Dynamic Detection of Thrombolysis in Embolic Stroke Rats by Synchrotron Radiation Angiography
- 10 Downloads
A rodent model of embolic middle cerebral artery occlusion is used to mimic cerebral embolism in clinical patients. Thrombolytic therapy is the effective treatment for this ischemic injury. However, it is difficult to detect thrombolysis dynamically in living animals. Synchrotron radiation angiography may provide a novel approach to directly monitor the thrombolytic process and assess collateral circulation after embolic stroke. Thirty-six adult Sprague-Dawley rats underwent the embolic stroke model procedure and were then treated with tissue plasminogen activator. The angiographic images were obtained in vivo by synchrotron radiation angiography. Synchrotron radiation angiography confirmed the successful establishment of occlusion and detected the thrombolysis process after the thrombolytic treatment. The time of thrombolytic recanalization was unstable during embolic stroke. The infarct volume increased as the recanalization time was delayed from 2 to 6 h (p < 0.05). The collateral circulation of the internal carotid artery to the ophthalmic artery, the olfactory artery to the ophthalmic artery, and the posterior cerebral artery to the middle cerebral artery opened after embolic stroke and manifested different opening rates (59%, 24%, and 75%, respectively) in the rats. The opening of the collateral circulation from the posterior cerebral artery to the middle cerebral artery alleviated infarction in rats with successful thrombolysis (p < 0.05). The cerebral vessels of the circle of Willis narrowed after thrombolysis (p < 0.05). Synchrotron radiation angiography provided a unique tool to dynamically detect and assess the thrombolysis process and the collateral circulation during thrombolytic therapy.
KeywordsAngiography Collateral circulation Ischemia Thrombolysis Synchrotron radiation
Anterior cerebral artery
Digital subtraction angiography
External carotid artery
Embolic middle cerebral artery occlusion
Internal carotid artery
Middle cerebral artery
Magnetic resonance imaging
Posterior cerebral artery
- SD rats
Tissue plasminogen activator
The authors thank BL13W station at Shanghai Synchrotron Radiation Facility.
This study was supported by grants from the National Natural Science Foundation of China (81771251, GYY; 81771244, ZJZ), the National Key Research and Development Program of China (2016YFC1300600), K. C. Wong Education Foundation (GYY), and the Science and Technology Commission of Shanghai Municipality (17ZR1413600, ZJZ).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
Informed consent was obtained from all individual participants included in the study.
- 3.Krishnamurthi RV, Feigin VL, Forouzanfar MH, Mensah GA, Connor M, Bennett DA, et al. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the global burden of disease study 2010. Lancet Glob Health. 2013;1(5):e259–81. https://doi.org/10.1016/S2214-109X(13)70089-5.CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016;387(10029):1723–31. https://doi.org/10.1016/S0140-6736(16)00163-X.CrossRefPubMedGoogle Scholar
- 7.dela Pena IC, Yoo A, Tajiri N, Acosta SA, Ji X, Kaneko Y, et al. Granulocyte colony-stimulating factor attenuates delayed tPA-induced hemorrhagic transformation in ischemic stroke rats by enhancing angiogenesis and vasculogenesis. J Cereb Blood Flow Metab. 2015;35(2):338–46. https://doi.org/10.1038/jcbfm.2014.208.CrossRefGoogle Scholar
- 8.Ishiguro M, Mishiro K, Fujiwara Y, Chen H, Izuta H, Tsuruma K, et al. Phosphodiesterase-III inhibitor prevents hemorrhagic transformation induced by focal cerebral ischemia in mice treated with tPA. PLoS One. 2010;5(12):e15178. https://doi.org/10.1371/journal.pone.0015178.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Ishiguro M, Kawasaki K, Suzuki Y, Ishizuka F, Mishiro K, Egashira Y, et al. A rho kinase (ROCK) inhibitor, fasudil, prevents matrix metalloproteinase-9-related hemorrhagic transformation in mice treated with tissue plasminogen activator. Neuroscience. 2012;220:302–12. https://doi.org/10.1016/j.neuroscience.2012.06.015.CrossRefPubMedGoogle Scholar
- 11.Jiang W, Hu W, Ye L, Tian Y, Zhao R, Du J et al. Contribution of Apelin-17 to collateral circulation following cerebral ischemic stroke. Transl Stroke Res 2018. https://doi.org/10.1007/s12975-018-0638-7.
