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Brain Edema Formation and Complement Activation in a Rat Model of Subarachnoid Hemorrhage

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Brain Edema XV

Part of the book series: Acta Neurochirurgica Supplement ((NEUROCHIRURGICA,volume 118))

Abstract

Previous studies have demonstrated that erythrocyte lysis and brain iron overload contribute to early brain injury after subarachnoid hemorrhage (SAH). Activation of the complement system and formation of the membrane attack complex can result in erythrocyte lysis and might, therefore, participate in such injury. This study, therefore, examined complement activation, blood–brain barrier (BBB) disruption, and brain edema in a rat SAH model.

Subarachnoid hemorrhage was induced using a modified endovascular perforation technique. Brain complement activation was determined by Western blotting and immunohistochemistry. Brain edema was measured by dry/wet weight and BBB permeability assessed by measuring brain albumin levels.

We found that there was expression of the membrane attack complex and clusterin in the frontal basal cortex and clot after SAH. The protein levels of the membrane attack complex were much higher in the frontal basal cortex at 72 h after SAH than those in sham (p < 0.01). We also found that brain water content was increased (81.9 ± 1.4 vs. 79.1 ± 0.2 % in sham, p < 0.05) and BBB was disrupted (albumin content: 10,695 ± 865 vs. 4,935 ± 3,121 pixels in sham, p < 0.01) 24 h after SAH.

Our results suggest that complement activation after SAH might contribute to brain edema formation and BBB disruption after SAH.

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References

  1. Bellander BM, von Holst H, Fredman P, Svensson M (1996) Activation of the complement cascade and increase of clusterin in the brain following a cortical contusion in the adult rat. J Neurosurg 85:468–475

    Article  PubMed  CAS  Google Scholar 

  2. Brouwers PJ, Dippel DW, Vermeulen M, Lindsay KW, Hasan D, van Gijn J (1993) Amount of blood on computed tomography as an independent predictor after aneurysm rupture. Stroke 24:809–814

    Article  PubMed  CAS  Google Scholar 

  3. Ducruet AF, Hassid BG, Mack WJ, Sosunov SA, Otten ML, Fusco DJ, Hickman ZL, Kim GH, Komotar RJ, Mocco J, Connolly ES (2008) C3a receptor modulation of granulocyte infiltration after murine focal cerebral ischemia is reperfusion dependent. J Cereb Blood Flow Metab 28:1048–1058

    Article  PubMed  CAS  Google Scholar 

  4. Endo H, Nito C, Kamada H, Yu F, Chan PH (2007) Reduction in oxidative stress by superoxide dismutase overexpression attenuates acute brain injury after subarachnoid hemorrhage via activation of Akt/glycogen synthase kinase-3beta survival signaling. J Cereb Blood Flow Metab 27:975–982

    PubMed  CAS  Google Scholar 

  5. Esser AF (1991) Big MAC attack: complement proteins cause leaky patches. Immunol Today 12:316–318; discussion 321

    Article  PubMed  CAS  Google Scholar 

  6. Hua Y, Xi G, Keep RF, Hoff JT (2000) Complement activation in the brain after experimental intracerebral hemorrhage. J Neurosurg 92:1016–1022

    Article  PubMed  CAS  Google Scholar 

  7. Kasuya H, Shimizu T (1989) Activated complement components C3a and C4a in cerebrospinal fluid and plasma following subarachnoid hemorrhage. J Neurosurg 71:741–746

    Article  PubMed  CAS  Google Scholar 

  8. Kusaka G, Ishikawa M, Nanda A, Granger DN, Zhang JH (2004) Signaling pathways for early brain injury after subarachnoid hemorrhage. J Cereb Blood Flow Metab 24:916–925

    Article  PubMed  CAS  Google Scholar 

  9. Lee JY, He Y, Sagher O, Keep R, Hua Y, Xi G (2009) Activated autophagy pathway in experimental subarachnoid hemorrhage. Brain Res 1287:126–135

    Article  PubMed  CAS  Google Scholar 

  10. Lee JY, Keep RF, He Y, Sagher O, Hua Y, Xi G (2010) Hemoglobin and iron handling in brain after subarachnoid hemorrhage and the effect of deferoxamine on early brain injury. J Cereb Blood Flow Metab 30:1793–1803

    Article  PubMed  CAS  Google Scholar 

  11. Lindsberg PJ, Ohman J, Lehto T, Karjalainen-Lindsberg ML, Paetau A, Wuorimaa T, Carpen O, Kaste M, Meri S (1996) Complement activation in the central nervous system following blood-brain barrier damage in man. Ann Neurol 40:587–596

    Article  PubMed  CAS  Google Scholar 

  12. Mack WJ, Ducruet AF, Hickman ZL, Garrett MC, Albert EJ, Kellner CP, Mocco J, Connolly ES Jr (2007) Early plasma complement C3a levels correlate with functional outcome after aneurysmal subarachnoid hemorrhage. Neurosurgery 61:255–260; discussion 260–261

