Perihemorrhagic edema in non-traumatic intracerebral hematomas


  • Yuris L. Dzenis Pauls Stradins Clinical University Hospital, Riga, Latvia
  • Aivars Yu. Olmanis Pauls Stradins Clinical University Hospital, Riga, Latvia



brain edema, perihematomal edema, non-traumatic cerebral hemorrhage, treatment


This scientific review deals with the issues of etiological, pathophysiological treatment of the peri-hemorragic edema (PHE) in non-traumatic intracerebral hematomas (NICH). In the experimental studies there has been shown the role of hemoglobin and the breakdown products in the PHE formation process associated with oxidative damage to cells, reaction of free radicals, metalloproteinases activation, etc. The review presents the results of the experiment PHE treatment with a new medication of deferoxamine, antioxidant alpha tocopherol and local inhibitor of protease — contrycal. PHE staging: ionic edema; vasogenic edema and delayed vasogenic edema has been presented. The article demonstrates the results of diagnostic radiological methods in clinical settings (CT, perfusion CT, and MRI) and various aspects of PHE: regional cerebral blood flow; time of peak values; correlatons of the iron level in NICH and NICH size; correlations of PHE size and of the nearest functional outcome, etc. The review presents the results of broad spectrum of treatment measures for PHE and NICH: operative techniques (minimally invasive technique are prioritized); drug therapy (osmotic diuretics; deferoxamine; gamma agonists; antioxidant — cytoflavin) as well as prolonged hypothermia (35°C).

Author Biographies

Yuris L. Dzenis, Pauls Stradins Clinical University Hospital, Riga

Neurosurgical Clinic

Aivars Yu. Olmanis, Pauls Stradins Clinical University Hospital, Riga

Neurosurgical Clinic


1. Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012 Aug;11(8):720-31. [CrossRef] [PubMed] [PubMed Central]

2. Hemphill JC 3rd, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, Fung GL, Goldstein JN, Macdonald RL, Mitchell PH, Scott PA, Selim MH, Woo D; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/ American Stroke Association. Stroke. 2015 Jul;46(7):2032-60. [CrossRef] [PubMed]

3. Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke. 1993 Jul;24(7):987-93. [CrossRef] [PubMed]

4. 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 Apr;39(4):1165-70. [CrossRef] [PubMed]

5. Kim H, Edwards NJ, Choi HA, Chang TR, Jo KW, Lee K. Treatment Strategies to Attenuate Perihematomal Edema in Patients With Intracerebral Hemorrhage. World Neurosurg. 2016 Oct;94:32-41. [CrossRef] [PubMed]

6. Yang J, Arima H, Wu G, Heeley E, Delcourt C, Zhou J, Chen G, Wang X, Zhang S, Yu S, Chalmers J, Anderson CS; INTERACT Investigators. Prognostic significance of perihematomal edema in acute intracerebral hemorrhage: pooled analysis from the intensive blood pressure reduction in acute cerebral hemorrhage trial studies. Stroke. 2015 Apr;46(4):1009-13. [CrossRef] [PubMed]

7. Rincon F, Mayer SA. Novel therapies for intracerebral hemorrhage. Curr Opin Crit Care. 2004 Apr;10(2):94-100. [CrossRef] [PubMed]

8. Urday S, Beslow LA, Goldstein DW, Vashkevich A, Ayres AM, Battey TW, Selim MH, Kimberly WT, Rosand J, Sheth KN. Measurement of perihematomal edema in intracerebral hemorrhage. Stroke. 2015 Apr;46(4):1116-9. [CrossRef] [PubMed] [PubMed Central]

9. McCourt R, Gould B, Gioia L, Kate M, Coutts SB, Dowlatshahi D, Asdaghi N, Jeerakathil T, Hill MD, Demchuk AM, Buck B, Emery D, Butcher K; ICH ADAPT Investigators. Cerebral perfusion and blood pressure do not affect perihematoma edema growth in acute intracerebral hemorrhage. Stroke. 2014 May;45(5):1292-8. [CrossRef] [PubMed]

10. Clasen RA, Huckman MS, Von Roenn KA, Pandolfi S, Laing I, Lobick JJ. A correlative study of computed tomography and histology in human and experimental vasogenic cerebral edema. J Comput Assist Tomogr. 1981 Jun;5(3):313-27. [CrossRef] [PubMed]

11. Peresedov V.V. Differentsirovannoe khirurgicheskoe lechenie netravmaticheskikh supratentorial’nykh vnutrimozgovykh krovoizliyaniy [dissertatsiya]. Moscow (Russia): Burdenko Neurosurgery Institute of the USSR AMS; 1990. Russian.

