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Translational Stroke Research

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09.01.2019 | Original Article

The Role of Oxidative Stress in Microvascular Disturbances after Experimental Subarachnoid Hemorrhage

verfasst von: Toshio Fumoto, Masato Naraoka, Takeshi Katagai, Yuchen Li, Norihito Shimamura, Hiroki Ohkuma

Erschienen in: Translational Stroke Research | Ausgabe 6/2019

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Abstract

Oxidative stress was shown to play a crucial role in the diverse pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Microcirculatory dysfunction is thought to be an important and fundamental pathological change in EBI. However, other than blood-brain barrier (BBB) disruption, the influence of oxidative stress on microvessels remains to be elucidated. The aim of this study was to investigate the role of oxidative stress on microcirculatory integrity in EBI. SAH was induced in male Sprague-Dawley rats using an endovascular perforation technique. A free radical scavenger, edaravone, was administered prophylactically by intraperitoneal injection. SAH grade, neurological score, brain water content, and BBB permeability were measured at 24 h after SAH induction. In addition, cortical samples taken at 24 h after SAH were analyzed to explore oxidative stress, microvascular mural cell apoptosis, microspasm, and microthrombosis. Edaravone treatment significantly ameliorated neurological deficits, brain edema, and BBB disruption. In addition, oxidative stress-induced modifications and subsequent apoptosis of microvascular endothelial cells and pericytes increased after SAH induction, while the administration of edaravone suppressed this. Consistent with apoptotic cell inhibition, microthromboses were also inhibited by edaravone administration. Oxidative stress plays a pivotal role in the induction of multiple pathological changes in microvessels in EBI. Antioxidants are potential candidates for the treatment of microvascular disturbances after SAH.

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Macdonald RL, Schweizer TA. Spontaneous subarachnoid haemorrhage. Lancet. 2017;389(10069):655–66.PubMedCrossRef

Macdonald RL. Origins of the concept of vasospasm. Stroke. 2016;47(1):e11–5.PubMedCrossRef

Macdonald RL, Kassell NF, Mayer S, Ruefenacht D, Schmiedek P, Weidauer S, et al. Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (conscious-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial. Stroke. 2008;39(11):3015–21.PubMedCrossRef

Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, et al. Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid haemorrhage undergoing surgical clipping: a randomised, double-blind, placebo-controlled phase 3 trial (conscious-2). Lancet Neurol. 2011;10(7):618–25.PubMedCrossRef

Sehba FA, Pluta RM, Zhang JH. Metamorphosis of subarachnoid hemorrhage research: from delayed vasospasm to early brain injury. Mol Neurobiol. 2011;43(1):27–40.PubMedCrossRef

Sehba FA, Hou J, Pluta RM, Zhang JH. The importance of early brain injury after subarachnoid hemorrhage. Prog Neurobiol. 2012;97(1):14–37.PubMedPubMedCentralCrossRef

Fujii M, Yan J, Rolland WB, Soejima Y, Caner B, Zhang JH. Early brain injury, an evolving frontier in subarachnoid hemorrhage research. Transl Stroke Res. 2013;4(4):432–46.PubMedPubMedCentralCrossRef

Neulen A, Meyer S, Kramer A, Pantel T, Kosterhon M, Kunzelmann S, et al. Large vessel vasospasm is not associated with cerebral cortical hypoperfusion in a murine model of subarachnoid hemorrhage. Transl Stroke Res. 2018. https://doi.org/10.1007/s12975-018-0647-6.PubMedCentralCrossRef

Conzen C, Albanna W, Weiss M, Kürten D, Vilser W, Kotliar K, et al. Vasoconstriction and impairment of neurovascular coupling after subarachnoid hemorrhage: a descriptive analysis of retinal changes. Transl Stroke Res. 2018;9(3):284–93.PubMedCrossRef

10.

Suzuki H, Shiba M, Nakatsuka Y, Nakano F, Nishikawa H. Higher cerebrospinal fluid pH may contribute to the development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Transl Stroke Res. 2017;8(2):165–73.PubMedCrossRef

11.

Terpolilli NA, Brem C, Bühler D, Plesnila N. Are we barking up the wrong vessels? Cerebral microcirculation after subarachnoid hemorrhage. Stroke. 2015;46(10):3014–9.PubMedCrossRef

12.

Ayer RE, Zhang JH. Oxidative stress in subarachnoid haemorrhage: significance in acute brain injury and vasospasm. Acta Neurochir Suppl. 2008;104:33–41.PubMedPubMedCentralCrossRef

13.

