Korean Journal of Radiology

The Korean Society of Radiology (대한영상의학회)
권호 표지
DOI QR코드

DOI QR Code

Assessment of Blood-Brain Barrier Permeability by Dynamic Contrast-Enhanced MRI in Transient Middle Cerebral Artery Occlusion Model after Localized Brain Cooling in Rats

  • Kim, Eun Soo (Department of Radiology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Lee, Seung-Koo (Department of Radiology, Yonsei University College of Medicine) ;
  • Kwon, Mi Jung (Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Lee, Phil Hye (Department of Neurology, Yonsei University College of Medicine) ;
  • Ju, Young-Su (Department of Industrial Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Yoon, Dae Young (Department of Radiology, Hallym University Kangdong Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Kim, Hye Jeong (Department of Radiology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Lee, Kwan Seop (Department of Radiology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine)
  • Received : 2016.02.22
  • Accepted : 2016.05.17
  • Published : 2016.09.01
⟨ Previous Next ⟩

Abstract

Objective: The purpose of this study was to evaluate the effects of localized brain cooling on blood-brain barrier (BBB) permeability following transient middle cerebral artery occlusion (tMCAO) in rats, by using dynamic contrast-enhanced (DCE)-MRI. Materials and Methods: Thirty rats were divided into 3 groups of 10 rats each: control group, localized cold-saline ($20^{\circ}C$) infusion group, and localized warm-saline ($37^{\circ}C$) infusion group. The left middle cerebral artery (MCA) was occluded for 1 hour in anesthetized rats, followed by 3 hours of reperfusion. In the localized saline infusion group, 6 mL of cold or warm saline was infused through the hollow filament for 10 minutes after MCA occlusion. DCE-MRI investigations were performed after 3 hours and 24 hours of reperfusion. Pharmacokinetic parameters of the extended Tofts-Kety model were calculated for each DCE-MRI. In addition, rotarod testing was performed before tMCAO, and on days 1-9 after tMCAO. Myeloperoxidase (MPO) immunohisto-chemistry was performed to identify infiltrating neutrophils associated with the inflammatory response in the rat brain. Results: Permeability parameters showed no statistical significance between cold and warm saline infusion groups after 3-hour reperfusion $0.09{\pm}0.01min^{-1}$ vs. $0.07{\pm}0.02min^{-1}$, p = 0.661 for $K^{trans}$; $0.30{\pm}0.05min^{-1}$ vs. $0.37{\pm}0.11min^{-1}$, p = 0.394 for kep, respectively. Behavioral testing revealed no significant difference among the three groups. However, the percentage of MPO-positive cells in the cold-saline group was significantly lower than those in the control and warm-saline groups (p < 0.05). Conclusion: Localized brain cooling ($20^{\circ}C$) does not confer a benefit to inhibit the increase in BBB permeability that follows transient cerebral ischemia and reperfusion in an animal model, as compared with localized warm-saline ($37^{\circ}C$) infusion group.

