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

Kevin R. Lee Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor, Michigan; and Department of Neurological Surgery, Wayne State University, Detroit, Michigan

Search for other papers by Kevin R. Lee in
Current site
Google Scholar
PubMed Close
 M.D.
,
Nobuyuki Kawai Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor, Michigan; and Department of Neurological Surgery, Wayne State University, Detroit, Michigan

Search for other papers by Nobuyuki Kawai in
Current site
Google Scholar
PubMed Close
 M.D.
,
Seoung Kim Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor, Michigan; and Department of Neurological Surgery, Wayne State University, Detroit, Michigan

Search for other papers by Seoung Kim in
Current site
Google Scholar
PubMed Close
 B.A.
,
Oren Sagher Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor, Michigan; and Department of Neurological Surgery, Wayne State University, Detroit, Michigan

Search for other papers by Oren Sagher in
Current site
Google Scholar
PubMed Close
 M.D.
, and
Julian T. Hoff Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor, Michigan; and Department of Neurological Surgery, Wayne State University, Detroit, Michigan

Search for other papers by Julian T. Hoff in
Current site
Google Scholar
PubMed Close
 M.D.
Page Range:
272–278
Volume/Issue:
Volume 86: Issue 2
DOI link:
https://doi.org/10.3171/jns.1997.86.2.0272
Restricted access

Purchase Now

USD  $45.00

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

USD  $525.00

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

USD  $624.00
Click here for subscription options

  • Purchase Now

    USD  $45.00

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

    USD  $525.00

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

    USD  $624.00
USD  $45.00
USD  $525.00
USD  $624.00
Print or Print + Online Sign in

✓ Recently, the authors showed that thrombin contributes to the formation of brain edema following intracerebral hemorrhage. The current study examines whether the action of thrombin is due to an effect on cerebral blood flow (CBF), vasoreactivity, blood-brain barrier (BBB) function, or cell viability. In vivo solutions of thrombin were infused stereotactically into the right basal ganglia of rats. The animals were sacrificed 24 hours later; CBF and BBB permeability were measured. The actions of thrombin on vasoreactivity were examined in vitro by superfusing thrombin on cortical brain slices while monitoring microvessel diameter with videomicroscopy. In separate experiments C6 glioma cells were exposed to various concentrations of thrombin, and lactate dehydrogenase release, a marker of cell death, was measured. The results indicate that thrombin induces BBB disruption as well as death of parenchymal cells, whereas CBF and vasoreactivity are not altered. The authors conclude that cell toxicity and BBB disruption by thrombin are triggering mechanisms for the edema formation that follows intracerebral hemorrhage.

  • Collapse
  • Expand

Contributor Notes

Address reprint requests to: Kevin R. Lee, M.D., Department of Neurological Surgery, Wayne State University, 6E UHC, 4201 St. Antoine, Detroit, Michigan 48201.
  • 1.

    Bacic 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 Bacic 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
  • 2.

    Blasberg RG, , Fenstermacher JD, & Patlak CS: Transport of alphaaminoisobutyric acid across brain capillary and cellular membranes. J Cereb Blood Flow Metab 3:8–32, 1983 Blasberg RG, Fenstermacher JD, Patlak CS: Transport of alphaaminoisobutyric acid across brain capillary and cellular membranes. J Cereb Blood Flow Metab 3:8–32, 1983

    • Search Google Scholar
    • Export Citation
  • 3.

    Bullock R, , Mendelow AD, & Teasdale GM, et al: Intracranial haemorrhage induced at arterial pressure in the rat. Part 1. Description of technique, ICP changes and neuropathological findings. Neurol Res 6:184–188, 1984 Bullock R, Mendelow AD, Teasdale GM, et al: Intracranial haemorrhage induced at arterial pressure in the rat. Part 1. Description of technique, ICP changes and neuropathological findings. Neurol Res 6:184–188, 1984

    • Search Google Scholar
    • Export Citation
  • 4.

    Chen MH, , Bullock R, & Graham DI, et al: Ischemic neuronal damage after acute subdural hematoma in the rat: effects of pretreatment with a glutamate antagonist. J Neurosurg 74:944–950, 1991 Chen MH, Bullock R, Graham DI, et al: Ischemic neuronal damage after acute subdural hematoma in the rat: effects of pretreatment with a glutamate antagonist. J Neurosurg 74:944–950, 1991

    • Search Google Scholar
    • Export Citation
  • 5.

    Cushing H: Some experimental and clinical observations concerning states of increased intracranial tension. Am J Med Sci 124:375–400, 1902 Cushing H: Some experimental and clinical observations concerning states of increased intracranial tension. Am J Med Sci 124:375–400, 1902

    • Search Google Scholar
    • Export Citation
  • 6.

    Delin 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 Delin 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
  • 7.

    Glusa E: Vascular effects of thrombin. Semin Thromb Hemost 18:296–304, 1992 Glusa E: Vascular effects of thrombin. Semin Thromb Hemost 18:296–304, 1992

    • Search Google Scholar
    • Export Citation
  • 8.