12. Shirshov A.V. Supratentorial’nye gipertezivnye vnutrimozgovye krovoizliyaniya, oslozhnennye ostroy obstruktivnoy gidrotsefaliey i proryvam krovi v zheludochkovuyu sistemu [dissertatsiya]. Moscow (Russia): Scientific Research Institute of Neurology of the RAMS; 2006. Russian.

13. NINDS ICH Workshop Participants. Priorities for clinical research in intracerebral hemorrhage: report from a National Institute of Neurological Disorders and Stroke workshop. Stroke. 2005 Mar;36(3):e23-41. [CrossRef] [PubMed]

14. Suzuki J., Ebina T. Sequential changes in tissue surrounding ICH. In: Pia HW, Langmaid C, Zierski J, editors. Spontaneous intracerebral haematomas: advances in diagnosis and therapy. Berlin; New York: Springer-Verlag; 1980. p. 121-128.

15. Huang FP, Xi G, Keep RF, Hua Y, Nemoianu A, Hoff JT. Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products. J Neurosurg. 2002 Feb;96(2):287-93. [CrossRef] [PubMed]

16. Qing WG, Dong YQ, Ping TQ, Lai LG, Fang LD, Min HW, Xia L, Heng PY. Brain edema after intracerebral hemorrhage in rats: the role of iron overload and aquaporin 4. J Neurosurg. 2009 Mar;110(3):462-8. [CrossRef] [PubMed]

17. Gong C, Hoff JT, Keep RF. Acute inflammatory reaction following experimental intracerebral hemorrhage in rat. Brain Res. 2000 Jul 14;871(1):57-65. [CrossRef] [PubMed]

18. Bodmer D, Vaughan KA, Zacharia BE, Hickman ZL, Connolly ES. The Molecular Mechanisms that Promote Edema After Intracerebral Hemorrhage. Transl Stroke Res. 2012 Jul;3(Suppl 1):52-61. [CrossRef] [PubMed]

19. Stokum JA, Gerzanich V, Simard JM. Molecular pathophysiology of cerebral edema. J Cereb Blood Flow Metab. 2016 Mar;36(3):513-38. [CrossRef] [PubMed] [PubMed Central]

20. Xi G, Keep RF, Hoff JT. Erythrocytes and delayed brain edema formation following intracerebral hemorrhage in rats. J Neurosurg. 1998 Dec;89(6):991-6. [CrossRef] [PubMed]

21. Garrett MC, Otten ML, Starke RM, Komotar RJ, Magotti P, Lambris JD, Rynkowski MA, Connolly ES. Synergistic neuroprotective effects of C3a and C5a receptor blockade following intracerebral hemorrhage. Brain Res. 2009 Nov 17;1298:171-7. [CrossRef] [PubMed] [PubMed Central]

22. Nakamura T, Keep RF, Hua Y, Schallert T, Hoff JT, Xi G. Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage. J Neurosurg. 2004 pr;100(4):672-8. [CrossRef] [PubMed]

23. Dzenis J. Preoperative pharmacoprotection of patients in coma with nontraumatic intracranial hematoma. In: Mental recovery after traumatic brain injury: a multidisciplinary approach. Conferecnce materials; 2-4 July 2008; Moscow, Russia: Burdenko Neurosurgery Institute; 2008. P. 35.

24. Urday S, Kimberly WT, Beslow LA, Vortmeyer AO, Selim MH, Rosand J, Simard JM, Sheth KN. Targeting secondary injury in intracerebral haemorrhage—perihaematomal oedema. Nat Rev Neurol. 2015 Feb;11(2):111-22. [CrossRef] [PubMed]

25. Simard JM, Kent TA, Chen M, Tarasov KV, Gerzanich V. Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications. Lancet Neurol. 2007 Mar;6(3):258-68. [CrossRef] [PubMed] [PubMed Central]

26. Wagner KR, Xi G, Hua Y, Kleinholz M, de Courten-Myers GM, Myers RE, Broderick JP, Brott TG. Lobar intracerebral hemorrhage model in pigs: rapid edema development in perihematomal white matter. Stroke. 1996 Mar;27(3):490-7. [CrossRef] [PubMed]