Keywords

Acknowledgement

Supported by : Yonsei University College of Medicine

References

  1. Kataoka K, Yanase H. Mild hypothermia--a revived countermeasure against ischemic neuronal damages. Neurosci Res 1998;32:103-117 https://doi.org/10.1016/S0168-0102(98)00076-5
  2. Chopp M, Knight R, Tidwell CD, Helpern JA, Brown E, Welch KM. The metabolic effects of mild hypothermia on global cerebral ischemia and recirculation in the cat: comparison to normothermia and hyperthermia. J Cereb Blood Flow Metab 1989;9:141-148 https://doi.org/10.1038/jcbfm.1989.21
  3. Colbourne F, Sutherland G, Corbett D. Postischemic hypothermia. A critical appraisal with implications for clinical treatment. Mol Neurobiol 1997;14:171-201 https://doi.org/10.1007/BF02740655
  4. Barone FC, Feuerstein GZ, White RF. Brain cooling during transient focal ischemia provides complete neuroprotection. Neurosci Biobehav Rev 1997;21:31-44 https://doi.org/10.1016/0149-7634(95)00080-1
  5. Ginsberg MD, Sternau LL, Globus MY, Dietrich WD, Busto R. Therapeutic modulation of brain temperature: relevance to ischemic brain injury. Cerebrovasc Brain Metab Rev 1992;4:189-225
  6. Schwab S. Therapy of severe ischemic stroke: breaking the conventional thinking. Cerebrovasc Dis 2005;20 Suppl 2:169-178 https://doi.org/10.1159/000089371
  7. Kallmunzer B, Kollmar R. Temperature management in stroke - an unsolved, but important topic. Cerebrovasc Dis 2011;31:532-543 https://doi.org/10.1159/000324621
  8. Schwab S, Schwarz S, Spranger M, Keller E, Bertram M, Hacke W. Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction. Stroke 1998;29:2461-2466 https://doi.org/10.1161/01.STR.29.12.2461
  9. Huang FP, Zhou LF, Yang GY. The effect of extending mild hypothermia on focal cerebral ischemia and reperfusion in the rat. Neurol Res 1998;20:57-62 https://doi.org/10.1080/01616412.1998.11740485
  10. Colbourne F, Sutherland GR, Auer RN. An automated system for regulating brain temperature in awake and freely moving rodents. J Neurosci Methods 1996;67:185-190 https://doi.org/10.1016/0165-0270(96)00047-7
  11. Kawai N, Okauchi M, Morisaki K, Nagao S. Effects of delayed intraischemic and postischemic hypothermia on a focal model of transient cerebral ischemia in rats. Stroke 2000;31:1982-1989; discussion 1989 https://doi.org/10.1161/01.STR.31.8.1982
  12. Maier CM, Sun GH, Kunis D, Yenari MA, Steinberg GK. Delayed induction and long-term effects of mild hypothermia in a focal model of transient cerebral ischemia: neurological outcome and infarct size. J Neurosurg 2001;94:90-96 https://doi.org/10.3171/jns.2001.94.1.0090
  13. Xue D, Huang ZG, Smith KE, Buchan AM. Immediate or delayed mild hypothermia prevents focal cerebral infarction. Brain Res 1992;587:66-72 https://doi.org/10.1016/0006-8993(92)91428-H
  14. Yanamoto H, Hong SC, Soleau S, Kassell NF, Lee KS. Mild postischemic hypothermia limits cerebral injury following transient focal ischemia in rat neocortex. Brain Res 1996;718:207-211 https://doi.org/10.1016/0006-8993(96)00122-9
  15. Hewawasam P, Ding M, Chen N, King D, Knipe J, Pajor L, et al. Synthesis of water-soluble prodrugs of BMS-191011: a maxi-K channel opener targeted for post-stroke neuroprotection. Bioorg Med Chem Lett 2003;13:1695-1698 https://doi.org/10.1016/S0960-894X(03)00296-8
  16. Ding Y, Li J, Luan X, Lai Q, McAllister JP 2nd, Phillis JW, et al. Local saline infusion into ischemic territory induces regional brain cooling and neuroprotection in rats with transient middle cerebral artery occlusion. Neurosurgery 2004;54:956-964; discussion 964-965 https://doi.org/10.1227/01.NEU.0000114513.96704.29
  17. Luan X, Li J, McAllister JP 2nd, Diaz FG, Clark JC, Fessler RD, et al. Regional brain cooling induced by vascular saline infusion into ischemic territory reduces brain inflammation in stroke. Acta Neuropathol 2004;107:227-234 https://doi.org/10.1007/s00401-003-0802-2
  18. Ding Y, Li J, Rafols JA, Phillis JW, Diaz FG. Prereperfusion saline infusion into ischemic territory reduces inflammatory injury after transient middle cerebral artery occlusion in rats. Stroke 2002;33:2492-2498 https://doi.org/10.1161/01.STR.0000028237.15541.CC
