Top

Published in:

01-06-2020 | Stroke | Original Article

Beneficial Effects of Theta-Burst Transcranial Magnetic Stimulation on Stroke Injury via Improving Neuronal Microenvironment and Mitochondrial Integrity

Authors: Xuemei Zong, Yan Dong, Yuyu Li, Luodan Yang, Yong Li, Baocheng Yang, Lorelei Tucker, Ningjun Zhao, Darrell W. Brann, Xianliang Yan, Shuqun Hu, Quanguang Zhang

Published in: Translational Stroke Research | Issue 3/2020

Abstract

Recent work suggests that repetitive transcranial magnetic stimulation (rTMS) may beneficially alter the pathological status of several neurological disorders, although the mechanism remains unclear. The current study was designed to investigate the effects of rTMS on behavioral deficits and potential underlying mechanisms in a rat photothrombotic (PT) stroke model. From day 0 (3 h) to day 5 after the establishment of PT stroke, 5-min daily continuous theta-burst rTMS (3 pulses of 50 Hz repeated every 200 ms, intensity at 200 G) was applied on the infarct hemisphere. We report that rTMS significantly attenuated behavioral deficits and infarct volume after PT stroke. Further investigation demonstrated that rTMS remarkably reduced synaptic loss and neuronal degeneration in the peri-infarct cortical region. Mechanistic studies displayed that beneficial effects of rTMS were associated with robust suppression of reactive micro/astrogliosis and the overproduction of pro-inflammatory cytokines, as well as oxidative stress and oxidative neuronal damage especially at the late stage following PT stroke. Intriguingly, rTMS could effectively induce a shift in microglial M1/M2 phenotype activation and an A1 to A2 switch in astrocytic phenotypes. In addition, the release of anti-inflammatory cytokines and mitochondrial MnSOD in peri-infarct regions were elevated following rTMS treatment. Finally, rTMS treatment efficaciously preserved mitochondrial membrane integrity and suppressed the intrinsic mitochondrial caspase-9/3 apoptotic pathway within the peri-infarct cortex. Our novel findings indicate that rTMS treatment exerted robust neuroprotection when applied at least 3 h after ischemic stroke. The underlying mechanisms are partially associated with improvement of the local neuronal microenvironment by altering inflammatory and oxidative status and preserving mitochondrial integrity in the peri-infarct zone. These findings provide strong support for the promising therapeutic effect of rTMS against ischemic neuronal injury and functional deficits following stroke.

Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56–e528. https://doi.org/10.1161/CIR.0000000000000659.CrossRefPubMed

Kirmani JF, Alkawi A, Panezai S, Gizzi M. Advances in thrombolytics for treatment of acute ischemic stroke. Neurology. 2012;79(13 Suppl 1):S119–25. https://doi.org/10.1212/WNL.0b013e3182695882.CrossRefPubMed

Derex L, Cho TH. Mechanical thrombectomy in acute ischemic stroke. Rev Neurol (Paris). 2017;173(3):106–13. https://doi.org/10.1016/j.neurol.2016.06.008.CrossRef

Akbar M, Essa MM, Daradkeh G, Abdelmegeed MA, Choi Y, Mahmood L, et al. Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress. Brain Res. 2016;1637:34–55. https://doi.org/10.1016/j.brainres.2016.02.016.CrossRefPubMedPubMedCentral

Ferrer I. Apoptosis: future targets for neuroprotective strategies. Cerebrovasc Dis. 2006;21(Suppl 2):9–20. https://doi.org/10.1159/000091699.CrossRefPubMed

Pekny M, Wilhelmsson U, Tatlisumak T, Pekna M. Astrocyte activation and reactive gliosis-a new target in stroke? Neurosci Lett. 2019;689:45–55. https://doi.org/10.1016/j.neulet.2018.07.021.CrossRefPubMed

