Edema from intracerebral hemorrhage: the role of thrombin

Restricted access

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

✓ The mechanism by which intracerebral hemorrhage leads to the formation of brain edema is unknown. This study assesses the components of blood to determine if any are toxic to surrounding brain. Various solutions were infused stereotactically into the right basal ganglia of rats. The animals were sacrificed 24 hours later; brain edema and ion contents were measured. Whole blood caused an increase in brain water content and ion changes consistent with brain edema. Concentrated blood cells, serum from clotted blood, and plasma from unclotted blood all failed to provoke edema formation when infused directly into the brain. On the other hand, activation of the coagulation cascade by adding prothrombinase to plasma did produce brain edema. The edema response to whole blood could be prevented by adding a specific thrombin inhibitor, hirudin, to the injected blood. This study indicates that thrombin plays an important role in edema formation from an intracerebral blood clot.

Article Information

Contributor Notes

Address reprint requests to: Kevin R. Lee, M.D., R5605 Kresge I, University of Michigan, Ann Arbor, Michigan 48109–0532.
Headings
References
  • 1.

    Arand AGSawaya R: Intraoperative chemical hemostasis in neurosurgery. Neurosurgery 18:2232331986Arand AG Sawaya R: Intraoperative chemical hemostasis in neurosurgery. Neurosurgery 18:223–233 1986

    • Search Google Scholar
    • Export Citation
  • 2.

    Bacic FUematsu SMcCarron RMet al: Secretion of immunoreactive endothelin-1 by capillary and microvascular endothelium of human brain. Neurochem Res 17:6997021992Bacic F Uematsu S McCarron RM et al: Secretion of immunoreactive endothelin-1 by capillary and microvascular endothelium of human brain. Neurochem Res 17:699–702 1992

    • Search Google Scholar
    • Export Citation
  • 3.

    Bar-Shavit RBenezra MSabbah Vet al: Thrombin as a multifunctional protein: induction of cell adhesion and proliferation. Am J Respir Cell Mol Biol 6:1231301992Bar-Shavit R Benezra M Sabbah V et al: Thrombin as a multifunctional protein: induction of cell adhesion and proliferation. Am J Respir Cell Mol Biol 6:123–130 1992

    • Search Google Scholar
    • Export Citation
  • 4.

    Belloni PNCarney DHNicolson GL: Organ-derived microvessel endothelial cells exhibit differential responsiveness to thrombin and other growth factors. Microvasc Res 43:20451992Belloni PN Carney DH Nicolson GL: Organ-derived microvessel endothelial cells exhibit differential responsiveness to thrombin and other growth factors. Microvasc Res 43:20–45 1992

    • Search Google Scholar
    • Export Citation
  • 5.

    Bichler JFritz H: Hirudin, a new therapeutic tool? Ann Hematol 63:67761991Bichler J Fritz H: Hirudin a new therapeutic tool? Ann Hematol 63:67–76 1991

    • Search Google Scholar
    • Export Citation
  • 6.

    Broderick JPBrott TTomsick Tet al: Intracerebral hemorrhage more than twice as common as subarachnoid hemorrhage. J Neurosurg 78:1881911993Broderick JP Brott T Tomsick T et al: Intracerebral hemorrhage more than twice as common as subarachnoid hemorrhage. J Neurosurg 78:188–191 1993

    • Search Google Scholar
    • Export Citation
  • 7.

    Chimowitz MIPessin MS: Is there a role for heparin in the management of complications of subarachnoid hemorrhage? Stroke 18:116911721987Chimowitz MI Pessin MS: Is there a role for heparin in the management of complications of subarachnoid hemorrhage? Stroke 18:1169–1172 1987

    • Search Google Scholar
    • Export Citation
  • 8.

    Delin AOlsson PTeger-Nilsson AC: Vasodilatation in the canine leg caused by intraarterial infusion of thrombin and tissue thromboplastin. Cardiovasc Res 1:3713781967Delin A Olsson P Teger-Nilsson AC: Vasodilatation in the canine leg caused by intraarterial infusion of thrombin and tissue thromboplastin. Cardiovasc Res 1:371–378 1967

    • Search Google Scholar
    • Export Citation
  • 9.