  19. Zhang RL, Chopp M, Zhang ZG, Jiang Q, Ewing JR. A rat model of focal embolic cerebral ischemia. Brain Res 1997;766:83-92 https://doi.org/10.1016/S0006-8993(97)00580-5
  20. Busto R, Dietrich WD, Globus MY, Ginsberg MD. Postischemic moderate hypothermia inhibits CA1 hippocampal ischemic neuronal injury. Neurosci Lett 1989;101:299-304 https://doi.org/10.1016/0304-3940(89)90549-1
  21. Kassner A, Roberts TP, Moran B, Silver FL, Mikulis DJ. Recombinant tissue plasminogen activator increases blood-brain barrier disruption in acute ischemic stroke: an MR imaging permeability study. AJNR Am J Neuroradiol 2009;30:1864-1869 https://doi.org/10.3174/ajnr.A1774
  22. Larsson HB, Courivaud F, Rostrup E, Hansen AE. Measurement of brain perfusion, blood volume, and blood-brain barrier permeability, using dynamic contrast-enhanced T(1)-weighted MRI at 3 tesla. Magn Reson Med 2009;62:1270-1281 https://doi.org/10.1002/mrm.22136
  23. Choi HS, Ahn SS, Shin NY, Kim J, Kim JH, Lee JE, et al. Permeability parameters measured with dynamic contrastenhanced MRI: correlation with the extravasation of evans blue in a rat model of transient cerebral ischemia. Korean J Radiol 2015;16:791-797 https://doi.org/10.3348/kjr.2015.16.4.791
  24. Durukan A, Marinkovic I, Strbian D, Pitkonen M, Pedrono E, Soinne L, et al. Post-ischemic blood-brain barrier leakage in rats: one-week follow-up by MRI. Brain Res 2009;1280:158-165 https://doi.org/10.1016/j.brainres.2009.05.025
  25. Ding G, Jiang Q, Li L, Zhang L, Gang Zhang Z, Ledbetter KA, et al. Detection of BBB disruption and hemorrhage by Gd-DTPA enhanced MRI after embolic stroke in rat. Brain Res 2006;1114:195-203 https://doi.org/10.1016/j.brainres.2006.07.116
  26. Jahng GH, Li KL, Ostergaard L, Calamante F. Perfusion magnetic resonance imaging: a comprehensive update on principles and techniques. Korean J Radiol 2014;15:554-577 https://doi.org/10.3348/kjr.2014.15.5.554
  27. Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 1989;20:84-91 https://doi.org/10.1161/01.STR.20.1.84
  28. Kim SJ, Choi CG, Kim JK, Yun SC, Jahng GH, Jeong HK, et al. Effects of MR parameter changes on the quantification of diffusion anisotropy and apparent diffusion coefficient in diffusion tensor imaging: evaluation using a diffusional anisotropic phantom. Korean J Radiol 2015;16:297-303 https://doi.org/10.3348/kjr.2015.16.2.297
  29. Tofts PS, Kermode AG. Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts. Magn Reson Med 1991;17:357-367 https://doi.org/10.1002/mrm.1910170208
  30. Tofts PS, Brix G, Buckley DL, Evelhoch JL, Henderson E, Knopp MV, et al. Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging 1999;10:223-232 https://doi.org/10.1002/(SICI)1522-2586(199909)10:3<223::AID-JMRI2>3.0.CO;2-S
  31. Gupta YK, Sinha K, Chaudhary G. Transient focal ischemia induces motor deficit but does not impair the cognitive function in middle cerebral artery occlusion model of stroke in rats. J Neurol Sci 2002;203-204:267-271 https://doi.org/10.1016/S0022-510X(02)00303-9
  32. Chu HX, Kim HA, Lee S, Moore JP, Chan CT, Vinh A, et al. Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia. J Cereb Blood Flow Metab 2014;34:450-459 https://doi.org/10.1038/jcbfm.2013.217
  33. Zhou W, Liesz A, Bauer H, Sommer C, Lahrmann B, Valous N, et al. Postischemic brain infiltration of leukocyte subpopulations differs among murine permanent and transient focal cerebral ischemia models. Brain Pathol 2013;23:34-44 https://doi.org/10.1111/j.1750-3639.2012.00614.x
  34. Walter B, Bauer R, Kuhnen G, Fritz H, Zwiener U. Coupling of cerebral blood flow and oxygen metabolism in infant pigs during selective brain hypothermia. J Cereb Blood Flow Metab 2000;20:1215-1224 https://doi.org/10.1097/00004647-200008000-00007
  35. Choi JH, Marshall RS, Neimark MA, Konstas AA, Lin E, Chiang YT, et al. Selective brain cooling with endovascular intracarotid infusion of cold saline: a pilot feasibility study. AJNR Am J Neuroradiol 2010;31:928-934 https://doi.org/10.3174/ajnr.A1961
