Skip to main content

Advertisement

SpringerLink
Log in

MRI Characterization in the Acute Phase of Experimental Subarachnoid Hemorrhage

  • Original Article
  • Published:
Translational Stroke Research Aims and scope Submit manuscript

Abstract

A number of mechanisms have been proposed for the early brain injury after subarachnoid hemorrhage (SAH). In this study, we investigated the radiographic characteristics and influence of gender on early brain injury after experimental SAH. SAH was induced by endovascular perforation in male and female rats. Magnetic resonance imaging was performed in a 7.0-T Varian MR scanner at 24 h after SAH. The occurrence and size of T2 lesions, ventricular dilation, and white matter injury (WMI) were determined on T2-weighted images (T2WI). The effects of SAH on heme oxygenase-1 and fibrin/fibrinogen were examined by Western blotting and immunohistochemistry. SAH severity was assessed using a MRI grading system, and neurological function was evaluated according to a modified Garcia’s scoring system. T2 hyperintensity areas and enlarged ventricles were observed in T2WI coronal sections 24 h after SAH. The overall incidence of T2 lesions, WMI, and hydrocephalus was 54, 20, and 63%, respectively. Female rats had a higher incidence of T2 hyperintensity lesions and hydrocephalus, as well as larger T2 lesion volumes and higher average ventricular volume. SAH rats graded at 3–4 (our previously validated MRI grading scale) had larger T2 lesion volumes, more hydrocephalus, and worse neurological function compared with those graded at 0–2. In conclusion, T2 lesion, WMI, and hydrocephalus were the most prevalent MRI characteristics 24 h after experimental SAH. The T2 lesion area matched with fibrinogen/fibrin positive staining in the acute phase of SAH. SAH induced more severe brain injury in females compared to males in the acute phase of SAH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Etminan N. Aneurysmal subarachnoid hemorrhage—status quo and perspective. Transl Stroke Res. 2015;6(3):167–70.

    Article  PubMed  Google Scholar 

  2. Macdonald RL, Pluta RM, Zhang JH. Cerebral vasospasm after subarachnoid hemorrhage: the emerging revolution. Nat Clin Pract Neurol. 2007;3(5):256–63.

    Article  CAS  PubMed  Google Scholar 

  3. Zhang JH. Vascular neural network in subarachnoid hemorrhage. Transl Stroke Res. 2014;5(4):423–8.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 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.

    Article  PubMed  Google Scholar 

  5. Sun Y, Shen Q, Watts LT, Muir ER, Huang S, Yang GY, et al. Multimodal MRI characterization of experimental subarachnoid hemorrhage. Neuroscience. 2016;316:53–62.

    Article  CAS  PubMed  Google Scholar 

  6. Shishido H, Zhang H, Okubo S, Hua Y, Keep RF, Xi G. The effect of gender on acute hydrocephalus after experimental subarachnoid hemorrhage. Acta Neurochir Suppl. 2016;121:335–9.

    Article  PubMed  Google Scholar 

  7. Okubo S, Strahle J, Keep RF, Hua Y, Xi G. Subarachnoid hemorrhage-induced hydrocephalus in rats. Stroke. 2013;44(2):547–50.

    Article  PubMed  Google Scholar 

  8. Tiebosch IA, van den Bergh WM, Bouts MJ, Zwartbol R, van der Toorn A, Dijkhuizen RM. Progression of brain lesions in relation to hyperperfusion from subacute to chronic stages after experimental subarachnoid hemorrhage: a multiparametric MRI study. Cerebrovasc Dis. 2013;36(3):167–72.

    Article  PubMed  Google Scholar 

  9. Egashira Y, Hua Y, Keep RF, Xi G. Acute white matter injury after experimental subarachnoid hemorrhage: potential role of lipocalin 2. Stroke. 2014;45(7):2141–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kummer TT, Magnoni S, MacDonald CL, Dikranian K, Milner E, Sorrell J, et al. Experimental subarachnoid haemorrhage results in multifocal axonal injury. Brain. 2015 Sep;138(Pt 9):2608–18.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Egashira Y, Hua Y, Keep RF, Iwama T, Xi G. Lipocalin 2 and blood-brain barrier disruption in white matter after experimental subarachnoid hemorrhage. Acta Neurochir Suppl. 2016;121:131–4.