- 13.Hoshikawa R, Kawaguchi H, Takuwa H, Ikoma Y, Tomita Y, Unekawa M, et al. Dynamic flow velocity mapping from fluorescent dye transit times in the brain surface microcirculation of anesthetized rats and mice. Microcirculation. 2016;23(6):416–25. https://doi.org/10.1111/micc.12285.CrossRefPubMedGoogle Scholar
- 14.Su T, Wang YB, Wang JD, Han D, Ma S, Cao JB, et al. In vivo magnetic resonance and fluorescence dual-modality imaging of tumor angiogenesis in rats using GEBP11 peptide targeted magnetic nanoparticles. J Biomed Nanotechnol. 2016;12(5):1011–22. https://doi.org/10.1166/jbn.2016.2233.CrossRefPubMedGoogle Scholar
- 16.Wu XP, Ni JM, Zhang ZY, Lu FQ, Li B, Jin HH, et al. Preoperative evaluation of malignant perihilar biliary obstruction: negative-contrast CT cholangiopancreatography and CT angiography versus MRCP and MR angiography. Am J Roentgenol. 2015;205(4):780–8. https://doi.org/10.2214/Ajr.14.13983.CrossRefGoogle Scholar
- 17.Dehkharghani S, Qiu DQ, Albin LS, Saindane AM. Dose reduction in contrast-enhanced cervical MR angiography: field strength dependency of vascular signal intensity, contrast administration, and arteriographic quality. Am J Roentgenol. 2015;204(6):W701–W6. https://doi.org/10.2214/Ajr.14.13435.CrossRefGoogle Scholar
- 18.Liu P, Sun J, Guan Y, Zhang G, Xu LX. Detection of lung cancer with phase-contrast X-ray imaging using synchrotron radiation. Conf Proc : Annual International Conference of the IEEE Engineering in Medicine and Biology Society IEEE Engineering in Medicine and Biology Society Annual Conference. 2006;1:2001–4. https://doi.org/10.1109/IEMBS.2006.260802.CrossRefGoogle Scholar
- 24.Zhang Z, Zhang RL, Jiang Q, Raman SB, Cantwell L, Chopp M. A new rat model of thrombotic focal cerebral ischemia. J Cereb Blood Flow Metab : official journal of the International Society of Cerebral Blood Flow and Metabolism. 1997;17(2):123–35. https://doi.org/10.1097/00004647-199702000-00001.CrossRefGoogle Scholar
- 29.Tang Y, Zhang C, Wang J, Lin X, Zhang L, Yang Y, et al. MRI/SPECT/fluorescent tri-modal probe for evaluating the homing and therapeutic efficacy of transplanted mesenchymal stem cells in a rat ischemic stroke model. Adv Funct Mater. 2015;25(7):1024–34. https://doi.org/10.1002/adfm.201402930.CrossRefPubMedGoogle Scholar
- 31.Qin C, Zhou P, Wang L, Mamtilahun M, Li W, Zhang Z, et al. Dl-3-N-butylphthalide attenuates ischemic reperfusion injury by improving the function of cerebral artery and circulation. J Cereb Blood Flow Metab : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2018;15:271678X18776833. https://doi.org/10.1177/0271678X18776833.CrossRefGoogle Scholar
- 32.Lin X, Miao P, Wang J, Yuan F, Guan Y, Tang Y, et al. Surgery-related thrombosis critically affects the brain infarct volume in mice following transient middle cerebral artery occlusion. PLoS One. 2013;8(9):e75561. https://doi.org/10.1371/journal.pone.0075561.CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Dalkara T, Arsava EM. Can restoring incomplete microcirculatory reperfusion improve stroke outcome after thrombolysis? J Cereb Blood Flow Metab : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2012;32(12):2091–9. https://doi.org/10.1038/jcbfm.2012.139.CrossRefGoogle Scholar
- 37.Armitage GA, Todd KG, Shuaib A, Winship IR. Laser speckle contrast imaging of collateral blood flow during acute ischemic stroke. J Cereb Blood Flow Metab : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2010;30(8):1432–6. https://doi.org/10.1038/jcbfm.2010.73.CrossRefGoogle Scholar
- 38.Rosenthal ES, Schwamm LH, Roccatagliata L, Coutts SB, Demchuk AM, Schaefer PW, et al. Role of recanalization in acute stroke outcome: rationale for a CT angiogram-based “benefit of recanalization” model. AJNR Am J Neuroradiol. 2008;29(8):1471–5. https://doi.org/10.3174/ajnr.A1153.CrossRefPubMedGoogle Scholar
- 39.Higashida RT, Furlan AJ, Roberts H, Tomsick T, Connors B, Barr J, et al. Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke. 2003;34(8):e109–37. https://doi.org/10.1161/01.STR.0000082721.62796.09.CrossRefPubMedGoogle Scholar