Shu L, Chen B, Chen B, Xu H, Wang G, Huang Y, et al. Brain ischemic insult induces cofilin rod formation leading to synaptic dysfunction in neurons. J Cereb Blood Flow Metab. 2018;2018:271678X18785567. https://doi.org/10.1177/0271678X18785567.CrossRef

Hofmeijer J, van Putten MJ. Ischemic cerebral damage: an appraisal of synaptic failure. Stroke. 2012;43(2):607–15. https://doi.org/10.1161/STROKEAHA.111.632943. CrossRefPubMed

Andrabi SS, Parvez S, Tabassum H. Progesterone induces neuroprotection following reperfusion-promoted mitochondrial dysfunction after focal cerebral ischemia in rats. Dis Model Mech. 2017;10(6):787–96. https://doi.org/10.1242/dmm.025692.CrossRefPubMedPubMedCentral

10.

Wang LL, Li J, Gu X, Wei L, Yu SP. Delayed treatment of 6-Bromoindirubin-3′-oxime stimulates neurogenesis and functional recovery after focal ischemic stroke in mice. Int J Dev Neurosci. 2017;57:77–84. https://doi.org/10.1016/j.ijdevneu.2017.01.002.CrossRefPubMedPubMedCentral

11.

Ahmed ME, Tucker D, Dong Y, Lu Y, Zhao N, Wang R, et al. Methylene Blue promotes cortical neurogenesis and ameliorates behavioral deficit after photothrombotic stroke in rats. Neuroscience. 2016;336:39–48. https://doi.org/10.1016/j.neuroscience.2016.08.036.CrossRefPubMedPubMedCentral

12.

Yang L, Tucker D, Dong Y, Wu C, Lu Y, Li Y, et al. Photobiomodulation therapy promotes neurogenesis by improving post-stroke local microenvironment and stimulating neuroprogenitor cells. Exp Neurol. 2018;299(Pt A:86–96. https://doi.org/10.1016/j.expneurol.2017.10.013.CrossRefPubMed

13.

Giannakopoulou A, Lyras GA, Grigoriadis N. Long-term effects of autoimmune CNS inflammation on adult hippocampal neurogenesis. J Neurosci Res. 2017;95(7):1446–58. https://doi.org/10.1002/jnr.23982.CrossRefPubMed

14.

Hamblin MR. Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys. 2017;4(3):337–61. https://doi.org/10.3934/biophy.2017.3.337.CrossRefPubMedPubMedCentral

15.

Gulke E, Gelderblom M, Magnus T. Danger signals in stroke and their role on microglia activation after ischemia. Ther Adv Neurol Disord. 2018;11:1756286418774254. https://doi.org/10.1177/1756286418774254. CrossRefPubMedPubMedCentral

16.

Dheen ST, Kaur C, Ling EA. Microglial activation and its implications in the brain diseases. Curr Med Chem. 2007;14(11):1189–97.CrossRefPubMed

17.

Zhao SC, Ma LS, Chu ZH, Xu H, Wu WQ, Liu F. Regulation of microglial activation in stroke. Acta Pharmacol Sin. 2017;38(4):445–58. https://doi.org/10.1038/aps.2016.162.CrossRefPubMedPubMedCentral

18.

Liu R, Liao XY, Tang JC, Pan MX, Chen SF, Lu PX, et al. BpV(pic) confers neuroprotection by inhibiting M1 microglial polarization and MCP-1 expression in rat traumatic brain injury. Mol Immunol. 2019;112:30–9. https://doi.org/10.1016/j.molimm.2019.04.010.CrossRefPubMed

19.

Li Q, Dai Z, Cao Y, Wang L. Caspase-1 inhibition mediates neuroprotection in experimental stroke by polarizing M2 microglia/macrophage and suppressing NF-kappaB activation. Biochem Biophys Res Commun. 2019;513(2):479–85. https://doi.org/10.1016/j.bbrc.2019.03.202.CrossRefPubMed

20.

Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017;541(7638):481–7. https://doi.org/10.1038/nature21029.CrossRefPubMedPubMedCentral

21.