    Article  PubMed  Google Scholar 

  12. Kivisaari RP, Salonen O, Servo A, Autti T, Hernesniemi J, Ohman J. MR imaging after aneurysmal subarachnoid hemorrhage and surgery: a long-term follow-up study. AJNR Am J Neuroradiol. 2001;22(6):1143–8.

    CAS  PubMed  Google Scholar 

  13. Shimoda M, Takeuchi M, Tominaga J, Oda S, Kumasaka A, Tsugane R. Asymptomatic versus symptomatic infarcts from vasospasm in patients with subarachnoid hemorrhage: serial magnetic resonance imaging. Neurosurgery. 2001;49(6):1341–8. discussion 8-50

    Article  CAS  PubMed  Google Scholar 

  14. Longstreth Jr WT, Koepsell TD, Yerby MS, van Belle G. Risk factors for subarachnoid hemorrhage. Stroke. 1985;16(3):377–85.

    Article  PubMed  Google Scholar 

  15. Rothwell PM, Coull AJ, Silver LE, Fairhead JF, Giles MF, Lovelock CE, et al. Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford vascular study). Lancet. 2005;366(9499):1773–83.

    Article  CAS  PubMed  Google Scholar 

  16. Kongable GL, Lanzino G, Germanson TP, Truskowski LL, Alves WM, Torner JC, et al. Gender-related differences in aneurysmal subarachnoid hemorrhage. J Neurosurg. 1996;84(1):43–8.

    Article  CAS  PubMed  Google Scholar 

  17. van Asch CJ, van der Schaaf IC, Rinkel GJ. Acute hydrocephalus and cerebral perfusion after aneurysmal subarachnoid hemorrhage. AJNR Am J Neuroradiol. 2010;31(1):67–70.

    Article  PubMed  Google Scholar 

  18. Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006;5(1):53–63.

    Article  PubMed  Google Scholar 

  19. Xiong XY, Yang QW. Rethinking the roles of inflammation in the intracerebral hemorrhage. Transl Stroke Res. 2015;6(5):339–41.

    Article  PubMed  Google Scholar 

  20. Zhao H, Garton T, Keep RF, Hua Y, Xi G. Microglia/macrophage polarization after experimental intracerebral hemorrhage. Transl Stroke Res. 2015;6(6):407–9.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chen Z, Gao C, Hua Y, Keep RF, Muraszko K, Xi G. Role of iron in brain injury after intraventricular hemorrhage. Stroke. 2011;42(2):465–70.

    Article  PubMed  Google Scholar 

  22. Garton T, Keep RF, Wilkinson DA, Strahle JM, Hua Y, Garton HJ, et al. Intraventricular hemorrhage: the role of blood components in secondary injury and hydrocephalus. Transl Stroke Res. 2016;7(6):447–51.

  23. Lee JY, Keep RF, He Y, Sagher O, Hua Y, Xi G. Hemoglobin and iron handling in brain after subarachnoid hemorrhage and the effect of deferoxamine on early brain injury. J Cereb Blood Flow Metab. 2010;30(11):1793–803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hua Y, Nakamura T, Keep RF, Wu J, Schallert T, Hoff JT, et al. Long-term effects of experimental intracerebral hemorrhage: the role of iron. J Neurosurg. 2006;104(2):305–12.

    Article  CAS  PubMed  Google Scholar 

  25. Xi G, Strahle J, Hua Y, Keep RF. Progress in translational research on intracerebral hemorrhage: is there an end in sight? Prog Neurobiol. 2014;115C:45–63.

