(Stroke. 1998;29:2580-2586.)
© 1998 American Heart Association, Inc.
Original Contributions |
Role of Blood Clot Formation on Early Edema Development After Experimental Intracerebral Hemorrhage
From the Department of Surgery (Neurosurgery) (G.X., R.F.K., J.T.H.), University of Michigan, Ann Arbor, Mich; the Departments of Neurology (K.R.W., Y.H., J.P.B., T.G.B.) and Pathology and Laboratory Medicine (G.M. de C.-M.), University of Cincinnati College of Medicine, Cincinnati, Ohio; and the Medical Research Service (K.R.W.), Department of Veterans Affairs Medical Center, Cincinnati, Ohio.
Correspondence and reprint requests to Kenneth R. Wagner, PhD, Research Service (151), Department of Veterans Affairs Medical Center, 3200 Vine St, Cincinnati, OH 45220.
Background and Purpose—Blood "toxicity" is hypothesized to induce edema and brain tissue injury following intracerebral hemorrhage (ICH). Lobar ICH in pigs produces rapidly developing, marked perihematomal edema (>10% increase in water content) associated with clot-derived plasma protein accumulation. Coagulation cascade activation and, specifically, thrombin itself contribute to edema development during the first 24 hours after gray matter ICH in rats. In the present study, we sought to determine whether blood clot formation is necessary for edema development by comparing intracerebral infusions of heparinized and unheparinized blood in pig (white matter) and in rat (gray matter). We also examined heparin's effect on thrombin-induced gray matter edema.
Methods—In pigs, we infused autologous blood (with or without heparin) into the cerebral white matter to produce lobar hematomas and froze the brains in situ at 1, 4, or 24 hours after ICH. We determined hematomal and perihematomal edema volumes on coronal sections by computer-assisted morphometry. In rats, we infused either blood or thrombin (with or without heparin) into the basal ganglia and measured water, sodium, and potassium contents at 24 hours after ICH.
Results—In pigs, unheparinized blood induced rapid (at 1 hour) and prolonged (24 hours) perihematomal edema (average volume, 1.29±0.20 mL; n=6). No perihematomal edema was present following heparinized blood infusions (n=6). In rats, unheparinized blood produced significantly greater edema than heparinized blood infusions. As with whole blood, thrombin-induced gray matter edema at 24 hours was significantly reduced by coinjection of heparin.
Conclusions—After ICH, blood clot formation is required for rapid and prolonged edema development in perihematomal white and gray matter. Thrombin also contributes to prolonged edema in gray matter.
Editorial Comment
Department of Neurosurgery, University of California, Davis, Sacramento, California
This article has been cited by other articles:
 |
|
 |
|
  M. Mehdiratta, S. Kumar, D. Hackney, G. Schlaug, and M. Selim Association Between Serum Ferritin Level and Perihematoma Edema Volume in Patients With Spontaneous Intracerebral Hemorrhage Stroke, April 1, 2008; 39(4): 1165 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.J. Yun, D.G. Na, B.J. Kwon, H.G. Rho, S.-H. Park, Y.-L. Suh, and K.-H. Chang A T1 Hyperintense Perilesional Signal Aids in the Differentiation of a Cavernous Angioma from Other Hemorrhagic Masses AJNR Am. J. Neuroradiol., March 1, 2008; 29(3): 494 - 500. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakamura, Y. Kuroda, S. Yamashita, X. Zhang, O. Miyamoto, T. Tamiya, S. Nagao, G. Xi, R. F. Keep, and T. Itano Edaravone Attenuates Brain Edema and Neurologic Deficits in a Rat Model of Acute Intracerebral Hemorrhage Stroke, February 1, 2008; 39(2): 463 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Broderick, S. Connolly, E. Feldmann, D. Hanley, C. Kase, D. Krieger, M. Mayberg, L. Morgenstern, C. S. Ogilvy, P. Vespa, et al. REPRINT: 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, October 16, 2007; 116(16): e391 - e413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Broderick, S. Connolly, E. Feldmann, D. Hanley, C. Kase, D. Krieger, M. Mayberg, L. Morgenstern, C. S. Ogilvy, P. Vespa, 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. Stroke, June 1, 2007; 38(6): 2001 - 2023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. D. Ardizzone, X. Zhan, B. P. Ander, and F. R. Sharp Src Kinase Inhibition Improves Acute Outcomes After Experimental Intracerebral Hemorrhage Stroke, May 1, 2007; 38(5): 1621 - 1625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Wagner Modeling Intracerebal Hemorrhage: Glutamate, Nuclear Factor-{kappa}B Signaling and Cytokines Stroke, February 1, 2007; 38(2): 753 - 758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hua, R. F. Keep, J. T. Hoff, and G. Xi Brain Injury After Intracerebral Hemorrhage: The Role of Thrombin and Iron Stroke, February 1, 2007; 38(2): 759 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Kase Hemostatic Treatment in the Early Stage of Intracerebral Hemorrhage: The Recombinant Factor VIIa Experience Stroke, October 1, 2005; 36(10): 2321 - 2322. [Full Text] [PDF]
|
|
|
|
|
|
J. Shao, G. Xi, Y. Hua, T. Schallert, and B. Felt Intracerebral Hemorrhage in the Iron-Deficient Rat Stroke, March 1, 2005; 36(3): 660 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Belayev, I. Saul, R. Busto, K. Danielyan, A. Vigdorchik, L. Khoutorova, and M. D. Ginsberg Albumin Treatment Reduces Neurological Deficit and Protects Blood-Brain Barrier Integrity After Acute Intracortical Hematoma in the Rat Stroke, February 1, 2005; 36(2): 326 - 331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Silva, R. Leira, J. Tejada, J. M. Lainez, J. Castillo, A. Davalos, and by the Stroke Project, Cerebrovascular Diseases Gr Molecular Signatures of Vascular Injury Are Associated With Early Growth of Intracerebral Hemorrhage Stroke, January 1, 2005; 36(1): 86 - 91. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. D. Ardizzone, A. Lu, K. R. Wagner, Y. Tang, R. Ran, and F. R. Sharp Glutamate Receptor Blockade Attenuates Glucose Hypermetabolism in Perihematomal Brain After Experimental Intracerebral Hemorrhage in Rat Stroke, November 1, 2004; 35(11): 2587 - 2591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Gong, Y. Hua, R. F. Keep, J. T. Hoff, and G. Xi Intracerebral Hemorrhage: Effects of Aging on Brain Edema and Neurological Deficits Stroke, November 1, 2004; 35(11): 2571 - 2575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wu, Y. Hua, R. F. Keep, T. Nakamura, J. T. Hoff, and G. Xi Iron and Iron-Handling Proteins in the Brain After Intracerebral Hemorrhage Stroke, December 1, 2003; 34(12): 2964 - 2969. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Belayev, I. Saul, K. Curbelo, R. Busto, A. Belayev, Y. Zhang, P. Riyamongkol, W. Zhao, and M. D. Ginsberg Experimental Intracerebral Hemorrhage in the Mouse: Histological, Behavioral, and Hemodynamic Characterization of a Double-Injection Model Stroke, September 1, 2003; 34(9): 2221 - 2227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Kamal, J. P. Dyke, J. M. Katz, B. Liberato, C. G. Filippi, R. D. Zimmerman, and A. M. Ulug Temporal Evolution of Diffusion after Spontaneous Supratentorial Intracranial Hemorrhage AJNR Am. J. Neuroradiol., May 1, 2003; 24(5): 895 - 901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O.P.M. Teernstra, S.M.A.A. Evers, J. Lodder, P. Leffers, C.L. Franke, and G. Blaauw Stereotactic Treatment of Intracerebral Hematoma by Means of a Plasminogen Activator: A Multicenter Randomized Controlled Trial (SICHPA) Stroke, April 1, 2003; 34(4): 968 - 974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Mayer Ultra-Early Hemostatic Therapy for Intracerebral Hemorrhage Stroke, January 1, 2003; 34(1): 224 