Endo H, Nito C, Kamada H, Yu F, Chan PH. Reduction in oxidative stress by superoxide dismutase overexpression attenuates acute brain injury after subarachnoid hemorrhage via activation of Akt/glycogen synthase kinase-3beta survival signaling. J Cereb Blood Flow Metab. 2007;27(5):975–82.PubMedCrossRef

14.

Matz PG, Fujimura M, Lewen A, Morita-Fujimura Y, Chan PH. Increased cytochrome c-mediated DNA fragmentation and cell death in manganese-superoxide dismutase-deficient mice after exposure to subarachnoid hemolysate. Stroke. 2001;32(2):506–15.PubMedCrossRef

15.

Liu H, Zhao L, Yue L, Wang B, Li X, Guo H, et al. Pterostilbene attenuates early brain injury following subarachnoid hemorrhage via inhibition of the NLRP3 inflammasome and Nox2-related oxidative stress. Mol Neurobiol. 2017;54(8):5928–40.PubMedCrossRef

16.

Shi X, Fu Y, Zhang S, Ding H, Chen J. Baicalin attenuates subarachnoid hemorrhagic brain injury by modulating blood-brain barrier disruption, inflammation, and oxidative damage in mice. Oxidative Med Cell Longev. 2017;2017:1401790.CrossRef

17.

Zhan Y, Chen C, Suzuki H, Hu Q, Zhi X, Zhang JH. Hydrogen gas ameliorates oxidative stress in early brain injury after subarachnoid hemorrhage in rats. Crit Care Med. 2012;40(4):1291–6.PubMedPubMedCentralCrossRef

18.

Park IS, Meno JR, Witt CE, Suttle TK, Chowdhary A, Nguyen TS, et al. Subarachnoid hemorrhage model in the rat: modification of the endovascular filament model. J Neurosci Methods. 2008;172(2):195–200.PubMedCrossRef

19.

Sugawara T, Ayer R, Jadhav V, Zhang JH. A new grading system evaluating bleeding scale in filament perforation subarachnoid hemorrhage rat model. J Neurosci Methods. 2008;167(2):327–34.PubMedCrossRef

20.

Garcia JH, Wagner S, Liu KF, Hu XJ. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke. 1995;26(4):627–34 discussion 635.PubMedCrossRef

21.

Wang L, Fumoto T, Masumoto S, Shoji T, Miura T, Naraoka M, et al. Regression of atherosclerosis with apple procyanidins by activating the ATP-binding cassette subfamily a member 1 in a rabbit model. Atherosclerosis. 2017;258:56–64.PubMedCrossRef

22.

Munakata A, Naraoka M, Katagai T, Shimamura N, Ohkuma H. Role of cyclooxygenase-2 in relation to nitric oxide and endothelin-1 on pathogenesis of cerebral vasospasm after subarachnoid hemorrhage in rabbit. Transl Stroke Res. 2016;7(3):220–7.PubMedCrossRef

23.

Chen J, Chen G, Li J, Qian C, Mo H, Gu C, et al. 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. 2014;57(3):340–7.PubMedCrossRef

24.

Han Y, Zhang T, Su J, Zhao Y, Chenchen W, et al. Apigenin attenuates oxidative stress and neuronal apoptosis in early brain injury following subarachnoid hemorrhage. J Clin Neurosci. 2017;40:157–62.PubMedCrossRef

25.

Zhang ZY, Jiang M, Fang J, Yang MF, Zhang S, Yin YX, et al. Enhanced therapeutic potential of nano-curcumin against subarachnoid hemorrhage-induced blood-brain barrier disruption through inhibition of inflammatory response and oxidative stress. Mol Neurobiol. 2017;54(1):1–14.PubMedCrossRef

26.

Yabluchanskiy A, Ma Y, Iyer RP, Hall ME, Lindsey ML. Matrix metalloproteinase-9: many shades of function in cardiovascular disease. Physiology (Bethesda). 2013;28(6):391–403.

27.

O'Sullivan S, Medina C, Ledwidge M, Radomski MW, Gilmer JF. Nitric oxide-matrix metaloproteinase-9 interactions: biological and pharmacological significance—NO and MMP-9 interactions. Biochim Biophys Acta. 2014;1843(3):603–17.PubMedCrossRef

28.

Duris K, Lipkova J, Splichal Z, Madaraszova T, Jurajda M. Early inflammatory response in the brain and anesthesia recovery time evaluation after experimental subarachnoid hemorrhage. Transl Stroke Res. 2018. https://doi.org/10.1007/s12975-018-0641-z.CrossRef

29.

Blecharz-Lang KG, Wagner J, Fries A, Nieminen-Kelhä M, Rösner J, Schneider UC, et al. Interleukin 6-mediated endothelial barrier disturbances can be attenuated by blockade of the IL6 receptor expressed in brain microvascular endothelial cells. Transl Stroke Res. 2018;9:631–42. https://doi.org/10.1007/s12975-018-0614-2.PubMedCrossRef

30.