    Jones TH, , Morawetz RB, & Crowell RM, et al: Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg 54:773–782, 1981 Jones TH, Morawetz RB, Crowell RM, et al: Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg 54:773–782, 1981

    • Search Google Scholar
    • Export Citation
  • 9.

    Kempski O, , Staub F, & Schneider GH, et al: Swelling of C6 glioma cells and astrocytes from glutamate, high K+ concentrations or acidosis. Prog Brain Res 94:69–75, 1992 Kempski O, Staub F, Schneider GH, et al: Swelling of C6 glioma cells and astrocytes from glutamate, high K+ concentrations or acidosis. Prog Brain Res 94:69–75, 1992

    • Search Google Scholar
    • Export Citation
  • 10.

    Kingman TA, , Mendelow AD, & Graham DI, et al: Experimental intracerebral mass: description of model, intracranial pressure changes and neuropathology. J Neuropathol Exp Neurol 47:128–137, 1988 Kingman TA, Mendelow AD, Graham DI, et al: Experimental intracerebral mass: description of model, intracranial pressure changes and neuropathology. J Neuropathol Exp Neurol 47:128–137, 1988

    • Search Google Scholar
    • Export Citation
  • 11.

    Koh JY, & Choi DW: Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. J Neurosci Meth 20:83–90, 1987 Koh JY, Choi DW: Quantitative determination of glutamate mediated cortical neuronal injury in cell culture by lactate dehydrogenase efflux assay. J Neurosci Meth 20:83–90, 1987

    • Search Google Scholar
    • Export Citation
  • 12.

    Kuroda Y, & Bullock R: Failure of cerebral blood flow-metabolism coupling after acute subdural hematoma in the rat. Neurosurgery 31:1062–1071, 1992 Kuroda Y, Bullock R: Failure of cerebral blood flow-metabolism coupling after acute subdural hematoma in the rat. Neurosurgery 31:1062–1071, 1992

    • Search Google Scholar
    • Export Citation
  • 13.

    Kuroda Y, , Inglis FM, & Miller JD, et al: Transient glucose hypermetabolism after acute subdural hematoma in the rat. J Neurosurg 76:471–477, 1992 Kuroda Y, Inglis FM, Miller JD, et al: Transient glucose hypermetabolism after acute subdural hematoma in the rat. J Neurosurg 76:471–477, 1992

    • Search Google Scholar
    • Export Citation
  • 14.

    Lee KR, , Betz AL, & Keep RF, et al: Intracerebral infusion of thrombin as a cause of brain edema. J Neurosurg 83:1045–1050, 1995 Lee 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 KR, , Betz AL, & Kim S, et al: The role of the coagulation cascade in brain edema formation after intracerebral hemorrhage. Acta Neurochir 138:396–401, 1996 Lee KR, Betz AL, Kim S, et al: The role of the coagulation cascade in brain edema formation after intracerebral hemorrhage. Acta Neurochir 138:396–401, 1996

    • Search Google Scholar
    • Export Citation
  • 16.

    Lee KR, , Colon GP, & Betz AL, et al: Edema from intracerebral hemorrhage: the role of thrombin. J Neurosurg 84:91–96, 1996 Lee KR, Colon GP, Betz AL, et al: Edema from intracerebral hemorrhage: the role of thrombin. J Neurosurg 84:91–96, 1996

    • Search Google Scholar
    • Export Citation
  • 17.

    Lee KR, , Keep RF, & Betz AL, et al: A thrombin antagonist, hirudin, inhibits brain edema formation in a model of intracerebral hemorrhage, in Nagai H, , Kamiya K, & Ishii S (eds): Intracranial Pressure IX. Tokyo: Springer-Verlag, 1994, pp 70–75 Lee KR, Keep RF, Betz AL, et al: A thrombin antagonist, hirudin, inhibits brain edema formation in a model of intracerebral hemorrhage, in Nagai H, Kamiya K, Ishii S (eds): Intracranial Pressure IX. Tokyo: Springer-Verlag, 1994, pp 70–75

    • Search Google Scholar
    • Export Citation
  • 18.

    Maier-Hauff K, , Baethmann AJ, & Lange M, et al: The kallikreinkinin system as mediator in vasogenic brain edema. Part 2: Studies on kinin formation in focal and perifocal brain tissue. J Neurosurg 61:97–106, 1984 Maier-Hauff K, Baethmann AJ, Lange M, et al: The kallikreinkinin system as mediator in vasogenic brain edema. Part 2: Studies on kinin formation in focal and perifocal brain tissue. J Neurosurg 61:97–106, 1984

    • Search Google Scholar
    • Export Citation
  • 19.