Huang L, Wu ZB, Zhuge Q, Zheng W, Shao B, Wang B, et al. Glial scar formation occurs in the human brain after ischemic stroke. Int J Med Sci. 2014;11(4):344–8. https://doi.org/10.7150/ijms.8140.CrossRefPubMedPubMedCentral

22.

Wang H, Song G, Chuang H, Chiu C, Abdelmaksoud A, Ye Y, et al. Portrait of glial scar in neurological diseases. Int J Immunopathol Pharmacol. 2018;31:2058738418801406. https://doi.org/10.1177/2058738418801406.CrossRefPubMedPubMedCentral

23.

Strubakos CD, Malik M, Wider JM, Lee I, Reynolds CA, Mitsias P, et al. Non-invasive treatment with near-infrared light: a novel mechanisms-based strategy that evokes sustained reduction in brain injury after stroke. J Cereb Blood Flow Metab. 2019;2019:271678X19845149. https://doi.org/10.1177/0271678X19845149.CrossRef

24.

Ojo OB, Amoo ZA, Saliu IO, Olaleye MT, Farombi EO, Akinmoladun AC. Neurotherapeutic potential of kolaviron on neurotransmitter dysregulation, excitotoxicity, mitochondrial electron transport chain dysfunction and redox imbalance in 2-VO brain ischemia/reperfusion injury. Biomed Pharmacother. 2019;111:859–72. https://doi.org/10.1016/j.biopha.2018.12.144.CrossRefPubMed

25.

Tucker LD, Lu Y, Dong Y, Yang L, Li Y, Zhao N, et al. Photobiomodulation therapy attenuates hypoxic-ischemic injury in a neonatal rat model. J Mol Neurosci. 2018;65(4):514–26. https://doi.org/10.1007/s12031-018-1121-3.CrossRefPubMedPubMedCentral

26.

Lu Q, Tucker D, Dong Y, Zhao N, Zhang Q. Neuroprotective and functional improvement effects of methylene blue in global cerebral ischemia. Mol Neurobiol. 2016;53(8):5344–55. https://doi.org/10.1007/s12035-015-9455-0.CrossRefPubMed

27.

Nataraj J, Manivasagam T, Thenmozhi AJ, Essa MM. Lutein protects dopaminergic neurons against MPTP-induced apoptotic death and motor dysfunction by ameliorating mitochondrial disruption and oxidative stress. Nutr Neurosci. 2016;19(6):237–46. https://doi.org/10.1179/1476830515Y.0000000010.CrossRefPubMed

28.

Lee Y, Park HR, Chun HJ, Lee J. Silibinin prevents dopaminergic neuronal loss in a mouse model of Parkinson’s disease via mitochondrial stabilization. J Neurosci Res. 2015;93(5):755–65. https://doi.org/10.1002/jnr.23544.CrossRefPubMed

29.

Costa C, Tozzi A, Luchetti E, Siliquini S, Belcastro V, Tantucci M, et al. Electrophysiological actions of zonisamide on striatal neurons: selective neuroprotection against complex I mitochondrial dysfunction. Exp Neurol. 2010;221(1):217–24. https://doi.org/10.1016/j.expneurol.2009.11.002.CrossRefPubMed

30.

Peng Z, Zhou C, Xue S, Bai J, Yu S, Li X, et al. Mechanism of repetitive transcranial magnetic stimulation for depression. Shanghai Arch Psychiatry. 2018;30(2):84–92. https://doi.org/10.11919/j.issn.1002-0829.217047. CrossRefPubMedPubMedCentral

31.

Sasaki N, Mizutani S, Kakuda W, Abo M. Comparison of the effects of high- and low-frequency repetitive transcranial magnetic stimulation on upper limb hemiparesis in the early phase of stroke. J Stroke Cerebrovasc Dis. 2013;22(4):413–8. https://doi.org/10.1016/j.jstrokecerebrovasdis.2011.10.004. CrossRefPubMed

32.

