Large Vessel Vasospasm Is Not Associated with Cerebral Cortical Hypoperfusion in a Murine Model of Subarachnoid Hemorrhage

Translational Stroke Research - Tập 10 - Trang 319-326 - 2018
Axel Neulen1, Simon Meyer2, Andreas Kramer1, Tobias Pantel1, Michael Kosterhon1, Svenja Kunzelmann1, Hermann Goetz3, Serge C. Thal2
1Department of Neurosurgery, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
2Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
3Platform for Biomaterial Research, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany

Tóm tắt

Clinical studies on subarachnoid hemorrhage (SAH) have shown discrepancies between large vessel vasospasm, cerebral perfusion, and clinical outcome. We set out to analyze the contribution of large vessel vasospasm to impaired cerebral perfusion and neurological impairment in a murine model of SAH. SAH was induced in C57BL/6 mice by endovascular filament perforation. Vasospasm was analyzed with microcomputed tomography, cortical perfusion by laser SPECKLE contrast imaging, and functional impairment with a quantitative neuroscore. SAH animals developed large vessel vasospasm, as shown by significantly lower vessel volumes of a 2.5-mm segment of the left middle cerebral artery (MCA) (SAH 5.6 ± 0.6 nL, sham 8.3 ± 0.5 nL, p < 0.01). Induction of SAH significantly reduced cerebral perfusion of the corresponding left MCA territory compared to values before SAH, which only recovered partly (SAH vs. sham, 15 min 35.7 ± 3.1 vs. 101.4 ± 10.2%, p < 0.01; 3 h, 85.0 ± 8.6 vs. 121.9 ± 13.4, p < 0.05; 24 h, 75.3 ± 4.6 vs. 110.6 ± 11.4%, p < 0.01; 72 h, 81.8 ± 4.8 vs. 108.5 ± 14.5%, n.s.). MCA vessel volume did not correlate significantly with MCA perfusion after 72 h (r = 0.34, p = 0.25). Perfusion correlated moderately with neuroscore (24 h: r = − 0.58, p < 0.05; 72 h: r = − 0.44, p = 0.14). There was no significant correlation between vessel volume and neuroscore after 72 h (r = − 0.21, p = 0.50). In the murine SAH model, cerebral hypoperfusion occurs independently of large vessel vasospasm. Neurological outcome is associated with cortical hypoperfusion rather than large vessel vasospasm.