    Article  Google Scholar 

  26. Lee JY, Sagher O, Keep R, Hua Y, Xi G. Comparison of experimental rat models of early brain injury after subarachnoid hemorrhage. Neurosurgery. 2009;65(2):331–43. discussion 43

    Article  PubMed  Google Scholar 

  27. Soares MP, Hamza I. Macrophages and iron metabolism. Immunity. 2016;44(3):492–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Garland P, Durnford AJ, Okemefuna AI, Dunbar J, Nicoll JA, Galea J, et al. Heme-hemopexin scavenging is active in the brain and associates with outcome after subarachnoid hemorrhage. Stroke. 2016;47(3):872–6.

    CAS  PubMed  Google Scholar 

  29. Gozzelino R, Soares MP. Coupling heme and iron metabolism via ferritin H chain. Antioxid Redox Signal. 2014;20(11):1754–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhao J, Chen Z, Xi G, Keep RF, Hua Y. Deferoxamine attenuates acute hydrocephalus after traumatic brain injury in rats. Transl Stroke Res. 2014;5:586–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Li L, Jiang Q, Ding G, Zhang L, Zhang ZG, Ewing JR, et al. Map-ISODATA demarcates regional response to combination rt-PA and 7E3 F(ab’)2 treatment of embolic stroke in the rat. J Magn Reson Imaging. 2005;21(6):726–34.

    Article  PubMed  Google Scholar 

  32. Ni W, Gao F, Zheng M, Koch LG, Britton SL, Keep RF, et al. Effects of aerobic capacity on thrombin-induced hydrocephalus and white matter injury. Acta Neurochir Suppl. 2016;121:379–84.

    Article  PubMed  Google Scholar 

  33. Shishido H, Egashira Y, Okubo S, Zhang H, Hua Y, Keep RF, et al. A magnetic resonance imaging grading system for subarachnoid hemorrhage severity in a rat model. J Neurosci Methods. 2015;243:115–9.

    Article  PubMed  PubMed Central  Google Scholar 

  34. 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(4):627–34. discussion 35

  35. Jeon H, Ai J, Sabri M, Tariq A, Shang X, Chen G, et al. Neurological and neurobehavioral assessment of experimental subarachnoid hemorrhage. BMC Neurosci. 2009;10:103.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Zheng M, Du H, Ni W, Koch LG, Britton SL, Keep RF, et al. Iron-induced necrotic brain cell death in rats with different aerobic capacity. Transl Stroke Res. 2015;6(3):215–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Song J, Li P, Chaudhary N, Gemmete JJ, Thompson BG, Xi G, et al. Correlating cerebral (18)FDG PET-CT patterns with histological analysis during early brain injury in a rat subarachnoid hemorrhage model. Transl Stroke Res. 2015;6(4):290–5.

    Article  CAS  PubMed  Google Scholar 

  38. Wan S, Cheng Y, Jin H, Guo D, Hua Y, Keep RF, et al. Microglia activation and polarization after intracerebral hemorrhage in mice: the role of protease-activated receptor-1. Transl Stroke Res. 2016;21

  39. Park J, Woo H, Kang DH, Kim YS, Kim MY, Shin IH, et al. Formal protocol for emergency treatment of ruptured intracranial aneurysms to reduce in-hospital rebleeding and improve clinical outcomes. J Neurosurg. 2015 Feb;122(2):383–91.

    Article  PubMed  Google Scholar 

  40. van Donkelaar CE, Bakker NA, Veeger NJ, Uyttenboogaart M, Metzemaekers JD, Luijckx GJ, et al. Predictive factors for rebleeding after aneurysmal subarachnoid hemorrhage: rebleeding aneurysmal subarachnoid hemorrhage study. Stroke. 2015;46(8):2100–6.

    Article  PubMed  Google Scholar 

  41. Nau R, Haase S, Bunkowski S, Bruck W. Neuronal apoptosis in the dentate gyrus in humans with subarachnoid hemorrhage and cerebral hypoxia. Brain Pathol. 2002 12(3):329–336.