Siddiqi SH, Trapp NT, Shahim P, Hacker CD, Laumann TO, Kandala S, et al. Individualized connectome-targeted transcranial magnetic stimulation for neuropsychiatric sequelae of repetitive traumatic brain injury in a retired NFL player. J Neuropsychiatry Clin Neurosci. 2019;2019:appineuropsych18100230. https://doi.org/10.1176/appi.neuropsych.18100230.CrossRef

33.

Manor B, Greenstein PE, Davila-Perez P, Wakefield S, Zhou J, Pascual-Leone A. Repetitive transcranial magnetic stimulation in spinocerebellar ataxia: a pilot randomized controlled trial. Front Neurol. 2019;10:73. https://doi.org/10.3389/fneur.2019.00073.CrossRefPubMedPubMedCentral

34.

Ba F, Zhou Y, Zhou J, Chen X. Repetitive transcranial magnetic stimulation protects mice against 6-OHDA-induced Parkinson’s disease symptoms by regulating brain amyloid beta1-42 level. Mol Cell Biochem. 2019;458:71–8. https://doi.org/10.1007/s11010-019-03531-w.CrossRefPubMed

35.

Chen X, Chen S, Liang W, Ba F. Administration of repetitive transcranial magnetic stimulation attenuates abeta 1-42-induced Alzheimer’s disease in mice by activating beta-catenin signaling. Biomed Res Int. 2019;2019:1431760. https://doi.org/10.1155/2019/1431760.CrossRefPubMedPubMedCentral

36.

Ljubisavljevic MR, Javid A, Oommen J, Parekh K, Nagelkerke N, Shehab S, et al. The effects of different repetitive transcranial magnetic stimulation (rTMS) protocols on cortical gene expression in a rat model of cerebral ischemic-reperfusion injury. PLoS One. 2015;10(10):e0139892. https://doi.org/10.1371/journal.pone.0139892.CrossRefPubMedPubMedCentral

37.

Zhang J, Tucker LD, DongYan LY, Yang L, Wu C, et al. Tert-butylhydroquinone post-treatment attenuates neonatal hypoxic-ischemic brain damage in rats. Neurochem Int. 2018;116:1–12. https://doi.org/10.1016/j.neuint.2018.03.004.CrossRefPubMedPubMedCentral

38.

Zhang QG, Raz L, Wang R, Han D, De Sevilla L, Yang F, et al. Estrogen attenuates ischemic oxidative damage via an estrogen receptor alpha-mediated inhibition of NADPH oxidase activation. J Neurosci. 2009;29(44):13823–36. https://doi.org/10.1523/JNEUROSCI.3574-09.2009.CrossRefPubMedPubMedCentral

39.

Metz GA, Whishaw IQ. Cortical and subcortical lesions impair skilled walking in the ladder rung walking test: a new task to evaluate fore- and hindlimb stepping, placing, and co-ordination. J Neurosci Methods. 2002;115(2):169–79.CrossRefPubMed

40.

Lu Y, Wang R, Dong Y, Tucker D, Zhao N, Ahmed ME, et al. Low-level laser therapy for beta amyloid toxicity in rat hippocampus. Neurobiol Aging. 2017;49:165–82. https://doi.org/10.1016/j.neurobiolaging.2016.10.003.CrossRefPubMed

41.

Silver J, Miller JH. Regeneration beyond the glial scar. Nat Rev Neurosci. 2004;5(2):146–56. https://doi.org/10.1038/nrn1326.CrossRefPubMed

42.

Ma MW, Wang J, Zhang Q, Wang R, Dhandapani KM, Vadlamudi RK, et al. NADPH oxidase in brain injury and neurodegenerative disorders. Mol Neurodegener. 2017;12(1):7. https://doi.org/10.1186/s13024-017-0150-7.CrossRefPubMedPubMedCentral

43.

