Advertisement

Cerebral Hemorrhage, Brain Edema, and Heme Oxygenase-1 Expression After Experimental Traumatic Brain Injury

Conference paper
First Online:
Part of the Acta Neurochirurgica Supplement book series (NEUROCHIRURGICA, volume 118)

Abstract

Intracranial bleeding is a common and serious consequence of traumatic brain injury (TBI). In the present study, we investigated cerebral hematoma occurrence, brain edema formation, blood–brain barrier (BBB) disruption, and heme oxygenase-1 (HO-1) expression after TBI. Moderate severity (1.8–2.2 atmospheres [ATM]) TBI was induced by lateral fluid percussion in male adult Sprague–Dawley rats. Sham rats underwent only a craniotomy. Rats were euthanized 24 h later for brain histology and immunoblotting analysis. We found TBI-induced cerebral hematomas and iron deposition in the ipsilateral hemisphere in all rats. TBI also caused marked BBB disruption (p < 0.05) and brain swelling (p < 0.05). HO-1, a key enzyme for heme degradation, was upregulated significantly after TBI (419 ± 89 vs 194 ± 59 pixels in the sham, p < 0.05). These results suggest that cerebral hematomas might play a role in brain injury after TBI. Future studies should determine the role of iron released from the cerebral hematoma in TBI.

Keywords

Brain edema Cerebral hemorrhage Iron Traumatic brain injury 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This study was supported by grants NS-017760, NS-039866, and NS-057539 from the National Institutes of Health (NIH) and 0840016 N from the 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.