  42. Chen S, Feng H, Sherchan P, Klebe D, Zhao G, Sun X, et al. Controversies and evolving new mechanisms in subarachnoid hemorrhage. Prog Neurobiol. 2014 Apr;115:64–91.

    Article  PubMed  Google Scholar 

  43. Frontera JA, Ahmed W, Zach V, Jovine M, Tanenbaum L, Sehba F, et al. Acute ischaemia after subarachnoid haemorrhage, relationship with early brain injury and impact on outcome: a prospective quantitative MRI study. J Neurol Neurosurg Psychiatry. 2015 Jan;86(1):71–8.

    Article  PubMed  Google Scholar 

  44. Cahill J, Calvert JW, Zhang JH. Mechanisms of early brain injury after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2006;26(11):1341–53.

    Article  CAS  PubMed  Google Scholar 

  45. Sabri M, Lass E, Macdonald RL. Early brain injury: a common mechanism in subarachnoid hemorrhage and global cerebral ischemia. Stroke Res Treat. 2013;2013:394036.

    PubMed  PubMed Central  Google Scholar 

  46. Seder DB, Mayer SA. Critical care management of subarachnoid hemorrhage and ischemic stroke. Clin Chest Med. 2009;30(1):103–22. viii-ix

    Article  PubMed  Google Scholar 

  47. van Gijn J, Hijdra A, Wijdicks EF, Vermeulen M, van Crevel H. Acute hydrocephalus after aneurysmal subarachnoid hemorrhage. J Neurosurg. 1985;63(3):355–62.

    Article  PubMed  Google Scholar 

  48. Gao C, Du H, Hua Y, Keep RF, Strahle J, Xi G. Role of red blood cell lysis and iron in hydrocephalus after intraventricular hemorrhage. J Cereb Blood Flow Metab. 2014;34(6):1070–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Strahle JM, Garton T, Bazzi AA, Kilaru H, Garton HJ, Maher CO, et al. Role of hemoglobin and iron in hydrocephalus after neonatal intraventricular hemorrhage. Neurosurgery. 2014;75(6):696–705. discussion 6

    Article  PubMed  PubMed Central  Google Scholar 

  50. Dewar D, Underhill SM, Goldberg MP. Oligodendrocytes and ischemic brain injury. J Cereb Blood Flow Metab. 2003;23(3):263–74.

    Article  PubMed  Google Scholar 

  51. Muroi C, Kashiwagi Y, Rokugawa T, Tonomura M, Obata A, Nevzati E, et al. Evaluation of a filament perforation model for mouse subarachnoid hemorrhage using 7.0 tesla MRI. J Clin Neurosci. 2016;28:141–7.

    Article  PubMed  Google Scholar 

  52. Qureshi AI, Malik AA, Saeed O, Defillo A, Sherr GT, Suri MF. Hormone replacement therapy and the risk of subarachnoid hemorrhage in postmenopausal women. J Neurosurg. 2016;124(1):45–50.

    Article  PubMed  Google Scholar 

  53. Hamdan A, Barnes J, Mitchell P. Subarachnoid hemorrhage and the female sex: analysis of risk factors, aneurysm characteristics, and outcomes. J Neurosurg. 2014;121(6):1367–73.

    Article  PubMed  Google Scholar 

  54. Xie Q, Xi G, Keep RF, Hua Y. Effects of gender and estrogen receptors on iron-induced brain edema formation. Acta Neurochir Suppl. 2016;121:341–5.

    Article  PubMed  Google Scholar 

  55. Tada Y, Wada K, Shimada K, Makino H, Liang EI, Murakami S, et al. Estrogen protects against intracranial aneurysm rupture in ovariectomized mice. Hypertension. 2014;63(6):1339–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Sampei K, Goto S, Alkayed NJ, Crain BJ, Korach KS, Traystman RJ, et al. Stroke in estrogen receptor-alpha-deficient mice. Stroke. 2000;31(3):738–43. discussion 44

    Article  CAS  PubMed  Google Scholar 

  57. Mhurchu CN, Anderson C, Jamrozik K, Hankey G, Dunbabin D. Australasian cooperative research on subarachnoid hemorrhage study G. Hormonal factors and risk of aneurysmal subarachnoid hemorrhage: an international population-based, case-control study. Stroke. 2001;32(3):606–12.