    DeMichele MAMinnear FL: Modulation of vascular endothelial permeability by thrombin. Semin Thromb Hemostat 18:2872951992DeMichele MA Minnear FL: Modulation of vascular endothelial permeability by thrombin. Semin Thromb Hemostat 18:287–295 1992

    • Search Google Scholar
    • Export Citation
  • 10.

    Frankowski RF: Epidemiology of stroke and intracerebral hemorrhage in Kaufman HH (ed): Intracerebral Hematomas. New York: Raven Press1992 pp 112Frankowski RF: Epidemiology of stroke and intracerebral hemorrhage in Kaufman HH (ed): Intracerebral Hematomas. New York: Raven Press 1992 pp 1–12

    • Search Google Scholar
    • Export Citation
  • 11.

    Glusa E: Vascular effects of thrombin. Semin Thromb Hemostat 18:2963041992Glusa E: Vascular effects of thrombin. Semin Thromb Hemostat 18:296–304 1992

    • Search Google Scholar
    • Export Citation
  • 12.

    Ishii HSalem HHBell CEet al: Thrombomodulin, an endothelial anticoagulant protein, is absent from the human brain. Blood 67:3623651986Ishii H Salem HH Bell CE et al: Thrombomodulin an endothelial anticoagulant protein is absent from the human brain. Blood 67:362–365 1986

    • Search Google Scholar
    • Export Citation
  • 13.

    Kaneko MTanaka KShimada Tet al: Long-term evaluation of ultra-early operation for hypertensive intracerebral hemorrhage in 100 cases. J Neurosurg 58:8388421983Kaneko M Tanaka K Shimada T et al: Long-term evaluation of ultra-early operation for hypertensive intracerebral hemorrhage in 100 cases. J Neurosurg 58:838–842 1983

    • Search Google Scholar
    • Export Citation
  • 14.

    Lee KRBetz ALKeep RFet al: Intracerebral infusion of thrombin as a cause of brain edema. J Neurosurg 83:104510501995Lee KR Betz AL Keep RF et al: Intracerebral infusion of thrombin as a cause of brain edema. J Neurosurg 83:1045–1050 1995

    • Search Google Scholar
    • Export Citation
  • 15.

    Lee KRKeep RBetz ALet al: Toxic effect of thrombin in the brain. Stroke 25:2651994 (Abstract)Lee KR Keep R Betz AL et al: Toxic effect of thrombin in the brain. Stroke 25:265 1994 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 16.

    Maffrand JP: Direct thrombin inhibitors. Nouv Rev Fr Hematol 34:4054191992Maffrand JP: Direct thrombin inhibitors. Nouv Rev Fr Hematol 34:405–419 1992

    • Search Google Scholar
    • Export Citation
  • 17.

    Malik ABFenton JWII: Thrombin-mediated increase in vascular endothelial permeability. Semin Thromb Hemostat 18:1931991992Malik AB Fenton JW II: Thrombin-mediated increase in vascular endothelial permeability. Semin Thromb Hemostat 18:193–199 1992

    • Search Google Scholar
    • Export Citation
  • 18.

    Markwardt F: Hirudin and derivatives as anticoagulant agents. Thromb Haemostasis 66:1411521991Markwardt F: Hirudin and derivatives as anticoagulant agents. Thromb Haemostasis 66:141–152 1991

    • Search Google Scholar
    • Export Citation
  • 19.

    McKinney MSnider RMRichelson E: Thrombin binding to human brain and spinal cord. Mayo Clin Proc 58:8298311983McKinney M Snider RM Richelson E: Thrombin binding to human brain and spinal cord. Mayo Clin Proc 58:829–831 1983

    • Search Google Scholar
    • Export Citation
  • 20.

    Nishino ASuzuki MOhtani Het al: Thrombin may contribute to the pathophysiology of central nervous system injury. J Neurotrauma 10:1671791993Nishino A Suzuki M Ohtani H et al: Thrombin may contribute to the pathophysiology of central nervous system injury. J Neurotrauma 10:167–179 1993

    • Search Google Scholar
    • Export Citation
  • 21.