References

  1. 1.
    Bramlett HM, Dietrich WD (2002) Quantitative structural changes in white and gray matter 1 year following traumatic brain injury in rats. Acta Neuropathol 103:607–614PubMedCrossRefGoogle Scholar
  2. 2.
    Cortez SC, McIntosh TK, Noble LJ (1989) Experimental fluid percussion brain injury: vascular disruption and neuronal and glial alterations. Brain Res 482:271–282PubMedCrossRefGoogle Scholar
  3. 3.
    Dixon CE, Lyeth BG, Povlishock JT, Findling RL, Hamm RJ, Marmarou A, Young HF, Hayes RL (1987) A fluid percussion model of experimental brain injury in the rat. J Neurosurg 67:110–119PubMedCrossRefGoogle Scholar
  4. 4.
    Fukuda K, Panter SS, Sharp FR, Noble LJ (1995) Induction of heme oxygenase-1 (HO-1) after traumatic brain injury in the rat. Neurosci Lett 199:127–130PubMedCrossRefGoogle Scholar
  5. 5.
    Fukuda K, Richmon JD, Sato M, Sharp FR, Panter SS, Noble LJ (1996) Induction of heme oxygenase-1 (HO-1) in glia after traumatic brain injury. Brain Res 736:68–75PubMedCrossRefGoogle Scholar
  6. 6.
    Ghajar J (2000) Traumatic brain injury. Lancet 356:923–929PubMedCrossRefGoogle Scholar
  7. 7.
    Hicks R, Soares H, Smith D, McIntosh T (1996) Temporal and spatial characterization of neuronal injury following lateral fluid-percussion brain injury in the rat. Acta Neuropathol 91:236–246PubMedCrossRefGoogle Scholar
  8. 8.
    Hua Y, Nakamura T, Keep R, Wu J, Schallert T, Hoff J, Xi G (2006) Long-term effects of experimental intracerebral hemorrhage: the role of iron. J Neurosurg 104:305–312PubMedCrossRefGoogle Scholar
  9. 9.
    Khoshyomn S, Tranmer BI (2004) Diagnosis and management of pediatric closed head injury. Semin Pediatr Surg 13:80–86PubMedCrossRefGoogle Scholar
  10. 10.
    Langlois JA, Rutland-Brown W, Wald MM (2006) The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil 21:375–378PubMedCrossRefGoogle Scholar
  11. 11.
    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 30:1793–1803PubMedCrossRefGoogle Scholar
  12. 12.
    Maas AI, Stocchetti N, Bullock R (2008) Moderate and severe traumatic brain injury in adults. Lancet Neurol 7:728–741PubMedCrossRefGoogle Scholar
  13. 13.
    Marcoux J, McArthur DA, Miller C, Glenn TC, Villablanca P, Martin NA, Hovda DA, Alger JR, Vespa PM (2008) Persistent metabolic crisis as measured by elevated cerebral microdialysis lactate-pyruvate ratio predicts chronic frontal lobe brain atrophy after traumatic brain injury. Crit Care Med 36:2871–2877PubMedCrossRefGoogle Scholar
  14. 14.
    Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H, Demetriadou K (1994) A new model of diffuse brain injury in rats. Part I: pathophysiology and biomechanics. Neurosurg 80:291–300CrossRefGoogle Scholar
  15. 15.
    McIntosh TK, Vink R, Noble L, Yamakami I, Fernyak S, Soares H, Faden AL (1989) Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model. Neuroscience 28:233–244PubMedCrossRefGoogle Scholar
  16. 16.
    Nakamura T, Keep RF, Hua Y, Schallert T, Hoff JT, Xi G (2004) Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage. J Neurosurg 100:672–678PubMedCrossRefGoogle Scholar
  17. 17.
    Pierce JE, Trojanowski JQ, Graham DI, Smith DH, McIntosh TK (1996) Immunohistochemical characterization of alterations in the distribution of amyloid precursor proteins and beta-amyloid peptide after experimental brain injury in the rat. J Neurosci 16:1083–1090PubMedGoogle Scholar
  18. 18.
    Wan S, Hua Y, Keep RF, Hoff JT, Xi G (2006) Deferoxamine reduces CSF free iron levels following intracerebral hemorrhage. Acta Neurochir Suppl 96:215–218Google Scholar
  19. 19.
    Schmidt RH, Grady MS (1993) Regional patterns of blood-brain barrier breakdown following central and lateral fluid percussion injury in rodents. J Neurotrauma 10:415–430PubMedCrossRefGoogle Scholar
  20. 20.
    Thompson HJ, Lifshitz J, Marklund N, Grady MS, Graham DI, Hovda DA, McIntosh TK (2005) Lateral fluid percussion brain injury: a 15-year review and evaluation. J Neurotrauma 22:42–75PubMedCrossRefGoogle Scholar
  21. 21.
    Wu J, Hua Y, Keep R, Schallert T, Hoff J, Xi G (2002) Oxidative brain injury from extravasated erythrocytes after intracerebral hemorrhage. Brain Res 953:45PubMedCrossRefGoogle Scholar
  22. 22.
    Wu J, Hua Y, Keep RF, Nakamura T, Hoff JT, Xi G (2003) Iron and iron-handling proteins in the brain after intracerebral hemorrhage. Stroke 34:2964–2969PubMedCrossRefGoogle Scholar
  23. 23.
    Xi G, Keep RF, Hoff JT (2006) Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 5:53–63PubMedCrossRefGoogle Scholar
  24. 24.
    Xi G, Keep RF, Hua Y, Xiang JM, Hoff JT (1999) Attenuation of thrombin-induced brain edema by cerebral thrombin preconditioning. Stroke 30:1247–1255PubMedCrossRefGoogle Scholar
  25. 25.
    Xu Y, McArthur DL, Alger JR, Etchepare M, Hovda DA, Glenn TC, Huang S, Dinov I, Vespa PM (2010) Early nonischemic oxidative metabolic dysfunction leads to chronic brain atrophy in traumatic brain injury. J Cereb Blood Flow Metab 30:883–894PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  1. 1.Department of NeurosurgeryUniversity of Michigan Medical SchoolAnn ArborUSA
  2. 2.Department of NeurosurgeryKagawa Medical UniversityKagawaJapan

Personalised recommendations

Cite paper

Buy options