Caglayan AB, Beker MC, Caglayan B, Yalcin E, Caglayan A, Yulug B, et al. Acute and post-acute neuromodulation induces stroke recovery by promoting survival signaling, neurogenesis, and pyramidal tract plasticity. Front Cell Neurosci. 2019;13:144. https://doi.org/10.3389/fncel.2019.00144.CrossRefPubMedPubMedCentral

44.

Orosz A, Jann K, Wirth M, Wiest R, Dierks T, Federspiel A. Theta burst TMS increases cerebral blood flow in the primary motor cortex during motor performance as assessed by arterial spin labeling (ASL). NeuroImage. 2012;61(3):599–605. https://doi.org/10.1016/j.neuroimage.2012.03.084.CrossRefPubMed

45.

Gersner R, Kravetz E, Feil J, Pell G, Zangen A. Long-term effects of repetitive transcranial magnetic stimulation on markers for neuroplasticity: differential outcomes in anesthetized and awake animals. J Neurosci. 2011;31(20):7521–6. https://doi.org/10.1523/JNEUROSCI.6751-10.2011.CrossRefPubMedPubMedCentral

46.

Hallett M. Transcranial magnetic stimulation and the human brain. Nature. 2000;406(6792):147–50. https://doi.org/10.1038/35018000.CrossRefPubMed

47.

Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005;45(2):201–6. https://doi.org/10.1016/j.neuron.2004.12.033.CrossRefPubMed

48.

Huang YZ, Rothwell JC. The effect of short-duration bursts of high-frequency, low-intensity transcranial magnetic stimulation on the human motor cortex. Clin Neurophysiol. 2004;115(5):1069–75. https://doi.org/10.1016/j.clinph.2003.12.026.CrossRefPubMed

49.

Williams NR, Sudheimer KD, Bentzley BS, Pannu J, Stimpson KH, Duvio D, et al. High-dose spaced theta-burst TMS as a rapid-acting antidepressant in highly refractory depression. Brain. 2018;141(3):e18. https://doi.org/10.1093/brain/awx379.CrossRefPubMedPubMedCentral

50.

Fried PJ, Jannati A, Davila-Perez P, Pascual-Leone A. Reproducibility of single-pulse, paired-pulse, and intermittent theta-burst TMS measures in healthy aging, type-2 diabetes, and Alzheimer’s disease. Front Aging Neurosci. 2017;9:263. https://doi.org/10.3389/fnagi.2017.00263.CrossRefPubMedPubMedCentral

51.

Kanazawa M, Ninomiya I, Hatakeyama M, Takahashi T, Shimohata T. Microglia and monocytes/macrophages polarization reveal novel therapeutic mechanism against stroke. Int J Mol Sci. 2017;18(10). https://doi.org/10.3390/ijms18102135.

52.

Kim JY, Park J, Chang JY, Kim SH, Lee JE. Inflammation after ischemic stroke: the role of leukocytes and glial cells. Exp Neurobiol. 2016;25(5):241–51. https://doi.org/10.5607/en.2016.25.5.241.CrossRefPubMedPubMedCentral

53.

Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol. 2010;87(5):779–89. https://doi.org/10.1189/jlb.1109766.CrossRefPubMedPubMedCentral

54.

Liu NW, Ke CC, Zhao Y, Chen YA, Chan KC, Tan DT, et al. Evolutional characterization of photochemically induced stroke in rats: a multimodality imaging and molecular biological study. Transl Stroke Res. 2017;8(3):244–56. https://doi.org/10.1007/s12975-016-0512-4.CrossRefPubMed

55.

Ellison JA, Velier JJ, Spera P, Jonak ZL, Wang X, Barone FC, et al. Osteopontin and its integrin receptor alpha(v)beta3 are upregulated during formation of the glial scar after focal stroke. Stroke. 1998;29(8):1698–706; discussion 707.CrossRefPubMed

56.