    Olson JD: Mechanisms of hemostasis. Effect on intracerebral hemorrhage. Stroke 24 (Suppl 12): I109I1141993Olson JD: Mechanisms of hemostasis. Effect on intracerebral hemorrhage. Stroke 24 (Suppl 12): I109–I114 1993

    • Search Google Scholar
    • Export Citation
  • 22.

    Paxinos GWatson C: The Rat Brain in Stereotaxic Coordinates. Sydney: Academic Press1982Paxinos G Watson C: The Rat Brain in Stereotaxic Coordinates. Sydney: Academic Press 1982

    • Search Google Scholar
    • Export Citation
  • 23.

    Schiele JHeuck CC: Modulations of thrombin activity by poly-electrolytes in the presence of antithrombin III. Semin Thromb Hemostat 17 (Suppl 1): 35411991Schiele J Heuck CC: Modulations of thrombin activity by poly-electrolytes in the presence of antithrombin III. Semin Thromb Hemostat 17 (Suppl 1):35–41 1991

    • Search Google Scholar
    • Export Citation
  • 24.

    Seegers WH: Prothrombin. Cambridge, MA: Harvard University Press1962 pp 417443Seegers WH: Prothrombin. Cambridge MA: Harvard University Press 1962 pp 417–443

    • Search Google Scholar
    • Export Citation
  • 25.

    Vaughan PJCunningham DD: Regulation of protease nexin-1 synthesis and secretion in cultured brain cells by injury-related factors. J Biol Chem 268:372037271993Vaughan PJ Cunningham DD: Regulation of protease nexin-1 synthesis and secretion in cultured brain cells by injury-related factors. J Biol Chem 268:3720–3727 1993

    • Search Google Scholar
    • Export Citation
  • 26.

    Vollmer DGHongo KKassell NFet al: Effect of intracisternal antithrombin III on subarachnoid hemorrhage-induced arterial narrowing. J Neurosurg 70:5996041989Vollmer DG Hongo K Kassell NF et al: Effect of intracisternal antithrombin III on subarachnoid hemorrhage-induced arterial narrowing. J Neurosurg 70:599–604 1989

    • Search Google Scholar
    • Export Citation
  • 27.

    Wagner RHGraham JBPenick GDet al: Estimation of prothrombin by the two-stage method in Tocantins LMKazal LA (eds): Blood Coagulation Hemorrhage and Thrombosis. Methods of Study. New York: Grune & Stratton1955 pp 159164Wagner RH Graham JB Penick GD et al: Estimation of prothrombin by the two-stage method in Tocantins LM Kazal LA (eds): Blood Coagulation Hemorrhage and Thrombosis. Methods of Study. New York: Grune & Stratton 1955 pp 159–164

    • Search Google Scholar
    • Export Citation
  • 28.

    White RP: Comparison of the inhibitory effects of antithrombin III, macroglobulin, and thrombin in human basilar arteries: relevance to cerebral vasospasm. J Cereb Blood Flow Metab 7:68731987White RP: Comparison of the inhibitory effects of antithrombin III macroglobulin and thrombin in human basilar arteries: relevance to cerebral vasospasm. J Cereb Blood Flow Metab 7:68–73 1987

    • Search Google Scholar
    • Export Citation
  • 29.

    Yang GYBetz ALChenevert TLet al: Experimental intracerebral hemorrhage: relationship between brain edema, blood flow, and blood-brain barrier permeability in rats. J Neurosurg 81:931021993Yang GY Betz AL Chenevert TL et al: Experimental intracerebral hemorrhage: relationship between brain edema blood flow and blood-brain barrier permeability in rats. J Neurosurg 81:93–102 1993

    • Search Google Scholar
    • Export Citation
Cited By
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 454 342 10
Full Text Views 173 26 4
PDF Downloads 111 13 1
EPUB Downloads 0 0 0
PubMed
Google Scholar