Pang J, Chen Y, Kuai L, Yang P, Peng J, Wu Y, et al. Inhibition of blood-brain barrier disruption by an apolipoprotein E-mimetic peptide ameliorates early brain injury in experimental subarachnoid hemorrhage. Transl Stroke Res. 2017;8:257–72.PubMedCrossRef

31.

Zhang XS, Zhang X, Zhang QR, Wu Q, Li W, Jiang TW, et al. Astaxanthin reduces matrix metalloproteinase-9 expression and activity in the brain after experimental subarachnoid hemorrhage in rats. Brain Res. 2015;1624:113–24.PubMedCrossRef

32.

Zhang T, Su J, Guo B, Zhu T, Wang K, Li X. Ursolic acid alleviates early brain injury after experimental subarachnoid hemorrhage by suppressing TLR4-mediated inflammatory pathway. Int Immunopharmacol. 2014;23(2):585–91.PubMedCrossRef

33.

Fujiwara N, Som AT, Pham LD, Lee BJ, Mandeville ET, Lo EH, et al. A free radical scavenger edaravone suppresses systemic inflammatory responses in a rat transient focal ischemia model. Neurosci Lett. 2016;633:7–13.PubMedPubMedCentralCrossRef

34.

Yuan Y, Zha H, Rangarajan P, Ling EA, Wu C. Anti-inflammatory effects of edaravone and scutellarin in activated microglia in experimentally induced ischemia injury in rats and in BV-2 microglia. BMC Neurosci. 2014;15:125.PubMedPubMedCentralCrossRef

35.

Yagi K, Kitazato KT, Uno M, Tada Y, Kinouchi T, Shimada K, et al. Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator. Stroke. 2009;40(2):626–31.PubMedCrossRef

36.

Bache S, Rasmussen R, Rossing M, Laigaard FP, Nielsen FC, Møller K. MicroRNA changes in cerebrospinal fluid after subarachnoid hemorrhage. Stroke. 2017;48(9):2391–8.PubMedPubMedCentralCrossRef

37.

Xu G, Meng L, Yauan D, Li K, Zhang Y, Dang C, et al. MEG3/miR-21 axis affects cell mobility by suppressing epithelial-mesenchymal transition in gastric cancer. Oncol Rep. 2018;40(1):39–48.PubMedPubMedCentral

38.

Zhou C, Ding J, Wu Y. Resveratrol induces apoptosis of bladder cancer cell via miR-21 regulation of Akt/Bcl-2 signaling pathway. Mol Med Rep. 2014;9(4):1467–73.PubMedCrossRef

39.

Obermeier B, Daneman R, Ransohoff RM. Development, maintenance and disruption of the blood-brain barrier. Nat Med. 2013;19(12):1584–96.PubMedPubMedCentralCrossRef

40.

Tso MK, Macdonald RL. Subarachnoid hemorrhage: a review of experimental studies on the microcirculation and the neurovascular unit. Transl Stroke Res. 2014;5(2):174–89.PubMedCrossRef

41.

Friedrich B, Müller F, Feiler S, Schöller K, Plesnila N. Experimental subarachnoid hemorrhage causes early and long-lasting microarterial constriction and microthrombosis: an in-vivo microscopy study. J Cereb Blood Flow Metab. 2012;32(3):447–55.PubMedCrossRef

42.

Sehba FA, Friedrich V, Makonnen G, Bederson JB. Acute cerebral vascular injury after subarachnoid hemorrhage and its prevention by administration of a nitric oxide donor. J Neurosurg. 2007;106(2):321–9.PubMedCrossRef

43.

Ohkuma H, Itoh K, Shibata S, Suzuki S. Morphological changes of intraparenchymal arterioles after experimental subarachnoid hemorrhage in dogs. Neurosurgery. 1997;41(1):230–5 discussion 235-6.PubMedCrossRef

44.

Uhl E, Lehmberg J, Steiger HJ, Messmer K. Intraoperative detection of early microvasospasm in patients with subarachnoid hemorrhage by using orthogonal polarization spectral imaging. Neurosurgery. 2003;52(6):1307–15 discussion 1315-7.PubMedCrossRef

45.

Sun BL, Zheng CB, Yang MF, Yuan H, Zhang SM, Wang LX. Dynamic alterations of cerebral pial microcirculation during experimental subarachnoid hemorrhage. Cell Mol Neurobiol. 2009;29(2):235–41.PubMedCrossRef

46.