27. Fujimoto S, Katsuki H, Ohnishi M, Takagi M, Kume T, Akaike A. Thrombin inducēs striatal neurotoxicity depending on mitogen-activated protein kinase pathways in vivo. Neuroscience. 2007 Jan 19;144(2):694-701. [CrossRef] [PubMed]

28. Ohnishi M, Monda A, Takemoto R, Matsuoka Y, Kitamura C, Ohashi K, Shibuya H, Inoue A. Sesamin suppresses activation of microglia and p44/42 MAPK pathway, which confers neuroprotection in rat intracerebral hemorrhage. Neuroscience. 2013 Mar 1;232:45-52. [CrossRef] [PubMed]

29. Ohnishi M, Katsuki H, Izumi Y, Kume T, Takada-Takatori Y, Akaike A. Mitogen-activated protein kinases support survival of activated microglia that mediate thrombin-induced striatal injury in organotypic slice culture. J Neurosci Res. 2010 Aug 1;88(10):2155-64. [CrossRef] [PubMed]

30. Lei B, Dawson HN, Roulhac-Wilson B, Wang H, Laskowitz DT, James ML. Tumor necrosis factor α antagonism improves neurological recovery in murine intracerebral hemorrhage. J Neuroinflammation. 2013 Aug 20;10:103. [CrossRef] [PubMed] [PubMed Central]

31. Masada T, Hua Y, Xi G, Yang GY, Hoff JT, Keep RF. Attenuation of intracerebral hemorrhage and thrombin-induced brain edema by overexpression of interleukin-1receptor antagonist. J Neurosurg. 2001 Oct;95(4):680-6. [CrossRef] [PubMed]

32. Megyeri P, Abrahбm CS, Temesvбri P, Kovбcs J, Vas T, Speer CP. Recombinant human tumor necrosis factor alpha constricts pial arterioles and increases blood-brain barrier permeability in newborn piglets. Neurosci Lett. 1992 Dec 14;148(1-2):137-40. [CrossRef] [PubMed]

33. Sun Z, Zhao Z, Zhao S, Sheng Y, Zhao Z, Gao C, Li J, Liu X. Recombinant hirudin treatment modulates aquaporin-4 and aquaporin-9 expression after intracerebral hemorrhage in vivo. Mol Biol Rep. 2009 May;36(5):1119-27. [CrossRef] [PubMed]

34. Lee KR, Colon GP, Betz AL, Keep RF, Kim S, Hoff JT. Edema from intracerebral hemorrhage: the role of thrombin. J Neurosurg. 1996 Jan;84(1):91-6. [CrossRef] [PubMed]

35. Aslam M, Ahmad N, Srivastava R, Hemmer B. TNF-alpha induced NFκB signaling and p65 (RelA) overexpression repress Cldn5 promoter in mouse brain endothelial cells. Cytokine. 2012 Feb;57(2):269-75. [CrossRef] [PubMed]

36. Zheng GQ, Wang XT, Wang XM, Gao RR, Zeng XL, Fu XL, Wang Y. Long-time course of protease-activated receptor-1 expression after intracerebral hemorrhage in rats. Neurosci Lett. 2009 Aug 7;459(2):62-5. [CrossRef] [PubMed]

37. Bijli KM, Minhajuddin M, Fazal F, O’Reilly MA, Platanias LC, Rahman A. c-Src interacts with and phosphorylates RelA/p65 to promote thrombin-induced ICAM-1 expression in endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2007 Feb;292(2):L396-404. [PubMed]

38. Katsu M, Niizuma K, Yoshioka H, Okami N, Sakata H, Chan PH. Hemoglobin-induced oxidative stress contributes to matrix metalloproteinase activation and blood-brain barrier dysfunction in vivo. J Cereb Blood Flow Metab. 2010 Dec;30(12):1939-50. [CrossRef] [PubMed] [PubMed Central]

39. Florczak-Rzepka M, Grond-Ginsbach C, Montaner J, Steiner T. Matrix metalloproteinases in human spontaneous intracerebral hemorrhage: an update. Cerebrovasc Dis. 2012;34(4):249-62. [CrossRef] [PubMed]