Yong YX, Li YM, Lian J, Luo CM, Zhong DX, Han K. Inhibitory role of lentivirus-mediated aquaporin-4 gene silencing in the formation of glial scar in a rat model of traumatic brain injury. J Cell Biochem. 2019;120(1):368–79. https://doi.org/10.1002/jcb.27390.CrossRefPubMed

57.

Fan YY, Nan F, Guo BL, Liao Y, Zhang MS, Guo J, et al. Effects of long-term rapamycin treatment on glial scar formation after cryogenic traumatic brain injury in mice. Neurosci Lett. 2018;678:68–75. https://doi.org/10.1016/j.neulet.2018.05.002.CrossRefPubMed

58.

Cai H, Ma Y, Jiang L, Mu Z, Jiang Z, Chen X, et al. Hypoxia response element-regulated MMP-9 promotes neurological recovery via glial scar degradation and angiogenesis in delayed stroke. Mol Ther. 2017;25(6):1448–59. https://doi.org/10.1016/j.ymthe.2017.03.020. CrossRefPubMedPubMedCentral

59.

Hill JJ, Jin K, Mao XO, Xie L, Greenberg DA. Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats. Proc Natl Acad Sci U S A. 2012;109(23):9155–60. https://doi.org/10.1073/pnas.1205697109.CrossRefPubMedPubMedCentral

60.

Li HP, Komuta Y, Kimura-Kuroda J, van Kuppevelt TH, Kawano H. Roles of chondroitin sulfate and dermatan sulfate in the formation of a lesion scar and axonal regeneration after traumatic injury of the mouse brain. J Neurotrauma. 2013;30(5):413–25. https://doi.org/10.1089/neu.2012.2513.CrossRefPubMedPubMedCentral

61.

Rocamonde B, Paradells S, Barcia JM, Barcia C, Garcia Verdugo JM, Miranda M, et al. Neuroprotection of lipoic acid treatment promotes angiogenesis and reduces the glial scar formation after brain injury. Neuroscience. 2012;224:102–15. https://doi.org/10.1016/j.neuroscience.2012.08.028.CrossRefPubMed

62.

Huang X, Kim JM, Kong TH, Park SR, Ha Y, Kim MH, et al. GM-CSF inhibits glial scar formation and shows long-term protective effect after spinal cord injury. J Neurol Sci. 2009;277(1–2):87–97. https://doi.org/10.1016/j.jns.2008.10.022.CrossRefPubMed

63.

Zamanian JL, Xu L, Foo LC, Nouri N, Zhou L, Giffard RG, et al. Genomic analysis of reactive astrogliosis. J Neurosci. 2012;32(18):6391–410. https://doi.org/10.1523/JNEUROSCI.6221-11.2012.CrossRefPubMedPubMedCentral

64.

Li W, Yang S. Targeting oxidative stress for the treatment of ischemic stroke: upstream and downstream therapeutic strategies. Brain Circ. 2016;2(4):153–63. https://doi.org/10.4103/2394-8108.195279.CrossRefPubMedPubMedCentral

65.

Chen H, Yoshioka H, Kim GS, Jung JE, Okami N, Sakata H, et al. Oxidative stress in ischemic brain damage: mechanisms of cell death and potential molecular targets for neuroprotection. Antioxid Redox Signal. 2011;14(8):1505–17. https://doi.org/10.1089/ars.2010.3576.CrossRefPubMedPubMedCentral

66.

Allen CL, Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int J Stroke. 2009;4(6):461–70. https://doi.org/10.1111/j.1747-4949.2009.00387.x.CrossRefPubMed

67.

Facecchia K, Fochesato LA, Ray SD, Stohs SJ, Pandey S. Oxidative toxicity in neurodegenerative diseases: role of mitochondrial dysfunction and therapeutic strategies. J Toxicol. 2011;2011:683728. https://doi.org/10.1155/2011/683728.CrossRefPubMedPubMedCentral

68.