Liu H, Dienel A, Schöller K, Schwarzmaier SM, Nehrkorn K, Plesnila N, et al. Microvasospasms after experimental subarachnoid hemorrhage do not depend on endothelin a receptors. Stroke. 2018;49(3):693–9.PubMedCrossRef

47.

Sweeney MD, Ayyadurai S, Zlokovic BV. Pericytes of the neurovascular unit: key functions and signaling pathways. Nat Neurosci. 2016;19(6):771–83.PubMedPubMedCentralCrossRef

48.

Peppiatt CM, Howarth C, Mobbs P, Attwell D. Bidirectional control of CNS capillary diameter by pericytes. Nature. 2006;443(7112):700–4.PubMedPubMedCentralCrossRef

49.

Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA, et al. Capillary pericytes regulate cerebral blood flow in health and disease. Nature. 2014;508(7494):55–60.PubMedPubMedCentralCrossRef

50.

Yemisci M, Gursoy-Ozdemir Y, Vural A, Can A, Topalkara K, Dalkara T. Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med. 2009;15(9):1031–7.PubMedCrossRef

51.

Zhang T, Su J, Wang K, Zhu T, Li X. Ursolic acid reduces oxidative stress to alleviate early brain injury following experimental subarachnoid hemorrhage. Neurosci Lett. 2014;579:12–7.PubMedCrossRef

52.

Zhang XS, Zhang X, Zhou ML, Zhou XM, Li N, Li W, et al. Amelioration of oxidative stress and protection against early brain injury by astaxanthin after experimental subarachnoid hemorrhage. J Neurosurg. 2014;121(1):42–5.PubMedCrossRef

53.

Guo D, Wilkinson DA, Thompson BG, Pandey AS, Keep RF, Xi G, et al. MRI characterization in the acute phase of experimental subarachnoid hemorrhage. Transl Stroke Res. 2017;8(3):234–43.PubMedCrossRef

54.

Sehba FA, Mostafa G, Friedrich V, Bederson JB. Acute microvascular platelet aggregation after subarachnoid hemorrhage. J Neurosurg. 2005;102(6):1094–100.PubMedCrossRef

55.

Suzuki S, Kimura M, Souma M, Ohkima H, Shimizu T, Iwabuchi T. Cerebral microthrombosis in symptomatic cerebral vasospasm—a quantitative histological study in autopsy cases. Neurol Med Chir (Tokyo). 1990;30(5):309–16.CrossRef

56.

Pisapia JM, Xu X, Kelly J, Yeung J, Carrion G, Tong H, et al. Microthrombosis after experimental subarachnoid hemorrhage: time course and effect of red blood cell-bound thrombin-activated pro-urokinase and clazosentan. Exp Neurol. 2012;233(1):357–63.PubMedCrossRef

57.

Muroi C, Fujioka M, Mishima K, Irie K, Fujimura Y, Nakano T, et al. Effect of ADAMTS-13 on cerebrovascular microthrombosis and neuronal injury after experimental subarachnoid hemorrhage. J Thromb Haemost. 2014;12(4):505–14.PubMedCrossRef

58.

Liu ZW, Gu H, Zhang BF, Zhao YH, Zhao JJ, Zhao YL, et al. Rapidly increased vasopressin promotes acute platelet aggregation and early brain injury after experimental subarachnoid hemorrhage in a rat model. Brain Res. 2016;1639:108–19.PubMedCrossRef

59.

Sabri M, Ai J, Knight B, Tariq A, Jeon H, Shang X, et al. Uncoupling of endothelial nitric oxide synthase after experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2011;31(1):190–9.PubMedCrossRef

60.

Sabri M, Ai J, Marsden PA, Macdonald RL. Simvastatin re-couples dysfunctional endothelial nitric oxide synthase in experimental subarachnoid hemorrhage. PLoS One. 2011;6(2):e17062.PubMedPubMedCentralCrossRef

61.

Sabri M, Ai J, Lass E, D'abbondanza J, Macdonald RL. Genetic elimination of eNOS reduces secondary complications of experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2013;33(7):1008–14.PubMedPubMedCentralCrossRef

Titel: The Role of Oxidative Stress in Microvascular Disturbances after Experimental Subarachnoid Hemorrhage
verfasst von: Toshio Fumoto
Masato Naraoka
Takeshi Katagai
Yuchen Li
Norihito Shimamura
Hiroki Ohkuma
Publikationsdatum: 09.01.2019
Verlag: Springer US
Erschienen in: Translational Stroke Research / Ausgabe 6/2019
Print ISSN: 1868-4483
Elektronische ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-018-0685-0

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The Role of Oxidative Stress in Microvascular Disturbances after Experimental Subarachnoid Hemorrhage

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