40. Fainardi E, Borrelli M, Saletti A, Schivalocchi R, Azzini C, Cavallo M, Ceruti S, Tamarozzi R, Chieregato A. CT perfusion mapping of hemodynamic disturbances associated to acute spontaneous intracerebral hemorrhage. Neuroradiology. 2008 Aug;50(8):729-40. [CrossRef] [PubMed]

41. Gould B, McCourt R, Gioia LC, Kate M, Hill MD, Asdaghi N, Dowlatshahi D, Jeerakathil T, Coutts SB, Demchuk AM, Emery D, Shuaib A, Butcher K; ICH ADAPT Investigators. Acute blood pressure reduction in patients with intracerebral hemorrhage does not result in borderzone region hypoperfusion. Stroke. 2014 Oct;45(10):2894-9. [CrossRef] [PubMed]

42. Herweh C, Jьttler E, Schellinger PD, Klotz E, Schramm P. Perfusion CT in hyperacute cerebral hemorrhage within 3 hours after symptom onset: is there an early perihemorrhagic penumbra? J Neuroimaging. 2010 Oct;20(4):350-3. [CrossRef] [PubMed]

43. Wagner I, Volbers B, Hilz MJ, Schwab S, Doerfler A, Staykov D. Radiopacity of intracerebral hemorrhage correlates with perihemorrhagic edema. Eur J Neurol. 2012 Mar;19(3):525-8. [CrossRef] [PubMed]

44. Butcher KS, Baird T, MacGregor L, Desmond P, Tress B, Davis S. Perihematomal edema in primary intracerebral hemorrhage is plasma derived. Stroke. 2004 Aug;35(8):1879-85. [CrossRef] [PubMed]

45. Venkatasubramanian C, Mlynash M, Finley-Caulfield A, Eyngorn I, Kalimuthu R, Snider RW, Wijman CA. Natural history of perihematomal edema after intracerebral hemorrhage measured by serial magnetic resonance imaging. Stroke. 2011 Jan;42(1):73-80. [CrossRef] [PubMed] [PubMed Central]

46. Volbers B, Willfarth W, Kuramatsu JB, Struffert T, Dцrfler A, Huttner HB, Schwab S, Staykov D. Impact of Perihemorrhagic Edema on Short-Term Outcome After Intracerebral Hemorrhage. Neurocrit Care. 2016 Jun;24(3):404-12. [CrossRef] [PubMed]

47. Urday S, Beslow LA, Dai F, Zhang F, Battey TW, Vashkevich A, Ayres AM, Leasure AC, Selim MH, Simard JM, Rosand J, Kimberly WT, Sheth KN. Rate of Perihematomal Edema Expansion Predicts Outcome After Intracerebral Hemorrhage. Crit Care Med. 2016 Apr;44(4):790-7. [CrossRef] [PubMed] [PubMed Central]

48. Fung C, Murek M, Z’Graggen WJ, Krдhenbьhl AK, Gautschi OP, Schucht P, Gralla J, Schaller K, Arnold M, Fischer U, Mattle HP, Raabe A, Beck J. Decompressive hemicraniectomy in patients with supratentorial intracerebral hemorrhage. Stroke. 2012 Dec;43(12):3207-11. [CrossRef] [PubMed]

49. Weiner GM, Lacey MR, Mackenzie L, Shah DP, Frangos SG, Grady MS, Kofke A, Levine J, Schuster J, Le Roux PD. Decompressive craniectomy for elevated intracranial pressure and its effect on the cumulative ischemic burden and therapeutic intensity levels after severe traumatic brain injury. Neurosurgery. 2010 Jun;66(6):1111-8; discussion 1118-9. [CrossRef] [PubMed]

50. Gьresir E, Vatter H, Schuss P, Oszvald A, Raabe A, Seifert V, Beck J. Rapid closure technique in decompressive craniectomy. J Neurosurg. 2011 Apr;114(4):954-60. [CrossRef] [PubMed]

51. Dzenis YuL, Kupchs K, Buivids N. [Combination of internal and external brain decompression due to repeated rupture and thrombosis of aneurysm with intracerebral haematoma: case report]. Ukrainian Neurosurgical Journal. 2015;(4):69-75. Russian. [CrossRef]

52. Аronowski J, Zhao X. Molecular pathophysiology of cerebral hemorrhage: secondary brain injury. Stroke. 2011 Jun;42(6):1781-6. [CrossRef] [PubMed] [PubMed Central]