Moro MA, Almeida A, Bolanos JP, Lizasoain I. Mitochondrial respiratory chain and free radical generation in stroke. Free Radic Biol Med. 2005;39(10):1291–304. https://doi.org/10.1016/j.freeradbiomed.2005.07.010.CrossRefPubMed

69.

Margaill I, Plotkine M, Lerouet D. Antioxidant strategies in the treatment of stroke. Free Radic Biol Med. 2005;39(4):429–43. https://doi.org/10.1016/j.freeradbiomed.2005.05.003.CrossRefPubMed

70.

Brown GC. Nitric oxide and neuronal death. Nitric Oxide. 2010;23(3):153–65. https://doi.org/10.1016/j.niox.2010.06.001.CrossRefPubMed

71.

Fridovich I. Superoxide radical and superoxide dismutases. Annu Rev Biochem. 1995;64:97–112. https://doi.org/10.1146/annurev.bi.64.070195.000525.CrossRefPubMed

72.

Bidmon HJ, Kato K, Schleicher A, Witte OW, Zilles K. Transient increase of manganese-superoxide dismutase in remote brain areas after focal photothrombotic cortical lesion. Stroke. 1998;29(1):203–10 discussion 11.CrossRefPubMed

73.

Yao H, Ago T, Kitazono T, Nabika T. NADPH oxidase-related pathophysiology in experimental models of stroke. Int J Mol Sci. 2017;18(10). https://doi.org/10.3390/ijms18102123.

74.

Zhang QG, Wang RM, Scott E, Han D, Dong Y, Tu JY, et al. Hypersensitivity of the hippocampal CA3 region to stress-induced neurodegeneration and amyloidogenesis in a rat model of surgical menopause. Brain. 2013;136(Pt 5:1432–45. https://doi.org/10.1093/brain/awt046.CrossRefPubMedPubMedCentral

75.

Raz L, Zhang QG, Zhou CF, Han D, Gulati P, Yang LC, et al. Role of Rac1 GTPase in NADPH oxidase activation and cognitive impairment following cerebral ischemia in the rat. PLoS One. 2010;5(9):e12606. https://doi.org/10.1371/journal.pone.0012606.CrossRefPubMedPubMedCentral

Title: Beneficial Effects of Theta-Burst Transcranial Magnetic Stimulation on Stroke Injury via Improving Neuronal Microenvironment and Mitochondrial Integrity
Authors: Xuemei Zong
Yan Dong
Yuyu Li
Luodan Yang
Yong Li
Baocheng Yang
Lorelei Tucker
Ningjun Zhao
Darrell W. Brann
Xianliang Yan
Shuqun Hu
Quanguang Zhang
Publication date: 01-06-2020
Publisher: Springer US
Keywords: Stroke
Transcranial Magnetic Stimulation
Repetitive Transcranial Magnetic Stimulation
Cytokines
Transcranial Magnetic Stimulation
Published in: Translational Stroke Research / Issue 3/2020
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-019-00731-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Beneficial Effects of Theta-Burst Transcranial Magnetic Stimulation on Stroke Injury via Improving Neuronal Microenvironment and Mitochondrial Integrity

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2020

Effect of Simvastatin on Permeability in Cerebral Cavernous Malformation Type 1 Patients: Results from a Pilot Small Randomized Controlled Clinical Trial

Progression and Classification of Granular Osmiophilic Material (GOM) Deposits in Functionally Characterized Human NOTCH3 Transgenic Mice

A Brain-Targeted Orally Available ROCK2 Inhibitor Benefits Mild and Aggressive Cavernous Angioma Disease

CD47 Blocking Antibody Accelerates Hematoma Clearance After Intracerebral Hemorrhage in Aged Rats

Treadmill Exercise Suppresses Cognitive Decline and Increases White Matter Oligodendrocyte Precursor Cells in a Mouse Model of Prolonged Cerebral Hypoperfusion

The Stabilization of Central Sympathetic Nerve Activation by Renal Denervation Prevents Cerebral Vasospasm after Subarachnoid Hemorrhage in Rats