  36. Huang ZG, Xue D, Preston E, Karbalai H, Buchan AM. Biphasic opening of the blood-brain barrier following transient focal ischemia: effects of hypothermia. Can J Neurol Sci 1999;26:298-304 https://doi.org/10.1017/S0317167100000421
  37. Nguyen GT, Coulthard A, Wong A, Sheikh N, Henderson R, O'Sullivan JD, et al. Measurement of blood-brain barrier permeability in acute ischemic stroke using standard firstpass perfusion CT data. Neuroimage Clin 2013;2:658-662 https://doi.org/10.1016/j.nicl.2013.04.004
  38. Na DG, Sohn CH, Kim EY. Imaging-based management of acute ischemic stroke patients: current neuroradiological perspectives. Korean J Radiol 2015;16:372-390 https://doi.org/10.3348/kjr.2015.16.2.372
  39. Ding Y, Young CN, Li J, Luan X, McAllister JP 2nd, Clark JD, et al. Reduced inflammatory mediator expression by prereperfusion infusion into ischemic territory in rats: a realtime polymerase chain reaction analysis. Neurosci Lett 2003;353:173-176 https://doi.org/10.1016/j.neulet.2003.09.055
  40. Schwartz AE, Stone JG, Pile-Spellman J, Finck AD, Sandhu AA, Mongero LB, et al. Selective cerebral hypothermia by means of transfemoral internal carotid artery catheterization. Radiology 1996;201:571-572 https://doi.org/10.1148/radiology.201.2.8888261
  41. Zhao WH, Ji XM, Ling F, Ding YC, Xing CH, Wu H, et al. Local mild hypothermia induced by intra-arterial cold saline infusion prolongs the time window of onset of reperfusion injury after transient focal ischemia in rats. Neurol Res 2009;31:43-51 https://doi.org/10.1179/174313208X327982
  42. Okamoto K, Nagao K, Miki T, Nitobe E, Arima K, Hayashi N. New hypothermia method using blood cooling system: MONAN and KANEM method. In: Hayashi N, ed. Brain Hypothermia. Tokyo: Springer-Verlag Tokyo, 2000:203-209
  43. Wei XE, Zhang YZ, Li YH, Li MH, Li WB. Dynamics of rabbit brain edema in focal lesion and perilesion area after traumatic brain injury: a MRI study. J Neurotrauma 2012;29:2413-2420 https://doi.org/10.1089/neu.2010.1510
  44. Beaumont A, Marmarou A, Hayasaki K, Barzo P, Fatouros P, Corwin F, et al. The permissive nature of blood brain barrier (BBB) opening in edema formation following traumatic brain injury. Acta Neurochir Suppl 2000;76:125-129
  45. Bisdas S, Naegele T, Ritz R, Dimostheni A, Pfannenberg C, Reimold M, et al. Distinguishing recurrent high-grade gliomas from radiation injury: a pilot study using dynamic contrastenhanced MR imaging. Acad Radiol 2011;18:575-583 https://doi.org/10.1016/j.acra.2011.01.018
  46. Calamante F, Gadian DG, Connelly A. Delay and dispersion effects in dynamic susceptibility contrast MRI: simulations using singular value decomposition. Magn Reson Med 2000;44:466-473 https://doi.org/10.1002/1522-2594(200009)44:3<466::AID-MRM18>3.0.CO;2-M
  47. Thacker NA, Scott ML, Jackson A. Can dynamic susceptibility contrast magnetic resonance imaging perfusion data be analyzed using a model based on directional flow? J Magn Reson Imaging 2003;17:241-255 https://doi.org/10.1002/jmri.10240
  48. Kassner A, Annesley DJ, Zhu XP, Li KL, Kamaly-Asl ID, Watson Y, et al. Abnormalities of the contrast re-circulation phase in cerebral tumors demonstrated using dynamic susceptibility contrast-enhanced imaging: a possible marker of vascular tortuosity. J Magn Reson Imaging 2000;11:103-113 https://doi.org/10.1002/(SICI)1522-2586(200002)11:2<103::AID-JMRI5>3.0.CO;2-Z
  49. Weisskoff RM, Zuo CS, Boxerman JL, Rosen BR. Microscopic susceptibility variation and transverse relaxation: theory and experiment. Magn Reson Med 1994;31:601-610 https://doi.org/10.1002/mrm.1910310605
  50. Leach MO, Brindle KM, Evelhoch JL, Griffiths JR, Horsman MR, Jackson A, et al. The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations. Br J Cancer 2005;92:1599-1610 https://doi.org/10.1038/sj.bjc.6602550

Cited by

  1. The blood-brain barrier is disrupted in Machado-Joseph disease/spinocerebellar ataxia type 3: evidence from transgenic mice and human post-mortem samples vol.8, pp.1, 2020, https://doi.org/10.1186/s40478-020-00955-0