    Mendelow AD, , Bullock R, & Teasdale GM, et al: Intracranial haemorrhage induced at arterial pressure in the rat. Part 2: Short term changes in local cerebral blood flow measured by autoradiography. Neurol Res 6:189–193, 1984 Mendelow AD, Bullock R, Teasdale GM, et al: Intracranial haemorrhage induced at arterial pressure in the rat. Part 2: Short term changes in local cerebral blood flow measured by autoradiography. Neurol Res 6:189–193, 1984

    • Search Google Scholar
    • Export Citation
  • 20.

    Nath FP, , Jenkins A, & Mendelow AD, et al: Early hemodynamic changes in experimental intracerebral hemorrhage. J Neurosurg 65:697–703, 1986 Nath FP, Jenkins A, Mendelow AD, et al: Early hemodynamic changes in experimental intracerebral hemorrhage. J Neurosurg 65:697–703, 1986

    • Search Google Scholar
    • Export Citation
  • 21.

    Nath FP, , Kelly PT, & Jenkins A, et al: Effects of experimental intracerebral hemorrhage on blood flow, capillary permeability, and histochemistry. J Neurosurg 66:555–562, 1987 Nath FP, Kelly PT, Jenkins A, et al: Effects of experimental intracerebral hemorrhage on blood flow, capillary permeability, and histochemistry. J Neurosurg 66:555–562, 1987

    • Search Google Scholar
    • Export Citation
  • 22.

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

    • Search Google Scholar
    • Export Citation
  • 23.

    Sagher O, , Zhang XQ, & Szeto W, et al: Live computerized videomicroscopy of cerebral microvessels in brain slices. J Cereb Blood Flow Metab 13:676–682, 1993 Sagher O, Zhang XQ, Szeto W, et al: Live computerized videomicroscopy of cerebral microvessels in brain slices. J Cereb Blood Flow Metab 13:676–682, 1993

    • Search Google Scholar
    • Export Citation
  • 24.

    Seegers WH: Prothrombin. Cambridge, Mass: Harvard University Press, 1962, pp 417–443 Seegers WH: Prothrombin. Cambridge, Mass: Harvard University Press, 1962, pp 417–443

    • Search Google Scholar
    • Export Citation
  • 25.

    Sinar EJ, , Mendelow AD, & Graham DI, et al: Experimental intracerebral hemorrhage: effects of a temporary mass lesion. J Neurosurg 66:568–576, 1987 Sinar EJ, Mendelow AD, Graham DI, et al: Experimental intracerebral hemorrhage: effects of a temporary mass lesion. J Neurosurg 66:568–576, 1987

    • Search Google Scholar
    • Export Citation
  • 26.

    Van Uitert RL, & Levy DE: Regional brain blood flow in the conscious gerbil. Stroke 9:67–72, 1978 Van Uitert RL, Levy DE: Regional brain blood flow in the conscious gerbil. Stroke 9:67–72, 1978

    • Search Google Scholar
    • Export Citation
  • 27.

    Vaughan PJ, , Pike CJ, & Cotman CW, et al: Thrombin receptor activation protects neurons and astrocytes from cell death produced by environmental insults. J Neurosci 15:5389–5401, 1995 Vaughan PJ, Pike CJ, Cotman CW, et al: Thrombin receptor activation protects neurons and astrocytes from cell death produced by environmental insults. J Neurosci 15:5389–5401, 1995

    • Search Google Scholar
    • Export Citation
  • 28.

    Volpin L, , Cervellini P, & Colombo F, et al: Spontaneous intracerebral hematomas: a new proposal about the usefulness and limits of surgical treatment. Neurosurgery 15:663–666, 1984 Volpin L, Cervellini P, Colombo F, et al: Spontaneous intracerebral hematomas: a new proposal about the usefulness and limits of surgical treatment. Neurosurgery 15:663–666, 1984

    • Search Google Scholar
    • Export Citation
  • 29.

    Wagner 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 Wagner 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
  • 30.

    Weinstein JR, , Gold SJ, & Cunningham DD, et al: Cellular localization of thrombin receptor mRNA in rat brain: expression by mesencephalic dopaminergic neurons and codistribution with prothrombin mRNA. J Neurosci 15:2906–2919, 1995 Weinstein JR, Gold SJ, Cunningham DD, et al: Cellular localization of thrombin receptor mRNA in rat brain: expression by mesencephalic dopaminergic neurons and codistribution with prothrombin mRNA. J Neurosci 15:2906–2919, 1995

    • Search Google Scholar
    • Export Citation
  • 31.

    White RP: Comparison of the inhibitory effects of antithrombin III, α2-macroglobulin, and thrombin in human basilar arteries: relevance to cerebral vasospasm. J Cereb Blood Flow Metab 7:68–73, 1987 White RP: Comparison of the inhibitory effects of antithrombin III, α2-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
  • 32.

    Yang 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, 1994 Yang 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, 1994

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 1873 451 37
Full Text Views 387 24 2
PDF Downloads 176 22 1
EPUB Downloads 0 0 0