Tài liệu tham khảo

Steiner T, Juvela S, Unterberg A, Jung C, Forsting M, Rinkel G, et al. European Stroke Organization guidelines for the management of intracranial aneurysms and subarachnoid haemorrhage. Cerebrovasc Dis. 2013;35(2):93–112. https://doi.org/10.1159/000346087. Diringer MN, Bleck TP, Claude Hemphill J 3rd, Menon D, Shutter L, Vespa P, et al. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. Neurocrit Care. 2011;15(2):211–40. https://doi.org/10.1007/s12028-011-9605-9. Connolly ES, Jr., Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, Hoh BL, Kirkness CJ, Naidech AM, Ogilvy CS, Patel AB, Thompson BG, Vespa P, American Heart Association Stroke C, Council on Cardiovascular R, Intervention, Council on Cardiovascular N, Council on Cardiovascular S, Anesthesia, Council on Clinical C. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association. Stroke. 2012;43(6):1711–37. https://doi.org/10.1161/STR.0b013e3182587839. Macdonald RL. Delayed neurological deterioration after subarachnoid haemorrhage. Nat Rev Neurol. 2014;10(1):44–58. https://doi.org/10.1038/nrneurol.2013.246. Kamp MA, Heiroth HJ, Beseoglu K, Turowski B, Steiger HJ, Hanggi D. Early CT perfusion measurement after aneurysmal subarachnoid hemorrhage: a screening method to predict outcome? Acta Neurochir Suppl. 2012;114:329–32. https://doi.org/10.1007/978-3-7091-0956-4_63. Schubert GA, Seiz M, Hegewald AA, Manville J, Thome C. Acute hypoperfusion immediately after subarachnoid hemorrhage: a xenon contrast-enhanced CT study. J Neurotrauma. 2009;26(12):2225–31. https://doi.org/10.1089/neu.2009.0924. Pearl JD, Macdonald RL. Vasospasm after aneurysmal subarachnoid hemorrhage: need for further study. Acta Neurochir Suppl. 2008;105:207–10. Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, et al. Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke. 2012;43(6):1463–9. https://doi.org/10.1161/STROKEAHA.111.648980. 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. https://doi.org/10.1161/STROKEAHA.108.519942. Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A, et al. Randomised trial of clazosentan, an endothelin receptor antagonist, in patients with aneurysmal subarachnoid hemorrhage undergoing surgical clipping (CONSCIOUS-2). Acta Neurochir Suppl. 2013;115:27–31. https://doi.org/10.1007/978-3-7091-1192-5_7. Etminan N, Vergouwen MD, Ilodigwe D, Macdonald RL. Effect of pharmaceutical treatment on vasospasm, delayed cerebral ischemia, and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J Cereb Blood Flow Metab. 2011;31(6):1443–51. https://doi.org/10.1038/jcbfm.2011.7. Altay T, Smithason S, Volokh N, Rasmussen PA, Ransohoff RM, Provencio JJ. A novel method for subarachnoid hemorrhage to induce vasospasm in mice. J Neurosci Methods. 2009;183(2):136–40. https://doi.org/10.1016/j.jneumeth.2009.06.027. Froehler MT, Kooshkabadi A, Miller-Lotan R, Blum S, Sher S, Levy A, et al. Vasospasm after subarachnoid hemorrhage in haptoglobin 2-2 mice can be prevented with a glutathione peroxidase mimetic. J Clin Neurosci. 2010;17(9):1169–72. https://doi.org/10.1016/j.jocn.2010.04.014. Momin EN, Schwab KE, Chaichana KL, Miller-Lotan R, Levy AP, Tamargo RJ. Controlled delivery of nitric oxide inhibits leukocyte migration and prevents vasospasm in haptoglobin 2-2 mice after subarachnoid hemorrhage. Neurosurgery. 2009;65(5):937–45; discussion 945. https://doi.org/10.1227/01.NEU.0000356974.14230.B8. McGirt MJ, Lynch JR, Parra A, Sheng H, Pearlstein RD, Laskowitz DT, et al. Simvastatin increases endothelial nitric oxide synthase and ameliorates cerebral vasospasm resulting from subarachnoid hemorrhage. Stroke. 2002;33(12):2950–6. Kamii H, Kato I, Kinouchi H, Chan PH, Epstein CJ, Akabane A, et al. Amelioration of vasospasm after subarachnoid hemorrhage in transgenic mice overexpressing CuZn-superoxide dismutase. Stroke. 1999;30(4):867–71. discussion 872 Smithason S, Moore SK, Provencio JJ. Systemic administration of LPS worsens delayed deterioration associated with vasospasm after subarachnoid hemorrhage through a myeloid cell-dependent mechanism. Neurocrit Care. 2012;16(2):327–34. https://doi.org/10.1007/s12028-011-9651-3. Provencio JJ, Altay T, Smithason S, Moore SK, Ransohoff RM. Depletion of Ly6G/C(+) cells ameliorates delayed cerebral vasospasm in subarachnoid hemorrhage. J Neuroimmunol. 