    Article  CAS  PubMed  Google Scholar 

  58. Tabuchi S. Relationship between postmenopausal estrogen deficiency and aneurysmal subarachnoid hemorrhage. Behav Neurol. 2015;2015:720141.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Horiuchi T, Tanaka Y, Hongo K. Sex-related differences in patients treated surgically for aneurysmal subarachnoid hemorrhage. Neurol Med Chir (Tokyo). 2006;46(7):328–32. discussion 32

    Article  Google Scholar 

  60. Baron JA, La Vecchia C, Levi F. The antiestrogenic effect of cigarette smoking in women. Am J Obstet Gynecol. 1990;162(2):502–14.

    Article  CAS  PubMed  Google Scholar 

  61. Longstreth WT, Nelson LM, Koepsell TD, van Belle G. Subarachnoid hemorrhage and hormonal factors in women. A population-based case-control study. Ann Intern Med. 1994;121(3):168–73.

    Article  CAS  PubMed  Google Scholar 

  62. Asl SZ, Khaksari M, Khachki AS, Shahrokhi N, Nourizade S. Contribution of estrogen receptors alpha and beta in the brain response to traumatic brain injury. J Neurosurg. 2013;119(2):353–61.

    Article  PubMed  Google Scholar 

  63. Khaksari M, Hajializadeh Z, Shahrokhi N, Esmaeili-Mahani S. Changes in the gene expression of estrogen recseptors involved in the protective effect of estrogen in rat’s trumatic brain injury. Brain Res. 2015;1618:1–8.

    Article  CAS  PubMed  Google Scholar 

  64. Nakamura T, Hua Y, Keep RF, Park JW, Xi G, Hoff JT. Estrogen therapy for experimental intracerebral hemorrhage in rats. J Neurosurg. 2005;103(1):97–103.

    Article  CAS  PubMed  Google Scholar 

  65. Liu R, Yang SH. Window of opportunity: estrogen as a treatment for ischemic stroke. Brain Res. 2013;1514:83–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Qian Y, Yin C, Chen Y, Zhang S, Jiang L, Wang F, et al. Estrogen contributes to regulating iron metabolism through governing ferroportin signaling via an estrogen response element. Cell Signal. 2015;27(5):934–42.

    Article  CAS  PubMed  Google Scholar 

  67. Kim DK, Jeong JH, Lee JM, Kim KS, Park SH, Kim YD, et al. Inverse agonist of estrogen-related receptor gamma controls salmonella typhimurium infection by modulating host iron homeostasis. Nat Med. 2014;20(4):419–24.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosurgery, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA

    Dewei Guo, D. Andrew Wilkinson, B. Gregory Thompson, Aditya S. Pandey, Richard F Keep, Guohua Xi & Ya Hua

  2. Department of Neurosurgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Dewei Guo

Authors
  1. Dewei Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Andrew Wilkinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Gregory Thompson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aditya S. Pandey
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard F Keep
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guohua Xi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ya Hua
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ya Hua.

Ethics declarations

All institutional and national guidelines for the care and use of laboratory animals were followed.

Conflict of Interest

The authors declare that they have no conflict of interest.

Disclosure

This study was supported by grants NS-073959, NS-079157, NS-090925, NS-084049, NS-091545, NS-096917, and NS-007222 from the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, D., Wilkinson, D.A., Thompson, B.G. et al. MRI Characterization in the Acute Phase of Experimental Subarachnoid Hemorrhage. Transl. Stroke Res. 8, 234–243 (2017). https://doi.org/10.1007/s12975-016-0511-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12975-016-0511-5

Keywords

Search

Navigation