The relationship between the serum levels of ferritin and the radiological brain injury indices in patients with spontaneous intracerebral hemorrhage

Document Type : Original Article


1 Department of Neuroscience, Guilan Trauma Research Center, Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran

2 Department of Neurology, Poursina Hospital, Guilan University of Medical Sciences, Rasht, Iran

3 Health Sciences Research Center, School of Health, Mazandaran University of Medical Sciences, Sari, Iran

4 Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran


Objective(s): Preclinical studies show that iron plays a key role in mediating neuronal injury. This study was performedin order to identify the relationship between the serum level of ferritin and severity of the brain injury which occur after an Intracerebral hemorrhage (ICH).
Materials and Methods:This was a cross sectional descriptive – analytic study, which was conducted on those patients who had suffered from an ICH and had attended Poursina Hospital. The Serum levels of ferritin were measured at admittance.  A Cranial CT scan was performed at admission and also 72 hr afterward.  Hematoma and edema surrounding the hematoma volumes were also measured at entrance and 72 hr afterward.  Data analysis was carried out by a descriptive - analytic statistics approach and calculated later on by the Spss-20 software.
Results:In this investigation, 63 patients were studied, from which 34 (54%) were male and 29 (46%) female. The average age of the patients was 69.7± 11.9 (Min 43 and Max 94 years old). A significant relationship was observed between the level of ferritin and the edema volume surrounding the hematoma at first and next 72 hr after the patients were admitted.
Conclusion:These results delineated the effective role of iron on the edema volume elevation. More studies are essentially urged to ascertain the clinical evaluation of the curing effect of iron chelators in those patients who suffer from ICH.


