512143332401
98. Trotti LM, Karroum EG (2016) Melatonin for sleep disorders in patients with neurodegenerative diseases. Curr Neurol Neurosci Rep 16(7):63. doi:10.1007/s11910-016-0664-3
99. Tsai MC, Chen WJ, Tsai MS, Ching CH, Chuang JI (2011) Melatonin attenuates brain contusion-induced oxidative insult, inactivation of signal transducers and activators of transcription 1, and upregulation of suppressor of cytokine signaling-3 in rats. J Pineal Res 51(2):233–245. doi:10.1111/j.1600-079X.2011.00885.x
100. Tunez I, Montilla P, Del Carmen Munoz M, Feijoo M, Salcedo M (2004) Protective effect of melatonin on 3-nitropropionic acid-induced oxidative stress in synaptosomes in an animal model of Huntington’s disease. J Pineal Res 37(4):252–256. doi:10.1111/j.1600-079X.2004.00163.x
101. Turjanski AG, Rosenstein RE, Estrin DA (1998) Reactions of melatonin and related indoles with free radicals: a computational study. J Med Chem 41(19):3684–3689. doi:10.1021/jm980117m
102. Ueda Y, Masuda T, Ishida A, Misumi S, Shimizu Y, Jung CG, Hida H (2014) Enhanced electrical responsiveness in the cerebral cortex with oral melatonin administration after a small hemorrhage near the internal capsule in rats. J Neurosci Res 92(11):1499–1508. doi:10.1002/jnr.23434
103. van Gijn J, Kerr RS, Rinkel GJ (2007) Subarachnoid haemorrhage. Lancet 369(9558):306–318. doi:10.1016/S0140-6736(07)60153-6
104. Wang J, Dore S (2007) Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab 27(5):894–908. doi:10.1038/sj.jcbfm.9600403
105. Wang X, Lo EH (2003) Triggers and mediators of hemorrhagic transformation in cerebral ischemia. Mol Neurobiol 28(3):229–244. doi:10.1385/MN:28:3:229
106. Wang Z, Ma C, Meng CJ, Zhu GQ, Sun XB, Huo L, Zhang J, Liu HX, He WC, Shen XM, Shu Z, Chen G (2012) Melatonin activates the Nrf2-ARE pathway when it protects against early brain injury in a subarachnoid hemorrhage model. J Pineal Res 53(2):129–137. doi:10.1111/j.1600-079X.2012.00978.x
107. Wang X, Wang ZH, Wu YY, Tang H, Tan L, Wang X, Gao XY, Xiong YS, Liu D, Wang JZ, Zhu LQ (2013a) Melatonin attenuates scopolamine-induced memory/synaptic disorder by rescuing EPACs/miR-124/Egr1 pathway. Mol Neurobiol 47(1):373–381. doi:10.1007/s12035-012-8355-9
108. Wang Z, Wu L, You W, Ji C, Chen G (2013b) Melatonin alleviates secondary brain damage and neurobehavioral dysfunction after experimental subarachnoid hemorrhage: possible involvement of TLR4-mediated inflammatory pathway. J Pineal Res 55(4):399–408. doi:10.1111/jpi.12087
109. Wang W, Li M, Chen Q, Wang J (2015) Hemorrhagic transformation after tissue plasminogen activator reperfusion therapy for ischemic stroke: mechanisms, models, and biomarkers. Mol Neurobiol 52(3):1572–1579. doi:10.1007/s12035-014-8952-x
110. Wasserman JK, Schlichter LC (2007) Minocycline protects the blood-brain barrier and reduces edema following intracerebral hemorrhage in the rat. Exp Neurol 207(2):227–237. doi:10.1016/j.expneurol.2007.06.025
111. Weishaupt JH, Bartels C, Polking E, Dietrich J, Rohde G, Poeggeler B, Mertens N, Sperling S, Bohn M, Huther G, Schneider A, Bach A, Siren AL, Hardeland R, Bahr M, Nave KA, Ehrenreich H (2006) Reduced oxidative damage in ALS by high-dose enteral melatonin treatment. J Pineal Res 41(4):313–323. doi:10.1111/j.1600-079X.2006.00377.x
112. − cotransporter KCC2 expression following traumatic brain injury in rats. J Pineal Res 61(2):241–250. doi:10.1111/jpi.12344
113. Xi G, Keep RF, Hoff JT (2006) Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 5(1):53–63. doi:10.1016/S1474-4422(05)70283-0
114. Zacharia BE, Hickman ZL, Grobelny BT, DeRosa P, Kotchetkov I, Ducruet AF, Connolly ES Jr (2010) Epidemiology of aneurysmal subarachnoid hemorrhage. Neurosurg Clin N Am 21(2):221–233. doi:10.1016/j.nec.2009.10.002
115. Zhang Y, Li X, Grailer JJ, Wang N, Wang M, Yao J, Zhong R, Gao GF, Ward PA, Tan DX, Li X (2016) Melatonin alleviates acute lung injury through inhibiting the NLRP3 inflammasome. J Pineal Res 60(4):405–414. doi:10.1111/jpi.12322
116. Zhao L, An R, Yang Y, Yang X, Liu H, Yue L, Li X, Lin Y, Reiter RJ, Qu Y (2015) Melatonin alleviates brain injury in mice subjected to cecal ligation and puncture via attenuating inflammation, apoptosis, and oxidative stress: the role of SIRT1 signaling. J Pineal Res 59(2):230–239. doi:10.1111/jpi.12254
117. Zhou C, Yamaguchi M, Kusaka G, Schonholz C, Nanda A, Zhang JH (2004) Caspase inhibitors prevent endothelial apoptosis and cerebral vasospasm in dog model of experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab 24(4):419–431. doi:10.1097/00004647-200404000-00007
118. Zhou Y, Wang Y, Wang J, Anne Stetler R, Yang QW (2014) Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation. Prog Neurobiol 115:25–44. doi:10.1016/j.pneurobio.2013.11.003