2011;232(1–2):94–100. https://doi.org/10.1016/j.jneuroim.2010.10.016. Provencio JJ, Fu X, Siu A, Rasmussen PA, Hazen SL, Ransohoff RM. CSF neutrophils are implicated in the development of vasospasm in subarachnoid hemorrhage. Neurocrit Care. 2010;12(2):244–51. https://doi.org/10.1007/s12028-009-9308-7. Yagi K, Lidington D, Wan H, Fares JC, Meissner A, Sumiyoshi M, et al. Therapeutically targeting tumor necrosis factor-alpha/sphingosine-1-phosphate signaling corrects myogenic reactivity in subarachnoid hemorrhage. Stroke. 2015;46(8):2260–70. https://doi.org/10.1161/STROKEAHA.114.006365. Terpolilli NA, Feiler S, Dienel A, Muller F, Heumos N, Friedrich B, et al. Nitric oxide inhalation reduces brain damage, prevents mortality, and improves neurological outcome after subarachnoid hemorrhage by resolving early pial microvasospasms. J Cereb Blood Flow Metab. 2016;36(12):2096–107. https://doi.org/10.1177/0271678X15605848. Friedrich B, Muller F, Feiler S, Scholler 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. https://doi.org/10.1038/jcbfm.2011.154. Han BH, Vellimana AK, Zhou ML, Milner E, Zipfel GJ. Phosphodiesterase 5 inhibition attenuates cerebral vasospasm and improves functional recovery after experimental subarachnoid hemorrhage. Neurosurgery. 2012;70(1):178–86; discussion 186-177. https://doi.org/10.1227/NEU.0b013e31822ec2b0. Muroi C, Fujioka M, Okuchi K, Fandino J, Keller E, Sakamoto Y, et al. Filament perforation model for mouse subarachnoid hemorrhage: surgical-technical considerations. Br J Neurosurg. 2014;28(6):722–32. https://doi.org/10.3109/02688697.2014.918579. Nittel N (2012) PhD thesis. https://www.edocubuni-muenchende/15329/1/Nittel_Nadinepdf Thal SC, Sporer S, Klopotowski M, Thal SE, Woitzik J, Schmid-Elsaesser R, et al. Brain edema formation and neurological impairment after subarachnoid hemorrhage in rats. Laboratory investigation J Neurosurg. 2009;111(5):988–94. https://doi.org/10.3171/2009.3.JNS08412. Feiler S, Friedrich B, Scholler K, Thal SC, Plesnila N. Standardized induction of subarachnoid hemorrhage in mice by intracranial pressure monitoring. J Neurosci Methods. 2010;190(2):164–70. https://doi.org/10.1016/j.jneumeth.2010.05.005. Neulen A, Pantel T, Kosterhon M, Kirschner S, Brockmann MA, Kantelhardt SR, et al. A segmentation-based volumetric approach to localize and quantify cerebral vasospasm based on tomographic imaging data. PLoS One. 2017;12(2):e0172010. https://doi.org/10.1371/journal.pone.0172010. Dorr A, Sled JG, Kabani N. Three-dimensional cerebral vasculature of the CBA mouse brain: a magnetic resonance imaging and micro computed tomography study. Neuroimage. 2007;35(4):1409–23. https://doi.org/10.1016/j.neuroimage.2006.12.040. Neulen A, Kosterhon, M., Pantel, T., Kirschner, S., Goetz, H., Brockmann, M. A., Kantelhardt, S. R., Thal, S. C. A Volumetric Method for Quantification of Cerebral Vasospasm in a Murine Model of Subarachnoid Hemorrhage (In-press (2018)) A Volumetric Method for Quantification of Cerebral Vasospasm in a Murine Model of Subarachnoid Hemorrhage. J Vis Exp (Pending Publication) e57997. https://doi.org/10.3791/57997 Friedrich B, Michalik R, Oniszczuk A, Abubaker K, Kozniewska E, Plesnila N. CO2 has no therapeutic effect on early microvasospasm after experimental subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2014;34(8):e1–6. https://doi.org/10.1038/jcbfm.2014.96. Pickard JD, Murray GD, Illingworth R, Shaw MD, Teasdale GM, Foy PM, et al. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ. 1989;298(6674):636–42. Stein SC, Browne KD, Chen XH, Smith DH, Graham DI. Thromboembolism and delayed cerebral ischemia after subarachnoid hemorrhage: an autopsy study. Neurosurgery. 2006;59(4):781–7; discussion 787-788. https://doi.org/10.1227/01.NEU.0000227519.27569.45. 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. disacussion 1315–1307 Attwell D, Buchan AM, Charpak S, Lauritzen M, Macvicar BA, Newman EA. Glial and neuronal control of brain blood flow. Nature. 2010;468(7321):232–43. https://doi.org/10.1038/nature09613. Matta BF, Mayberg TS, Lam AM. Direct cerebrovasodilatory effects of halothane, isoflurane, and desflurane during propofol-induced isoelectric electroencephalogram in humans. Anesthesiology. 1995;83(5):980–5. discussion 927A.