53. Keep RF, Xiang J, Ennis SR, Andjelkovic A, Hua Y, Xi G, Hoff JT. Blood-brain barrier function in intracerebral hemorrhage. Acta Neurochir Suppl. 2008;105:73-7. [CrossRef] [PubMed]

54. Han N, Ding SJ, Wu T, Zhu YL. Correlation of free radical level and apoptosis after intracerebral hemorrhage in rats. Neurosci Bull. 2008 Dec;24(6):351-8. [CrossRef] [PubMed] [PubMed Central]

55. Mould WA, Carhuapoma JR, Muschelli J, Lane K, Morgan TC, McBee NA, Bistran-Hall AJ, Ullman NL, Vespa P, Martin NA, Awad I, Zuccarello M, Hanley DF; MISTIE Investigators. Minimally invasive surgery plus recombinant tissue-type plasminogen activator for intracerebral hemorrhage evacuation decreases perihematomal edema. Stroke. 2013 Mar;44(3):627-34. [CrossRef] [PubMed] [PubMed Central]

56. Carvi y Nievas MN. Why, when, and how spontaneous intracerebral hematomas should be operated. Med Sci Monit. 2005 Jan;11(1):RA24-31. [cited 2018 March 20]. Avaliable from: [PubMed]

57. Thiex R, Rohde V, Rohde I, Mayfrank L, Zeki Z, Thron A, Gilsbach JM, Uhl E. Frame-based and frameless stereotactic hematoma puncture and subsequent fibrinolytic therapy for the treatment of spontaneous intracerebral hemorrhage. J Neurol. 2004 ec;251(12):1443-50. [CrossRef] [PubMed]

58. Carhuapoma JR, Barrett RJ, Keyl PM, Hanley DF, Johnson RR. Stereotactic aspiration-thrombolysis of intracerebral hemorrhage and its impact on perihematoma brain edema. Neurocrit Care. 2008;8(3):322-9. [CrossRef] [PubMed] PubMed Central PMC ID: PMC 3138497.

59. Wang GQ, Li SQ, Huang YH, Zhang WW, Ruan WW, Qin JZ, Li Y, Yin WM, Li YJ, Ren ZJ, Zhu JQ, Ding YY, Peng JQ, Li PJ. Can minimally invasive puncture and drainage for hypertensive spontaneous Basal Ganglia intracerebral hemorrhage improve patient outcome: a prospective non-randomized comparative study. Mil Med Res. 2014 Jun 1;1:10. [CrossRef] [PubMed] [PubMed Central]

60. Akhigbe T, Okafor U, Sattar T, Rawluk D, Fahey T. Stereotactic-Guided Evacuation of Spontaneous Supratentorial Intracerebral Hemorrhage: Systematic Review and Meta-Analysis. World Neurosurg. 2015 ug;84(2):451-60. [CrossRef] [PubMed]

61. Vespa P, McArthur D, Miller C, O‘Phelan K, Frazee J, Kidwell C, Saver J, Starkman S, Martin N. Frameless stereotactic aspiration and thrombolysis of deep intracerebral hemorrhage is associated with reduction of hemorrhage volume and neurological improvement. Neurocrit Care. 2005;2(3):274-81. [CrossRef] [PubMed]

62. Zhou H, Zhang Y, Liu L, Han X, Tao Y, Tang Y, Hua W, Xue J, Dong Q. A prospective controlled study: minimally invasive stereotactic puncture therapy versus conventional craniotomy in the treatment of acute intracerebral hemorrhage. BMC Neurol. 2011 Jun 23;11:76. [CrossRef] [PubMed] [PubMed Central]

63. Fink ME. Osmotherapy for intracranial hypertension: mannitol versus hypertonic saline. Continuum (Minneap Minn). 2012 Jun;18(3):640-54. [CrossRef] [PubMed]

64. Kamel H, Navi BB, Nakagawa K, Hemphill JC 3rd, Ko NU. Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials. Crit Care Med. 2011 Mar;39(3):554-9. [CrossRef] [PubMed]

65. Larive LL, Carhuapoma JR. Perihematoma brain metabolism and edema: thus far, an elusive piece of a complex puzzle. J Neurol Sci. 2004 Sep 15;224(1-2):1-2. [CrossRef] [PubMed]

66. Staykov D, Kцhrmann M, Unterberg A. [Management of intracerebral hemorrhage: can we still learn something?]. Nervenarzt. 2012 Dec;83(12):1569-74. German. [CrossRef] [PubMed]