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kitaoka, Y. Hua, G. Xi, J. T. Hoff, and R. F. Keep Delayed Argatroban Treatment Reduces Edema in a Rat Model of Intracerebral Hemorrhage Stroke, December 1, 2002; 33(12): 3012 - 3018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Gebel Jr, E. C. Jauch, T. G. Brott, J. Khoury, L. Sauerbeck, S. Salisbury, J. Spilker, T. A. Tomsick, J. Duldner, and J. P. Broderick Natural History of Perihematomal Edema in Patients With Hyperacute Spontaneous Intracerebral Hemorrhage Stroke, November 1, 2002; 33(11): 2631 - 2635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hua, T. Schallert, R. F. Keep, J. Wu, J. T. Hoff, and G. Xi Behavioral Tests After Intracerebral Hemorrhage in the Rat Stroke, October 1, 2002; 33(10): 2478 - 2484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Carhuapoma, P. B. Barker, D. F. Hanley, P. Wang, and N. J. Beauchamp Human Brain Hemorrhage: Quantification of Perihematoma Edema by Use of Diffusion-Weighted MR Imaging AJNR Am. J. Neuroradiol., September 1, 2002; 23(8): 1322 - 1326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Claassen, J. R. Carhuapoma, K. T. Kreiter, E. Y. Du, E. S. Connolly, and S. A. Mayer Global Cerebral Edema After Subarachnoid Hemorrhage: Frequency, Predictors, and Impact on Outcome Stroke, May 1, 2002; 33(5): 1225 - 1232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Castillo, A. Davalos, J. Alvarez-Sabin, J. M. Pumar, R. Leira, Y. Silva, J. Montaner, and C.S. Kase Molecular signatures of brain injury after intracerebral hemorrhage Neurology, February 26, 2002; 58(4): 624 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Xi, Y. Hua, R. R. Bhasin, S. R. Ennis, R. F. Keep, and J. T. Hoff Mechanisms of Edema Formation After Intracerebral Hemorrhage: Effects of Extravasated Red Blood Cells on Blood Flow and Blood-Brain Barrier Integrity Stroke, December 1, 2001; 32(12): 2932 - 2938. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Sjoblom, H.-G. Hardemark, A. Lindgren, B. Norrving, M. Fahlen, M. Samuelsson, L. Stigendal, D. Stockelberg, A. Taghavi, L. Wallrup, et al. Management and Prognostic Features of Intracerebral Hemorrhage During Anticoagulant Therapy: A Swedish Multicenter Study Stroke, November 1, 2001; 32(11): 2567 - 2574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xue and M. R. Del Bigio Acute Tissue Damage After Injections of Thrombin and Plasmin into Rat Striatum Stroke, September 1, 2001; 32(9): 2164 - 2169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. Qureshi, S. Tuhrim, J. P. Broderick, H. H. Batjer, H. Hondo, and D. F. Hanley Spontaneous Intracerebral Hemorrhage N. Engl. J. Med., May 10, 2001; 344(19): 1450 - 1460. [Full Text] [PDF]
|
|
|
|
|
|
G. Xi, Y. Hua, R. F. Keep, J. G. Younger, and J. T. Hoff Systemic Complement Depletion Diminishes Perihematomal Brain Edema in Rats Stroke, January 1, 2001; 32(1): 162 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xue, M. R. Del Bigio, and J. P. Muizelaar Intracortical Hemorrhage Injury in Rats : Relationship Between Blood Fractions and Brain Cell Death Editorial Comment: Relationship Between Blood Fractions and Brain Cell Death Stroke, July 1, 2000; 31(7): 1721 - 1727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Gebel, T. G. Brott, C. A. Sila, T. A. Tomsick, E. Jauch, S. Salisbury, J. Khoury, R. Miller, A. Pancioli, J. E. Duldner, et al. Decreased Perihematomal Edema in Thrombolysis-Related Intracerebral Hemorrhage Compared With Spontaneous Intracerebral Hemorrhage Stroke, March 1, 2000; 31(3): 596 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Xi, R. F. Keep, Y. Hua, J. Xiang, J. T. Hoff, and R. L. Macdonald Attenuation of Thrombin-Induced Brain Edema by Cerebral Thrombin Preconditioning • Editorial Comment Stroke, June 1, 1999; 30(6): 1247 - 1255. [Abstract] [Full Text] [PDF]
|
|