    Article  PubMed  Google Scholar 

  13. Matz P, Turner C, Weinstein PR, Massa SM, Panter SS, Sharp FR (1996) Heme-oxygenase-1 induction in glia throughout rat brain following experimental subarachnoid hemorrhage. Brain Res 713:211–222

    Article  PubMed  CAS  Google Scholar 

  14. McDonald JF, Nelsestuen GL (1997) Potent inhibition of terminal complement assembly by clusterin: characterization of its impact on C9 polymerization. Biochemistry 36:7464–7473

    Article  PubMed  CAS  Google Scholar 

  15. Mocco J, Mack WJ, Ducruet AF, Sosunov SA, Sughrue ME, Hassid BG, Nair MN, Laufer I, Komotar RJ, Claire M, Holland H, Pinsky DJ, Connolly ES Jr (2006) Complement component C3 mediates inflammatory injury following focal cerebral ischemia. Circ Res 99:209–217

    Article  PubMed  CAS  Google Scholar 

  16. Nina P, Schisano G, Chiappetta F, Luisa Papa M, Maddaloni E, Brunori A, Capasso F, Corpetti MG, Demurtas F (2001) A study of blood coagulation and fibrinolytic system in spontaneous subarachnoid hemorrhage. Correlation with hunt-hess grade and outcome. Surg Neurol 55:197–203

    Article  PubMed  CAS  Google Scholar 

  17. Park CC, Shin ML, Simard JM (1997) The complement membrane attack complex and the bystander effect in cerebral vasospasm. J Neurosurg 87:294–300

    Article  PubMed  CAS  Google Scholar 

  18. Sercombe R, Dinh YR, Gomis P (2002) Cerebrovascular inflammation following subarachnoid hemorrhage. Jpn J Pharmacol 88:227–249

    Article  PubMed  CAS  Google Scholar 

  19. Xi G, Hua Y, Keep RF, Younger JG, Hoff JT (2001) Systemic complement depletion diminishes perihematomal brain edema in rats. Stroke 32:162–167

    Article  PubMed  CAS  Google Scholar 

  20. Xi G, Hua Y, Keep RF, Younger JG, Hoff JT (2002) Brain edema after intracerebral hemorrhage: the effects of systemic complement depletion. Acta Neurochir Suppl 81:253–256

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  22. Yang S, Nakamura T, Hua Y, Keep RF, Younger JG, He Y, Hoff JT, Xi G (2006) The role of complement C3 in intracerebral ­hemorrhage-induced brain injury. J Cereb Blood Flow Metab 26:1490–1495

    Article  PubMed  CAS  Google Scholar 

  23. Yates JR, Sepp T, Matharu BK, Khan JC, Thurlby DA, Shahid H, Clayton DG, Hayward C, Morgan J, Wright AF, Armbrecht AM, Dhillon B, Deary IJ, Redmond E, Bird AC, Moore AT (2007) Complement C3 variant and the risk of age-related macular degeneration. N Engl J Med 357:553–561

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This study was supported by grants NS-017760, NS-039866, and NS-057539 from the National Institutes of Health (NIH) and 0840016N from American Heart Association (AHA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH and AHA.

Conflict of InterestWe declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA

    Chao Zhang, Jin-Yul Lee, Richard F. Keep, Aditya Pandey & Ya Hua

  2. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China

    Chao Zhang

  3. Department of Radiology and Neurosurgery, University of Michigan, Ann Arbor, MI, USA

    Neeraj Chaudhary

  4. Department of Neurosurgery, University of Michigan, R5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, 48109-2200, MI, USA

    Guohua Xi MD

Authors
  1. Chao Zhang
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  2. Jin-Yul Lee
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  3. Richard F. Keep
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  4. Aditya Pandey
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  5. Neeraj Chaudhary
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  6. Ya Hua
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  7. Guohua Xi MD
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Corresponding author

Correspondence to Guohua Xi MD .

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Editors and Affiliations

  1. School of Medicine, Dept. Neurological Surgery, Nihon University, Oyaguchikami-machi 30-1, Tokyo, 173-8610, Japan

    Yoichi Katayama

  2. School of Medicine, Departments of Neurological Surgery and, Nihon University, 30-1 Oyaguchi Kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan

    Takeshi Maeda

  3. , Department of Clinical Laboratory, Namegata District General Hospital, 98-8 Inouefujii, Namegata 98-8, Ibaraki, 311-3516, Japan

    Toshihiko Kuroiwa

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Zhang, C. et al. (2013). Brain Edema Formation and Complement Activation in a Rat Model of Subarachnoid Hemorrhage. In: Katayama, Y., Maeda, T., Kuroiwa, T. (eds) Brain Edema XV. Acta Neurochirurgica Supplement, vol 118. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1434-6_29

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  • DOI: https://doi.org/10.1007/978-3-7091-1434-6_29

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  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-1433-9

  • Online ISBN: 978-3-7091-1434-6

  • eBook Packages: MedicineMedicine (R0)

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