67. Kollmar R, Staykov D, Dцrfler A, Schellinger PD, Schwab S, Bardutzky J. Hypothermia reduces perihemorrhagic edema after intracerebral hemorrhage. Stroke. 2010 Aug;41(8):1684-9. [CrossRef] [PubMed]

68. Wagner I, Hauer EM, Staykov D, Volbers B, Dцrfler A, Schwab S, Bardutzky J. Effects of continuous hypertonic saline infusion on perihemorrhagic edema evolution. Stroke. 2011 Jun;42(6):1540-5. [CrossRef] [PubMed]

69. Sandercock PA, Soane T. Corticosteroids for acute ischaemic stroke. Cochrane Database Syst Rev. 2011 Sep ;(9):CD000064. [CrossRef] [PubMed]

70. Gomes JA, Stevens RD, Lewin JJ 3rd, Mirski MA, Bhardwaj A. Glucocorticoid therapy in neurologic critical care. Crit Care Med. 2005 Jun;33(6):1214-24. [CrossRef] [PubMed]

71. Poungvarin N, Bhoopat W, Viriyavejakul A, Rodprasert P, Buranasiri P, Sukondhabhant S, Hensley MJ, Strom BL. Effects of dexamethasone in primary supratentorial intracerebral hemorrhage. N Engl J Med. 1987 May 14;316(20):1229-33. [CrossRef] [PubMed]

72. Yeatts SD, Palesch YY, Moy CS, Selim M. High dose deferoxamine in intracerebral hemorrhage (HI-DEF) trial: rationale, design, and methods. Neurocrit Care. 2013 Oct;19(2):257-66. [CrossRef] [PubMed] [PubMed Central]

73. Yenari MA, Xu L, Tang XN, Qiao Y, Giffard RG. Microglia potentiate damage to blood-brain barrier constituents: improvement by minocycline in vivo and in vitro. Stroke. 2006 Apr;37(4):1087-93. [CrossRef] [PubMed]

74. Chen-Roetling J, Chen L, Regan RF. Minocycline attenuates iron neurotoxicity in cortical cell cultures. Biochem Biophys Res Commun. 2009 Aug 21;386(2):322-6. [CrossRef] [PubMed] [PubMed Central]

75. Zhao F, Hua Y, He Y, Keep RF, Xi G. Minocycline-induced attenuation of iron overload and brain injury after experimental intracerebral hemorrhage. Stroke. 2011 Dec;42(12):3587-93. [CrossRef] [PubMed] [PubMed Central]

76. Gonzales NR, Shah J, Sangha N, Sosa L, Martinez R, Shen L, Kasam M, Morales MM, Hossain MM, Barreto AD, Savitz SI, Lopez G, Misra V, Wu TC, El Khoury R, Sarraj A, Sahota P, Hicks W, Acosta I, Sline MR, Rahbar MH, Zhao X, Aronowski J, Grotta JC. Design of a prospective, dose-escalation study evaluating the Safety of Pioglitazone for Hematoma Resolution in Intracerebral Hemorrhage (SHRINC). Int J Stroke. 2013 Jul;8(5):388-96. [CrossRef] [PubMed]

77. Lu L, Barfejani AH, Qin T, Dong Q, Ayata C, Waeber C. Fingolimod exerts neuroprotective effects in a mouse model of intracerebral hemorrhage. Brain Res. 2014 Mar 25;1555:89-96. [CrossRef] [PubMed] [PubMed Central]

78. Rolland WB, Lekic T, Krafft PR, Hasegawa Y, Altay O, Hartman R, Ostrowski R, Manaenko A, Tang J, Zhang JH. Fingolimod reduces cerebral lymphocyte infiltration in experimental models of rodent intracerebral hemorrhage. Exp Neurol. 2013 Mar;241:45-55. [CrossRef] [PubMed] [PubMed Central]

79. Fu Y, Hao J, Zhang N, Ren L, Sun N, Li YJ, Yan Y, Huang D, Yu C, Shi FD. Fingolimod for the treatment of intracerebral hemorrhage: a 2-arm proof-of-concept study. JAMA Neurol. 2014 Sep;71(9):1092-101. [CrossRef] [PubMed]