1. Anderson CS, Chakera T, Stewart-Wynne EG, Jamrozik KD. Spectrum of primary intracerebral haemorrhage in Perth, Western Australia, 1989-90: incidence and outcome. J Neurol Neurosurg Psychiatry 1994; 57:936-940.
2. Adeoye O, Broderick JP. Advances in the management of intracerebral hemorrhage. Nat Rev Neurol  2010; 6:593-601.
3. Counsell C, Boonyakarnkul S, Dennis M, Sandercock P, Bamford J, Burn J, et al. Primary intracerebral haemorrhage in the Oxfordshire community stroke project. Cerebrovasc Dis 1995; 5:26-34.
4. Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets.  Lancet Neurol 2012; 11:720-731.
5. Morgenstern LB, Hemphill JC, Anderson C, Becker K, Broderick JP, Connolly ES, et al. Guidelines for             the management of spontaneous intracerebral hemorrhage a guideline for healthcare professionals from the american heart association/american stroke association. Stroke 2010; 41:2108-2129.
6. Balami JS, Buchan AM. Complications of intracerebral haemorrhage. Lancet Neurol 2012; 11:101-118.
7. Broderick J, Connolly S, Feldmann E, Hanley D, Kase C, Krieger D, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation 2007; 116:e391-e413.
8. Zhang Z, Wei T, Hou J, Li G, Yu S, Xin W. Iron-induced oxidative damage and apoptosis in cerebellar granule cells: attenuation by tetramethylpyrazine and ferulic acid. Eur J Pharmacol 2003; 467:41-47.
9. Inaji M, Tomita H, Tone O, Tamaki M, Suzuki R, Ohno K. Chronological changes of perihematomal edema of human intracerebral hematoma.  Brain Edema XII: Springer; 2003. p. 445-448.
10. Gebel JM, Jauch EC, Brott TG, Khoury J, Sauerbeck L, Salisbury S, et al. Relative edema volume is a predictor of outcome in patients with hyperacute spontaneous intracerebral hemorrhage. Stroke 2002; 33:2636-2641.
11. Thiex R, Tsirka SE. Brain edema after intracerebral hemorrhage: mechanisms, treatment options, management strategies, and operative indications. Neurosurg Focus 2007; 22:1-7.
12. Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 2006; 5:53-63.
13. Hua Y, Keep RF, Hoff JT, Xi G. Brain injury after intracerebral hemorrhage the role of thrombin and iron. Stroke 2007; 38:759-762.
14. Jeong S-W, Chu K, Jung K-H, Kim SU, Kim M, Roh J-K. Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage. Stroke 2003; 34:2258-2263.
15. Khaksari M, Mahmmodi R, Shahrokhi N, Shabani M, Joukar S, Aqapour M. The effects of shilajit on brain edema, intracranial pressure and neurologic outcomes following the traumatic brain injury in rat. Iran J Basic Med Sci 2013; 16:858.
16. Seghatoleslam M, Jalali M, Nikravesh MR, Hosseini M, Alamdari DH, Fazel A. Therapeutic benefit of intravenous administration of human umbilical cord blood-mononuclear cells following intracerebral hemorrhage in rat. Iran J Basic Med Sci 2012; 15:860.
17. Moussouttas M. Challenges and controversies in the medical management of primary and antithrombotic-related intracerebral hemorrhage. Ther Adv Neurol Disord 2012; 5:43-56.
18. Leonardo CC, Robbins S, Doré S. Translating basic science research to clinical application: models and strategies for intracerebral hemorrhage. Front  Neurol  2012 ;3.
19. Wagner K, Hua Y, de Courten-Myers G, Broderick J, Nishimura R, Lu S, et al. Tin-mesoporphyrin, a potent heme oxygenase inhibitor, for treatment of intracerebral hemorrhage: in vivo and in vitro studies. Cell Mol Biol 2000; 46:597-608.
20. Gu Y, Hua Y, Keep RF, Morgenstern LB, Xi G. Deferoxamine reduces intracerebral hematoma-induced iron accumulation and neuronal death in piglets. Stroke 2009; 40:2241-2243.
21. Okauchi M, Hua Y, Keep RF, Morgenstern LB, Xi G. Effects of deferoxamine on intracerebral hemorrhage-induced brain injury in aged rats. Stroke 2009; 40:1858-1863.
22. Nakamura T, Kuroda Y, Yamashita S, Zhang X, Miyamoto O, Tamiya T, et al. Edaravone attenuates brain edema and neurologic deficits in a rat model of acute intracerebral hemorrhage. Stroke 2008; 39:463-469.
23. Wu J, Hua Y, Keep RF, Nakamura T, Hoff JT, Xi G. Iron and iron-handling proteins in the brain after intracerebral hemorrhage. Stroke 2003; 34:2964-2969.
24. Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996; 27:1304-1305.
25. Mehdiratta M, Kumar S, Hackney D, Schlaug G, Selim M. Association between serum ferritin level and perihematoma edema volume in patients with spontaneous intracerebral hemorrhage. Stroke 2008; 39:1165-1170.
26. Huang F-P, Xi G, Keep RF, Hua Y, Nemoianu A, Hoff JT. Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products. J Neurosurg 2002; 96:287-293.
27. van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis.  Lancet Neurol 2010; 9:167-176.
28. Flaherty ML, Woo D, Haverbusch M, Sekar P, Khoury J, Sauerbeck L, et al. Racial variations in location and risk of intracerebral hemorrhage. Stroke 2005; 36:934-937.
29. Woo D, Haverbusch M, Sekar P, Kissela B, Khoury J, Schneider A, et al. Effect of untreated hypertension on hemorrhagic stroke. Stroke 2004; 35:1703-1708.
30. Testai FD, Aiyagari V. Acute hemorrhagic stroke pathophysiology and medical interventions: blood pressure control, management of anticoagulant-associated brain hemorrhage and general management principles. Neurol Clin 2008; 26:963-985.
31. de la Ossa NP, Sobrino T, Silva Y, Blanco M, Millán M, Gomis M, et al. Iron-related brain damage in patients with intracerebral hemorrhage. Stroke 2010; 41:810-813.
32. Gebel JM, Sila CA, Sloan MA, Granger CB, Weisenberger JP, Green CL, et al. Comparison of the ABC/2 estimation technique to computer-assisted volumetric analysis of intraparenchymal and subdural hematomas complicating the GUSTO-1 trial. Stroke 1998; 29:1799-1801.
33. 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; 104:305-312.
34. Selim M, Yeatts S, Goldstein JN, Gomes J, Greenberg S, Morgenstern LB, et al. Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage. Stroke 2011; 42:3067-3074.
35. Butcher KS, Baird T, MacGregor L, Desmond P, Tress B, Davis S. Perihematomal edema in primary intracerebral hemorrhage is plasma derived. Stroke 2004; 35:1879-1885.
36. Lee KR, Kawai N, Kim S, Sagher O, Hoff JT. Mechanisms of edema formation after intracerebral hemorrhage: effects of thrombin on cerebral blood flow, blood-brain barrier permeability, and cell survival in a rat model. J Neurosurg 1997; 86:272-278.