80. Hou J, Manaenko A, Hakon J, Hansen-Schwartz J, Tang J, Zhang JH. Liraglutide, a long-acting GLP-1 mimetic, and its metabolite attenuate inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab. 2012 Dec;32(12):2201-10. [CrossRef] [PubMed] [PubMed Central]

81. Sinn DI, Lee ST, Chu K, Jung KH, Kim EH, Kim JM, Park DK, Song EC, Kim BS, Yoon SS, Kim M, Roh JK. Proteasomal inhibition in intracerebral hemorrhage: neuroprotective and anti-inflammatory effects of bortezomib. Neurosci Res. 2007 May;58(1):12-8. [CrossRef] [PubMed]

82. Zhou ZH, Qu F, Zhang CD. Systemic administration of argatroban inhibits protease-activated receptor-1 expression in perihematomal tissue in rats with intracerebral hemorrhage. Brain Res Bull. 2011 Oct 10;86(3-4):235-8. [CrossRef] [PubMed]

83. Kitaoka T, Hua Y, Xi G, Nagao S, Hoff JT, Keep RF. Effect of delayed argatroban treatment on intracerebral hemorrhage-induced edema in the rat. Acta Neurochir Suppl. 2003;86:457-61. [CrossRef] [PubMed]

84. Gao D, Ding F, Lei G, Luan G, Zhang S, Li K, Wang D, Zhang L, Dai D. Effects of focal mild hypothermia on thrombin-induced brain edema formation and the expression of protease activated receptor-1, matrix metalloproteinase-9 and aquaporin 4 in rats. Mol Med Rep. 2015 Apr;11(4):3009-14. [CrossRef] [PubMed]

85. MacLellan CL, Clark DL, Silasi G, Colbourne F. Use of prolonged hypothermia to treat ischemic and hemorrhagic stroke. J Neurotrauma. 2009 Mar;26(3):313-23. [CrossRef] [PubMed]

86. Fingas M, Penner M, Silasi G, Colbourne F. Treatment of intracerebral hemorrhage in rats with 12 h, 3 days and 6 days of selective brain hypothermia. Exp Neurol. 2009 ep;219(1):156-62. [CrossRef] [PubMed]

87. Staykov D, Wagner I, Volbers B, Doerfler A, Schwab S, Kollmar R. Mild prolonged hypothermia for large intracerebral hemorrhage. Neurocrit Care. 2013 Apr;18(2):178-83. [CrossRef] [PubMed]

88. Kollmar R, Juettler E, Huttner HB, Dцrfler A, Staykov D, Kallmuenzer B, Schmutzhard E, Schwab S, Broessner G; CINCH investigators. Cooling in intracerebral hemorrhage (CINCH) trial: protocol of a randomized German-Austrian clinical trial. Int J Stroke. 2012 Feb;7(2):168-72. [CrossRef] [PubMed]

89. Vilenskiy B.S., Kuznetsov A.N., Vinogradov O.I. [The hemorrhagic form of stroke: cerebral hemorrhage, subarachnoid hemorrhage]. Directory. St. Petersburg: Foliant; 2008. Russian.

90. Aghi M, Ogilvy C, Carter B. Surgical Management of Intracerebral Hemorrhage. In: Quiсones-Hinojosa A, ed. Schmidek And Sweet‘s Operative Neurosurgical Techniques: Indications, Methods And Results. Vol.2. 6th ed. Philadelphia, PA: Elsevier/Saunders; 2012. p.823-836. [CrossRef]

91. Vilenskiy B.S. [Emergencies in neurology]. St. Petersburg: Foliant; 2006. Russian.

92. Slaughter TF, Greenberg CS. Antifibrinolytic drugs and perioperative hemostasis. American journal of hematology. 1997 Sep;56(1):32-6. [CrossRef] [PubMed]

93. Dzenis YuL. [Microsurgical removal of non-traumatic intracerebral hematoma cerebral hemispheres]. Ukrainian Neurosurgical Journal. 2014;(2):48-54. Russian. [CrossRef]

94. Rumyantseva SA, Bolevich SB, Silina EV, Fedin AI. [Antioxidant therapy of hemorrhagic stroke]. Moscow: Meditsinskaya kniga; 2007. Russian.



How to Cite

Dzenis, Y. L., & Olmanis, A. Y. (2018). Perihemorrhagic edema in non-traumatic intracerebral hematomas. Ukrainian Neurosurgical Journal, (3), 5–14.



Review articles